Was It Worth It? Critical Evaluation of a Novel Outcomes Measure in Oncologic Palliative Surgery.

BACKGROUND: Patient selection for palliative surgery is complex, and appropriate outcomes measures are incompletely defined. We explored the usefulness of a specific outcomes measure "was it worth it" in patients after palliative-intent operations for advanced malignancy. STUDY DESIGN: A retrospective review of a comprehensive longitudinal palliative surgery database was performed at an academic tertiary care center. All patients who underwent palliative-intent operation for advanced cancer from 2003 to 2022 were included. Patient satisfaction ("was it worth it") was reported within 30 days of operation after palliative-intent surgery. RESULTS: A total of 180 patients were identified, and 81.7% self-reported that their palliative surgery was "worth it." Patients who reported that their surgery was "not worth it" were significantly older and were more likely to have recurrent symptoms and to need reoperation. There was no significant difference in overall, recurrence-free, and reoperation-free survival for patients when comparing "worth it" with "not worth it." Initial symptom improvement was not significantly different between groups. Age older than 65 years (hazard ratio 0.25, 95% CI 0.07 to 0.80, p = 0.03), family engagement (hazard ratio 6.71, 95% CI 1.49 to 31.8, p = 0.01), and need for reoperation (hazard ratio 0.042, 95% CI 0.01 to 0.16, p < 0.0001) were all independently associated with patients reporting that their operation was "worth it." CONCLUSIONS: Here we demonstrate that simply asking a patient "was it worth it" after a palliative-intent operation identifies a distinct cohort of patients that traditional outcomes measures fail to distinguish. Family engagement and durability of an intervention are critical factors in determining patient satisfaction after palliative intervention. These data highlight the need for highly individualized care with special attention paid to patients self-reporting that their operation was "not worth it."

Integrated postoperative care model for older colorectal surgery patients improves outcomes and reduces healthcare costs.

BACKGROUND: Older surgical patients have an increased risk for postoperative complications, driving up healthcare costs. We determined if postoperative co-management of older surgery patients is associated with postoperative outcomes and hospital costs. METHODS: Retrospective data were collected for patients ≥70 years old undergoing colorectal surgery at a community teaching hospital. Patient outcomes were compared between those receiving postoperative surgery co-management care through the Optimization of Senior Care and Recovery (OSCAR) program and controls who received standard of care. Main outcome measures were postoperative complications and hospital charges, 30-day readmission rate, length of stay (LOS), and transfer to intensive care during hospitalization. Multivariable linear regression was used to model total charge and multivariable logistic regression to model complications, adjusted for multiple variables (e.g., age, sex, race, body mass index, Charlson Comorbidity Index [CCI], American Society of Anesthesiologists score, surgery duration). RESULTS: All 187 patients in the OSCAR and control groups had a similar mean CCI score of 2.7 (p = 0.95). Compared to the control group, OSCAR recipients experienced less postoperative delirium (17% vs. 8%; p = 0.05), cardiac arrhythmia (12% vs. 3%; p = 0.03), and clinical worsening requiring transfer to intensive care (20% vs. 6%; p < 0.005). OSCAR group patients had a shorter mean LOS among high-risk patients (CCI ≥3) (-1.8 days; p = 0.09) and those ≥80 years old (-2.3 days; p = 0.07) compared to the control group. Mean total hospital charge was $10,297 less per patient in the OSCAR group (p = 0.01), with $17,832 less per patient with CCI ≥3 (p = 0.01), than the control group. CONCLUSIONS: A co-management care approach after colorectal surgery in older patients improves outcomes and decreases costs, with the most benefit going to the oldest patients and those with higher comorbidity scores.

Deep RNA sequencing of intensive care unit patients with COVID-19.

COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.

Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations.

Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (>100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments. Clinical data were prospectively collected at multiple time points during ICU admission, and amino acid sequences for the NAb CDR3 segments were identified. Patients who survived severe COVID-19 had significantly more of a Class 3 antibody (C135) to SARS-CoV-2 compared to non-survivors (15059.4 vs. 1412.7, p = 0.016). In addition to highlighting the utility of RNA sequencing in revealing unique NAb profiles in COVID-19 patients with different outcomes, we provided a physical basis for our findings via atomistic modeling combined with molecular dynamics simulations. We established the interactions of the Class 3 NAb C135 with the SARS-CoV-2 spike protein, proposing a mechanistic basis for inhibition via multiple conformations that can effectively prevent ACE2 from binding to the spike protein, despite C135 not directly blocking the ACE2 binding motif. Overall, we demonstrate that deep RNA sequencing combined with structural modeling offers the new potential to identify and understand novel therapeutic(s) NAbs in individuals lacking certain immune responses due to their poor endogenous production. Our results suggest a possible window of opportunity for administration of such NAbs when their full sequence becomes available. A method involving rapid deep RNA sequencing of patients infected with SARS-CoV-2 or its variants at the earliest infection time could help to develop personalized treatments using the identified specific NAbs.

Predicting Anastomotic Leak After Elective Colectomy: Utility of a Modified Frailty Index.

BACKGROUND: Anastomotic leak is the most dreaded complication following colonic resection. While patient frailty is increasingly being recognized as a risk factor for surgical morbidity and mortality, the current colorectal body of literature has not assessed the relationship between frailty and anastomotic leak. OBJECTIVE: Evaluate the relationship between patient frailty and anastomotic leak as well as patient frailty and failure to rescue in patients who experienced an anastomotic leak. DESIGN: Retrospective cohort study. SETTING: American College of Surgeons National Surgical Quality Improvement Program Database from 2015 to 2017. PATIENTS: Patients with the diagnosis of colonic neoplasia undergoing an elective colectomy during the study time period. MAIN OUTCOME MEASURE: Anastomotic leak, failure to rescue. RESULTS: A total of 30,180 elective colectomies for neoplasia were identified. The leak rate was 2.9% (n = 880). Compared to nonfrail patients, frail patients were at increased odds of anastomotic leak (frailty score = 1: OR 1.34, 95% CI 1.10-1.63; frailty score = 2: OR 1.32, 95% CI 1.04-1.68; frailty score = 3: OR = 2.41, 95% CI 1.47-3.96). After an anastomotic leak, compared to nonfrail patient, a greater proportion of frail patients experienced mortality (3.4% vs 5.9%), septic shock (16.1% vs 21.0%), myocardial infarction (1.1% vs 2.9%), and pneumonia (6.8% vs 11.8%). Furthermore, the odds of mortality, septic shock, myocardial infarction, and pneumonia increased in frail patients with higher frailty scores. LIMITATIONS: Potential misclassification bias from lack of a strict definition of anastomotic leak and retrospective design of the study. CONCLUSION: Frail patients undergoing colectomy for colonic neoplasia are at increased risk of an anastomotic leak. Furthermore, once a leak occurs, they are more vulnerable to failure to rescue. See Video Abstract at http://links.lww.com/DCR/B784. PREDICCIN DE LA FUGA ANASTOMTICA DESPUS DE UNA COLECTOMA ELECTIVA UTILIDAD DE UN NDICE DE FRAGILIDAD MODIFICADO: ANTECEDENTES:La fuga anastomótica es la complicación más temida después de la resección colónica. Si bien la fragilidad del paciente se reconoce cada vez más como un factor de riesgo de morbilidad y mortalidad quirúrgicas, la bibliografía colorrectal actual no ha evaluado la relación entre la fragilidad y la fuga anastomótica.OBJETIVO:Evaluar la relación entre la fragilidad del paciente y la fuga anastomótica, así como la fragilidad del paciente y la falta de rescate en pacientes que sufrieron una fuga anastomótica.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos de 2015 a 2017.PACIENTES:Pacientes con diagnóstico de neoplasia de colon sometidos a colectomía electiva durante el período de estudio.PRINCIPAL MEDIDA DE RESULTADO:Fuga anastomótica, falta de rescate.RESULTADOS:Se identificaron 30.180 colectomías electivas por neoplasia. La tasa de fuga fue del 2,9% (n = 880). En comparación con los pacientes no frágiles, los pacientes frágiles tenían mayores probabilidades de fuga anastomótica para (puntuación de fragilidad = 1: OR = 1,34, IC del 95%: 1,10-1,63; puntuación de fragilidad = 2: OR = 1,32, IC del 95%: 1,04- 1,68; puntuación de fragilidad = 3: OR 2,41; IC del 95%: 1,47-3,96). Después de una fuga anastomótica, en comparación con un paciente no frágil, una mayor proporción de pacientes frágiles experimentó mortalidad (3,4% frente a 5,9%), choque séptico (16,1% frente a 21,0%), infarto de miocardio (1,1% frente a 2,9%) y neumonía (6,8% vs 11,8%). Además, las probabilidades de mortalidad, choque séptico, infarto de miocardio y neumonía aumentaron en pacientes frágiles con puntuaciones de fragilidad más altas.LIMITACIONES:Posible sesgo de clasificación errónea debido a la falta de una definición estricta de fuga anastomótica, diseño retrospectivo del estudio.CONCLUSIÓN:Los pacientes frágiles sometidos a colectomía por neoplasia de colon tienen un mayor riesgo de una fuga anastomótica. Además, una vez que ocurre una fuga, son más vulnerables a fallas en el rescate. Consulte Video Resumen en http://links.lww.com/DCR/B784.

Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation.

BACKGROUNDS/AIMS: Post-operative pancreatic fistulas (POPF) are a major source of morbidity following pancreaticoduodenectomy (PD). This study aims to investigate if persistent lymphopenia, a known marker of sepsis, can act as an additional marker of POPF with clinical implications that could help direct drain management. METHODS: A retrospective chart review of all patients who underwent PD in a single hospital network from 2008 to 2018. Persistent lymphopenia was defined as lymphopenia beyond post-operative day #3. RESULTS: Of the 201 patients who underwent PD during the study period 161 patients had relevant laboratory data, 81 of whom had persistent lymphopenia. 17 patients with persistent lymphopenia went on to develop a POPF, compared to 7 patients without. Persistent lymphopenia had a negative predictive value of 91.3%. Multivariate analysis revealed only persistent lymphopenia as being independently associated with POPF (HR 2.57, 95% CI 1.07-6.643, p=0.039). Patients with persistent lymphopenia were more likely to have a complication requiring intervention (56.8% vs 35.0%, p<0.001). CONCLUSIONS: Persistent lymphopenia is a readily available early marker of POPF that holds the potential to identify clinically relevant POPF in patients where no surgical drain is present, and to act as an adjunct of drain amylase helping to guide drain management.

Deep RNA Sequencing of Intensive Care Unit Patients with COVID-19.

PURPOSE: COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. METHODS: Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (>100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. RESULTS: We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. CONCLUSIONS: Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies. TAKE HOME MESSAGE: Deep RNA sequencing provides a novel diagnostic tool for critically ill patients. Among ICU patients with COVID-19, RNA sequencings can identify gene expression, pathogens (including SARS-CoV-2), and can predict mortality. TWEET: Deep RNA sequencing is a novel technology that can assist in the care of critically ill COVID-19 patients & can be applied to other disease.

Improving the value of palliative surgery by optimizing patient selection: The role of long-term survival on high impact palliative intent operations.

BACKGROUND: In order to better characterize outcomes of palliative surgery (PS), we evaluated patients that experienced top quartile survival to elucidate predictors of high impact PS. METHODS: All PS performed on advanced cancer patients from 2003 to 2017 were identified from a PS database. RESULTS: 167 patients were identified. Multivariate analysis demonstrated the ability to rise from a chair was independently associated with top quartile survival (HR 7.61, 95% CI 2.12-48.82, p=0.008) as was the need for re-operation (HR 2.81, 95% CI 1.26-6.30, p=0.0012). Patients who were able to rise from a chair had significantly prolonged overall survival (320 vs 87 days, p < 0.001). CONCLUSIONS: Although not the primary goal, long-term survival can be achieved following PS and is associated with re-operation and the ability to rise from a chair. These patients experience the benefits of PS for a longer period of time, which in turn maximizes value and positive impact. SUMMARY: Long-term survival and symptom control can be achieved in highly selected advanced cancer patients following palliative surgery. The ability of the patient to independently rise from a chair and the provider to offer a re-operation when indicated are associated with long-term survival following a palliative operation.

Inhalation injury is associated with long-term employment outcomes in the burn population: Findings from a cross-sectional examination of the Burn Model System National Database.

INTRODUCTION: Inhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury. METHODS: Data collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics. RESULTS: Data from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (p<0.001). Individuals with inhalation injury were less likely to be employed at 24 months post-injury compared to survivors without inhalation injury (OR = 0.63, p = 0.028). There were no significant differences in PCS, MCS, or SWLS scores between groups in adjusted regression analyses. CONCLUSIONS: Burn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms.

The Resident Outcome Project: Increased Academic Productivity Associated with a Formal Clinical Research Curriculum.

PURPOSE: A formal 2-year clinical research project in conjunction with a system-based practice and practice-based learning and improvement curriculum was initiated for all residents in our program. Within the structure of this formal clinical research curriculum, residents are required to develop a research hypothesis, develop an appropriate study design, collect and analyze data, and present a completed project. METHODS: At the end of the PGY1 year, residents select a project with an emphasis on quality improvement or clinical outcomes. The first 6 months of the 2-year program are dedicated to the identification of a faculty mentor and submission of a formal proposal to both the departmental education committee and to the institutional IRB. Over the following 12 months, residents meet monthly for required group research meetings. The final 6 months are focused on data analysis and project completion. RESULTS: Seventy-five residents have successfully completed the clinical research program since it was initiated in 2002. Completed projects led to abstracts accepted at 33 national or regional meetings and 11 peer reviewed publications to date. In addition, 3 major hospital wide quality improvement measures were initiated based on project findings. Following the first peer reviewed publication associated with these research projects in 2006, there have been significant increases in not only the number of accepted abstracts from these resident projects (3/18 [17%] vs 30/57 [53%], p = 0.008) but also the total number of all accepted resident clinical research (mean accepted abstracts per year 7.9 vs 1.0, p = 0.009 and mean peer reviewed publications per year 6.8 vs 2.0, p = 0.003.) DISCUSSION: Increased academic productivity was observed after a formal resident clinical research program was initiated in our program. Resident research efforts extended beyond the specific initial outcome projects as skills gained allowed for future independent clinical research.

Intoxication and Flame Burn Injuries in Young Adults in the United States.

Flame injuries are the primary cause of burns in young adults. Although drug and alcohol intoxication has been associated with other types of trauma, its role in burn injury has not been well described in this population. The purpose of this study was to investigate the association of intoxication and flame burn injuries in young adults in the United States. The 2014 Nationwide Emergency Department Sample was queried for burn injury visits of young adult patients, 13-25 years old. This data is weighted to allow for national estimates. Burn mechanism and intoxication status were determined by International Classification of Diseases, Ninth Revision codes. Multivariable logistic regression analysis was used to assess the association of intoxication and emergency department (ED) visits due to flame burns, adjusting for patient age, gender, zip code median income, zip code rural-urban designation, timing of visit, and hospital region. Further analyses assessed the odds of admission or transfer, as a possible proxy of injury severity, in patients with flame or other burns, with and without intoxication adjusting for patient age, gender, primary insurance, and hospital trauma designation. There were 20,787 visits for patients 13-25 years old with burn injuries and 12.9% (n = 2678) had a codiagnosis of intoxication. There was an increasing proportion of intoxication by age (5.8% 13-17 years old, 25% 18-20 years old, 69% 21-25 years old, P < .001). ED visits for burns with a codiagnosis of intoxication had 1.34 times ([95% confidence interval (CI): 1.18, 1.52], P < .01) higher odds of having flame burns compared to other burn mechanisms. Those with flame burns and intoxication were most likely to be admitted or transferred when compared to nonflame, nonintoxication visits in the adjusted model (odds ratio [OR] 5.49, [95% CI: 4.29, 7.02], P < .01). Furthermore, the odds of admission or transfer in visits with the combined exposure of intoxication and flame mechanism were significantly higher than visits due to nonflame burns and intoxication (OR 2.75, [2.25, 3.36], P < .01) or flame burns without intoxication (OR 3.00, [95% CI: 2.61, 3.42], P < .01). This study identified a significant association between flame-burn-related ED visits and intoxication in the young adult population in the United States. In addition, the combination of flame mechanism and intoxication appears to result in more substantial injury compared with either exposure alone. The relationship seen between intoxication and flame burn injury underscores a major target for burn prevention efforts in the young adult population.

Population of Patients With Traumatic Brain Injury in Skilled Nursing Facilities: A Decade of Change.

OBJECTIVE: To describe the natural history of patients with traumatic brain injury (TBI) admitted to skilled nursing facilities (SNFs) following hospitalizations. SETTING: Between 2005 and 2014. PARTICIPANTS: Adults who had incident admissions to skilled nursing facilities (SNFs) with a diagnosis of TBI. DESIGN: Retrospective review of the Minimum Data Set. MAIN MEASURES: Main variables were cognitive and physical function, length of stay, presence of feeding tube, terminal condition, and dementia. RESULTS: Incident admissions to SNFs increased annually from 17 247 patients to 20 787 from 2005 to 2014. The percentage of patients with activities of daily living score 23 or more decreased from 25% to 14% (P < .05). The overall percentage of patients with severe cognitive impairment decreased from 18% to 10% (P < .05). More patients had a diagnosis of dementia in 2014 compared with previous years (P < .05), and the presence of a terminal condition increased from 1% to 1.5% over the 10-year period (P < .05). The percentage of patients who stayed fewer than 30 days was noted to increase steadily over the 10 years, starting with 48% in 2005 and ending with 53% in 2013 (P < .05). CONCLUSION: Understanding past trends in TBI admissions to SNFs is necessary to guide appropriate discharge and predict future demand, as well as inform SNF policy and practice necessary to care for this subgroup of patients.

Changes in the process of alternative RNA splicing results in soluble B and T lymphocyte attenuator with biological and clinical implications in critical illness.

BACKGROUND: Critically ill patients with sepsis and acute respiratory distress syndrome have severely altered physiology and immune system modifications. RNA splicing is a basic molecular mechanism influenced by physiologic alterations. Immune checkpoint inhibitors, such as B and T Lymphocyte Attenuator (BTLA) have previously been shown to influence outcomes in critical illness. We hypothesize altered physiology in critical illness results in alternative RNA splicing of the immune checkpoint protein, BTLA, resulting in a soluble form with biologic and clinical significance. METHODS: Samples were collected from critically ill humans and mice. Levels soluble BTLA (sBTLA) were measured. Ex vivo experiments assessing for cellular proliferation and cytokine production were done using splenocytes from critically ill mice cultured with sBTLA. Deep RNA sequencing was done to look for alternative splicing of BTLA. sBTLA levels were fitted to models to predict sepsis diagnosis. RESULTS: sBTLA is increased in the blood of critically ill humans and mice and can predict a sepsis diagnosis on hospital day 0 in humans. Alternative RNA splicing results in a premature stop codon that results in the soluble form. sBTLA has a clinically relevant impact as splenocytes from mice with critical illness cultured with soluble BTLA have increased cellular proliferation. CONCLUSION: sBTLA is produced as a result of alternative RNA splicing. This isoform of BTLA has biological significance through changes in cellular proliferation and can predict the diagnosis of sepsis.

Group 2 Innate Lymphoid Cells (ILC2s) Are Key Mediators of the Inflammatory Response in Polymicrobial Sepsis.

Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells and inversely decline in the liver at 24 hours after septic insult. Sepsis also resulted in changes in ILC2 effector cytokine (IL-13) and activating cytokine (IL-33) in the plasma of mice and human patients in septic shock. Of interest, the sepsis-induced changes in cytokines were abrogated in mice deficient in functionally invariant natural killer T cells. Mice deficient in IL-13-producing cells, including ILC2s, had a survival advantage after sepsis along with decreased morphologic evidence of tissue injury and reduced IL-10 levels in the peritoneal fluid. Administration of a suppressor of tumorigenicity 2 (IL-33R) receptor-blocking antibody led to a transient survival advantage. Taken together, these findings suggest that ILC2s may play an unappreciated role in mediating the inflammatory response in both mice and humans; further, modulating ILC2 response in vivo may allow development of immunomodulatory strategies directed against sepsis.

Outcomes in nursing home patients with traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability in the United States. In survivors, traumatic brain injury remains a leading contributor to long-term disability and results in many patients being admitted to skilled nursing facilities for postacute care. Despite this very large population of traumatic brain injury patients, very little is known about the long-term outcomes of traumatic brain injury survivors, including rates of discharge to home or risk of death in long-term nursing facilities. We hypothesized that patient demographics and functional status influence outcomes of patients with traumatic brain injury admitted to skilled nursing facilities. METHODS: We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries aged 65 and older discharged alive and directly from hospital to a skilled nursing facility between 2011 and 2014 using the prospectively maintained Federal Minimum Data Set combined with Medicare claims data and the Centers for Medicare and Medicaid Services Vital Status files. Records were reviewed for demographic and clinical characteristics at admission to the skilled nursing facility, including age, sex, cognitive function, ability to communicate, and motor function. Activities of daily living were reassessed at discharge to calculate functional improvement. We used robust Poisson regression with skilled nursing facility fixed effects to calculate relative risks and 99% confidence intervals for mortality and functional improvement associated with the demographic and clinical characteristics present at admission. Linear regression was used to calculate adjusted mean duration of stay. RESULTS: Overall, 87,292 Medicare fee-for-service beneficiaries with traumatic brain injury were admitted to skilled nursing facilities. The mean age was 84 years, with 74% of patients older than age 80. Generally, older age, male sex, and poor cognitive or functional status at admission to a skilled nursing facility were associated with increased risk for poorer outcomes. Older patients (age ≥80 years) with traumatic brain injury had a 1.5 times greater risk of death within 30 days of admission compared with adults younger than 80 years (relative risk = 1.49, 99% confidence interval = 1.36, 1.64). Women were 37% less likely to die than men were (relative risk = 0.63, 99% confidence interval = 0.59, 0.68). The risk of death was greater for patients with poor cognitive function (relative risk = 2.55, 99% confidence interval = 2.32, 2.77), substantial motor impairment (relative risk = 2.44, 99% confidence interval = 2.16, 2.77), and patients with impairment in communication (relative risk = 2.58, 99% confidence interval = 2.32, 2.86) compared with those without the respective deficits. One year after admission, these risk factors continued to confer excess risk for mortality. Duration of stay was somewhat greater for older patients (30.1 compared with 27.5 average days) and patients with cognitive impairment (31.7 vs 27.5 average days). At discharge, patients with cognitive impairment (relative risk = 0.86, 99% confidence interval = 0.83, 0.88) and impairment in the ability to communicate (relative risk = 0.67, 99% confidence interval = 0.54, 0.82) were less likely to improve in physical function. CONCLUSION: Our results suggest that among patients with traumatic brain injury admitted to skilled nursing facilities, the likelihood of adverse outcomes varies significantly by key demographic and clinical characteristics. These findings may facilitate setting expectations among patients and families as well as providers when these patients are admitted to skilled nursing facilities for rehabilitation after their acute episode.

Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from critically ill patients.

BACKGROUND: Multi-organ failure occurs during critical illness and is mediated in part by destructive neutrophil-to-endothelial interactions. The ß2 integrin receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the adhesion of activated neutrophils to inflamed endothelia which, when prolonged and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small molecule allosteric activator of CR3 and has been shown to promote adhesion of blood neutrophils to inflamed endothelium and restrict tissue infiltration. Therefore, LA-1 offers a novel mechanism of anti-inflammatory action by activation, rather than inhibition, of the neutrophil CR3 integrin. However, whether promotion of neutrophil-to-endothelial interaction by this novel therapeutic is of benefit or detriment to endothelial barrier function is not known. METHODS: Critically ill septic and trauma patients were prospectively enrolled from the surgical and the trauma ICU. Blood was collected from these patients and healthy volunteers. Neutrophils were isolated by dextran sedimentation and adhered to TNF-α (tumor necrosis factor-α)-activated human umbilical vein endothelial (HUVEC) monolayers in the presence or absence of fMLP (formylmethionine-leucine-phenylalanine) and/or LA-1. Electric cell-substrate impedance sensing (ECIS) and exposure of underlying collagen were used to quantify endothelial barrier function and permeability. RESULTS: Neutrophils from critically ill trauma and septic patients caused similar degrees of endothelial barrier disruption which exceeded that caused by cells obtained from healthy controls both kinetically and quantitatively. LA-1 protected barrier function in the absence and presence of fMLP which served as a secondary stimulant to cause maximal loss of barrier function. LA-1 protection was also observed by quantifying collagen exposure underlying endothelial cells challenged with fMLP-stimulated neutrophils. LA-1 treatment resulted in decreased migration dynamics of neutrophils crawling on an endothelial monolayer with reduced speed (µm/s = 0.25 ± 0.01 vs. 0.06 ± 0.01, p < 0.05), path length (µm = 199.5 ± 14.3 vs. 42.1 ± 13.0, p < 0.05), and displacement (µm = 65.2 ± 4.7 vs. 10.4 ± 1.3; p < 0.05). CONCLUSION: Neutrophils from patients with trauma or sepsis cause endothelial barrier disruption to a similar extent relative to each other. The CR3 agonist LA-1 protects endothelial barrier function from damage caused by neutrophils obtained from both populations of critically ill patients even when exposed to secondary stimulation.

Trauma morning report is the ideal environment to teach and evaluate resident communication and sign-outs in the 80 hour work week.

BACKGROUND: The 80h work week has raised concerns that complications may increase due to multiple sign-outs or poor communication. Trauma Surgery manages complex trauma and acute care surgical patients with rapidly changing physiology, clinical demands and a large volume of data that must be communicated to render safe, effective patient care. Trauma Morning Report format may offer the ideal situation to study and teach sign-outs and resident communication. MATERIALS AND METHODS: Surgery Residents were assessed on a 1-5 scale for their ability to communicate to their fellow residents. This consisted of 10 critical points of the presentation, treatment and workup from the previous night's trauma admissions. Scores were grouped into three areas. Each area was scored out of 15. Area 1 consisted of Initial patient presentation. Area 2 consisted of events in the trauma bay. Area 3 assessed clarity of language and ability to communicate to their fellow residents. The residents were assessed for inclusion of pertinent positive and negative findings, as well as overall clarity of communication. In phase 1, residents were unaware of the evaluation process. Phase 2 followed a series of resident education session about effective communication, sign-out techniques and delineation of evaluation criteria. Phase 3 was a resident-blinded phase which evaluated the sustainability of the improvements in resident communication. RESULTS: 50 patient presentations in phase 1, 200 in phase 2, and 50 presentations in phase 3 were evaluated. Comparisons were made between the Phase 1 and Phase 2 evaluations. Area 1 (initial events) improved from 6.18 to 12.4 out of 15 (p<0.0001). Area 2 (events in the trauma bay) improved from 9.78 to 16.53 (p<0.0077). Area 3 (communication and language) improved from 8.36 to 12.22 out of 15 (P<0.001). Phase 2 to Phase 3 evaluations were similar, showing no deterioration of skills. CONCLUSIONS: Trauma Surgery manages complex surgical patients, with rapidly changing physiologic and clinical demands. Trauma Morning Report, with diverse attendance including surgical attendings and residents in various training years, is the ideal venue for real-time teaching and evaluation of sign-outs and reinforcing good communication skills in residents.

Predictors of 30-Day Pulmonary Complications after Outpatient Surgery: Relative Importance of Body Mass Index Weight Classifications in Risk Assessment.

BACKGROUND: Current literature is controversial regarding the importance of obese BMI classifications as a risk factor for pulmonary complications after outpatient surgery. The objective of the current investigation was to evaluate predictors of pulmonary outcomes after outpatient surgery and to assess the importance of BMI weight classifications in risk assessment. STUDY DESIGN: Patients with "outpatient" recorded as their inpatient/outpatient status in the 2012 to 2013 NSQIP database were included. The primary outcome of interest was the occurrence of a new pulmonary complication (eg pneumonia, pulmonary embolism, unplanned intubation, or ventilator-assisted respiration for greater than 48 hours) within 30 days of surgery. RESULTS: There were 444,532 cases included in the final analysis. There were 996 (0.22%; 99% CI 0.21% to 0.24%) all-cause pulmonary complications. Binary logistic regression identified BMI as an independent predictor of a pulmonary complication, unadjusted odds ratio 1.091 (99.75% CI 1.026 to 1.160) per 5 kg/m2 change in BMI, p < 0.001. Adjusted odds of a pulmonary complication with a BMI of 35 to 39.99 kg/m2 was 1.44 (99.75% CI 1.01 to 2.06; p = 0.002) and with a BMI of 40 to 49.99 kg/m2 was 1.68 (99.75% CI 1.13 to 2.50; p < 0.001) compared with a BMI of 18.5 to 24.99 kg/m2. CONCLUSIONS: Obese classes II and III were associated with an independent risk of a pulmonary complication. The risk associated with obesity was low compared with the risk associated with advanced age, prolonged surgical duration, and the risk of comorbidities including congestive heart failure, COPD, and renal failure.

Postoperative Infections are Associated with Increased Risk of Cardiac Events in Vascular Patients.

BACKGROUND: Despite advances in perioperative care, the rate of cardiac events in vascular patients remains high. We have previously shown that infections in trauma patients are associated with higher rates of subsequent cardiac complications, likely due to the additive effect of a second hit of an infection following the trauma. The aim of this study was to investigate whether there is an association between postoperative infections and subsequent cardiac events in vascular patients. METHODS: A 5-year retrospective review of demographics, comorbidities, operative interventions, infectious, and cardiac events in all vascular patients who underwent an operative intervention at a single tertiary referral center was performed. In patients with clinical suspicion of myocardial injury, myocardial damage was defined as troponin >0.15 ng/mL and myocardial infarction (MI) as troponin >1 ng/mL. Pneumonia was diagnosed using bronchoalveolar lavage (BAL) and considered positive if BAL fluid culture contained >10,000 colony-forming units (cfu). Urinary tract infection (UTI) was diagnosed if the urine culture contained >100,000 cfu. All other infections were diagnosed by culture data. Regression analysis was performed to assess risk of cardiac events as a function of infections adjusting for age, gender, and comorbidities. RESULTS: We analyzed 1,835 vascular operative interventions with the mean age of the cohort 65.5 years (65.9% male). The overall infection rate was 13.2%, with UTI being the most common (60.3%). The overall rate of myocardial damage was 8.1% and the rate of MI 3.8%. Rates of both myocardial damage (15.5 vs. 7.7%; P = 0.0015) and MI (7.1 vs. 3.4%; P = 0.018) were significantly higher in patients with infections, compared to those without infections. Adjusting for age, gender, medical comorbidities, open versus endovascular cases as well as statin and steroid use, patients with UTI were more likely to subsequently develop either myocardial damage (odds ratio [OR] = 3.57 [95% confidence interval = 1.51-8.45]) or MI (OR = 4.20 [1.23-14.3]). A similar association was noted between any infections and either myocardial damage (OR = 2.97 [1.32-6.65]) or MI (OR = 4.31 [1.44-12.94]). CONCLUSIONS: We herein describe an association between postoperative infections, most commonly UTI, and subsequent cardiac events. Efforts should be made to minimize the risk of developing infections to ensure cardioprotection in vascular patients during perioperative period.