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.

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.

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.

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.

Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS).

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. DESIGN, SETTING, AND SUBJECTS: Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10-13) with ARDS and controls (n = 5-10) as well as a murine model of ARDS (n = 5-6) with controls (n = 6-7) were studied. METHODS: ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). RESULTS: Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1-1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717-1.093), p = 0.015), and human BAL (AUC = 1(1-1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). CONCLUSIONS: This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.

Elevated C-reactive protein as a predictor of patient outcomes following palliative surgery.

BACKGROUND AND OBJECTIVES: Optimal surgical decision-making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data. Elevated C-reactive protein (CRP) may help guide patient selection for palliative surgery. METHODS: Procedures to palliate symptoms of advanced cancer were identified from a prospective palliative surgery database. Patients with a recorded preoperative serum CRP were identified and observed for at least 180 days or until death. RESULTS: Fifty patients were identified who underwent an elective palliative procedure from July 2006 to June 2012. Presenting symptoms included gastrointestinal obstruction (40%), tumor-related pain (38%) or bleeding (12%), and other (10%). Symptom improvement was documented for 37 patients (74%). Palliative procedures were associated with 30-day postoperative morbidity (42%) and mortality (10%). CRP (range 1-144 mg/L, median 9.7 mg/L) was elevated in 27 patients (54%) and was independently associated with developing a major complication (P = 0.005) and decreased overall survival (166 vs. 659 days, P < 0.0001). CONCLUSIONS: Patients with advanced cancer can be afforded symptom improvement and the opportunity for improved quality of life following palliative procedures. Elevated preoperative CRP may help identify patients who are less likely to realize the benefits of palliative operations.

Assessment of surgical residents in a vascular anastomosis laboratory.

BACKGROUND: We designed a simple, low-cost workshop to teach surgical residents the basic skills of vascular anastomosis. We studied our ability to identify objective procedural and end-product metrics that could be used to measure improvement in vascular anastomotic skill before and after training. MATERIALS AND METHODS: Ten postgraduate year 2 residents without previous vascular surgery experience and four attending surgeons (expert) performed end-to-side anastomosis using a synthetic graft. The residents were taught the basic skills of vascular anastomosis during three didactic workshops. The objective metrics included volume leakage after saline perfusion (leak) and the time needed to complete the anastomosis. Penalty points were assigned for broken sutures, air knots, locking sutures, and failure to maintain an outside-in to inside-out technique. The leak, time, and penalties before and after training were compared. RESULTS: The mean leak was 70.4 ± 13.7 mL and the mean completion time was 18.7 ± 3 min for the pretraining group versus 45.3 ± 10.6 mL (P < 0.01) and 8.5 ± 1 min (P < 0.001), respectively, for the attending group. After training, significant improvement was seen in resident leak (46.7 ± 6.8 mL; P < 0.001) and completion time (14.4 ± 3 min; P < 0.01). Leak was similar between the post-training and expert groups (46.7 ± 6.8 mL and 45.3 ± 10.6 mL, respectively; P = 0.77); however, a significant difference for the completion time remained (14.4 ± 3.0 min and 8.5 ± 1 min, respectively; P < 0.01). The mean number of technical errors improved from 2.7 in the pretraining group to zero for the post-training group after completing the workshop. CONCLUSIONS: We have reported an easy to implement workshop for teaching surgical residents the basic skills of performing vascular anastomosis.

Empiric antibiotics pending bronchoalveolar lavage data in patients without pneumonia significantly alters the flora, but not the resistance profile, if a subsequent pneumonia develops.

INTRODUCTION: Ventilator-associated pneumonia (VAP) occurs in up to 25% of mechanically ventilated patients, with an associated mortality up to 50%. Early diagnosis and appropriate empiric antibiotic coverage of VAP are crucial. Given the multitude of noninfectious clinical and radiographic anomalies within trauma patients, microbiology from bronchioalveolar lavage (BAL) is often needed. Empiric antibiotics are administered while awaiting BAL culture data. Little is known about the effects of these empiric antibiotics on patients with negative BAL microbiology if a subsequent VAP occurs during the same hospital course. METHODS: This is a retrospective chart review of intubated trauma patients undergoing BAL for suspected pneumonia over a 3-y period at a Level 1 trauma center. All patients with suspected VAP undergoing a BAL receive empiric antibiotics. If microbiology data are negative at 72 h, all antibiotics are stopped; however, if the BAL returns with ≥10(5) colony-forming units per milliliter, the diagnosis of VAP is confirmed. We divided patients into three groups. Group 1 consisted of patients in whom the initial BAL was positive for VAP. Group 2 consisted of patients with an initial negative BAL, who subsequently developed VAP at a later point in the hospital course. Group 3 consisted of patients with negative BAL who did not develop a subsequent VAP. RESULTS: We obtained 499 BAL specimens in 185 patients over the 3-y period. A total of 14 patients with 23 BAL specimens initially negative for VAP subsequently developed VAP later during the same hospital stay. These patients did not have an increase in the hospital length of stay, intensive care unit days, ventilator days, or mortality compared with those who had a positive culture on the first suspicion of VAP. There was a significant increase in the percentage of Enterobacter (21% versus 8%) and Morganella (8% versus 0%) as the causative organism in these 14 patients when the VAP occurred. Furthermore, the profile of the top two organisms in each group changed. Enterobacter (21%) and Pseudomonas (17%) were the principal organisms in the initial BAL-negative group, whereas the two predominant strains in the initial positive BAL group were methicillin-sensitive Staphylococcus aureus (21%) and Haemophilus influenza (11%). Interestingly, methicillin-resistant S. aureus remained the third most common organism in both groups. Empiric antibiotics also did not seem to induce the growth of multidrug-resistant organisms, and there was no increased rate of secondary infections such as Clostridium difficile. CONCLUSIONS: Ventilator-associated pneumonia remains a significant cause of morbidity and mortality in mechanically ventilated trauma patients. The diagnosis and treatment of VAP continue to be challenging. Once clinically suspected, empiric coverage decreases morbidity and mortality. Our data demonstrate that patients who receive empiric coverage exhibit a significantly different microbiologic profile compared with those who had an initial positive BAL culture. Initial empiric antibiotics in BAL-negative patients were not associated with an increase in multidrug-resistant organisms, hospital, or intensive care unit length of stay, ventilator days, and mortality or secondary infections.

Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity.

INTRODUCTION: Sepsis is characterized by systemic immune activation and neutrophil-mediated endothelial barrier integrity compromise, contributing to end-organ dysfunction. Studies evaluating endothelial barrier dysfunction induced by neutrophils from septic patients are lacking, despite its clinical significance. We hypothesized that septic neutrophils would cause characteristic patterns of endothelial barrier dysfunction, distinct from experimental stimulation of normal neutrophils, and that treatment with the immunomodulatory drug ß-glucan would attenuate this effect. METHODS: Blood was obtained from critically ill septic patients. Patients were either general surgery patients (Primary Sepsis (PS)) or those with sepsis following trauma (Secondary Sepsis (SS)). Those with acute respiratory distress syndrome (ARDS) were identified. Healthy volunteers served as controls. Neutrophils were purified and aliquots were untreated, or treated with fMLP or ß-glucan. Endothelial cells were grown to confluence and activated with tissue necrosis factor (TNF)-α . Electric Cell-substrate Impedance Sensing (ECIS) was used to determine monolayer resistance after neutrophils were added. Groups were analyzed by two-way analysis of variance (ANOVA). RESULTS: Neutrophils from all septic patients, as well as fMLP-normal neutrophils, reduced endothelial barrier integrity to a greater extent than untreated normal neutrophils (normalized resistance of cells from septic patients at 30 mins = 0.90 ± 0.04; at 60 mins = 0.73 ± 0.6 and at 180 mins = 0.56 ± 0.05; p < 0.05 vs normal). Compared to untreated PS neutrophils, fMLP-treated PS neutrophils caused further loss of barrier function at all time points; no additive effect was noted in stimulation of SS neutrophils beyond 30 min. Neutrophils from ARDS patients caused greater loss of barrier integrity than those from non-ARDS patients, despite similarities in age, sex, septic source, and neutrophil count. Neutrophils obtained after resolution of sepsis caused less barrier dysfunction at all time points. ß-glucan treatment of septic patients' neutrophils attenuated barrier compromise, rendering the effect similar to that induced by neutrophils obtained once sepsis had resolved. CONCLUSIONS: Neutrophils from septic patients exert dramatic compromise of endothelial barrier integrity. This pattern is mimicked by experimental activation of healthy neutrophils. The effect of septic neutrophils on the endothelium depends upon the initial inflammatory event, correlates with organ dysfunction and resolution of sepsis, and is ameliorated by ß-glucan.

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.

Mechanisms of indirect acute lung injury: a novel role for the coinhibitory receptor, programmed death-1.

OBJECTIVE: To determine the contribution of programmed death receptor (PD)-1 in the morbidity and mortality associated with the development of indirect-acute lung injury. BACKGROUND: The immune cell interaction(s) leading to indirect-acute lung injury are not completely understood. In this respect, we have recently shown that the murine cell surface coinhibitory receptor, PD-1, has a role in septic morbidity/mortality that is mediated in part through the effects on the innate immune arm. However, it is not know if PD-1 has a role in the development of indirect-acute lung injury and how this may be mediated at a cellular level. METHODS: PD-1 -/- mice were used in a murine model of indirect-acute lung injury (hemorrhagic shock followed 24 hours after with cecal ligation and puncture-septic challenge) and compared to wild type controls. Groups were initially compared for survival and subsequently for markers of pulmonary inflammation, influx of lymphocytes and neutrophils, and expression of PD-1 and its ligand-PD-L1. In addition, peripheral blood leukocytes of patients with indirect-acute lung injury were examined to assess changes in cellular PD-1 expression relative to mortality. RESULTS: PD-1 -/- mice showed improved survival compared to wild type controls. In the mouse lung, CD4+, CD11c+, and Gr-1+ cells showed increased PD-1 expression in response to indirect-acute lung injury. However, although the rise in bronchial alveolar lavage fluid protein concentrations, lung IL-6, and lung MCP-1 were similar between PD-1 -/- and wild type animals subjected to indirect acute lung injury, the PD-1 -/- animals that were subjected to shock/septic challenge had reduced CD4:CD8 ratios, TNF-α levels, MPO activity, and Caspase 3 levels in the lung. Comparatively, we observed that humans, who survived their acute lung injury, had significantly lower expression of PD-1 on T cells. CONCLUSIONS: PD-1 expression contributes to mortality after the induction of indirect-acute lung injury and this seems to be associated with modifications in the cellular and cytokine profiles in the lung.

The reflective statement: a new tool to assess resident learning.

PURPOSE: Continued assessment and redesign of the curriculum is essential for optimal surgical education. For the last 3 y, we have asked the residents to reflect on the previous week and describe "the best thing" they learned. We hypothesize that this statement could be used to assess the weaknesses or strengths of our curriculum. METHODS: Starting in 2007, residents filled out surveys approximately 4 times/y at the start of a mandatory conference. They were asked to describe the "best thing" they learned that week, where it was learned, and who taught it. Residents were not asked to classify the item learned by core competency (communication, knowledge, patient care, practice-based learning, professionalism, and systems-based practice). This categorization into core competencies was done as part of our study design. Attending, fellow, resident, or other were used as groups designating who taught each item. Where the item was learned was fit into either clinic, conference, operating room (OR), wards, or self. The impact of postgraduate year (PGY) level on learning was also assessed. χ(2) analysis was used to compare groups. RESULTS: During the study period, 304 surveys were completed and returned by 65 residents. The majority of responses came from PGY 1 residents (134, 43%). Patient care and knowledge were the most common core competencies learned. As PGY level increased, learning of professionalism (P = 0.035) increased. A majority of learning was experiential (wards and OR, P < 0.0125). Self-learning and learning in clinic was a minor component of learning (P < 0.0125). Learning on wards (P < 0.001) decreased as residents progressed and learning from the OR (P = 0.002) had the opposite trend. CONCLUSIONS: Patient care and knowledge are the most frequently cited competencies learned by the residents. Self-learning is not a significant source of learning, and the majority of the learning is experiential. It is not known if this was a sign that there was a lack of self-directed learning or that self-directed learning was not an efficient method of learning. In addition, each PGY level learns differently (teacher and location of learning), perhaps reflecting the different needs and/or structure of each PGY. We believe the reflective statement has been and will be a useful tool to assess our curriculum.

Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern.

INTRODUCTION: Following trauma and systemic inflammatory response syndrome (SIRS), the typical response is an elevation of the total complete blood count (CBC) and a reduction of the lymphocyte count. This leukocytosis typically returns to normal within 48 hours. The persistence of a leukocytosis following trauma is associated with adverse outcomes. Although lymphocyte anergy and dysfunction following trauma is associated with increased risk for infection and sepsis, there is a paucity of data regarding the impact of a persistence of a low lymphocyte count in trauma patients. METHODS: This is a retrospective review of prospectively collected data from trauma patients collected over the 5 years of September 2003 to September 2008. Patients were included if the injury severity score (ISS) was >or=15, and they survived at least 3 days. Demographic data, mechanism and injury severity score, mortality, and length of stay were collected from the medical record. Laboratory values for the first 4 hospital days were collected. Leukocyte, neutrophil and lymphocyte counts were extracted from the daily complete blood count (CBC). Patients were then grouped based on response (elevation/depression) of each component of the CBC, and their return, or failure thereof, to normal. Proportional hazards regression with time-varying covariates as well as Kaplan-Meier curves were used to predict risk of death, time to death and time to healthy discharge based on fluctuations of the individual components of the CBC. RESULTS: There were 2448 patients admitted over the 5 years included in the analysis. When adjusting for age, gender and ISS the relative risk of death was elevated with a persistent leukocytosis (2.501 (95% CI=1.477-4.235)) or failure to normalize lymphopenia (1.639 (95% CI=10.17-2.643)) within the first 4 days following admission. Similar results were seen when Kaplan-Meier curves were created. Persistent lymphopenia was associated with shortest time to death. Paradoxically in survivors persistent lymphopenia was associated with the shortest time to discharge. CONCLUSIONS: Persistently abnormal CBC responses are associated with a higher mortality following trauma. This is the first report noting that a failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality.

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.

Impact of socioethnic factors on outcomes following traumatic brain injury.

BACKGROUND: Ethnic minorities and low income families tend to be in poorer health and have worse outcomes for a spectrum of diseases. Health care provider bias has been reported to potentially affect the distribution of care away from poorer communities, minorities, and patients with a history of substance abuse. Trauma is perceived as a disease of the poor and medically underserved. Minorities are overrepresented in low income populations and are also less likely to possess health insurance leading to a potential overlapping effect. Traumatic brain injury (TBI) is a predominant cause of mortality and long-term morbidity, which imposes a considerable social and financial burden. We therefore sought to determine the independent effect on outcome after TBI from race, insurance status, intoxication on presentation, and median income. METHODS: A 5-year retrospective chart review of admitted trauma patients aged 18 years and older to a Level I trauma center. Zip code of residency was a surrogate marker for socioeconomic status, because median income for each zip code is available from the US Census. Charts review included race, insurance status, mechanisms of trauma, and injuries sustained. Outcomes were placement of tracheostomy, hospital length of stay (HLOS), leaving Against Medical Advice (AMA), and discharge to home versus rehabilitation and mortality. RESULTS: A total of 3,101 TBI patients were included in the analyses. Multivariable logistic and proportional hazard regression analyses were undertaken adjusting for age, gender, Injury Severity Score, and mechanism. Rates of tracheostomy placement were unaffected by race, median income, or insurance status. Race and median income did not affect HLOS, but private insurance was associated with shorter HLOS and intoxication was associated with longer HLOS. Neither race nor intoxication affected rates of AMA, but higher income and private insurance was associated with lower rates of AMA. Non-Caucasian race and lack of insurance had significantly lower likelihood of placement in a rehabilitation center. Mortality was unaffected by race, increased in intoxicated patients, was variably affected by median income, and was lowest in patients with private insurance. CONCLUSIONS: An extremely complex interplay exists between socioethnic factors and outcomes after TBI. Few physicians would claim overt discrimination. Tracheostomy, the factor most directed by the surgeon, was unbiased by race, income, or insurance status. The likelihood of placement in a rehabilitation center was significantly impacted by both race and insurance status. Future prospective studies are needed to better address causation.

The development of a urinary tract infection is associated with increased mortality in trauma patients.

BACKGROUND: In October 2008, Medicare and Medicaid stopped paying for care associated with catheter-related urinary tract infections (UTIs). Although most clinicians agree UTIs are detrimental, there are little data to support this belief. METHODS: This is a retrospective review of trauma registry data from a Level I trauma center between 2003 and 2008. Two proportional hazards regressions were used for analyses. The first predicted acquisition of UTI as a function of indwelling urinary catheter use, adjusting for age, diabetes, gender, and injury severity. The second predicted hospital mortality as a function of UTI, covarying for age, gender, chronic obstructive pulmonary disease, congestive heart failure, hypertension, diabetes, pneumonia, and injury severity. RESULTS: After excluding patients who stayed in the hospital <3 days and those with a UTI on arrival, 5,736 patients were included in the study. Of these patients, 680 (11.9%) met criteria for a UTI, with 487 (71.6%) indwelling urinary catheter-related infections. Predictors of UTI included the interaction between age and gender (p = 0.0018), Injury Severity Score (p = 0.0021), and indwelling urinary catheter use (p < 0.001). The development of a UTI predicted the risk of in-hospital death as a patient's age increased (p = 0.002). Similar results were seen when only catheter-associated UTIs are included in the analysis. CONCLUSIONS: Indwelling urinary catheter use is connected to the development of UTIs, and these infections are associated with a greater mortality as the age of a trauma patients increases.

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.