Prevention of post-operative adhesions: Model development and pilot outcomes of human placental stem cell-based interventions.

BACKGROUND: Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)-based therapies. METHODS: Forty-four (n = 44) male Sprague-Dawley rats (250-350 g) were used in the experiment. Of these, thirty-eight (n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 106 cells/10 mL Plasmalyte A), hPSC-CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post-operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison. RESULTS: The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC-CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT. DISCUSSION: The presented rat model and scoring system represent the clinical adhesion disease process. hPSC-based interventions significantly reduce abdominal adhesions in this pilot dataset.

Geographic Variation in Operative Management of Adhesive Small Bowel Obstruction.

INTRODUCTION: Variation in surgical management exists nationally. We hypothesize that geographic variation exists in adhesive small bowel obstruction (aSBO) management. MATERIALS AND METHODS: A retrospective analysis of a national commercial insurance claims database (MarketScan) sample (2017-2019) was performed in adults with hospital admission due to aSBO. Geographic variation in rates of surgical intervention for aSBO was evaluated by state and compared to a risk-adjusted national baseline using a Bayesian spatial rates Poisson regression model. For individual-level analysis, patients were identified in 2018, with 365-d look back and follow-up periods. Logistic regression was performed for individual-level predictors of operative intervention for aSBO. RESULTS: Two thousand one hundred forty-five patients were included. State-level analysis revealed rates of operative intervention for aSBO were significantly higher in Missouri and lower in Florida. On individual-level analysis, age (P < 0.01) and male sex (P < 0.03) but not comorbidity profile or prior aSBO, were negatively associated with undergoing operative management for aSBO. Patients presenting in 2018 with a history of admission for aSBO the year prior experienced a five-fold increase in odds of representation (odds ratio: 5.4, 95% confidence interval: 3.1-9.6) in 2019. Patients who received an operation for aSBO in 2018 reduced the odds of readmission in the next year by 77% (odds ratio: 0.23, 95% confidence interval: 0.1-0.5). The volume of operations performed within a state did not influence readmission. CONCLUSIONS: Surgical management of aSBO varies across the continental USA. Operative intervention is associated with decreased rates of representation in the following year. These data highlight a critical need for standardized guidelines for emergency general surgery patients.

Regenerative Medicine Therapies for Prevention of Abdominal Adhesions: A Scoping Review.

INTRODUCTION: Globally, abdominal adhesions constitute a significant burden of morbidity and mortality. They represent the commonest complication of abdominal operations with a lifelong risk of multiple pathologies, including adhesive small bowel obstruction, female infertility, and chronic pain. Adhesions represent a problem of the entire abdomen, forming at the time of injury and progressing through multiple complex pathways. Clinically available preventative strategies are limited to barrier technologies. Significant knowledge gaps persist in the characterization and mitigation of the involved molecular pathways underlying adhesion formation. Thus, the objectives of this scoping review are to describe the known molecular pathophysiology implicated in abdominal adhesion formation and summarize novel preclinical regenerative medicine preventative strategies for potential future clinical investigation. METHODS: A literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews. Included peer-reviewed publications were published within the last 5 y and contained in vivo preclinical experimental studies of postoperative adhesions with the assessment of underlying mechanisms of adhesion formation and successful therapy for adhesion prevention. Studies not involving regenerative medicine strategies were excluded. Data were qualitatively synthesized. RESULTS: A total of 1762 articles were identified. Of these, 1001 records were excluded by the described screening criteria. Sixty-eight full-text articles were evaluated for eligibility, and 11 studies were included for review. CONCLUSIONS: Novel and reliable preventative strategies are urgently needed. Recent experimental data propose novel regenerative medicine targets for adhesion prevention.

Early outcomes of an enhanced recovery protocol for open repair of ventral hernia.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are evidence-based quality improvement pathways reported to be associated with improved patient outcomes. The purpose of this study was to compare short-term outcomes for open ventral hernia repair (VHR) before and after implementation of an ERAS protocol. METHODS: After obtaining IRB approval, surgical databases were searched for VHR cases for two years prior and eleven months after protocol implementation for retrospective review. Groups were compared on perioperative characteristics and clinical outcomes using chi-square, Fisher's exact, or Mann-Whitney U test, as appropriate. RESULTS: One hundred and seventy-one patients underwent VHR (46 patients with ERAS protocol in place and 125 historic controls). Age, gender, ASA Class, comorbidities, and smoking status were similar between the two groups. Body mass index was lower among ERAS patients (p = .038). ERAS patients had earlier return of bowel function (median 3 vs. 4 days) (p = .003) and decreased incidence of superficial surgical site infection (SSI) (7 vs. 25%) (p = .008) than controls. CONCLUSION: An ERAS protocol for VHR demonstrated improved patient outcomes. A system-wide culture focused on enhanced recovery is needed to ensure improved patient outcomes.

Categories of Evidence and Methods in Surgical Decision-Making.

Surgical decision-making is a continuum of judgments that take place during the preoperative, intraoperative, and postoperative periods. The fundamental, and most challenging, step is determining whether a patient will benefit from an intervention given the dynamic interplay of diagnostic, temporal, environmental, patient-centric, and surgeon-centric factors. The myriad combinations of these considerations generate a wide spectrum of reasonable therapeutic approaches within the standards of care. Although surgeons may seek evidenced-based practices to support their decision-making, threats to the validity of evidence and appropriate application of evidence may influence implementation. Furthermore, a surgeon's conscious and unconscious biases may additionally determine individual practice.

ENDOTHELIAL GLYCOCALYX SHEDDING IN INTRA-ABDOMINAL SEPSIS: A FEASIBILITY STUDY.

ABSTRACT: Background: The endothelial glycocalyx layer (EGL) is a complex meshwork of glycosaminoglycans and proteoglycans that protect the vascular endothelium. Cleavage or shedding of EGL-specific biomarkers, such as hyaluronic acid (HA) and syndecan-1 (SDC-1, CD138) in plasma, have been shown to be associated with poor clinical outcomes. However, it is unclear whether levels of circulating EGL biomarkers are representative of the EGL injury within the tissues. The objective of the present feasibility study was to describe a pathway for plasma and tissue procurement to quantify EGL components in a cohort of surgical patients with intra-abdominal sepsis. We sought to compare differences between tissue and plasma EGL biomarkers and to determine whether EGL shedding within the circulation and/or tissues correlated with clinical outcomes. Methods: This was a prospective, observational, single-center feasibility study of adult patients (N = 15) with intra-abdominal sepsis, conducted under an approved institutional review boards. Blood and resected tissue (pathologic specimen and unaffected peritoneum) samples were collected from consented subjects at the time of operation and 24-48 hours after surgery. Endothelial glycocalyx layer biomarkers (i.e., HA and SDC-1) were quantified in both tissue and plasma samples using a CD138 stain and ELISA kit, respectively. Pairwise comparisons were made between plasma and tissue levels. In addition, we tested the relationships between measured EGL biomarkers and clinical status and patient outcomes. Results: Fifteen patients with intra-abdominal sepsis were enrolled in the study. Elevations in EGL-specific circulating biomarkers (HA, SDC-1) were positively correlated with postoperative SOFA scores and weakly associated with resuscitative volumes at 24 hours. Syndecan-1 levels from resected pathologic tissue significantly correlated with SOFA scores at all time points ( R = 0.69 and P < 0.0001) and positively correlated with resuscitation volumes at 24 hours ( R = 0.41 and P = 0.15 for t = 24 hours). Tissue and circulating HA and SDC-1 positively correlated with SOFA >6. Conclusions: Elevations in both circulating and tissue EGL biomarkers were positively correlated with postoperative SOFA scores at 24 hours, with resected pathologic tissue EGL levels displaying significant correlations with SOFA scores at all time points. Tissue and circulating EGL biomarkers were positively correlated at higher SOFA scores (SOFA > 6) and could be used as indicators of resuscitative needs within 24 hours of surgery. The present study demonstrates the feasibility of tissue and plasma procurement in the operating room, although larger studies are needed to evaluate the predictive value of these EGL biomarkers for patients with intra-abdominal sepsis.

Spontaneous rupture of nontraumatic hepatic artery pseudoaneurysm.

Spontaneous rupture of hepatic artery pseudoaneurysms (HAP) is a rare cause of intra-abdominal hemorrhage. Herein, we present a case of a spontaneous rupture of a nontraumatic HAP. A 61-year-old female, not on any anticoagulant or antiplatelet medications, presented with abdominal pain and hemorrhagic shock. Cross-sectional imaging revealed a left HAP with evidence of active bleeding. Emergent diagnostic angiography was performed, and angioembolization of an actively bleeding pseudoaneurysm was performed. Given the risk of rupture and high mortality rate associated with rupture, aggressive treatment of HAP should be pursued.

The value of compassion: Healthcare savings of palliative care consults in trauma.

BACKGROUND: The effects of palliative care (PC) consultation on patient costs and hospitalization metrics in the adult trauma population are unclear. STUDY DESIGN: We interrogated our Level I trauma center databases from 1/1/19 to 3/31/21 for patients age ≥18 admitted to the trauma service. Patients undergoing PC consult were matched using propensity scoring to those without PC consultation based on age, admission Glasgow Coma Scale score, Injury Severity Score and Head Abbreviated Injury Scale. Total costs, total cost per day, hospital length of stay (LOS), ICU LOS, intubation days, discharge disposition, and rates of nephrology consultation and tracheostomy/feeding tube placements were compared. RESULTS: 140 unique patients underwent PC consultation and were matched to a group not receiving PC consult during the same period. Median total costs in the PC cohort were $39,532 compared to $70,330 in the controls (p<0.01).  Median costs per day in the PC cohort were $3,495 vs $17,970 in the controls (p<0.01).  Median costs per ICU day in the PC cohort were $3,774 vs $17,127 in the controls (p<0.01).  Mean hospital LOS (15.7 vs 7 days), ICU LOS (7.9 vs 2.9 days), and ventilator days (5.1 vs 1.5) were significantly higher in the PC cohort (all p<0.01).  Rates of nephrology consultation (8.6 vs 2.1%, p = 0.03) and tracheostomy/feeding tube placements (12.1 vs 1.4%, p<0.01) were also higher in the PC group.  Patients were more likely to discharge to hospice if they received a PC consult (33.6 vs 2.1%, p<0.01).  Mean time to PC consult was 7.2 days (range 1 hour to 45 days). LOS post-consult correlated positively with time to PC consultation (r = 0.27, p<0.01). CONCLUSION: Expert PC services are known to alleviate suffering and avert patient goal- and value-incongruent care. While trauma patients demand significant resources, PC consultation offered in concordance with life-sustaining interventions is associated with significant savings to patients and the healthcare system. Given the correlation between LOS following PC consult and time to PC consult, savings may be amplified by earlier PC consultation in appropriate patients.

Above the Clavicle: A Simplified Screening Method for Asymptomatic Blunt Cerebral Vascular Injury.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) is an increasingly detected pattern in trauma with significant morbidity, putting patients at risk for subsequent stoke. Complex screening protocols exist to determine who should undergo CT angiography of the neck (CTAN) to evaluate for BCVI. Once identified, stroke incidence may be reduced with appropriate treatment across grades. We hypothesize that an expanded and simplified method for identifying patients with clinical suspicion for BCVI based upon injury above the clavicle (ATC) will illustrate a previously undiagnosed cohort of patients. METHODS: A single-institution retrospective review of adult (age ≥18 years) blunt trauma patients with BCVI from January 1, 2010 to December 31, 2019 was conducted at a tertiary academic medical center. Patients undergoing CTAN were divided into 2 groups based upon qualification by either the expanded Denver criteria or clinical evidence of any injury ATC. RESULTS: A total of 219 patients were diagnosed with BCVI (25 566 blunt trauma admissions, .9% incidence). Seventeen patients (8%) who did not satisfy expanded Denver were diagnosed with BCVI by ATC, most commonly undergoing CTAN due to facial trauma (n = 8). There were no differences in distribution of carotid artery injuries (CAI) and vertebral artery injuries (VAI) in the expanded Denver criteria group compared to the ATC group. CONCLUSIONS: CTAN for blunt trauma with any injury ATC is an easy-to-use screening tool and may be seamlessly included with initial whole-body imaging.

Penetrating brain injury with hypopituitarism.

A 34-year-old healthy male presented as a trauma activation after sustaining a gunshot wound to his face. CT head imaging was suggestive of a ballistic fragment adjacent to a posterior wall sphenoid sinus fracture with likely a small volume of adjacent blood products. He was ultimately diagnosed with hypopituitarism which included central diabetes insipidus, central hypothyroid, and adrenocorticotropic hormone deficiency secondary to cortisol deficiency. This case illustrates the spectrum of endocrine dysfunction that can occur with skull base injuries, and the appropriate pituitary-function screening and treatment that should be performed if there is clinical concern. Early recognition and prompt treatment of pituitary insufficiency can facilitate overall rehabilitation after TBI.

Equivalent Operative Outcomes for Emergency Colon Cancer Resections Among Acute Care Surgeons and Specialists in Colorectal Surgery.

OBJECTIVES: Improved screening has decreased but not eliminated the need for emergent surgery for colon cancer (CC), many of which are performed by acute care surgery (ACS) surgeons. This retrospective review compares outcomes for CC resections on the ACS service to the surgical oncology and colorectal services (SO/CRS). METHODS: Retrospective review was performed for CC operations between 2014 and 2019. Data for margin status, cancer stage, number of lymph nodes dissected, time to medical oncology follow-up, and time to initiation of chemotherapy were collected. Patients with curative resection, who chose comfort care, presented on alternative services or with non-CC indications as well as those were lost to follow-up were excluded. RESULTS: 36 ACS patients and 269 SO/CRS patients underwent CC resections. Most ACS patients presented emergently compared to the SO/CC group (83.3% vs 1%, P < .05) as well as with more advanced tumor stage. There were no statistically significant differences for presence of metastatic disease, number of lymph nodes obtained, or time to post-surgical care (in days) and chemotherapy initiation (in days). 3 (8%) EGS patients had positive margins compared to 6 (2%) CRS/SO patients due to the presence of perforated tumors in the ACS group (p < .05). There were no statistically significant differences in 30- day or 1-year mortality despite the emergent presentation of the ACS patients. DISCUSSION: These findings suggest that despite emergent presentation and advanced disease burden, ACS surgeons provide quality care to CC patients, both in the operating room and in coordination of care.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Prevention of alcohol withdrawal syndrome in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Alcohol withdrawal syndrome is a common and challenging clinical entity present in trauma and surgical intensive care unit (ICU) patients. The screening tools, assessment strategies, and pharmacological methods for preventing alcohol withdrawal have significantly changed during the past 20 years. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews the best practices for screening, monitoring, and prophylactic treatment of alcohol withdrawal in the surgical ICU.

The Story of Blood for Shock Resuscitation: How the Pendulum Swings.

Whole blood transfusion (WBT) began in 1667 as a treatment for mental illness, with predictably poor results. Its therapeutic utility and widespread use were initially limited by deficiencies in transfusion science and antisepsis. James Blundell, a British obstetrician, was recognized for the first allotransfusion in 1825. However, WBT did not become safe and therapeutic until the early 20th century, with the advent of reliable equipment, sterilization, and blood typing. The discovery of citrate preservation in World War I allowed a separation of donor from recipient and introduced the practice of blood banking. During World War II, Elliott and Strumia were the first to separate whole blood into blood component therapy (BCT), producing dried plasma as a resuscitative product for "traumatic shock." During the 1970s, infectious disease, blood fractionation, and financial opportunities further drove the change from WBT to BCT, with few supporting data. Following a period of high-volume crystalloid and BCT resuscitation well into the early 2000s, measures to avoid the resulting iatrogenic resuscitation injury were developed under the concept of damage control resuscitation. Modern transfusion strategies for hemorrhagic shock target balanced BCT to reapproximate whole blood. Contemporary research has expanded the role of WBT to therapy for the acute coagulopathy of trauma and the damaged endothelium. Many US trauma centers are now using WBT as a front-line treatment in tandem with BCT for patients suffering hemorrhagic shock. Looking ahead, it is likely that WBT will once again be the resuscitative fluid of choice for patients in hemorrhagic shock.

Variable bites and dynamic populations; new insights in Leishmania transmission.

Leishmaniasis is a neglected tropical disease which kills an estimated 50,000 people each year, with its deadly impact confined mainly to lower to middle income countries. Leishmania parasites are transmitted to human hosts by sand fly vectors during blood feeding. Recent experimental work shows that transmission is modulated by the patchy landscape of infection in the host's skin, and the parasite population dynamics within the vector. Here we assimilate these new findings into a simple probabilistic model for disease transmission which replicates recent experimental results, and assesses their relative importance. The results of subsequent simulations, describing random parasite uptake and dynamics across multiple blood meals, show that skin heterogeneity is important for transmission by short-lived flies, but that for longer-lived flies with multiple bites the population dynamics within the vector dominate transmission probability. Our results indicate that efforts to reduce fly lifespan beneath a threshold of around two weeks may be especially helpful in reducing disease transmission.

Spatial Point Pattern Analysis Identifies Mechanisms Shaping the Skin Parasite Landscape in Leishmania donovani Infection.

Increasing evidence suggests that in hosts infected with parasites of the Leishmania donovani complex, transmission of infection to the sand fly vector is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal (the mechanism of spread) and dispersion (the observed state of spread) of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+ and CD11c+ cells) and predict dispersal mechanisms in a previously described immunodeficient model of L. donovani infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by L. donovani and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.

Forebrain osmotic regulation of the sympathetic nervous system.

1. Accumulating evidence in both humans and animals indicates that acute increases in plasma osmolality elevate sympathetic nerve activity (SNA). In addition, plasma hyperosmolality (or hypernatraemia) can produce sustained increases in SNA and arterial blood pressure (ABP) through stimulation of forebrain osmoreceptors. 2. Although an abundance of information exists regarding the osmoregulatory circuits for thirst and secretion of antidiuretic hormone, much less is known about those pathways and synaptic mechanisms linking osmotic perturbations and SNA. To date, the available evidence suggests that osmosensitive sites within the forebrain lamina terminalis, such as the organum vasculosum of the lamina terminalis, are key elements that link plasma hypertonicity to elevated SNA. 3. The major efferent target of osmosensitive regions in the forebrain lamina terminalis is the hypothalamic paraventricular nucleus (PVH). Evidence from a number of studies indicates that the PVH contributes to both acute and chronic osmotically driven increases in SNA. In turn, PVH neurons increase SNA through a direct vasopressinergic spinal pathway and/or a glutamatergic pathway to bulbospinal sympathetic neurons of the rostral ventrolateral medulla. 4. Future studies are needed to: (i) define the contribution of various osmosensitive regions of the forebrain lamina terminalis to acute and chronic osmotically driven increases in SNA; (ii) identify the cellular mechanisms and neural circuitry linking plasma osmolality and SNA; and (iii) define whether such mechanisms contribute to elevated SNA in salt-sensitive hypertension.

Patient-Surgeon Relationship Influences Outcomes in Bariatric Patients.

Bariatric surgery is an important therapy in weight loss. However, adherence to follow-up is critical and may be influenced by the patient-surgeon relationship. To test this hypothesis, bariatric surgical patients were surveyed from March 2013 to March 2015 via the National Association for Weight Loss Surgery webpage and social media outlets. Surgical outcomes and adherence to follow-up were collected, and aspects of the patient-surgeon relationship were assessed via the Likert scale. Correlations between survey item responses were calculated using Fisher's exact test, Student's t test, and Spearman's rho rank correlation. Three hundred twenty patients responded (n = 287 completed in entirety and n = 33 partially completed); 48 months was the median time to survey from operation (interquartile range, 22-84 months). Eighty-six per cent (n = 276) of patients rated their relationship with their operative surgeon as "average" to "very good." Thirteen per cent (n = 43) rated their relationship as "poor" to "very poor." Positive relationship with the operative surgeon and lack of complication were associated with adherence to follow-up (P = 0.0001 and P = 0.002, respectively). The presence of complication did not affect the overall patient-surgeon relationship (P = 0.5), although aspects of the patient-surgeon relationship were correlated to complications. There was no association between weight loss at one year and patient-surgeon relationship (P = 0.6) or presence of complication (P = 0.1). The findings of this study support the role of a positive patient-surgeon relationship in achieving long-term follow-up in post-bariatric surgical patients.

Emergency department repair of blunt right atrial rupture utilizing cardiopulmonary bypass.

Blunt cardiac injury (BCI) with free wall rupture carries a high risk of pre-hospital death. Cardiopulmonary bypass (CPB) has been utilized as a bridge to repair of cardiac lesions in select patients. We present an interesting case of emergency department repair of right atrial rupture with cardiopulmonary bypass.