An Exploratory and Qualitative Analysis of Self-Reported Evaluations for Fever.

Background: Despite the high prevalence of post-operative fever, a variety of approaches are taken as to the components of a fever evaluation, when it should be undertaken, and when empiric antibiotic agents should be started. Hypothesis: There is a lack of consensus surrounding many common components of a post-operative fever evaluation. Patients and Methods: The Surgical Infection Society membership was surveyed to determine practices surrounding evaluation of post-operative fever. Eight scenarios were posed in febrile (38.5°C), post-operative general surgery or trauma patients, with 19 possible components of work-up (physical examination, complete blood count [CBC], fungal biomarkers, lactate and procalcitonin [PCT] concentrations, cultures, imaging) and management (antibiotic agents). Each scenario was then re-considered for intensive care unit (ICU) patients (intubated/unstable hemodynamics). Agreement on a parameter (<1/4 or >3/4 of respondents) achieved consensus, positive or negative. Parameters between had equipoise; α was set at 0.05. Results: Among the examined scenarios, only CBC and physical examination received positive consensus across most scenarios. Blood/urine cultures, imaging, lactate, inflammatory biomarkers, and the empiric administration of antibiotic agents did not reach consensus; support was variable depending on the clinical scenario, illness severity, and the individual preferences of the answering clinician. The qualitative portion of the survey identified "fever threshold and duration," "clinical suspicion," and "physiologic manifestation" as the most important factors for deciding about the initiation of a fever evaluation and the potential empiric administration of antibiotic agents. Conclusions: There is consensus only for physical and examination routine laboratory work when initiating the evaluation of febrile post-operative patients. However, there are multiple components of a fever evaluation that individual respondents would select depending on the clinical scenario and severity of illness. Parameters demonstrating equipoise are potential candidates for formal guidance or pragmatic prospective trials.

Self-Reported Diagnosis and Management of Surgical Site Infection Highlights Lack of Objective Measures and Treatment Guidance.

Background: There is little guidance regarding empiric therapy for superficial surgical site infections (SSIs). Management of incisions with signs of SSI lacks consensus and management is variable among individual surgeons. Methods: The Surgical Infection Society was surveyed regarding management of SSIs. Cases were provided with varying wound descriptions, initial wound class (WC), post-operative day, and presence of a prosthesis. Responses were in multiple-choice format; statistics: χ2; α = 0.05. Results: Seventy-eight members responded. For appearance scenarios, respondents believed that both mild erythema (55%) and clear drainage (64%) could be observed, whereas substantial (>3 cm) erythema or purulence should be treated with complete (22% and 50%) or partial (55% and 40%) opening of the incision. Degree of erythema did not influence administration of antibiotic agents, but purulence was more likely than clear drainage to be treated with antibiotics (38% vs. 6%; p < 0.001). There were no differences based on WC, except that clean cases were more likely than higher WC scenarios to be treated with gram-positive coverage alone (WC 1 [26%] vs. 2 [10%] vs. 3 [13%] vs. 4 [4%]; p < 0.001). Post-operative day (POD) three appeared to be an inflection point for more aggressive treatment of suspected incisional SSI, with fewer (POD 0 [86%] vs. POD day 3 [54%]; p < 0.001) reporting observation. Respondents were more likely to obtain imaging, start broad-spectrum antibiotic agents, and return to the operating room for purulence in the presence of a mesh. Conclusions: Presented with escalating possibility of SSI, respondents reported lower rates of observation, increased use of antibiotic agents, and increased surgical drainage. Many scenarios lack consensus regarding appropriate therapy. The complete elimination of SSIs is unlikely to be accomplished soon, and this study provides a framework for understanding how surgeons approach SSIs, and potential areas for further research or pragmatic guidance.

Different Surgeon, Different Closure: Lack of Consensus on Appropriate Closure Technique for Various Case Scenarios.

Background: Many techniques for closure of surgical incisions are available to the surgeon, but there is minimal guidance regarding which technique(s) should be utilized at the conclusion of surgery and under what circumstances. Hypothesis: Management of incisions at the conclusion of surgery lacks consensus and varies among individual surgeons. Methods: The Surgical Infection Society membership was surveyed on the management of incisions at the conclusion of surgery. Several case scenarios were provided to test the influences of operation type, intra-operative contamination, and hemodynamic stability on incision management (e.g., close fascia or skin, use of incision/wound vacuum-assisted closure [VAC] device). Responses by two-thirds of participants were required to achieve consensus. Data analysis by χ2 test and logistic regression, a = 0.05. Response heterogeneity was quantified by the Shannon index (SI). Results: Among 78 respondents, consensus was achieved for elective splenectomy (91% close skin/dry dressing). Open appendectomy and left colectomy/end-colostomy had the greatest heterogeneity (SI, 1.68 and 1.63, respectively). During trauma laparotomy, the majority used damage control for hemodynamic instability (53%-67%) but not for hemodynamically stable patients (0%-1.3%; p < 0.001). Additional consensus was achieved for close skin/dry dressing for hemodynamically stable trauma splenectomy patients (87%) and fascia open/wound VAC for hemodynamically unstable colon resection/anastomosis (67%). Fecal diversion for rectal injury and colon resection/anastomosis (both when hemodynamically stable) had high heterogeneity (SI, 1.56 and 1.48, respectively). In penetrating trauma, sentiment was for more use of wet-to-dry dressings and incision/wound VAC with increased contamination in hemodynamically stable patients. Conclusions: Damage control was favored in hemodynamically unstable trauma patients, with use of wet-to-dry dressings and incision/wound VAC with spillage after penetrating trauma. However, most scenarios did not achieve consensus. High variability of practices regarding incision management at the conclusion of surgery was confirmed. Prospective studies and evidence-based guidance are needed to guide decision making at end-operation.

Longitudinal analysis of mucosa-associated invariant T cells in sepsis reveals their early numerical decline with prognostic implications and a progressive loss of antimicrobial functions.

Sepsis-elicited immunosuppression elevates the risk of secondary infections. We used a clinically relevant mouse model and serial peripheral blood samples from patients to assess the antimicrobial activities of mucosa-associated invariant T (MAIT) cells in sepsis. Hepatic and splenic MAIT cells from B6-MAITCAST mice displayed increased CD69 expression and a robust interferon-γ (IFNγ) production capacity shortly after sublethal cecal ligation and puncture, but not at a late timepoint. Peripheral blood MAIT cell frequencies were reduced in septic patients at the time of intensive care unit (ICU) admission, and more dramatically so among nonsurvivors, suggesting the predictive usefulness of early MAIT cell enumeration. In addition, at ICU admission, MAIT cells from sepsis survivors launched stronger IFNγ responses to several bacterial species compared with those from patients who subsequently died of sepsis. Of note, while low human leukocyte antigen (HLA)-DR+ monocyte frequencies, widely regarded as a surrogate indicator of sepsis-induced immunosuppression, were gradually corrected, the numerical insufficiency of MAIT cells was not resolved over time, and their CD69 expression continued to decline. MAIT cell responses to bacterial pathogens, a major histocompatibility complex-related protein 1 (MR1) ligand, and interleukin (IL)-12 and IL-18 were also progressively lost during sepsis and did not recover by the time of ICU/hospital discharge. We propose that MAIT cell dysfunctions contribute to post-sepsis immunosuppression.

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

BACKGROUND: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36261.

Different Surgeon, Different Duration: Lack of Consensus on the Appropriate Duration of Antimicrobial Prophylaxis and Therapy in Surgical Practice.

Background: The principles of antimicrobial stewardship promote the appropriate prescribing of agents with respect to efficacy, safety, duration, and cost. Antibiotic resistance often results from inappropriate use (e.g., indication, selection, duration). We evaluated practice variability in duration of antimicrobials in surgical infection treatment (Rx) or prophylaxis (Px). Hypothesis: There is lack of consensus regarding the duration of antibiotic Px and Rx for many common indications. Methods: A survey was distributed to the Surgical Infection Society (SIS) regarding the use of antimicrobial agents for a variety of scenarios. Standard descriptive statistics were used to compare survey responses. Heterogeneity among question responses were compared using the Shannon Index, expressed as natural units (nats). Results: Sixty-three SIS members responded, most of whom (67%) have held a leadership position within the SIS or contributed as an annual meeting moderator or discussant; 76% have been in practice for more than five years. Regarding peri-operative Px, more than 80% agreed that a single dose is adequate for most indications, with the exceptions of gangrenous cholecystitis (40% single dose, 38% pre-operative +24 hours) and inguinal hernia repair requiring a bowel resection (70% single dose). There was more variability regarding the use of antibiotic Px for various bedside procedures with respondents split between none needed (range, 27%-66%) versus a single dose (range, 31%-67%). Opinions regarding the duration of antimicrobial Rx for hospitalized patients who have undergone a source control operation or procedure varied widely based on indication. Only two of 20 indications achieved more than 60% consensus despite available class 1 evidence: seven days for ventilator-associated pneumonia (77%), and four plus one days for perforated appendicitis (62%). Conclusions: Except for peri-operative antibiotic Px, there is little consensus regarding antibiotic duration among surgical infection experts, despite class 1 evidence and several available guidelines. This highlights the need for further high-level research and better dissemination of guidelines.

Surgical Infections and the Future of Research: Re-Defining the Research Agenda for the Surgical Infection Society.

Background: Infections represent a major component of surgical practice. Risk mitigation, seeking eradication and optimal patient outcomes, require a concerted, multifocal effort to understand disease and microbiology, prevent infections, and treat them. The present study was undertaken to re-define the Surgical Infection Society (SIS) research agenda for the next decade. Hypothesis: We utilized the expertise of the SIS membership to identify research questions regarding surgical infections, hypothesizing that consensus among participants could be used to re-define the future research agenda. Methods: Members of the SIS were surveyed using a modified Delphi. The three rounds of the survey were targeted at: question generation; question ranking; and reaching consensus. Each of the 15 questions to emerge was evaluated according to level of consensus, feasibility, and data availability. Results: One hundred twenty-four participants contributed. Initially, 226 questions were generated that were condensed to 35 unique questions for consideration in the subsequent two rounds. The 35 questions encompassed several research themes, with antibiotic prophylaxis (n = 8), prevention of surgical site infections (SSIs; n = 6), and improved diagnostics (n = 5) being most common. Standard deviation of importance scores was inversely proportional to the question rank, indicating greater consensus among higher ranking questions. All 15 questions had a feasibility score of greater than three (five-point Likert scale), and the majority (12/15) had a mean data availability score of less than three. In the final round of the survey, the top three topics for further research surrounded non-antimicrobial treatments, optimal treatment duration for bacteremia, and treatment duration for necrotizing soft tissue infections. Conclusions: Using a modified Delphi process, 15 research questions addressing surgical infections were identified. Such questions can assist the SIS and the SIS Foundation for Research and Education in prioritizing and enabling research efforts, and development of a strategic research plan for the next decade.

Scoring Sepsis Severity in Mice.

A reliable scoring system that predicts the development of sepsis, septic shock, and death enables comparison of disease severity and treatment outcomes in animal models of sepsis. Mice are used in the majority of preclinical sepsis studies. We describe a murine sepsis score that evaluates seven clinical variables in an experimental mouse model of polymicrobial sepsis.

Harnessing the Versatility of Invariant NKT Cells in a Stepwise Approach to Sepsis Immunotherapy.

Sepsis results from a heavy-handed response to infection that may culminate in organ failure and death. Many patients who survive acute sepsis become immunosuppressed and succumb to opportunistic infections. Therefore, to be successful, sepsis immunotherapies must target both the initial and the protracted phase of the syndrome to relieve early immunopathology and late immunosuppression, respectively. Invariant NKT (iNKT) cells are attractive therapeutic targets in sepsis. However, repeated treatments with α-galactosylceramide, the prototypic glycolipid ligand of iNKT cells, result in anergy. We designed a double-hit treatment that allows iNKT cells to escape anergy and exert beneficial effects in biphasic sepsis. We tested the efficacy of this approach in the sublethal cecal ligation and puncture mouse model, which mirrors polymicrobial sepsis with progression to an immunosuppressed state. Septic mice were treated with [(C2S, 3S, 4R)-1-O-(α-d-galactopyranosyl)-N-tetracosanoyl-2-amino-1,3,4-nonanetriol] (OCH), a TH2-polarizing iNKT cell agonist, before they received α-galactosylceramide. This regimen reduced the morbidity and mortality of cecal ligation and puncture, induced a transient but robust IFN-γ burst within a proinflammatory cytokine/chemokine landscape, transactivated NK cells, increased MHC class II expression on macrophages, and restored delayed-type hypersensitivity to a model hapten, consistent with recovery of immunocompetence in protracted sepsis. Structurally distinct TH2-polarizing agonists varied in their ability to replace OCH as the initial hit, with their lipid chain length being a determinant of efficacy. The proposed approach effectively exploits iNKT cells' versatility in biphasic sepsis and may have translational potentials in the development of new therapies.

Surgical Infection Society Research Priorities: A Narrative Review of Fourteen Years of Progress.

Background: In 2006, the Surgical Infection Society (SIS) utilized a modified Delphi approach to define 15 specific priority research questions that remained unanswered in the field of surgical infections. The aim of the current study was to evaluate the scientific progress achieved during the ensuing period in answering each of the 15 research questions and to determine if additional research in these fields is warranted. Methods: For each of the questions, a literature search using the National Center for Biotechnology Information (NCBI) was performed by the Scientific Studies Committee of the SIS to identify studies that attempted to address each of the defined questions. This literature was analyzed and summarized. The data on each question were evaluated by a surgical infections expert to determine if the question was answered definitively or remains unanswered. Results: All 15 priority research questions were studied in the last 14 years; six questions (40%) were definitively answered and 9 questions (60%) remain unanswered in whole or in part, mainly because of the low quality of the studies available on this topic. Several of the 9 unanswered questions were deemed to remain research priorities in 2020 and warrant further investigation. These included, for example, the role of empiric antimicrobial agents in nosocomial infections, the use of inotropes/vasopressors versus volume loading to raise the mean arterial pressure, and the role of increased antimicrobial dosing and frequency in the obese patient. Conclusions: Several surgical infection-related research questions prioritized in 2006 remain unanswered. Further high-quality research is required to provide a definitive answer to many of these priority knowledge gaps. An updated research agenda by the SIS is warranted at this time to define research priorities for the future.

Gender Disparities in Medical Student Surgical Skills Education.

OBJECTIVE: Female medical students and surgical trainees are more likely to lack confidence in their clinical abilities than their male peers despite equal or superior performance. This study aims to examine the role of gender in medical student experience and confidence performing technical skills in surgical clerkship. DESIGN: This was a single-center survey study conducted over 2 academic years (2016-2018). Students were surveyed on their experience and confidence performing a set of 9 technical skills during surgical clerkship and to identify skill-specific barriers to learning. SETTING: This study was performed at Western University, London, Ontario, Canada. PARTICIPANTS: All third-year medical students were invited to participate. RESULTS: A total of 253 students participated yielding a survey response rate of 74.0%. Both male and female students reported similar levels of preclerkship interest in a surgical career, enjoyment in performing technical skills, confidence in ability to learn surgical skills and pursuit of available learning opportunities. At the conclusion of their surgical rotations, female students reported less experience and confidence performing technical skills compared to their male colleagues. Female students were more likely to cite an insufficient number of learning opportunities from consultant and resident teachers, time constraints, and lack of confidence as barriers to the achievement of technical proficiency. CONCLUSIONS: Female gender was associated with less procedural experience and inferior confidence performing procedural skills. It is important for educators to be aware of this gender disparity and to actively promote equitable learning opportunities for female trainees.

Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections.

Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8+ T cell (TCD8) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAVs are manipulated by SAgs remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, and WT, mouse-adapted and reassortant IAV strains in multiple in vivo settings to address the above questions. Contrary to the popular view that SAgs delete or anergize T cells, systemic administration of staphylococcal enterotoxin B (SEB) or Mycoplasma arthritidis mitogen before intraperitoneal IAV immunization enlarged the clonal size of 'select' IAV-specific TCD8 and reshuffled the hierarchical pattern of primary TCD8 responses. This was mechanistically linked to the TCR Vß makeup of the impacted clones rather than their immunodominance status. Importantly, SAg-expanded TCD8 retained their IFN-γ production and cognate cytolytic capacities. The enhancing effect of SEB on immunodominant TCD8 was also evident in primary responses to vaccination with heat-inactivated and live attenuated IAV strains administered intramuscularly and intranasally, respectively. Interestingly, in prime-boost immunization settings, the outcome of SEB administration depended strictly upon the time point at which this SAg was introduced. Accordingly, SEB injection before priming raised CD127highKLRG1low memory precursor frequencies and augmented the anamnestic responses of SEB-binding TCD8. By comparison, introducing SEB before boosting diminished recall responses to IAV-derived epitopes drastically and indiscriminately. This was accompanied by lower Ki67 and higher Fas, LAG-3 and PD-1 levels consistent with a pro-apoptotic and/or exhausted phenotype. Therefore, SAgs can have contrasting impacts on anti-IAV immunity depending on the naïve/memory status and the TCR composition of exposed TCD8. Finally, local administration of SEB or infection with SEB-producing S. aureus enhanced pulmonary TCD8 responses to IAV. Our findings have clear implications for superinfections and prophylactic vaccination.

Bacterial Superantigens Expand and Activate, Rather than Delete or Incapacitate, Preexisting Antigen-Specific Memory CD8+ T Cells.

Superantigens (SAgs) released by common Gram-positive bacterial pathogens have been reported to delete, anergize, or activate mouse T cells. However, little is known about their effects on preexisting memory CD8+ T cell (TCD8) pools. Furthermore, whether SAgs manipulate human memory TCD8 responses to cognate antigens is unknown. We used a human peripheral blood mononuclear cell culture system and a nontransgenic mouse model in which the impact of stimulation by two fundamentally distinct SAgs, staphylococcal enterotoxin B and Mycoplasma arthritidis mitogen, on influenza virus- and/or cytomegalovirus-specific memory TCD8 could be monitored. Bacterial SAgs surprisingly expanded antiviral memory TCD8 generated naturally through infection or artificially through vaccination. Mechanistically, this was a T cell-intrinsic and T cell receptor ß-chain variable-dependent phenomenon. Importantly, SAg-expanded TCD8 displayed an effector memory phenotype and were capable of producing interferon-γ and destroying target cells ex vivo or in vivo. These findings have clear implications for antimicrobial defense and rational vaccine design.

Early Rescue from Acute Severe Clostridium Difficile: A Novel Treatment Strategy.

BACKGROUND: Severe Clostridium difficile infections (CDI) can lead to significant impediments to effective treatment. We developed a novel treatment protocol utilizing bedside gastrointestinal lavage (GIL) for the management of patients with severe, complicated CDI. We describe the development and early outcomes of non-operative bedside GIL in hospitalized patients with severe, complicated CDI following the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework at the Idea stage. We compared our results with those of a cohort of patients managed with colectomy. METHODS: We conducted a retrospective cohort study of hospitalized patients with severe, complicated CDI who failed conventional medical therapy and were referred for surgical consultation at two academic tertiary-care hospitals between January 2009 and January 2015. After surgical assessment, the attending surgeon decided to proceed either with bedside GIL or directly to colectomy. Bedside GIL involved nasojejunal tube insertion followed by flushing with 8 L of polyethylene glycol 3350/electrolyte solution over 48 h. Both patient groups received standard medical treatment with vancomycin 500 mg q 6 h enterally and metronidazole 500 mg intravenously three times daily for 14 d. The main outcomes of interest were the incidence of colectomy, complications, and mortality rate. RESULTS: Nineteen and seventeen patients underwent GIL and direct colectomy, respectively. There were no significant differences between the groups in terms of demographics, American Society of Anesthesiologists class, disease severity, need for intensive care unit admission, mechanical ventilation, vasopressor use, serum lactate concentration, or proportion presenting with hypotension, acute kidney injury, or a white blood cell count >16,000/mcL or <4,000/mcL (p > 0.1). The in-hospital mortality rate was 26% (5/19) and 41% (7/17) for the GIL and colectomy groups, respectively (p = 0.35). Only one patient in the GIL group failed the protocol, requiring colectomy. There were no significant differences in complications in the two groups. CONCLUSIONS: Bedside GIL appeared to be safe for the treatment of patients with severe, complicated CDI who had failed conventional medical therapy. It did not appear to increase the risk of morbidity or death compared with the traditional strategy of proceeding directly to colectomy.

Acute care surgery: a means for providing cost-effective, quality care for gallstone pancreatitis.

BACKGROUND: Modern practice guidelines recommend index cholecystectomy (IC) for patients admitted with gallstone pancreatitis (GSP). However, this benchmark has been difficult to widely achieve. Previous work has demonstrated that dedicated acute care surgery (ACS) services can facilitate IC. However, the associated financial costs and economic effectiveness of this intervention are unknown and represent potential barriers to ACS adoption. We investigated the impact of an ACS service at two hospitals before and after implementation on cost effectiveness, patient quality-adjusted life years (QALY) and impact on rates of IC. METHODS: All patients admitted with non-severe GSP to two tertiary care teaching hospitals from January 2008-May 2015 were reviewed. The diagnosis of GSP was confirmed upon review of clinical, biochemical and radiographic criteria. Patients were divided into three time periods based on the presence of ACS (none, at one hospital, at both hospitals). Data were collected regarding demographics, cholecystectomy timing, resource utilization, and associated costs. QALY analyses were performed and incremental cost effectiveness ratios were calculated comparing pre-ACS to post-ACS periods. RESULTS: In 435 patients admitted for GSP, IC increased from 16 to 76% after implementing an ACS service at both hospitals. There was a significant reduction in admissions and emergency room visits for GSP after introduction of ACS services (p < 0.001). There was no difference in length of stay or conversion to an open operation. The implementation of the ACS service was associated with a decrease in cost of $1162 per patient undergoing cholecystectomy, representing a 12.6% savings. The time period with both hospitals having established ACS services resulted in a highly favorable cost to quality-adjusted life year ratio (QALY gained and financial costs decreased). CONCLUSIONS: ACS services facilitate cost-effective management of GSP. The result is improved and timelier patient care with decreased healthcare costs. Hospitals without a dedicated ACS service should strongly consider adopting this model of care.

Implementation of an Acute Care Surgery Service Facilitates Modern Clinical Practice Guidelines for Gallstone Pancreatitis.

BACKGROUND: Current practice guidelines for management of gallstone pancreatitis (GSP) recommend early cholecystectomy for patient stabilization and bile duct clearance, preferably at index admission. Historically, this has been difficult to achieve due to lack of emergency surgical resources. We investigated whether implementation of an acute care surgery (ACS) model would allow better adherence to current practice guidelines for GSP. STUDY DESIGN: A retrospective review was conducted of all patients admitted with the diagnosis of GSP to 2 tertiary care university teaching hospitals from January 2002 to October 2013. Diagnosis was confirmed on review of clinical, biochemical, and radiographic criteria. Patients were divided into pre-ACS (2002 to 2009) and post-ACS (2010 to 2013) eras. Only 1 of the 2 hospitals implemented an ACS service in the latter era. Data were collected on demographics, admissions, cholecystectomy timing, and emergency department visits. RESULTS: Before implementation of an ACS service, the rate of index cholecystectomy was 3% at both hospital sites. The rate of index cholecystectomy increased significantly with the addition of ACS, from 2.4% to 67% (p < 0.001). The presence of an ACS team was highly predictive of index cholecystectomy (odds ratio = 10.4; 95% CI 2.0 to 55.1). Patients who did not undergo cholecystectomy during the index admission had an overall readmission rate of 24.9% at both sites. In the ACS hospital, repeat emergency department visits decreased from 24.8% to 8.3% (p < 0.001) and readmission rate decreased from 16.8% to 7.3% (p = 0.04) in the pre-and post-ACS eras, respectively. CONCLUSIONS: Implementation of an ACS service resulted in a higher rate of index cholecystectomy and decreased emergency department visits and readmissions for biliary disease, and allowed for increased adherence to clinical practice guidelines for GSP.

Early mobilization in the critical care unit: A review of adult and pediatric literature.

Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization, including cost and health care provider views, are identified. Methods of overcoming barriers to early mobilization and enhancing sustainability of mobilization programs are discussed. Optimization of patient outcomes will require further studies on mobilization timing and intensity, particularly within specific ICU populations.

IFN-gamma is an absolute requirement for spontaneous acceptance of liver allografts.

Experimental liver allografts undergo spontaneous acceptance despite undergoing rejection during the first few weeks post transplant. We explored the role of interferon-gamma (IFN-gamma) in the spontaneous acceptance of mouse liver allografts. Strain of mouse (CBA) liver allografts transplanted into normal BALB/c mice developed histologic changes typical of rejection that spontaneously regressed, permitting long-term survival of these allografts similar to that of syngeneic grafts. In contrast, CBA liver allografts in IFN-gamma-deficient hosts manifested not only infiltration but also hemorrhage and necrosis, with no survival beyond 14 days. Despite differences in survival, local expression of cytotoxic T-cell genes in the transplant was not increased in IFN-gamma-deficient hosts, but livers in interferon-gamma-deficient mice (GKO) hosts displayed much less induction of major histocompatibility complex (MHC) class I and II expression. To determine whether the difference in survival was secondary to the direct effects of IFN-gamma on the liver, we transplanted livers from IFN-gamma-receptor-deficient mice into normal hosts. Liver allografts lacking IFN-gamma receptors also developed hemorrhage and necrosis with minimal induction of MHC expression. Thus IFN-gamma mediates a direct effect on rejecting liver allografts that reduces hemorrhage and necrosis, induces MHC expression, and is absolutely required for spontaneous acceptance.