Doxycycline prevents blood-brain barrier dysfunction and microvascular hyperpermeability after traumatic brain injury.

The main objective of this study was to determine the cellular and molecular effects of doxycycline on the blood-brain barrier (BBB) and protection against secondary injuries following traumatic brain injury (TBI). Microvascular hyperpermeability and cerebral edema resulting from BBB dysfunction after TBI leads to elevation of intracranial pressure, secondary brain ischemia, herniation, and brain death. There are currently no effective therapies to modulate the underlying pathophysiology responsible for TBI-induced BBB dysfunction and hyperpermeability. The loss of BBB integrity by the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) is critical to TBI-induced BBB hyperpermeability, and doxycycline possesses anti-MMP-9 effect. In this study, the effect of doxycycline on BBB hyperpermeability was studied utilizing molecular modeling (using Glide) in silico, cell culture-based models in vitro, and a mouse model of TBI in vivo. Brain microvascular endothelial cell assays of tight junction protein immunofluorescence and barrier permeability were performed. Adult C57BL/6 mice were subjected to sham versus TBI with or without doxycycline treatment and immediate intravital microscopic analysis for evaluating BBB integrity. Postmortem mouse brain tissue was collected to measure MMP-9 enzyme activity. It was found that doxycycline binding to the MMP-9 active sites have binding affinity of -7.07 kcal/mol. Doxycycline treated cell monolayers were protected from microvascular hyperpermeability and retained tight junction integrity (p < 0.05). Doxycycline treatment decreased BBB hyperpermeability following TBI in mice by 25% (p < 0.05). MMP-9 enzyme activity in brain tissue decreased with doxycycline treatment following TBI (p < 0.05). Doxycycline preserves BBB tight junction integrity following TBI via inhibiting MMP-9 activity. When established in human subjects, doxycycline, may provide readily accessible medical treatment after TBI to attenuate secondary injury.

Nonpharmacologic Pain Management Among Hospitalized Inpatients: A Randomized Waitlist-Controlled Trial of Standard Virtual Reality (CGI VR) Versus Video Capture VR (360 degrees 3D/Stereoscopic Video Capture VR).

OBJECTIVES: Nonpharmacologic pain management strategies are needed because of the growing opioid epidemic. While studies have examined the efficacy of virtual reality (VR) for pain reduction, there is little research in adult inpatient settings, and no studies comparing the relative efficacy of standard animated computer-generated imagery (CGI) VR to Video Capture VR (360 degrees 3D/stereoscopic Video Capture VR). Here, we report on a randomized controlled trial of the relative efficacy of standard CGI VR versus Video Capture VR (matched for content) and also compared the overall efficacy of VR to a waitlist control group. MATERIALS AND METHODS: Participants (N=103 hospitalized inpatients reporting pain) were randomized to 1 of 3 conditions: (1) waitlist control, (2) CGI VR, or (3) Video Capture VR. The VR and waitlist conditions were 10 minutes in length. Outcomes were assessed pretreatment, post-treatment, and after a brief follow-up. RESULTS: Consistent with hypotheses, both VR conditions reduced pain significantly more relative to the waitlist control condition (d=1.60, P<0.001) and pain reductions were largely maintained at the brief follow-up assessment. Both VR conditions reduced pain by ∼50% and led to improvements in mood, anxiety, and relaxation. Contrary to prediction, the Video Capture VR condition was not significantly more effective at reducing pain relative to the CGI VR condition (d=0.25, P=0.216). However, as expected, patients randomized to the Video Capture VR rated their experience as more positive and realistic (d=0.78, P=0.002). DISCUSSION: Video Capture VR was as effective as CGI VR for pain reduction and was rated as more realistic.

Resident-Championed Quality Improvement Provides Value: Confronting Prolonged Mechanical Ventilation.

BACKGROUND: The Quality In-Training Initiative (QITI) provides hands-on quality improvement education for residents. As our institution has ranked in the bottom quartile for prolonged mechanical ventilation (PMV) according to the National Surgical Quality Improvement Program (NSQIP), we sought to illustrate how our resident-led QITI could be used to determine perioperative contributors to PMV. MATERIALS AND METHODS: The Model for Improvement framework (developed by Associates in Process Improvement) was used to target postoperative ventilator management. However, baseline findings from our 2016 NSQIP data suggested that preoperative patient factors were more likely contributing to PMV. Subsequently, a retrospective one-to-one case-control study was developed, comparing preoperative NSQIP risk calculator profiles for PMV patients to case-matched patients for age, sex, procedure, and emergent case status. Chart review determined ventilator time, 30-d outcomes, and all-cause mortality. RESULTS: Forty-five patients with PMV (69% elective) had a median ventilator time of 134 h (interquartile range 87-254). The NSQIP calculator demonstrated increased preoperative risk percentages in PMV patients when compared to case-matched patients for any complication (includes PMV), predicted length of stay, and death (all P < 0.05). Thirty-day outcomes were worse for the PMV group in categories for sepsis, pneumonia, unplanned reoperation, 30-d mortality, rehab facility discharge, and length of stay (all P < 0.05). All-cause mortality was also significantly higher for PMV patients (P < 0.05). CONCLUSIONS: Resident-led QITI projects enhance resident education while exposing opportunities for improving care. Preoperative patient factors play a larger-than-anticipated role in PMV at our institution. Ongoing efforts are aimed toward preoperative identification and optimization of high-risk patients.

Doxycycline improves traumatic brain injury outcomes in a murine survival model.

BACKGROUND: Traumatic brain injury (TBI) has significant morbidity and cost implications. Primary treatment modalities aim to decrease intracranial pressure; however, therapies targeting the underlying pathophysiology of a TBI are limited. The TBI-induced microvascular leak and secondary injury are largely due to proteolysis of the blood-brain barrier (BBB) by matrix metalloproteinase-9. We previously observed doxycycline's inhibitory affinity on matrix metalloproteinase-9 resulting in preserved BBB integrity in nonsurvival murine studies. This study sought to determine the effect of doxycycline on functional motor and behavioral outcomes in the setting of a TBI murine survival model. METHODS: C57BL/6J mice were assigned to a sham, TBI, or TBI with doxycycline arm. A moderate TBI was induced utilizing a controlled cortical impactor. The TBI with doxycycline cohort received a dose of doxycycline (20 mg/kg) 2 hours after injury and every 12 hours until postoperative day (POD) 6. All mice underwent preoperative testing for weight, modified neurological severity score, wire grip, and ataxia analysis (DigiGait). Postoperative testing was performed on POD 1, POD 3, and POD 6 for the same measures. SAS 9.4 was used for comparative analysis. RESULTS: Fifteen sham mice, 15 TBI mice, and 10 TBI with doxycycline mice were studied. Mice treated with doxycycline had significantly improved modified neurological severity score and wire grip scores at POD 1 (all p < 0.05). Mice treated with doxycycline had significantly improved ataxia scores by POD 3 and POD 6 (all p < 0.05). There was no significant difference in rate of weight change between the three groups. CONCLUSION: Mice treated with doxycycline following TBI demonstrated improved behavioral and motor function suggesting doxycycline's role in preserving murine BBB integrity. Examining the role of doxycycline in human TBIs is warranted given the relative universal accessibility, affordability, and safety profile of doxycycline.

Exploring blood-brain barrier hyperpermeability and potential biomarkers in traumatic brain injury.

Blood-brain barrier breakdown and associated vascular hyperpermeability leads to vasogenic edema in traumatic brain injury (TBI). Tight junctions maintain blood-brain barrier integrity; their disruption in TBI holds significant promise for diagnosis and treatment. A controlled cortical impactor was used for TBI in mouse studies. Blood was collected 1 h after injury and sent for antibody microarray analysis. Twenty human subjects with radiographic evidence of TBI were enrolled and blood collected within 48 h of admission. Control subjects were individuals with nontrauma diagnoses. The subjects were matched by age and gender. Enzyme-linked immunosorbent assays were performed on each TBI and control sample for tight junction-associated proteins (TJPs), inflammatory markers, and S100ß. Plasma was used to conduct in vitro monolayer permeability studies with human brain endothelial cells. S100ß and the TJP occludin were significantly elevated in TBI plasma in both the murine and human studies. Monolayer permeability studies showed increased hyperpermeability in TBI groups. Plasma from TBI subjects increases microvascular hyperpermeability in vitro. TJPs in the blood may be a potential biomarker for TBI.

Postoperative Opioid Prescription Reduction Strategy in a Regional Healthcare System.

BACKGROUND: The CDC reported in 2017 that the largest increments in probability of continued use were observed after days 5 and 31 on opioid therapy. This study demonstrates the correlation between a system-wide pain management and opioid stewardship effort with reductions in discharge prescriptions for elective surgical patients. STUDY DESIGN: Discharge prescriptions were monitored through the electronic health record. Baseline prescribing patterns were established for the first quarter of 2018, preceding the first intervention in the multipronged opioid reduction initiative. Beginning in the second quarter of 2018, a series of pain management and opioid stewardship educational conferences were provided. Enhanced Recovery after Surgery protocols were simultaneously implemented system-wide. In the third quarter of 2018, a quality metric linked to compensation rewarded surgeons for limiting postoperative discharge prescriptions to 5 or fewer days. Opioid prescriptions were compared by quarter from January 2018 to March 2019 using chi-square and Kruskal-Wallis test with significance of p < 0.05. RESULTS: There were 31,814 patients who underwent elective surgical procedures during the study period. At baseline, the rate of postoperative opioid prescriptions of 5 or fewer days was 81%. This rate increased to 82%, 86%, 89%, and 92% in each successive quarter (p < 0.0001 for quarters 3 to 5). CONCLUSIONS: A system-wide, multipronged pain management and opioid reduction program significantly reduced opioid discharge prescriptions written for more than 5 days. This approach can serve as a model for other healthcare systems attempting to reduce opioid prescribing and combat the opioid crisis in the US.

Preoperative Frailty and Surgical Outcomes Across Diverse Surgical Subspecialties in a Large Health Care System.

BACKGROUND: Frailty is an emerging risk factor for surgical outcomes; however, its application across large populations is not well defined. We hypothesized that frailty affects postoperative outcomes in a large health care system. STUDY DESIGN: Frailty was prospectively measured in elective surgery patients (January 2016 to June 2017) in a health care system (4 hospitals/901 beds). Frailty classifications-low (0), intermediate (1 to 2), high (3 to 5)-were assigned based on the modified Hopkins score. Operations were classified as inpatient (IP) vs outpatient (OP). Outcomes measured (30-day) included major morbidity, discharge location, emergency department (ED) visit, readmission, length of stay (LOS), mortality, and direct-cost/patient. RESULTS: There were 14,530 elective surgery patients (68.1% outpatient, 31.9% inpatient) preoperatively assessed (cardiothoracic 4%, colorectal 4%, general 29%, oral maxillofacial 2%, otolaryngology 8%, plastic surgery 13%, podiatry 6%, surgical oncology 5%, transplant 3%, urology 24%, vascular 2%). High frailty was found in 3.4% of patients (5.3% IP, 2.5% OP). Incidence of major morbidity, readmission, and mortality correlated with frailty classification in all patients (p < 0.05). In the IP cohort, length of stay in days (low 1.6, intermediate 2.3, high 4.1, p < 0.0001) and discharge to facility increased with frailty (p < 0.05). In the OP cohort, ED visits increased with frailty (p < 0.05). Frailty was associated with increased direct-cost in the IP cohort (low, $7,045; intermediate, $7,995; high, $8,599; p < 0.05). CONCLUSIONS: Frailty affects morbidity, mortality, and health care resource use in both IP and OP operations. Additionally, IP cost increased with frailty. The broad applicability of frailty (across surgical specialties) represents an opportunity for risk stratification and patient optimization across a large health care system.

The Tri-phasic Role of Hydrogen Peroxide in Blood-Brain Barrier Endothelial cells.

Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 µM to 1 µM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 µM and above induced monolayer hyperpermeability significantly (p < 0.05). H2O2 at 10 mM and above decreased cell viability and induced apoptosis (p < 0.05). There was a decrease of ZO-1 tight junction localization with 100 µm H2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 µm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.

Surgical Site Infection after Primary Closure of High-Risk Surgical Wounds in Emergency General Surgery Laparotomy and Closed Negative-Pressure Wound Therapy.

BACKGROUND: We hypothesized that the universal adoption of closed wounds with negative pressure wound therapy (NPWT) in emergency general surgery patients would result in low superficial surgical infection (SSI) rates. STUDY DESIGN: We performed a retrospective observational study using primary wound closure with external NPWT, from May 2017 to May 2018. Patients with active soft tissue infection of the abdominal wall were excluded. Data were analyzed by Fisher's exact tests and Wilcoxon-Mann-Whitney tests, with significance is set at a value of p < 0.05. RESULTS: Eighty-five patients (53% female) with a median age of 65 years (range 19 to 98 years) underwent laparotomies. Four patients were excluded for active soft tissue infection. Wounds were classified as dirty (n = 18), contaminated (n = 52), and clean contaminated (n = 11). Median BMI was 27 kg/m2 (interquartile range [IQR] 23.4 to 33.0 kg/m2). Median antibiotic therapy was 4 days (IQR 1 to 7 days). Twenty-six patients had open abdomen management. Patient follow-up was a median of 20 days (range 14 to 120 days). Six patients (7%) developed superficial SSI requiring conversion to open wound management. No patients developed fascial dehiscence. There were no statistically significant associations between SSI and wound class (p = 0.072), antibiotic duration (p = 0.702), open abdomen management, or preoperative risk factors (p < 0.1). Overall morbidity was 38% and mortality was 6%. CONCLUSIONS: Primary closure of high risk incisions combined with NPWT is associated with acceptably low SSI rates. Due to the low morbidity and decreased cost associated with this technique, primary closure with NPWT should replace open wound management in the emergency general surgery population.

Cirrhosis, Operative Trauma, Transfusion, and Mortality: A Multicenter Retrospective Observational Study.

BACKGROUND: In trauma patients with cirrhosis who require laparotomy, little data exists to establish clinical predictors of the outcome. We sought to determine the prognosticators of mortality in this population. METHODS: We performed a 10-year review at four, busy Level I trauma centers of patients with cirrhosis identified during trauma laparotomy. We compared vital signs, laboratory values, and transfusion requirements for those who survived versus those who died. A linear regression was then conducted to determine the variables associated with death in this population. RESULTS: A total of 66 patients were included and 47% (31/66) died. The model for end-stage liver disease (MELD) score was low (7.8 in Lived, 10.2 in Died). Packed red blood cell (PRBC) transfusion at six hours was greater in those who died; those receiving > 6 units of PRBCs at 6 hours had an increased likelihood of death (odds ratio OR 5.8 (95% CI 1.9, 17.4)). All patients receiving ≥ 17 units of PRBCs died. We found an association between lower preoperative platelets (PLTs), higher preoperative international normalized ratio (INR) and partial thromboplastin time (PTT), lower preoperative pH (presence of profound acidemia), increased intraoperative crystalloid use, and increased intraoperative blood product administration to be associated with death (p < 0.05). CONCLUSIONS: Cirrhotic trauma patients requiring laparotomy should be considered to have a high chance of mortality if they receive six or more PRBCs, are acidotic (pH ≤ 7.25) at the time of hospital arrival, or have coagulopathy at the time of admission (INR > 1.2, PTT > 40).

Quetiapine protects the blood-brain barrier in traumatic brain injury.

BACKGROUND: The integrity of the blood-brain barrier (BBB) is paramount in limiting vasogenic edema following traumatic brain injury (TBI). The purpose of this study was to ascertain if quetiapine, an atypical antipsychotic commonly used in trauma/critical care for delirium, protects the BBB and attenuates hyperpermeability in TBI. METHODS: The effect of quetiapine on hyperpermeability was examined through molecular modeling, cellular models in vitro and small animal models in vivo. Molecular docking was performed with AutoDock Vina to matrix metalloproteinase-9. Rat brain microvascular endothelial cells (BMECs) were pretreated with quetiapine (20 µM; 1 hour) followed by an inflammatory activator (20 µg/mL chitosan; 2 hours) and compared to controls. Immunofluorescence localization for tight junction proteins zonula occludens-1 and adherens junction protein ß-catenin was performed. Human BMECs were grown as a monolayer and pretreated with quetiapine (20 µM; 1 hour) followed by chitosan (20 µg/mL; 2 hours), and transendothelial electrical resistance was measured. C57BL/6 mice (n = 5/group) underwent mild to moderate TBI (controlled cortical impactor) or sham craniotomy. The treatment group was given 10 mg/kg quetiapine intravenously 10 minutes after TBI. The difference in fluorescence intensity between intravascular and interstitium (ΔI) represented BBB hyperpermeability. A matrix metalloproteinase-9 activity assay was performed in brain tissue from animals in the experimental groups ex vivo. RESULTS: In silico studies showed quetiapine thermodynamically favorable binding to MMP-9. Junctional localization of zonula occludens-1 and ß-catenin showed retained integrity in quetiapine-treated cells as compared with the chitosan group in rat BMECs. Quetiapine attenuated monolayer permeability compared with chitosan group (p < 0.05) in human BMECs. In the animal studies, there was a significant decrease in BBB hyperpermeability and MMP-9 activity when compared between the TBI and TBI plus quetiapine groups (p < 0.05). CONCLUSION: Quetiapine treatment may have novel anti-inflammatory properties to provide protection to the BBB by preserving tight junction integrity. LEVEL OF EVIDENCE: level IV.

Comparison of a standardized negative pressure wound therapy protocol after midline celiotomy to primary skin closure and traditional open wound vacuum-assisted closure management.

A negative pressure wound therapy (NPWT) protocol using Hydrofera Blue® bacteriostatic foam wicks and silver-impregnated foam overlay to close midline skin incisions after emergency celiotomy was compared to primary skin closure only and traditional open wound vacuum-assisted closure management as part of a quality improvement initiative. This single-institution retrospective cohort study assessed all consecutive emergency celiotomies from July 2013 to June 2014 excluding clean wounds. Included variables were demographics, wound classification, NPWT days, and surgical site occurrences (SSOs). Primary outcome was days of NPWT. Secondary outcomes included SSOs (surgical site infections, fascial dehiscence, return to operating room). Analysis used exact chi-square between categorical variables, Kruskal-Wallis for analysis of variance for ordinal and categorical variables, and Wilcoxon rank sum for total days of NPWT. One hundred fifty-eight patients underwent emergency celiotomy with primary skin closure (n = 51), open NPWT (n = 63), or the NPWT protocol (n = 44). There was no difference in American Society of Anesthesiologists Physical Status score, body mass index, wound classification, or SSO between the three groups. Total NPWT days were reduced in protocol versus open NPWT (median 3 vs 20.5 days, range 3-51 vs 3-405 days, P = 0.001). Primary skin closure and NPWT protocol had fewer patients discharged with NPWT than open NWPT (0% and 14% vs 63.5%, P < 0.0001, odds ratio = 10.7, 95% confidence interval 3.7-35.1). Primary skin closure and NPWT protocol decrease NPWT usage days and maintain low SSOs in emergency midline celiotomy incisions.

Open vs Closed Negative Pressure Wound Therapy for Contaminated and Dirty Surgical Wounds: A Prospective Randomized Comparison.

BACKGROUND: A new proprietary negative pressure wound device has been developed to apply negative pressure therapy to closed wounds (closed-NPWT). We postulated that closed-NPWT management of contaminated and dirty wounds would lead to faster wound healing and no significant difference in wound complications. STUDY DESIGN: An IRB approved, prospective randomized trial was performed. Patients were consented preoperatively, but not entered nor assigned treatment until intraoperative findings were known. Patients were randomly assigned to either open-NPWT or a wound closed with skin staples and external closed-NPWT. Primary outcome was time to complete wound healing, defined as complete epithelization of the wound. Secondary outcomes were wound complications including wound infection, seroma, and dehiscence. Statistical analysis was performed using chi-square test, Fisher exact test, t-test, and Wilcoxon Rank-Sum test with significance of p < 0.05. RESULTS: Twenty-five closed-NPWT and 24 open-NPWT patients were analyzed. There were no significant differences in sex, mean age, BMI, smoking history, steroid use, comorbidities, or indication for surgery in the 2 groups. One patient in the open-NPWT group and 2 patients in the closed-NPWT group developed a wound infection (p = 1.0). Four open-NPWT and 3 closed-NPWT patients died from complications unrelated to the wound. Wound healing occurred at a median of 48 days (range 6 to 126 days) for the open-NPWT group vs a median of 7 days (range 6 to 12 days) for the closed-NPWT group (p < 0.0001). CONCLUSIONS: Wound healing was significantly faster in contaminated and dirty wounds when managed with closed-NPWT. There was no difference in wound complications between the 2 treatment groups. This approach shows promise for closed management of contaminated and dirty wounds and warrants additional prospective studies with larger patient groups.

Impact of complications on length of stay in elective laparoscopic colectomies.

BACKGROUND: Length of hospital stay (LOS) is an indirect measure of surgical quality and a surrogate for cost. The impact of postoperative complications on LOS following elective colorectal surgery is not well defined. The purpose of this study is to determine the contribution of specific complications towards LOS in elective laparoscopic colectomy patients. MATERIALS AND METHODS: American College of Surgeon's National Surgical Quality Improvement Program database (2011-2014) was queried for patients undergoing elective laparoscopic partial colectomy with primary anastomosis. Demographics, specific 30 d postoperative complications and LOS, were evaluated. A negative binomial regression adjusting for demographic variables and complications was performed to explore the impact of individual complications on LOS, significance set at P < 0.05. RESULTS: A total of 42,365 patients were evaluated, with an overall median LOS 4.0 d (interquartile range, 3.0-5.0). Unplanned reoperation and pneumonia each increase LOS by 50%; superficial surgical site infections (SSIs), organ space SSI sepsis, urinary tract infection, ventilation >48 h, pulmonary embolism, and myocardial infarction each increase LOS by at least 25% (P < 0.0001). When accounting for additional LOS and rate of complications, unplanned reoperation, bleeding requiring transfusion within 72 h, and superficial SSIs were the highest impact complications. CONCLUSIONS: In laparoscopic colectomy, each complication uniquely impacts LOS, and therefore cost. Utilizing this model, individual hospitals can implement pathways targeting specific complication profiles to improve care and minimize health care cost.

NSQIP-Based Quality Improvement Curriculum for Surgical Residents.

BACKGROUND: General surgery training has historically lacked a standardized approach to resident quality improvement (QI) education aside from traditional morbidity and mortality conference. In 2013, the ACGME formalized QI as a component of residency training. Our residency chose the NSQIP Quality In-Training Initiative (QITI) as the foundation for our QI training. We hypothesized that a focused curriculum based on outcomes would produce change in culture and improve the quality of patient care. STUDY DESIGN: Quality improvement curriculum design and implementation were retrospectively reviewed. Institutional NSQIP data pre-, during, and post-curriculum implementation were reviewed for improvement. RESULTS: A QITI project committee designed a 2-year curriculum, with 3 parts: didactics, focused on methods of data collection, QI processes, and techniques; review of current institutional performance, practice, and complication rates; and QI breakout groups tasked with creating "best practice" guidelines addressing common complications in our NSQIP semi-annual reports. Educational presentations were given to the surgical department addressing reduction of cardiac complications, pneumonia, surgical site infections (SSIs), and urinary tract infections (UTIs). Twenty-four residents completed both years of the QITI curriculum. National NSQIP decile ranks improved in known high outlier areas: cardiac complications, ninth to fourth decile; pneumonia, eighth to first decile; SSIs, tenth to second decile; and UTIs, eighth to third decile. Pneumonia and SSI rates demonstrated statistical improvement after curriculum implementation (p < 0.003). CONCLUSIONS: Implementing a QITI curriculum with a full resident complement is feasible and can positively affect surgical morbidity and nationally benchmarked performance. Resident QI education is essential to future success in delivering high quality surgical care.

Protocol-Driven Management of Suspected Common Duct Stones.

BACKGROUND: Common duct stones can be diagnosed by magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS)/ERCP, and intraoperative cholangiogram (IOC). In 2015, our group adopted a standard approach of preoperative EUS/ERCP followed by laparoscopic cholecystectomy for patients with an admission bilirubin >4.0 mg/dL. For bilirubin <4.0 mg/dL, laparoscopic cholecystectomy with IOC was the initial procedure. Postoperative EUS/ERCP with endoscopic sphincterotomy was pursued for positive IOC. Exclusions included clinical suspicion of malignancy and surgically altered anatomy making endoscopic management impractical. STUDY DESIGN: A retrospective comparison of protocol and pre-protocol (baseline) patients was performed, looking at patient demographics, presence of pancreatitis, common duct stone risk factors, comorbidities, length of hospitalization, and postoperative morbidity. Statistical analysis was performed with t-test, chi-square, and Wilcoxon rank-sum test with significance at p < 0.05. RESULTS: There were 56 patients in each group, with a mean ± SD age of 50.5 ± 20.88 years and 49.3 ± 20.92 years, respectively (p = NS). There were no significant differences between baseline and protocol patients with respect to individual and cumulative preoperative comorbidities, pancreatitis, elevation of liver function tests, bilirubin, common duct size, and postoperative morbidity. There were fewer endoscopies (22 vs 35; p = 0.014), and shorter length of stay in protocol patients (2.8 days vs 3.8 days; p = 0.025). CONCLUSIONS: Protocol-driven management of patients with suspected common duct stones reduced the number of endoscopies and length of hospitalization, with no change in postoperative morbidity. This approach has the potential to decrease endoscopy-related morbidity and overall cost without affecting quality of care.

Elevations in growth hormone and glucagon-like peptide-2 levels on admission are associated with increased mortality in trauma patients.

BACKGROUND: Burn and trauma patients present a clinical challenge due to metabolic derangements and hypermetabolism that result in a prolonged catabolic state with impaired healing and secondary complications, including ventilator dependence. Previous work has shown that circulating levels of growth hormone (GH) are predictive of mortality in critically ill adults, but few studies have examined the prognostic potential of GH levels in adult trauma patients. METHODS: To investigate the utility of GH and other endocrine responses in the prediction of outcomes, we conducted a prospective, observational study of adult burn and trauma patients. We evaluated the serum concentration of GH, insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), and glucagon-like peptide-2 (GLP-2) weekly for up to 6 weeks in 36 adult burn and trauma patients admitted between 2010 and 2013. RESULTS: Non-survivors had significantly higher levels of GH and GLP-2 on admission than survivors. DISCUSSION: This study demonstrates that GH has potential as a predictor of mortality in critically ill trauma and burn patients. Future studies will focus on not only the role of GH, but also GLP-2, which was shown to correlate with mortality in this study with a goal of offering early, targeted therapeutic interventions aimed at decreasing mortality in the critically injured. CONCLUSIONS: GH and GLP-2 may have clinical utility for outcome prediction in adult trauma patients.

Characterizing End-of-Life Care after Geriatric Burns at a Verified Level I Burn Center.

BACKGROUND: End-of-life (EoL) care after geriatric burns (geri-burns) is understudied. OBJECTIVE: To examine the practices of burn surgeons for initiating EoL discussions and the impact of decisions made on the courses of geri-burn patients who died after injury. METHODS: This retrospective cohort study examined all subjects ≥65 years who died on our Level I burn service from April 1, 2009, to December 31, 2014. Measurements obtained were timing of first EoL discussion (EARLY <24 hours post-admission; LATE ≥24 hours post-admission), decisions made, age, total body surface area burned, and calculated probability of death at admission. RESULTS: The cohort consisted of 57 subjects, of whom 54 had at least one documented EoL care discussion between a burn physician and the patient/surrogate. No differences were seen between groups for the likelihood of an immediate decision for comfort care after the first discussion (p = 0.73) or the mean number of total discussions (p = 0.07). EARLY group subjects (n = 38) had significantly greater magnitudes of injury (p = 0.002), calculated probabilities of death at admission (p ≤ 0.001), shorter times to death (p ≤ 0.001), and fewer trips to the operating theater for burn excision and skin grafting (p ≤ 0.001) than LATE subjects (n = 16). LATE subjects' first discussion occurred at a mean of 9.3 ± 10.0 days. DISCUSSION: The vast majority of geri-burn deaths on our burn service occur after a discussion about EoL care. The timing of these discussions is driven by magnitude of injury, and it does not lead to higher proportions of an immediate decision for comfort care. The presence and timing of EoL discussions bears further study as a quality metric for geri-burn EoL care.

Outpatient Laparoscopic Appendectomy: Is It Time to End the Discussion?

BACKGROUND: Laparoscopic appendectomy is typically associated with inpatient hospitalization averaging between 1 and 2 days. In July 2010, a prospective protocol for outpatient laparoscopic appendectomy was adopted at our institution. Patients were dismissed from the post-anesthesia recovery room or day surgery if they met certain predefined criteria. Patients admitted to a hospital room as either full admission or observation status were considered failures of outpatient management. STUDY DESIGN: An IRB-approved, retrospective review of a prospective database was performed on all patients having laparoscopic appendectomy for uncomplicated appendicitis from July 2010 through December 2014. Study exclusions included age younger than 17 years, pregnancy, interval appendectomy, and gangrenous or perforated appendicitis. Patient demographics, success with outpatient management, morbidity, and readmissions were analyzed. RESULTS: Five hundred and sixty-three patients underwent laparoscopic appendectomy for uncomplicated appendicitis during this time frame. There were 281 men and 282 women, with a mean age of 35.5 years. Four hundred and eighty-four patients (86%) were managed as outpatients. Seventy-nine patients were admitted for pre-existing conditions (32 patients), postoperative morbidity (10 patients), physician discretion (6 patients), or lack of transportation or support at home (31 patients). Thirty-eight patients (6.7%) experienced postoperative morbidity. Seven patients (1.2%) were readmitted after outpatient management for transient fever, nausea/vomiting, migraine headache, urinary tract infection, partial small bowel obstruction, and deep venous thrombosis. There were no mortalities or reoperations. Including the readmissions, overall success with outpatient management was 85%. CONCLUSIONS: Outpatient laparoscopic appendectomy can be performed with a high rate of success, low morbidity, and low readmission rate. This protocol has withstood the test of time. Widespread adoption has the potential for substantial health care savings.

Acute blood loss during burn and soft tissue excisions: An observational study of blood product resuscitation practices and focused review.

BACKGROUND: Many military and civilian centers have shifted to a damage-control resuscitation approach, focused on providing oxygen-carrying capacity while simultaneously mitigating coagulopathy with a balanced ratio of platelets and plasma to red blood cells. It is unclear to what degree this strategy is used during burn or soft tissue excision. Here, we characterized blood product transfusion during burn and soft tissue surgery and reviewed the published literature regarding intraoperative coagulation changes. We hypothesized that blood product resuscitation during burn and soft tissue excision is not hemostatic and would be insufficient to address hemorrhage-induced coagulopathy. METHODS: Consented adult patients were enrolled into an institutional review board-approved prospective observational study. Number, component type, volume, and age of the blood products transfused were recorded during burn excision/grafting or soft tissue debridement. Component bags (packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate) were collected, and the remaining sample was harvested from the bag and tubing. Aliquots of 1/1,000th the original volume of each blood product were obtained and combined, producing an amalgam sample containing the same ratio of product transfused. Platelet count, rotational thromboelastometry, and impedance aggregometry were measured. Significance was set at p < 0.05. RESULTS: Amalgamated transfusate samples produced abnormally weak clots (p ≤ 0.001) particularly if they did not contain platelets. Clot strength (48.8 [2.6] mm; reference range, 49-71 mm) for platelet-containing amalgams was below the lower limit of the reference range despite platelet-red blood cell ratios greater than 1:1. Platelet aggregation was abnormally low; transfused platelets were functionally inferior to native platelets. CONCLUSION: Our study and focused review demonstrate that further work is needed to fully understand the needs of patients undergoing tissue excision. The three studies reviewed and the results of our observational work suggest that coagulopathy and thrombocytopenia may contribute to intraoperative hemorrhage. Blood product resuscitation during burn and soft tissue excision is not hemostatic. LEVEL OF EVIDENCE: Epidemiologic study, level V.