Adipose-Derived Inflammatory and Coagulant Mediators in Patients With Sepsis.

ABSTRACT: Results from preclinical sepsis studies using rodents are often criticized as not being reproducible in humans. Using a murine model, we previously reported that visceral adipose tissues (VAT) are highly active during the acute inflammatory response, serving as a major source of inflammatory and coagulant mediators. The purpose of this study was to determine whether these findings are recapitulated in patients with sepsis and to evaluate their clinical significance. VAT and plasma were obtained from patients undergoing intra-abdominal operations with noninflammatory conditions (control), local inflammation, or sepsis. In mesenteric and epiploic VAT, gene expression of pro-inflammatory (TNFα, IL-6, IL-1α, IL-1ß) and pro-coagulant (PAI-1, PAI-2, TSP-1, TF) mediators was increased in sepsis compared with control and local inflammation groups. In the omentum, increased expression was limited to IL-1ß, PAI-1, and PAI-2, showing a depot-specific regulation. Histological analyses showed little correlation between cellular infiltration and gene expression, indicating a resident source of these mediators. Notably, a strong correlation between PAI-1 expression in VAT and circulating protein levels was observed, both being positively associated with markers of acute kidney injury (AKI). In another cohort of septic patients stratified by incidence of AKI, circulating PAI-1 levels were higher in those with versus without AKI, thus extending these findings beyond intra-abdominal cases. This study is the first to translate upregulation of VAT mediators in sepsis from mouse to human. Collectively, the data suggest that development of AKI in septic patients is associated with high plasma levels of PAI-1, likely derived from resident cells within VAT.

Implementation of Opioid-Free Thyroid and Parathyroid Procedures: A Single Center Experience.

BACKGROUND: Initial opioid exposure for most individuals with substance use disorder comes from the healthcare system, and overprescription of opioids in ambulatory operations is common. This report describes an academic medical center's experience implementing opioid-free thyroid and parathyroid operations. MATERIALS AND METHODS: This is a retrospective chart review of patients undergoing a thyroid or parathyroid operation before and after implementation of an opioid-free analgesia protocol. The primary endpoint was new postoperative opioid prescription. Secondary endpoints included prescription characteristics and predictors of new opioid prescription. RESULTS: A total of 515 patients were enrolled in the study: 240 in the control or "pre-intervention" cohort (May through October 2017) and 275 in the intervention or "post" cohort (May through October 2018). Patients in the intervention cohort were significantly less likely to receive an opioid prescription (12.0% versus 59.6%, P < 0.001). When opioids were prescribed, they were used for shorter durations and at lower doses in the intervention cohort. Among the patients prescribed opioids in the intervention cohort (N = 33), the only significant predictor of postoperative opioid use was preoperative opioid use (P = 0.001). CONCLUSIONS: Opioids may not be required after thyroidectomy and parathyroidectomy, especially for opioid-naïve patients. Future research should examine patient satisfaction with opioid-sparing analgesia.

Opioid use in the acute setting: A survey of providers at an academic medical center.

OBJECTIVE: To examine attitudes, beliefs, and influencing factors of inpatient healthcare providers regarding prescription of opioid analgesics. DESIGN: Electronic cross-sectional survey. SETTING: Academic medical center. PARTICIPANTS: Physicians, advanced practice providers, and pharmacists from a single academic medical center in the southeast United States. MAIN OUTCOME MEASURES: Respondents completed survey items addressing: (1) their practice demographics, (2) their opinions regarding overall use, safety, and efficacy of opioids compared to other analgesics, (3) specific clinical scenarios, (4) main pressures to prescribe opioids, and (5) confidence/comfort prescribing opioids or nonopioids in select situations. RESULTS: The majority of the sample (n = 363) were physicians (60.4 percent), with 69.4 percent of physicians being attendings. Most respondents believed that opioids were overused at our institution (61.7 percent); nearly half thought opioids had similar efficacy to other analgesics (44.1 percent), and almost all believed opioids were more dangerous than other analgesics (88.1 percent). Many respondents indicated that they would modify a chronic regimen for a high-risk patient, and use of nonopioids in specific scenarios was high. However, this use was often in combination with opioids. Respondents identified patients (64 percent) and staff (43.1 percent) as the most significant sources of pressure to prescribe opioids during an admission; the most common sources of pressure to prescribe opioids on discharge were to facilitate discharge (44.8 percent) and to reduce follow-up requests, calls, or visits (36.3 percent). Resident physicians appear to experience more pressure to prescribe opioids than other providers. Managing pain in patients with substance use disorders and effectively using nonopioid analgesics were the most common educational needs identified by respondents. CONCLUSION: Most individuals believe opioid analgesics are overused in our specific setting, commonly to satisfy patient requests. In general, providers feel uncomfortable prescribing nonopioid analgesics to patients.

Procalcitonin: Usefulness in Acute Care Surgery and Trauma.

BACKGROUND: Procalcitonin (PCT) is a serum biomarker currently suggested by the Surviving Sepsis Campaign to aid in determination of the appropriate duration of therapy in sepsis patients. We review the use of procalcitonin in patients after trauma or acute care surgery. METHOD: A MEDLINE search via PubMed was performed using the combination of "procalcitonin" and "humans" and "injuries, trauma," "wounds and injuries," or "wounds." Studies of burn patients, children, other biomarkers, and non-acute care surgery were excluded. RESULTS: Procalcitonin may be useful in identifying infection in trauma and post-operative acute care surgery. However, heterogenity exists among patients, and surgery and trauma alone elevate PCT even in the absence of infection. CONCLUSIONS: Although trends in PCT concentrations may offer insight, no standard approach can be recommended currently.

Minimizing opioid use after acute major trauma.

PURPOSE: Results of an initiative at an academic medical center to reduce prescription opioid use in patients with acute traumatic injuries are reported. METHODS: In 2014, the University of Kentucky Hospital trauma service implemented a pain management strategy consisting of patient and provider education emphasizing the use of nonopioid analgesics to minimize opioid use without compromising analgesia effectiveness. To assess the impact of the initiative, a retrospective analysis of data on cohorts of patients admitted with acute trauma before (n = 489) and after (n = 424) project implementation was conducted. The primary endpoint was opioid use (prescribed daily milligram morphine equivalents [MME]) at discharge. Secondary endpoints included inpatient opioid and alternative analgesic use, pain control, ileus development, length of stay, and discharge disposition. RESULTS: Compared with the preintervention cohort, the postintervention cohort had a lower median daily discharge MME overall (45 MME versus 90 MME, p < 0.001); after stratification of MME data by baseline opioid use, this finding held true only for patients with no opioid prescription at admission. Although utilization of gabapentinoids, skeletal muscle relaxants, and clonidine increased during the postintervention period, inpatient opioid use did not differ significantly in the 2 cohorts. Utilization of both nonsteroidal antiinflammatory drugs and acetaminophen was lower in the postintervention cohort versus the preintervention cohort. CONCLUSION: Targeted provider and patient education on minimizing opioid use was associated with a reduction in MME on discharge from the hospital after traumatic injury.

Antibiotics vs. Appendectomy for Acute Uncomplicated Appendicitis in Adults: Review of the Evidence and Future Directions.

BACKGROUND: Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis. METHODS: Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial. RESULTS: According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship. CONCLUSION: Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.

Management and Novel Adjuncts of Necrotizing Soft Tissue Infections.

Necrotizing soft tissue infections (NSTI) have been recognized for millennia and continue to impose considerable burden on both patient and society in terms of morbidity, death, and the allocation of resources. With improvements in the delivery of critical care, outcomes have improved, although disease-specific therapies are lacking. The basic principles of early diagnosis, of prompt and broad antimicrobial therapy, and of aggressive debridement have remained unchanged. Clearly novel and new therapeutics are needed to combat this persistently lethal disease. This review emphasizes the pillars of NSTI management and then summarizes the contemporary evidence supporting the incorporation of novel adjuncts to the pharmacologic and operative foundations of managing this disease.

The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection.

BACKGROUND: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. METHODS: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. RESULTS: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. SUMMARY: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.

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.

Quality of Life in Vestibular Schwannoma Patients Managed by Surgical or Conservative Approaches.

OBJECTIVE: The aim of our study was to assess quality of life (QOL) among patients who underwent microsurgical excision of vestibular schwannoma (VS) compared with those managed conservatively. STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: There was a total sample population of 376 patients diagnosed with a unilateral VS. INTERVENTION: A total of 223 patients with unilateral VS returned the mailed questionnaires. These were then divided into two groups-78 that had undergone microsurgical excision and 145 that were managed conservatively. Subgroups within these primary groups were created for analysis. MAIN OUTCOME MEASURE: The primary outcome measure was the Medical Outcomes Study 36 Items Short Form (SF-36). The Dizziness Handicap Inventory test, Hearing Handicap Inventory test, and Tinnitus Handicap Inventory were also used. RESULTS: The surgically managed group had a worse QOL when compared with the conservatively managed group using SF-36, significantly so in the domains of physical role limitation and social functioning. Trends were seen toward a better QOL in some domains in the subgroups of male patients and patients younger than 65 years. Worse QOL scores in the Tinnitus Handicap Inventory were seen in the subgroups with larger tumor size. Finally, on correlation analysis between all handicap inventories and SF-36, handicap due to disequilibrium had the strongest correlation with worsening of QOL. In SF-36, the vitality domain showed the greatest correlation with otologic handicap overall, whereas the role emotional domain showed the least. CONCLUSION: This study found that worse QOL scores for surgically managed versus conservatively managed VS patients are most significant in the areas of physical role limitation and social functioning. In some areas, patients who are male and younger report better QOL. Handicap due to disequilibrium seems to have the greatest negative impact on QOL. These factors should be considered when counseling patients regarding approach to VS, in the context of an experienced management program.

Retained surgical sponges: findings from incident reports and a cost-benefit analysis of radiofrequency technology.

BACKGROUND: Retained surgical items (RSIs) are serious events with a high potential to harm patients. It is estimated that as many as 1 in 5,500 operations result in an RSI, and sponges are most commonly involved. The adverse outcomes, additional medical care needed, and medico-legal costs associated with these events are substantial. The objective of this analysis was to advance our understanding of the occurrence of RSIs, the methods of prevention, and the costs involved. STUDY DESIGN: Incident reports entered into the University HealthSystem Consortium (UHC) Safety Intelligence database on incorrect surgical counts and RSIs were analyzed. Reported cases of retained surgical sponges at organizations that use radiofrequency (RF) technology and those that do not were compared. A cost-benefit analysis on adopting RF technology was conducted. RESULTS: Five organizations that implemented RF technology between 2008 and 2012 collectively demonstrated a 93% reduction in the rate of reported retained surgical sponges. By comparison, there was a 77% reduction in the rate of retained sponges at 5 organizations that do not use RF technology. The UHC cost-benefit analysis showed that the savings in x-rays and time spent in the operating room and in the medical and legal costs that were avoided outweighed the expenses involved in using RF technology. CONCLUSIONS: Current standards for manual counting of sponges and the use of radiographs are not sufficient to prevent the occurrence of retained surgical sponges; our data support the use of adjunct technology. We recommend that hospitals evaluate and consider the use of an adjunct technology.

A prospective, controlled evaluation of the abdominal reapproximation anchor abdominal wall closure system in combination with VAC therapy compared with VAC alone in the management of an open abdomen.

Dramatic increases in damage control and decompressive laparotomies and a significant increase in patients with open abdominal cavities have resulted in numerous techniques to facilitate fascial closure. We hypothesized addition of the abdominal reapproximation anchor system (ABRA) to the KCI Abdominal Wound Vac™ (VAC) or KCI ABThera™ would increase successful primary closure rates and reduce operative costs. Fourteen patients with open abdomens were prospectively randomized into a control group using VAC alone (control) or a study group using VAC plus ABRA (VAC-ABRA). All patients underwent regular VAC changes; patients receiving VAC-ABRA also underwent concomitant daily elastomer adjustment of the ABRA system. Primary end points included abdominal closure, number of operating room (OR) visits, and OR time use. Eight patients were included in the VAC-ABRA group and six patients in the control group. Primary closure rates between groups were not statistically different; however, the number of trips to the OR and OR time use were different. Despite higher Acute Physiology and Chronic Health Evaluation II scores, larger starting wound size, and higher rates of abdominal compartment syndrome, closure rates in the VAC-ABRA group were similar to VAC alone. Importantly, however, fewer OR trips and less OR time were required for the VAC-ABRA group.

Influence of in-house attending presence on trauma outcomes and hospital efficiency.

BACKGROUND: The influence of in-house (IH) attendings on trauma patient survival and efficiency measures, such as emergency department length of stay (LOS), ICU LOS, and hospital LOS, has been debated for more than 20 years. No study has definitively shown improved outcomes with IH vs home-call attendings. This study examines trauma outcomes in a single, Level I trauma center before and after the institution of IH attending call. STUDY DESIGN: Patient data were collected from the University of Kentucky's trauma registry. Based on the Trauma-Related Injury Severity Score, survival rates were compared between the IH and home-call groups. To evaluate efficiency, emergency department LOS, ICU LOS, and hospital LOS were compared. A separate subanalysis for the most severely injured patients (trauma alert red) was also performed. RESULTS: The home-call group (n = 4,804) was younger (p = 0.018) and had a higher Injury Severity Score (p = 0.003) than the IH group (n = 5259), but there was no difference in Trauma-Related Injury Severity Score (p = 0.205) between groups. In-house attending presence did not reduce mortality. Emergency department LOS, ICU LOS, and hospital LOS were shorter during the IH period. Emergency department to operating room time was not different. There was no change in trauma alert red mortality with an attending present (20.7% vs 18.2%, p = 0.198). CONCLUSIONS: In-house attending presence does not improve trauma patient survival. For the most severely injured patients, attendings presence does not reduce mortality. In-house coverage can improve hospital efficiency by decreasing emergency department LOS, hospital LOS, and ICU LOS.

Skin necrosis as a complication of therapeutic hypothermia.

This case report describes a complication caused by cooling pads used for therapeutic hypothermic resuscitation. The authors hope to highlight and emphasize the importance of a thorough evaluation of all skin surfaces that are in direct contact with such cooling pads. Skin injury from the cooling pads used for therapeutic hypothermia should be recognized as a potential complication of treatment.

Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients.

BACKGROUND: Transfusion of packed red blood cells (PRBCs) increases morbidity and mortality in select surgical specialty patients. The impact of low-volume, leukoreduced RBC transfusion on general surgery patients is less well understood. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program participant use file was queried for general surgery patients recorded in 2005 to 2006 (n = 125,223). Thirty-day morbidity (21 uniformly defined complications) and mortality, demographic, preoperative, and intraoperative risk variables were obtained. Infectious complications and composite morbidity and mortality were stratified across intraoperative PRBCs units received. Multivariable logistic regression was used to assess influence of transfusion on outcomes, while adjusting for transfusion propensity, procedure type, wound class, operative duration, and 30+ patient risk factors. RESULTS: After adjustment for transfusion propensity, procedure group, wound class, operative duration, and all other important risk variables, 1 U PRBCs significantly (p < 0.05) increased risk of 30-day mortality (odds ratio [OR] = 1.32), composite morbidity (OR = 1.23), pneumonia (OR = 1.24), and sepsis/shock (OR = 1.29). Transfusion of 2 U additionally increased risk for these outcomes (OR = 1.38, 1.40, 1.25, 1.53, respectively; p

Imaging may delay transfer of rural trauma victims: a survey of referring physicians.

BACKGROUND: Delayed transfer to a trauma center due to unnecessary imaging results in suboptimal patient outcome and increases healthcare costs. Unnecessary imaging may result from beliefs regarding trauma center requirements and legal concerns. We hypothesized that referring physicians consider factors other than clinical criteria when deciding to order imaging studies before transfer of trauma patients. METHODS: A mail survey of 218 referring physicians to a level I trauma center elicited factors affecting decision to obtain imaging studies before transfer. Graded answers to six questions were obtained and demographics of the physician respondent. Statistical analysis was performed using Fisher's exact test. RESULTS: One hundred forty-nine of 218 surveys were returned (68.3%). One-third (33.1%) of respondents obtain imaging because of perceived expectations of the receiving trauma center, independent of patient acuity. Twenty percent incorrectly think that the law prohibits transfer before patients are stabilized. Twenty-eight percent obtain imaging because of liability concerns, even if that imaging delays transfer. Overall, 45% obtain imaging for either perceived requirement or liability concern. Non-advanced trauma life support (ATLS)-certified physicians are more likely to use all available resources before transfer than ATLS-certified physicians. CONCLUSIONS: Factors other than patient care dictate imaging acquisition in almost half of those surveyed. Misperception of expectations, misunderstanding of legal imperatives, and liability concerns all delay transport of the injured. ATLS-certified individuals use imaging more appropriately, thus, promoting more timely transfer. State-wide protocols, education, and liability reform may reduce transport delays.

Cholesteatoma--diagnosing the unsafe ear.

BACKGROUND: Cholesteatoma represents the most common destructive disease of the ear, affecting the adult and paediatric population alike. OBJECTIVE: This article describes the pathogenesis of cholesteatoma and provides a guide to the examination and management of this common disease. DISCUSSION: Despite advances in surgery and imaging, the diagnosis of cholesteatoma is often delayed. A favourable outcome following treatment of a cholesteatoma rests in part on an early diagnosis, and in reducing significant complications and associated morbidity. Primary care physicians should maintain a high index of suspicion for the presence of cholesteatoma, awareness of otoscopic findings and promptly refer for investigations and management.

Red blood cell arginase suppresses Jurkat (T cell) proliferation by depleting arginine.

BACKGROUND: Transfusion of packed red blood cells (PRBC) suppresses immunity, but the mechanisms are incompletely understood. PRBCs contain arginase, an enzyme which converts arginine to ornithine and depletes arginine in vitro. Arginine depletion suppresses proliferation of Jurkat T cells in other models. We hypothesize that PRBC arginase-mediated arginine depletion will suppress proliferation of T cells. METHODS: A transfusion model was designed adding PRBC to culture RPMI media with or without an irreversible arginase blocker (nor-NOHA), incubating for 6-48 hours and then removing the PRBCs. Amino acid concentrations in the media were measured using liquid chromatography mass spectrometry. T cells were then added to the pre-conditioned media, cultured for 24 hours, and proliferation was measured. RESULTS: PRBC depleted arginine significantly and increased ornithine in media compared to baseline PRBC treated wells and significantly decreased T cell proliferation. These effects were enhanced with volume of PRBC exposure. Nor-NOHA inhibition of arginase restored T cell proliferation in PRBC treated cultures. CONCLUSIONS: Jurkat T cell proliferation was impaired by PRBC in clinically relevant volumes. The mechanism influencing T cell impairment appears to result from arginine depletion by arginase. Arginine depletion by PRBC arginase may be a novel mechanism for immunosuppression after transfusion.

Packed red blood cell-associated arginine depletion is mediated by arginase.

BACKGROUND: Packed red blood cells (PRBCs) transfusion is associated with immune suppression, but these mechanisms are incompletely understood. PRBCs contain arginase, an enzyme that converts arginine to ornithine, and is known to limit arginine availability and suppress cellular immunity. We sought to determine whether PRBC arginase causes arginine depletion, potentially contributing to immunosuppression. METHODS: A model of transfusion was designed by adding either centrifuged acellular supernatant from the PRBC unit (plasma) or total fluid from the unit (plasma+RBC [red blood cells]) to cell culture media. Through an institutional review board-approved protocol, PRBC units were isolated and processed by an accredited blood bank and stored at 4 degrees C. Leukoreduced PRBCs or supernatant aliquots were withdrawn every 5 days to 7 days for 42 days. Cell cultures were created with standard Roswell Park Memorial Institute media, controlling the arginine level at 80 micromol/L (approximating human serum), and adding 20% plasma or plasma+RBC. An irreversible arginase blocker (nor-N-omega-OH-L-arginine) was added to selected cultures. After 24 hours, culture arginase activity was measured by ornithine synthesis, and amino acid levels were measured using mass spectroscopy. RESULTS: Culture arginase activity was increased by both plasma and plasma+RBC, but with plasma+RBC this did not reach statistical significance. Arginine levels were decreased and ornithine levels increased in cultures containing either supernatant or PRBC, as compared with control media. Addition of nor-N-omega-OH-l-arginine significantly decreased cell culture arginase activity, restored arginine levels, and diminished ornithine synthesis. CONCLUSIONS: Arginase is present in PRBC units and causes arginine depletion. Depletion of arginine by PRBC arginase is a potential novel mechanism for immunosuppression.