Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice.

Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.

Surgical Infection Society-Chest Wall Injury Society Recommendations for Management of Surgical Site or Implant-Related Infections After Surgical Stabilization of Traumatic Rib or Sternal Fractures.

Background: Surgical stabilization of rib fractures (SSRF) and surgical stabilization of sternal fractures (SSSF) involves open reduction and internal fixation of fractures with an implantable titanium plate to restore and maintain anatomic alignment. The presence of this foreign, non-absorbable material presents an opportunity for infection. Although surgical site infection (SSI) and implant infection rates after SSRF and SSSF are low, they present a challenging clinical entity. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee and Chest Wall Injury Society's Publication Committee convened to develop recommendations for management of SSIs or implant-related infections after SSRF or SSSF. PubMed, Embase, Web of Science and the Cochrane database were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: For patients undergoing SSRF or SSSF who develop an SSI or an implant-related infection, there is insufficient evidence to suggest a single optimal management strategy. For patients with an SSI, systemic antibiotic therapy, local wound debridement, and vacuum-assisted closure have been used in isolation or combination. For patients with an implant-related infection, initial implant removal with or without systemic antibiotic therapy, systemic antibiotic therapy with local wound drainage, and systemic antibiotic therapy with local antibiotic therapy have been documented. For patients who do not undergo initial implant removal, 68% ultimately require implant removal to achieve source control. Conclusions: Insufficient evidence precludes the ability to recommend guidelines for the treatment of SSI or implant-related infection following SSRF or SSSF. Further studies should be performed to identify the optimal management strategy in this population.

Omicron, Long-COVID, and the Safety of Elective Surgery for Adults and Children: Joint Guidance from the Therapeutics and Guidelines Committee of the Surgical Infection Society and the Surgery Strategic Clinical Network, Alberta Health Services.

Background: Active and recent coronavirus disease 2019 (COVID-19) infections are associated with morbidity and mortality after surgery in adults. Current recommendations suggest delaying elective surgery in survivors for four to 12 weeks, depending on initial illness severity. Recently, the predominant causes of COVID-19 are the highly transmissible/less virulent Omicron variant/subvariants. Moreover, increased survivability of primary infections has engendered the long-COVID syndrome, with protean manifestations that may persist for months. Considering the more than 600,000,000 COVID-19 survivors, surgeons will likely be consulted by recovered patients seeking elective operations. Knowledge gaps of the aftermath of Omicron infections raise questions whether extant guidance for timing of surgery still applies to adults or should apply to the pediatric population. Methods: Scoping review of relevant English-language literature. Results: Most supporting data derive from early in the pandemic when the Alpha variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predominated. The Omicron variant/subvariants generally cause milder infections with less organ dysfunction; many infections are asymptomatic, especially in children. Data are scant with respect to adult surgical outcomes after Omicron infection, and especially so for pediatric surgical outcomes at any stage of the pandemic. Conclusions: Numerous knowledge gaps persist with respect to the disease, the recovered pre-operative patient, the nature of the proposed procedure, and supporting data. For example, should the waiting period for all but urgent elective surgery be extended beyond 12 weeks, e.g., after serious/critical illness, or for patients with long-COVID and organ dysfunction? Conversely, can the waiting periods for asymptomatic patients or vaccinated patients be shortened? How shall children be risk-stratified, considering the distinctiveness of pediatric COVID-19 and the paucity of data? Forthcoming guidelines will hopefully answer these questions but may require ongoing modifications based on additional new data and the epidemiology of emerging strains.

Surgical Infection Society Guidelines: 2022 Updated Guidelines for Antibiotic Use in Open Extremity Fractures.

Background: Open fractures, defined as fractures communicating with the environment through a skin wound, cause substantial morbidity after traumatic injury. Current evidence supports administration of prophylactic systemic antibiotic agents to patients with open extremity fractures to decrease infectious complications. Methods: The Therapeutic and Guidelines Committee of The Surgical Infection Society convened to revise guidelines for antibiotic use in open fractures. PubMed was queried for pertinent studies. Evaluation of the published evidence was performed using the GRADE framework. All committee members voted to accept or reject each recommendation. Results: In type I or II open extremity fractures, we recommend against administration of extended-spectrum antibiotic coverage compared with gram-positive coverage alone to decrease infections complications, hospital length of stay or mortality. In type III open extremity fractures, we recommend antibiotic therapy for no more than 24 hrs after injury, in the absence of clinical signs of active infection, to decrease infectious complications, hospital length of stay or mortality, and we recommend against extended antimicrobial coverage beyond gram-positive organisms to decrease infectious complications, hospital length of stay or mortality. In type III open extremity fractures with associated bone loss, we recommend antibiotic therapy in addition to systemic therapy to decrease infectious complications. Conclusions: Although antibiotic agents remain a standard of care for infection prevention after open extremity fractures, our findings and surveys of clinical practice patterns clearly show that additional robust clinical trials are needed to provide stronger corroborating evidence.

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients.

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

Surgical Infection Society: Chest Wall Injury Society Recommendations for Antibiotic Use during Surgical Stabilization of Traumatic Rib or Sternal Fractures to Reduce Risk of Implant Infection.

Background: Surgical stabilization of rib fractures is recommended in patients with flail chest or multiple displaced rib fractures with physiologic compromise. Surgical stabilization of rib fractures (SSRF) and surgical stabilization of sternal fractures (SSSF) involve open reduction and internal fixation of fractures with a plate construct to restore anatomic alignment. Most plate constructs are composed of titanium and presence of this foreign, non-absorbable material presents opportunity for implant infection. Although implant infection rates after SSRF and SSSF are low, they present a challenging clinical entity often requiring prolonged antibiotic therapy, debridement, and potentially implant removal. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee and Chest Wall Injury Society's Publication Committee convened to develop recommendations for antibiotic use during and after surgical stabilization of traumatic rib and sternal fractures. Clinical scenarios included patients with concomitant infectious processes (sepsis, pneumonia, empyema, cellulitis) or sources of contamination (open chest, gross contamination) incurred as a result of their trauma and present at the time of their surgical stabilization. PubMed, Embase, and Cochrane databases were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: For patients undergoing SSRF or SSSF in the absence of pre-existing infectious process, there is insufficient evidence to suggest existing peri-operative guidelines or recommendations are inadequate. For patients undergoing SSRF or SSSF in the presence of sepsis, pneumonia, or an empyema, there is insufficient evidence to provide recommendations on duration and choice of antibiotic. This decision may be informed by existing guidelines for the concomitant infection. For patients undergoing SSRF or SSSF with an open or contaminated chest there is insufficient evidence to provide specific antibiotic recommendations. Conclusions: This guideline document summarizes the current Surgical Infection Society and Chest Wall Injury Society recommendations regarding antibiotic use during and after surgical stabilization of traumatic rib or sternal fractures. Limited evidence exists in the chest wall surgical stabilization literature and further studies should be performed to delineate risk of implant infection among patients undergoing SSSRF or SSSF with concomitant infectious processes.

Surgical Infection Society Guidelines for Antibiotic Use in Patients Undergoing Cholecystectomy for Gallbladder Disease.

Background: Manifestations of gallbladder disease range from intermittent abdominal pain (symptomatic cholelithiasis) to potentially life-threatening illness (gangrenous cholecystitis). Although surgical intervention to treat acute cholecystitis is well defined, the role of antibiotic administration before or after cholecystectomy to decrease morbidity or mortality is less clear. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee convened to develop guidelines for antibiotic use in patients undergoing cholecystectomy for gallbladder disease to prevent surgical site infection, other infection, hospital length of stay, or mortality. PubMed, Embase, and the Cochrane Database were searched for relevant studies. Evaluation of the published evidence was performed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Using a process of iterative consensus, all authors voted to accept or reject each recommendation. Results: We recommend against routine use of peri-operative antibiotic agents in low-risk patients undergoing elective laparoscopic cholecystectomy. We recommend use of peri-operative antibiotic agents for patients undergoing laparoscopic cholecystectomy for acute cholecystitis. We recommend against use of post-operative antibiotic agents after elective laparoscopic cholecystectomy for symptomatic cholelithiasis. We recommend against use of post-operative antibiotic agents in patients undergoing laparoscopic cholecystectomy for mild or moderate acute cholecystitis. We recommend a maximum of four days of antibiotic agents, and perhaps a shorter duration in patients undergoing cholecystectomy for severe (Tokyo Guidelines grade III) cholecystitis. Conclusions: This guideline summarizes the current Surgical Infection Society recommendations for antibiotic use in patients undergoing cholecystectomy for gallbladder disease.

Surgical Infection Society Guidelines for Total Abdominal Colectomy versus Diverting Loop Ileostomy with Antegrade Intra-Colonic Lavage for the Surgical Management of Severe or Fulminant, Non-Perforated Clostridioides difficile Colitis.

Background: Clostridioides difficile infection (CDI) can result in life-threatening illness requiring surgery. Surgical options for managing severe or fulminant, non-perforated C. difficile colitis include total abdominal colectomy with end ileostomy or creation of a diverting loop ileostomy with antegrade vancomycin lavage. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee convened to develop guidelines for summarizing the current SIS recommendations for total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for severe or fulminant, non-perforated C. difficile colitis. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Severe infection was defined as laboratory diagnosis of C. difficile infection with leukocytosis (white blood cell count of ≥15,000 cells/mL) or elevated creatinine (serum creatinine level >1.5 mg/dL). Fulminant infection was defined as laboratory diagnosis of C. difficile infection with hypotension or shock, ileus, or megacolon. Perforation was defined as complete disruption of the colon wall. Total abdominal colectomy was defined as resection of the ascending, transverse, descending, and sigmoid colon with end ileostomy. For the purpose of the guideline, the terms subtotal colectomy, total abdominal colectomy, and rectal-sparing total colectomy were used interchangeably. Diverting loop ileostomy with antegrade enema was defined as creation of both a diverting loop ileostomy with intra-operative colonic lavage and post-operative antegrade vancomycin unless otherwise specified. Evaluation of the published evidence was performed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: We recommend that total abdominal colectomy be the procedure of choice for definitive therapy of severe or fulminant, non-perforated C. difficile colitis. In select patients, colon preservation using diverting loop ileostomy with intra-colonic vancomycin may be associated with higher rates of ostomy reversal and restoration of gastrointestinal continuity but may lead to development of recurrent C. difficile colitis. Conclusions: This guideline summarizes the current Surgical Infection Society recommendations regarding use of total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for adults with severe or fulminant, non-perforated C. difficile infection.

Surgical Infection Society 2020 Updated Guidelines on the Management of Complicated Skin and Soft Tissue Infections.

Background: The Surgical Infection Society (SIS) Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in Surgical Infections. The purpose of this project was to provide a succinct update on the earlier guidelines based on an additional decade of data. Methods: We reviewed the previous guidelines eliminating bite wounds and diabetic foot infections including their associated references. Relevant articles on the topic of complicated SSTIs from 2008-2020 were reviewed and graded individually. Comparisons were then made between the old and the new graded recommendations with review of the older references by two authors when there was disparity between the grades. Results: The majority of new studies addressed antimicrobial options and duration of therapy particularly in complicated abscesses. There were fewer updated studies on diagnosis and specific operative interventions. Many of the topics addressed in the original guidelines had no new literature to evaluate. Conclusions: Most recommendations remain unchanged from the original guidelines with the exception of increased support for adjuvant antimicrobial therapy after drainage of complex abscess and increased data for the use of alternative antimicrobial agents.

Surgical Infection Society Guidance for Restoration of Surgical Services during the Coronavirus Disease-2019 Pandemic.

Background: As the coronavirus disease-2019 (COVID-19) pandemic continues globally, high numbers of new infections are developing nationwide, particularly in the U.S. Midwest and along both the Atlantic and Pacific coasts. The need to accommodate growing numbers of hospitalized patients has led facilities in affected areas to suspend anew or curtail normal hospital activities, including elective surgery, even as earlier-affected areas normalized surgical services. Backlogged surgical cases now number in the tens of millions globally. Facilities will be hard-pressed to address these backlogs, even absent the recrudescence of COVID-19. This document provides guidance for the safe and effective resumption of surgical services as circumstances permit. Methods: Review and synthesis of pertinent international peer-reviewed literature, with integration of expert opinion. Results: The "second-wave" of serious infections is placing the healthcare system under renewed stress. Surgical teams likely will encounter persons harboring the virus, whether symptomatic or not. Continued vigilance and protection of patients and staff remain paramount. Reviewed are the impact of COVID-19 on the surgical workforce, considerations for operating on a COVID-19 patient and the outcomes of such operations, the size and nature of the surgical backlog, and the logistics of resumption, including organizational considerations, patient and staff safety, preparation of the surgical candidate, and the role of enhanced recovery programs to reduce morbidity, length of stay, and cost by rational, equitable resource utilization. Conclusions: Resumption of surgical services requires institutional commitment (including teams of surgeons, anesthesiologists, nurses, pharmacists, therapists, dieticians, and administrators). Structured protocols and equitable implementation programs, and iterative audit, planning, and integration will improve outcomes, enhance safety, preserve resources, and reduce cost, all of which will contribute to safe and successful reduction of the surgical backlog.

Surgical Infection Society Guidelines for Antibiotic Use in Patients with Traumatic Facial Fractures.

Background: Facial fractures are common in traumatic injury. Antibiotic administration practices for traumatic facial fractures differ widely. Methods: The Surgical Infection Society's (SIS's) Therapeutics and Guidelines Committee convened to develop guidelines for antibiotic administration in the management of traumatic facial fractures. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Pre-operative antibiotics were defined as those administered more than 1 hour before surgery. Peri-operative antibiotics were those administered within 1 hour of the start of surgery depending on the type of antibiotic and as late as ≤24 hours after surgery. Post-operative antibiotics were defined as those administered >24 hours after surgery. Prophylactic antibiotics were those administered for >24 hours without a documented infection. Evaluation of the published evidence was performed with the GRADE system. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: We recommend that in adult patients with non-operative upper face, midface, or mandibular fractures, prophylactic antibiotics not be prescribed and that in adult patients with operative, non-mandibular fractures, pre-operative antibiotics likewise not be prescribed. We recommend that in adult patients with operative, mandibular fractures, pre-operative antibiotics not be prescribed; and in adult patients with operative, non-mandibular facial fractures, post-operative (>24 hours) antibiotics again not be prescribed. We recommend that in adult patients with operative, mandibular facial fractures, post-operative antibiotics (> 24 hours) not be prescribed. Conclusions: This guideline summarizes the current SIS recommendations regarding antibiotic management of patients with traumatic facial fractures.

Pro-Con Perspectives on Ethics in Surgical Research: Update from the 39th Annual Surgical Infection Society Meeting.

Background: Surgical research is potentially invasive, high-risk, and costly. Research that advances medical dogma must justify both its ends and its means. Although ethical questions do not always have simple answers, it is critically important for the clinician, researcher, and patient to approach these dilemmas and surgical research in a thoughtful, conscientious manner. Methods: We present four ethical issues in surgical research and discuss the opposing viewpoints. These topics were presented and discussed at the 39th Annual Meeting of the Surgical Infection Society as pro-con debates. The presenters of each opinion developed a succinct summary of their respective reviews for this publication. Results: The key subjects for these pro-con debates were: (1) Should patients be enrolled for time-sensitive surgical infection research using an opt-out or an opt-in strategy? (2) Should patients who are being enrolled in a randomized controlled trial (RCT) comparing surgery with a non-operative intervention pay the costs of their treatment arm? (3) Should the scientific community embrace open access journals as the future of scientific publishing? (4) Should the majority of funding go to clinical or basic science research? Important points were illustrated in each of the pro-con presentations and illustrated the difficulties that are facing the performance and payment of infection research in the future. Conclusions: Surgical research is ethically complex, with conflicting demands between individual patients, society, and healthcare economics. At present, there are no clear answers to these and the many other ethical issues facing research in the future. Answers will only come from continued robust dialogue among all stakeholders in surgical research.

Surgical Infection Society Guidance for Operative and Peri-Operative Care of Adult Patients Infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.

Role of Empiric Anti-Fungal Therapy in the Treatment of Perforated Peptic Ulcer Disease: Review of the Evidence and Future Directions.

Background: Peptic ulcer disease (PUD) affects four million people worldwide. Perforated peptic ulcer (PPU) occurs in less than 15% of cases but is associated with significant morbidity and mortality rates. Administration of antibiotics is standard treatment for gastrointestinal perforations, including PPU. Although fungal growth is common in peritoneal fluid cultures from patients with PPU, current data suggest empiric anti-fungal therapy fails to improve outcomes. To examine the role of anti-fungal agents in the treatment of PPU, the Surgical Infection Society hosted an Update Symposium at its 37th Annual Meeting. Here, we provide a synopsis of the symposium's findings and a brief review of prospective and retrospective reports on the subject. Methods: A search of Pubmed/MEDLINE, EMBASE, and the Cochrane Library was performed between January 1, 2000, and November 1, 2018, comparing outcomes of PPU following empiric anti-fungal treatment versus no anti-fungal therapy. We used the search terms "perforated peptic ulcer," "gastroduodenal ulcer," "anti-fungal," and "perforated" or "perforation." Results: There are no randomized clinical trials comparing outcomes specifically for patients with PPU treated with or without empiric anti-fungal therapy. We identified one randomized multi-center trial evaluating outcomes for patients with intra-abdominal perforations, including PPU, that were treated with or without empiric anti-fungal therapy. We identified one single-center prospective series and three additional retrospective studies comparing outcomes for patients with PPU treated with or without empiric anti-fungal therapy. Conclusion: The current evidence reviewed here does not demonstrate efficacy of anti-fungal agents in improving outcomes in patients with PPU. As such, we caution against the routine use of empiric anti-fungal agents in these patients. Further studies should help identify specific subpopulations of patients who might derive benefit from anti-fungal therapy and help define appropriate treatment regimens and durations that minimize the risk of resistance, adverse events, and cost.

Antibiotics versus No Antibiotics for the Treatment of Acute Uncomplicated Diverticulitis: Review of the Evidence and Future Directions.

BACKGROUND: Acute diverticulitis occurs in 25% of individuals with diverticular disease and is associated with significant morbidity and mortality rates. Disease severity is classified as uncomplicated or complicated, with the latter including perforation, fistula, obstruction, or distant abscess. Uncomplicated diverticulitis often improves without surgery or invasive therapies. Administration of antibiotics is a standard of care for treatment of acute uncomplicated diverticulitis. However, recent data suggest antibiotics do not influence outcomes significantly. To address these conflicting approaches, the Surgical Infection Society hosted an Update Symposium at its 37th Annual Meeting examining the role of antibiotics in the treatment of acute uncomplicated diverticulitis. Here, we provide a synopsis of the symposium's findings and a brief review of recent prospective and randomized clinical trials on the topic. METHODS: A search of Embase, MEDLINE, and the Cochrane Library was performed for prospective series and randomized clinical trials published between January 1, 2010, and January 1, 2018, comparing outcomes of antibiotic versus no antibiotic therapy for acute uncomplicated diverticulitis. RESULTS: We identified two single-center prospective series and two randomized clinical trials comparing outcomes for patients with acute uncomplicated diverticulitis treated with antibiotics versus no antibiotics. CONCLUSION: Current evidence does not support administration of antibiotics to improve outcomes in carefully selected healthy patients with acute uncomplicated left-sided diverticulitis. Further studies should help identify specific subpopulations of patients who would derive benefit from antibiotic therapy and help define appropriate antibiotic regimens and treatment durations that minimize cost, adverse effects, and risk of anti-microbial resistance.

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.

The vagus nerve and the inflammatory reflex: wandering on a new treatment paradigm for systemic inflammation and sepsis.

BACKGROUND: The immune system protects the host against dangerous pathogens and toxins. The central nervous system is charged with monitoring and coordinating appropriate responses to internal and external stimuli. The inflammatory reflex sits at the crossroads of these crucial homeostatic systems. This review highlights how the vagus nerve-mediated inflammatory reflex facilitates rapid and specific exchange of information between the nervous and immune systems to prevent tissue injury and infection. METHODS: Review of the pertinent English-language literature. Nearly two decades of research has elucidated some of the essential anatomic, physiologic, and molecular connections of the inflammatory reflex. The original descriptions of how these key components contribute to afferent and efferent anti-inflammatory vagus nerve signaling are summarized. RESULTS: The central nervous system recognizes peripheral inflammation via afferent vagus nerve signaling. The brain can attenuate peripheral innate immune responses, including pro-inflammatory cytokine production, leukocyte recruitment, and nuclear factor kappa ß activation via α7-nicotinic acetylcholine receptor subunit-dependent, T-lymphocyte-dependent, vagus nerve signaling to spleen. This efferent arm of the inflammatory reflex is referred to as the "cholinergic anti-inflammatory pathway." Activation of this pathway via vagus nerve stimulation or pharmacologic α7 agonists prevents tissue injury in multiple models of systemic inflammation, shock, and sepsis. CONCLUSIONS: The vagus nerve-mediated inflammatory reflex is a powerful ally in the fight against lethal tissue damage after injury and infection. Further studies will help translate the beneficial effects of this pathway into clinical use for our surgical patients.