Influenza Suppresses Neutrophil Recruitment to the Lung and Exacerbates Secondary Invasive Pulmonary Aspergillosis.

Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A-induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis.

The Ryder Cognitive Aid Checklist for Trauma Anesthesia.

Despite mixed results regarding the clinical utility of checklists, the anesthesia community is increasingly interested in advancing research around this important topic. Although several checklists have been developed to address routine perioperative care, few checklists in the anesthesia literature specifically target the management of trauma patients. We adapted a recently published "trauma and emergency checklist" for the initial phase of resuscitation and anesthesia of critically ill trauma patients into an applicable perioperative cognitive aid in the form of a pictogram that can be downloaded by the medical community. The Ryder Cognitive Aid Checklist for Trauma Anesthesia is a letter-sized, full-color document consisting of 2 pages and 5 sections. This cognitive aid describes the essential steps to be performed: before patient arrival to the hospital, on patient arrival to the hospital, during the initial assessment and management, during the resuscitation phase, and for postoperative care. A brief online survey is also presented to obtain feedback for improvement of this tool. The variability in utility of cognitive aids may be because of the specific clinical task being performed, the skill level of the individuals using the cognitive aid, overall quality of the cognitive aid, or organizational challenges. Once optimized, future research should be focused at ensuring successful implementation and customization of this tool.

Factor concentrates in trauma.

PURPOSE OF REVIEW: Recent advances in the understanding of transfusion practices during hemorrhagic shock in trauma have led to early administration of thawed plasma in increased ratios to packed red blood cells and have improved survival in the most severely injured patients. As an appreciation for the sequelae of massive transfusion continues to mature, it is becoming apparent that a more targeted approach to coagulation deficiencies may offer an advantage. RECENT FINDINGS: Factor concentrate therapy offers the advantage of smaller volumes of resuscitative fluids directed at specific phases of coagulation identified by alternative laboratory assays (e.g., viscoelastic testing). Case reports, animal studies, and retrospective reviews offer encouraging data on the ability of factor concentrates to reverse coagulopathy and reduce blood product usage. SUMMARY: The use of factor concentrates to target specific phases of coagulation may offer benefit over blood product ratio-driven transfusion. The outcome benefit of factor concentrates, however, has not yet been demonstrated in well powered prospective trials.

Developing a trauma curriculum for anesthesiology residents and fellows.

PURPOSE OF REVIEW: The board certification process for qualification by the American Board of Anesthesiology is undergoing significant review. A basic sciences examination has been added to the process and the traditional oral examination is evolving into a combined oral interview and practical skills assessment. These recent developments, as well as the growing body of evidence regarding the resuscitation of trauma patients, call for a revision in the curriculum beyond the documentation of participation in the anesthetics of 20 trauma patients. RECENT FINDINGS: The implications of the 80-h work week are beginning to be appreciated. The development of a new trauma curriculum must take this significant change in residency training into account while incorporating modern educational theory (e.g. simulation) and new data on the resuscitation of trauma patients. SUMMARY: Currently, the curriculum for trauma anesthesia requires only that residents participate in the anesthetics of 20 trauma patients. There is no plan for, and little literature regarding, a more extensive educational program. This offers a unique opportunity to innovate a novel curriculum in the anesthesiology residency. The American Society of Anesthesiologists Committee on Trauma and Emergency Preparedness has designed a curriculum that can serve as a template for this important step forward in anesthesiology education.

PTPN2 deficiency: Amping up JAK/STAT.

Identification of monogenic causes of immune dysregulation provides insight into human immune response and signaling pathways associated with autoimmunity. Here, Jeanpierre et al. (https://doi.org/10.1084/jem.20232337) identify new germline variants in the gene encoding PTPN2 associated with loss of regulatory function, enhanced JAK/STAT signaling, and early-onset autoimmunity.

Artificial intelligence and machine learning: Definition of terms and current concepts in critical care research.

With increasing computing power, artificial intelligence (AI) and machine learning (ML) have prospered, which facilitate the analysis of large datasets, especially those found in critical care. It is important to define these terminologies, to inform a standardized approach to critical care research. This manuscript hopes to clarify these terms with examples from medical literature. Three major components that are required for a successful ML implementation: (i) reliable dataset, (ii) ML algorithm, and (iii) unbiased model evaluation, are discussed. A reliable dataset can be structured or unstructured with limited noise, outliers, and missing values. ML, a subset of AI, is typically focused on supervised or unsupervised learning tasks in which the output is based on inputs and derived from iterative pattern recognition algorithms, while AI is the overall ability of a machine to "think" or mimic human behavior; and to analyze data free from human influence. Even with successful implementation, advanced AI and ML algorithms have faced challenges in adoption into practice, mainly due to their lack of interpretability, which hinders trust, buy-in, and engagement from clinicians. Consequently, traditional algorithms, such as linear and logistic regression, that may have reduced predictive power but are highly interpretable, continue to be widely used.

Designing the Prolonged Field Care Kit (PFAK) to Address the Logistical Challenges of Future Combat Casualty Care.

INTRODUCTION: Prolonged Casualty Care (PCC) is a military adaptation aimed at providing pre-hospital care in austere settings when evacuation is delayed or even impossible. Current lack of standardized medical equipment and size/weight restrictions of military packs during dismounted operations hinder effective PCC. We sought to design a standardized, practical, and effective prolonged field care kit (PFAK) to enable widespread implementation of PCC. MATERIALS AND METHODS: We reviewed Joint Trauma System Clinical Practice Guidelines to generate a list of potential contents of the PFAK. We obtained Institutional Review Board (IRB) exemption and then conducted stakeholder surveys of combat casualty care experts across the Joint Trauma System using a modified Delphi survey approach. We established a civil-military working group that provided in-depth qualitative feedback on the PFAK contents and provided an initial design of a long-range medical rucksack (LMR) to house it. Responses were analyzed using mean rank scores to help determine initial components of the PFAK. Tactical subject-matter experts tested and evaluated the PFAK and LMR prototype in austere conditions to refine the design. RESULTS: Review of the PCC Clinical Practice Guidelines generated 49 medications and 301 potential supplies as potential PFAK contents. The first Delphi survey was sent to 100 stakeholders (overall response rate of 60%). After the first survey, contents were narrowed to a list of the most essential 27 medications and 105 other components. Iterative prototypes of the PFAK and LMR were tested to determine ergonomics, portability, flexibility, and equipment compartmentalization to facilitate use in emergencies. The prototype was optimized to address the clinical, logistical, and tactical requirements of PCC across a variety of platforms and environmental conditions. CONCLUSIONS: Given the changing battlefield environment, efficient and effective PCC will play an increasingly important role in the management of combat trauma. The PFAK can meet this need by providing a practical and standardized resuscitation kit generated by expert military and trauma personnel consensus, carried conveniently in the LMR.

Prehospital Critical Care Blood Product Administration: Quantifying Clinical Benefit.

BACKGROUND: Prehospital blood transfusion has been widely practiced in the military and is drawing renewed scrutiny after many years of civilian use. OBJECTIVE: The objective of this article is to quantify the benefit derived from prehospital transfusion of blood products. METHODS: Deidentified data were extracted retrospectively from the flight records of a critical care transportation program between April 2018 and January 2020. Patients who were transported before a prehospital blood transfusion protocol were compared with patients after initiation of the blood transfusion protocol. Demographic data, vital signs, laboratory analytics, and other outcome measures were analyzed. RESULTS: Nine scene transport patients who met the transfusion criteria before a blood transfusion protocol were compared with 11 patients transported after initiation of the protocol. Identical outcome measures were analyzed. Patients who received prehospital blood transfusions had a statistically significantly longer hospital length of stay (16.5 vs 3.7 days, P = .03) and were more often taken directly to the operating room (80% vs 28%, P = .04). No statistically significant difference was identified when comparing mean arterial pressure, heart rate, respiratory rate, hemoglobin, hematocrit, or survival to hospital discharge. CONCLUSIONS: Trauma patients who received prehospital blood transfusion had a longer hospital length of stay and were more often taken directly to the operating room, but without improvement in survival.

Review article: update in trauma anesthesiology: perioperative resuscitation management.

The management of trauma patients has matured significantly since a systematic approach to trauma care was introduced nearly a half century ago. The resuscitation continuum emphasizes the effect that initial therapy has on the outcome of the trauma patient. The initiation of this continuum begins with prompt field medical care and efficient transportation to designated trauma centers, where lifesaving procedures are immediately undertaken. Resuscitation with packed red blood cells and plasma, in parallel with surgical or interventional radiologic source control of bleeding, are the cornerstones of trauma management. Adjunctive pharmacologic therapy can assist with resuscitation. Tranexamic acid is used in Europe with good results, but the drug is slowly being added to the pharmacy formulary of trauma centers in United States. Recombinant factor VIIa can correct abnormal coagulation values, but its outcome benefit is less clear. Vasopressin shows promise in animal studies and case reports, but has not been subjected to a large clinical trial. The concept of "early goal-directed therapy" used in sepsis may be applicable in trauma as well. An early, appropriately aggressive resuscitation with blood products, as well as adjunctive pharmacologic therapy, may attenuate the systemic inflammatory response of trauma. Future investigations will need to determine whether this approach offers a similar survival benefit.

Toward an Electrical Analog of the Cardiovascular System in Hemorrhage.

Current quantitative descriptions of the cardiovascular system in hemorrhagic shock focus on pressure based metrics. This approach is often incomplete; overlooking the important role of tissue perfusion. Electrical analogs to the cardiovascular system may offer a more complete description of hemorrhage. Application of fundamental concepts in electrical circuit theory (i.e.; Kirchhoff's Voltage Law and Ohm's Law) to analogs of the cardiovascular system offers a more refined description of this complex process. This manuscript hopes to serve as a starting point for a more mathematically robust, and clinically relevant description of hemorrhagic shock.

Impact of prehospital airway interventions on outcome in cardiac arrest following drowning: A study from the CARES Surveillance Group.

INTRODUCTION: Drowning results in more than 360,000 deaths annually, making it the 3rd leading cause of unintentional injury death worldwide. Prior studies have examined airway interventions affecting patient outcomes in cardiac arrest, but less is known about drowning patients in arrest. This study evaluated the outcomes of drowning patients in the Cardiac Arrest Registry to Enhance Survival (CARES) who received advanced airway management. METHODS: A retrospective analysis of the CARES database identified cases of drowning etiology between 2013 and 2018. Patients were stratified by airway intervention performed by EMS personnel. Demographics, sustained return of spontaneous circulation [ROSC], survival to hospital admission, survival to hospital discharge, and neurological outcomes were compared between airway groups using chi-squared tests and logistic regression. RESULTS: Among 2388 drowning patients, 70.4% were male, 41.8% white, and 13.1% survived to hospital discharge. Patients that received supraglottic airways [SGA] had statistically significantly lower odds of survival to hospital admission compared to endotracheal tube [ETT] use (adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI] 0.42-0.76) as well as lower odds of survival to discharge compared to bag valve mask [BVM] use (aOR = 0.40, 95% CI 0.19-0.86) when accounting for relative ROSC timing. CONCLUSION: In this national cohort of drowning patients in cardiac arrest, SGA use was associated with significantly lower odds of survival to hospital admission and discharge. However, survival to discharge with favorable neurological outcome did not differ significantly between airway management techniques. Further studies will need to examine if airway intervention order or time to intervention affects outcomes.

Defining Combat-Relevant Endpoints for Early Trauma Resuscitation Research in a Resource-Constrained Civilian Setting.

INTRODUCTION: Studies assessing early trauma resuscitation have used long-term endpoints, such as 28- or 30-day mortality or Glasgow Outcomes Scores at 6-months. These endpoints are convenient but may not accurately reflect the effect of early resuscitation. We sought expert opinion and consensus on endpoints and definitions of variables needed to conduct a Department of Defense- (DoD) funded study to epidemiologically assess combat-relevant mortality and morbidity due to timeliness of resuscitation among critically injured civilians internationally. METHODS: We conducted an online modified Delphi process with an international panel of civilian and US military experts. In several iterative rounds, experts reviewed background information, appraised relevant scientific evidence, provided comments, and rendered a vote on each variable. A-priori, we set consensus at ≥80% concordant votes. RESULTS: Twenty panelists participated with a 100% response rate. Eight items were presented, with the following outputs for the epidemiologic study: Assess mortality within 7-days of injury; assess multi-organ failure using SOFA scores measured early (at day 3) and late (at day 7); assess traumatic brain injury mortality early (≤7-days) and late (28-days); hybrid (anatomic and physiologic) injury severity scoring is optimal; capture comorbidities per the US National Trauma Data Standard list with specific additions; assign resuscitative interventions to one of five standardized phases of trauma care; and, use a novel trauma death categorization system. CONCLUSIONS: A modified Delphi process yielded expert-ratified definitions and endpoints of variables necessary to conduct a combat-relevant epidemiologic study assessing outcomes due to early trauma resuscitation. Outputs may also benefit other groups conducting trauma resuscitation research.

Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell expansion.

Natural killer (NK) cell effector functions are dependent on metabolic regulation of cellular function; however, less is known about in vivo metabolic pathways required for NK cell antiviral function. Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox10Δ/Δ mice had normal numbers of NK cells but impaired expansion of antigen-specific Ly49H+ NK cells and impaired NK cell memory formation. Proliferation in vitro and homeostatic expansion were intact, indicating a specific metabolic requirement for antigen-driven proliferation. Cox10-deficient NK cells upregulated glycolysis, associated with increased AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) activation, although this was insufficient to protect the host. These data demonstrate that oxidative metabolism is required for NK cell antiviral responses in vivo.

Joint Trauma System Clinical Practice Guideline (JTS CPG): Prehospital Blood Transfusion. 30 October 2020.

This Clinical Practice Guideline (CPG) provides a brief summary of the scientific literature for prehospital blood use, with an emphasis on the en route care environment. Updates include the importance of calcium administration to counteract the deleterious effects of hypocalcemia, minimal to no use of crystalloid, and stresses the importance of involved and educated en route care medical directors alongside at a competent prehospital and en route care providers (see Table 1). With the paradigm shift to use FDA-approved cold stored low titer group O whole blood (CS-LTOWB) along with the operational need for continued use of walking blood banks (WBB) and point of injury (POI) transfusion, there must be focused, deliberate training incorporating the different whole blood options. Appropriate supervision of autologous blood transfusion training is important for execution of this task in support of deployed combat operations as well as other operations in which traumatic injuries will occur. Command emphasis on the importance of this effort as well as appropriate logistical support are essential elements of a prehospital blood program as part of a prehospital/en route combat casualty care system.

Immunotherapeutic options for inflammation in trauma.

BACKGROUND: Surgical management of trauma in the last 20 years has evolved in parallel with the military's experience in the current conflicts. Therapies such as widespread tourniquet use, empiric administration of fresh frozen plasma, and airborne intensive care units had been viewed skeptically but are now common practice. There is an opportunity to expand the envelope of care even further through similarly innovative approaches and varied avenues of research. RESULTS: As the molecular biology of trauma is elucidated, research methodologies must also be developed to capitalize on innovative approaches to resuscitation. Blood component therapy and control of bleeding remain as the fundamental concepts in trauma care. The inflammo-immune response to injury, however, plays an increasingly recognized role in recovery of organ function. Perhaps the inflammatory cascade of trauma can be manipulated to extend the treatment envelope of at risk trauma patients.In trauma, the additional challenge of delivering effective treatment, often required very early after injury, necessitates the development of treatments to be implemented on the front lines of trauma care that are cost-effective, portable, and environmentally stable. Future conflicts may not offer ready access to high-level surgical care; therefore, resuscitative therapies will be needed for wounded service members because they are evacuated to the surgeon. Manipulation of the inflammatory response to trauma may offer a solution. As our understanding of the immune response continues to develop, the potential for improved outcomes for the wounded expands. CONCLUSION: A review of basic concepts in immunology is necessary to appreciate any potential impact of immunotherapeutic approaches to trauma and inflammation. An overview of current options will focus on outcome benefits of available therapies and suggest possible areas for future investigation. Quantitative approaches will leverage basic science to identify high-yield strategies to improve care of the injured combatant. LEVEL OF EVIDENCE: Review, level III.

Airway Management in Prolonged Field Care.

This Role 1, prolonged field care (PFC) clinical practice guideline (CPG) is intended to be used after Tactical Combat Casualty Care (TCCC) Guidelines, when evacuation to higher level of care is not immediately possible. A provider must first and foremost be an expert in TCCC, the Department of Defense standard of care for first responders. The intent of this PFC CPG is to provide evidence and experience-based solutions to those who manage airways in an austere environment. An emphasis is placed on utilizing the tools and adjuncts most familiar to a Role 1 provider. The PFC capability of airway is addressed to reflect the reality of managing an airway in a Role 1 resource-constrained environment. A separate Joint Trauma System CPG will address mechanical ventilation. This PFC CPG also introduces an acronym to assist providers and their teams in preparing for advanced procedures, to include airway management.

Outcome of Conventional Bystander Cardiopulmonary Resuscitation in Cardiac Arrest Following Drowning.

INTRODUCTION: The concept of compressions only cardiopulmonary resuscitation (CO-CPR) evolved from a perception that lay rescuers may be less likely to perform mouth-to-mouth ventilations during an emergency. This study hopes to describe the efficacy of bystander compressions and ventilations cardiopulmonary resuscitation (CV-CPR) in cardiac arrest following drowning. HYPOTHESIS/PROBLEM: The aim of this investigation is to test the hypothesis that bystander cardiopulmonary resuscitation (CPR) utilizing compressions and ventilations results in improved survival for cases of cardiac arrest following drowning compared to CPR involving compressions only. METHODS: The Cardiac Arrest Registry for Enhanced Survival (CARES) was queried for patients who suffered cardiac arrest following drowning from January 1, 2013 through December 31, 2017, and in whom data were available on type of bystander CPR delivered (ie, CV-CPR CO-CPR). The primary outcome of interest was neurologically favorable survival, as defined by cerebral performance category (CPC). RESULTS: Neurologically favorable survival was statistically significantly associated with CV-CPR in pediatric patients aged five to 15 years (aOR = 2.68; 95% CI, 1.10-6.77; P = .03), as well as all age group survival to hospital discharge (aOR = 1.54; 95% CI, 1.01-2.36; P = .046). There was a trend with CV-CPR toward neurologically favorable survival in all age groups (aOR = 1.35; 95% CI, 0.86-2.10; P = .19) and all age group survival to hospital admission (aOR = 1.29; 95% CI, 0.91-1.84; P = .157). CONCLUSION: In cases of cardiac arrest following drowning, bystander CV-CPR was statistically significantly associated with neurologically favorable survival in children aged five to 15 years and survival to hospital discharge.

A hemodynamic profile for consciousness during cardiopulmonary resuscitation.

We report the quantification of a hemodynamic profile sufficient to support consciousness during cardiopulmonary resuscitation. A 62-yr-old man experienced cardiac arrest while being evaluated for heart failure after heart transplantation. During the emergency, hemodynamic data were obtained from bedside monitors and reviewed at regular intervals. His mean arterial blood pressure and heart rate were correlated with consciousness during cardiopulmonary resuscitation. A mean arterial blood pressure of 50 mm Hg with a heart rate of 100 bpm supported consciousness during cardiac arrest. This case helps to validate the recent emphasis on hard, fast, basic life support.