Antifungal wound penetration of amphotericin and voriconazole in combat-related injuries: case report.

BACKGROUND: Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds. CASE PRESENTATION: Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters. CONCLUSION: These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.

Committee on Surgical Combat Casualty Care position statement: Neurosurgical capability for the optimal management of traumatic brain injury during deployed operations.

BACKGROUND: Experiences over the last three decades of war have demonstrated a high incidence of traumatic brain injury (TBI) resulting in a persistent need for a neurosurgical capability within the deployed theater of operations. Despite this, no doctrinal requirement for a deployed neurosurgical capability exists. Through an iterative process, the Joint Trauma System Committee on Surgical Combat Casualty Care (CoSCCC) developed a position statement to inform medical and nonmedical military leaders about the risks of the lack of a specialized neurosurgical capability. METHODS: The need for deployed neurosurgical capability position statement was identified during the spring 2021 CoSCCC meeting. A triservice working group of experienced forward-deployed caregivers developed a preliminary statement. An extensive iterative review process was then conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. To provide additional context and a civilian perspective, statement commentaries were solicited from civilian clinical experts including a recently retired military trauma surgeon boarded in neurocritical care, a trauma surgeon instrumental in developing the Brain Injury Guidelines, a practicing neurosurgeon with world-renowned expertise in TBI, and the chair of the Committee on Trauma. RESULTS: After multiple revisions, the position statement was finalized, and approved by the CoSCCC membership in February 2023. Challenges identified include (1) military neurosurgeon attrition, (2) the lack of a doctrinal neurosurgical capabilities requirement during deployed combat operations, and (3) the need for neurosurgical telemedicine capability and in-theater computed tomography scans to triage TBI casualties requiring neurosurgical care. CONCLUSION: Challenges identified regarding neurosurgical capabilities within the deployed trauma system include military neurosurgeon attrition and the lack of a doctrinal requirement for neurosurgical capability during deployed combat operations. To mitigate risk to the force in a future peer-peer conflict, several evidence-based recommendations are made. The solicited civilian commentaries strengthen these recommendations by putting them into the context of civilian TBI management. This neurosurgical capabilities position statement is intended to be a forcing function and a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level V.

Maintaining Surgical Readiness While Deployed to Low-Volume Military Treatment Facilities: A Pilot Program for Clinical and Operational Sustainment Training in the Deployed Environment.

INTRODUCTION: Maintaining readiness among Army surgeons is increasingly challenging because of declining operative experience during certain deployments. Novel solutions should be considered. MATERIALS AND METHODS: A pilot program was conducted to rotate surgical teams from a military treatment facility with a low volume of combat casualty care to one with a higher volume. Pre- and postrotation surveys were conducted to measure relative operative experience, trauma experience, and perceived readiness among rotators. RESULTS: Operative volumes and trauma volumes were increased and that perceived readiness among rotators, especially those with the fewest previous deployments, was improved. CONCLUSIONS: Maintaining readiness among Army surgeons is a difficult task, but a combination of increased trauma care while in garrison, as well as increased humanitarian care during deployments, may be helpful. Additionally, rotating providers from facilities caring for few combat casualties to facilities caring for more combat casualties may also be feasible, safe, and helpful.

Recurrent bacteremia: A 10-year retrospective study in combat-related burn casualties.

INTRODUCTION: Surviving the first episode of bacteremia predisposes burn casualties to its recurrence. Herein, we investigate the incidence, mortality, bacteriology, and source of infection of recurrent bacteremia in military burn casualties admitted to the U.S. Army Institute of Surgical Research Burn Center over a 10year period. METHODS: Bacteremia was defined as the growth of Gram-positive or Gram-negative organisms in a blood culture that excluded probable skin contaminants. Recurrent bacteremia was defined as a subsequent episode of bacteremia ≥7 days after the first episode. Polymicrobial bacteremia was the presence of more than one pathogen in the same blood culture. Bacteremia was attributed to UTI, pneumonia, or wound sepsis. All other bacteremias were considered non-attributable bloodstream infections. Univariate and multivariate analyses determined factors predictive of clinical outcome. RESULTS: Out of 952 combat-related burn casualties screened, 166 cases were identified; 63% (non-recurrent) and 37% (recurrent) with median time to recurrence of 20 days. Univariate and multivariate analysis showed that the mortality rate was two and nine-fold, respectively, higher with recurrent bacteremia. Univariate analysis found that except for urinary tract infection, large burn size (>20%), 3rd degree burns, increased injuiry severity, perineal burns, and mechanical ventilator days were independent factors predictive of recurrence of bacteremia as well as increased mortality in the recurrent bacteremia cohort. Acinetobacter baumannii complex (63%) was prevalent in the non-recurrent group, while Klebsiella pneumoniae (46% vs. 30%) and Pseudomonas aeruginosa (35% vs. 26%) were prevalent in recurrent bacteremia. Half of the recurrent bacteremia cases were polymicrobial, compared to 9% in non-recurrent bacteremia. Pneumonia was prevalent in non-recurrent bacteremia (38%) and a combination of pneumonia and wound sepsis (29%) in recurrent bacteremia casualties. CONCLUSIONS: Recurrent bacteremia increases mortality in military burn casualties. Additional research is needed to address and mitigate the underlying causes, thereby improving survival.

Burn Casualty Care in the Deployed Setting.

Management of wartime burn casualties can be very challenging. Burns frequently occur in the setting of other blunt and penetrating injuries. This clinical practice guideline provides a manual for burn injury assessment, resuscitation, wound care, and specific scenarios including chemical and electrical injuries in the deployed or austere setting. The clinical practice guideline also reviews considerations for the definitive care of local national patients, including pediatric patients, who are unable to be evacuated from theater. Medical providers are encouraged to contact the US Army Institute of Surgical Research (USAISR) Burn Center when caring for a burn casualty in the deployed setting.

The American Association for the Surgery of Trauma Severity Grade is valid and generalizable in adhesive small bowel obstruction.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) anatomic severity grading system for adhesive small bowel obstruction (ASBO) was validated at a single institution. We aimed to externally validate the AAST ASBO grading system using the Eastern Association for the Surgery of Trauma multi-institutional small bowel obstruction prospective observational study. METHODS: Adults (age ≥ 18) with (ASBO) were included. Baseline demographics, physiologic parameters (heart rate, blood pressure, respiratory rate), laboratory tests (lactate, hemoglobin, creatinine, leukocytosis), imaging findings, operative details, length of stay, and Clavien-Dindo complications were collected. The AAST ASBO grades were assigned by two independent reviewers based on imaging findings. Kappa statistic, univariate, and multivariable analyses were performed. RESULTS: There were 635 patients with a mean (±SD) age of 61 ± 17.8 years, 51% female, and mean body mass index was 27.5 ± 8.1. The AAST ASBO grades were: grade I (n = 386, 60.5%), grade II (n = 135, 21.2%), grade III (n = 59, 9.2%), grade IV (n = 55, 8.6%). Initial management included: nonoperative (n = 385; 61%), laparotomy (n = 200, 31.3%), laparoscopy (n = 13, 2.0%), and laparoscopy converted to laparotomy (n = 37, 5.8%). An increased median [IQR] AAST ASBO grade was associated with need for conversion to an open procedure (2 [1-3] vs. 3 [2-4], p = 0.008), small bowel resection (2 [2-2] vs. 3 [2-4], p < 0.0001), postoperative temporary abdominal closure (2 [2-3] vs. 3 [3-4], p < 0.0001), and stoma creation (2 [2-3] vs. 3 [2-4], p < 0.0001). Increasing AAST grade was associated with increased anatomic severity noted on imaging findings, longer duration of stay, need for intensive care, increased rate of complication, and higher Clavien-Dindo complication grade. CONCLUSION: The AAST ASBO severity grading system has predictive validity for important clinical outcomes and allows for standardization across institutions, providers, and future research focused on optimizing preoperative diagnosis and management algorithms. LEVEL OF EVIDENCE: Prognostic, level III.

Burns to the genitalia, perineum, and buttocks increase the risk of death among U.S. service members sustaining combat-related burns in Iraq and Afghanistan.

PURPOSE: Among service members injured in Iraq and Afghanistan, to determine the risk of mortality associated with combat-related burns to the genitalia, perineum, and buttocks. MATERIALS AND METHODS: The prospectively maintained burn registry from the United States Army Institute of Surgical Research was retrospectively reviewed to identify all service members with combat-related burns sustained in Iraq and Afghanistan from March 2003 to October 2013. The two primary risk factors of interest were (1) any burn to the genitals, perineum, and/or buttocks (PB) and (2) burns involving the entire perineal, genital, and buttock region (complete PB). Cox proportional hazard models were used to estimate the risk of mortality for both primary risk factors, and adjusted for severe non-burn-related trauma, percent of burn over total body surface area (TBSA), inhalational injury, time to urinary tract infection, and time to bacteremia. A post-hoc analysis was performed to explore the potential effect modification of TBSA burned on the relationship between PB and mortality. RESULTS: Among the 902 U.S. service members with combat-related burns sustained during the study period, 226 (25.0%) had involvement of the genitalia, perineum, and/or buttocks. Complete PB was associated with a crude risk of mortality (HR: 5.3; 2.9-9.7), but not an adjusted risk (HR=1.8; 0.8-4.0). However, TBSA burned was identified as a potential negative effect modifier. Among patients with burns <60% TBSA, sustaining a complete PB conferred an adjusted risk of death (HR=2.7; 1.1-6.8). Further, patients with a perineal burn had a five-fold increased incidence of bacteremia. In adjusted models, each event of bacteremia increased the risk of mortality by 92% (HR 1.92; 1.39-2.65). Perineal burns were associated with a two-fold increased incidence of severe non-burn related trauma that also doubled mortality risk in adjusted models (HR 2.29; 1.23-4.27). CONCLUSIONS: Among those with relatively survivable combat-related burns (<60% TBSA), genital/perineal/buttock involvement increases the risk of death. Bacteremia may account for part of this increased risk, but does not fully explain the independent risk associated with perineal burns.

Burn Shock and Resuscitation: Proceedings of a Symposium Conducted at the Meeting of the American Burn Association, Chicago, IL, 21 April 2015.

The Special Interest Groups of the American Burn Association provide a forum for interested members of the multidisciplinary burn team to congregate and discuss matters of mutual interest. At the 47th Annual Meeting of the American Burn Association in Chicago, IL, the Fluid Resuscitation Special Interest Group sponsored a special symposium on burn resuscitation. The purpose of the symposium was to review the history, current status, and future direction of fluid resuscitation of patients with burn shock. The reader will note several themes running through the following presentations. One is the perennial question of the proper role for albumin or other fluid-sparing strategies. Another is the unique characteristics of the pediatric burn patient. A third is the need for multicenter trials of burn resuscitation, while recognizing the obstacles to conducting randomized controlled trials in this setting.

Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation.

Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy.

Care of the Burn Casualty in the Prolonged Field Care Environment.

Burns are frequently encountered on the modern battlefield, with 5% - 20% of combat casualties expected to sustain some burn injury. Addressing immediate life-threatening conditions in accordance with the MARCH protocol (massive hemorrhage, airway, respirations, circulation, hypothermia/head injury) remains the top priority for burn casualties. Stopping the burning process, total burn surface area (TBSA) calculation, fluid resuscitation, covering the wounds, and hypothermia management are the next steps. If transport to definitive care is delayed and the prolonged field care stage is entered, the provider must be prepared to provide for the complex resuscitation and wound care needs of a critically ill burn casualty.

Impact of margin status and local recurrence on soft-tissue sarcoma outcomes.

BACKGROUND: The impact of local recurrence and surgical resection margin status on survival in extremity soft-tissue sarcomas remains to be clearly defined. Our aim was to conduct a retrospective analysis of prospectively collected data to determine the prognostic relevance of positive resection margins and local recurrence for extremity soft-tissue sarcomas for survival. METHODS: Three hundred and sixty-three patients who underwent resection of localized primary extremity soft-tissue sarcomas with curative intent were selected from the United States Department of Defense Automated Central Tumor Registry. Outcomes for local recurrence, distant recurrence, disease-specific survival, and overall survival were analyzed according to clinical, pathological, and treatment variables with use of the Kaplan-Meier method (log-rank test) and the multivariate Cox regression model. RESULTS: Positive margins (hazard ratio, 1.99 [95% confidence interval, 1.15 to 3.45]), local recurrence (hazard ratio, 2.93 [95% confidence interval, 1.38 to 6.23]), and distant recurrence (hazard ratio, 12.13 [95% confidence interval, 5.97 to 24.65]) were significantly associated with overall survival on multivariate Cox regression analysis. However, for disease-specific survival, local recurrence was not significant and tumor size of >10 cm (hazard ratio, 2.83 [95% confidence interval, 1.15 to 6.95]), positive margins (hazard ratio, 1.95 [95% confidence interval, 1.05 to 3.63]), and distant recurrence (hazard ratio, 9.46 [95% confidence interval, 4.37 to 20.47]) were independent adverse prognostic factors. The disease-specific survival rate for patients with localized soft-tissue sarcomas was 89% (95% confidence interval, 85% to 92%) for five years and 75% (95% confidence interval, 70% to 81%) for ten years. CONCLUSIONS: Positive surgical margins are consistently associated with adverse survival-related outcomes in localized soft-tissue sarcomas of the extremity. Local recurrence had a significant impact on overall survival, but not on disease-specific survival.