An Analysis of Essential Pediatric Surgical Cases Encountered During a Decade of Large-Scale Military Humanitarian Aid Missions.

INTRODUCTION: Disease Control Priorities, 3rd Edition (DCP3) is an evidence-based, published resource that outlines essential procedures recommended for developing health care systems. These systems must consider various populations and the incidence of certain surgical conditions that require treatment. In relation to pediatric patients, the prevalence of certain surgical conditions encountered remains unclear in several low- and middle-income countries. Over the past 15 years, the USNS Mercy, one of the U.S. Navy's large hospital ships, has led the Pacific Partnership missions, which provide large-scale humanitarian aid throughout Southeast Asia. The data collected during these missions provide an opportunity to analyze the scope of pediatric operations performed in resource-limited countries. This analysis may assist in future planning for specific needs during military humanitarian missions. MATERIALS AND METHODS: Surgical case data were prospectively collected during the six Pacific Partnership missions from 2006 to 2018. Demographic data were analyzed for all patients ≤8 years of age who underwent an operation. These data were retrospectively reviewed and all case logs were categorized by mission year, procedure-type, and host nation. Operations were classified based on 44 essential operations delineated in DCP3. Primary outcome was incidence of DCP3 essential operations. Secondary outcomes were perioperative complications. Standard statistical methods were performed for descriptive analysis. RESULTS: A total of 3,209 major and minor operations were performed during 24 port visits in nine countries. Pediatric cases represented 1,117 (38%) of these procedures. Pediatric surgeons performed 291 (26%) of these cases. Based on DCP3 criteria, 789 pediatric operations (71%) were considered essential procedures. The most common DCP3-aligned procedures were cleft lip repair (432, 57%), hernia repair (207, 27%), and hydrocelectomy (60, 8%). Operative volume for pediatric surgery was highest during the 2008 mission (522 cases), when two pediatric surgeons were deployed, and lowest during the 2018 mission (five cases), when the mission focus was on education rather than surgical procedures and lack of pediatric cases referred by the host nation. Overall complication rate for pediatric cases was 1%. CONCLUSIONS: This study represents the largest known analysis of military humanitarian assistance. Pediatric operations represented over one-third of the surgical volume during Pacific Partnership missions from 2006 to 2018. The majority of cases were DCP3-aligned and associated with a low complication rate. Future humanitarian aid missions and host nations should allocate appropriate medical and educational resources to treat DCP3 pediatric surgical diseases in low- and middle-income countries to support long-term capacity building while maintaining optimal surgical outcomes.

Spontaneous Pneumopericardium in a U.S. Marine: Do not Lose Heart.

We report an unusual case of extensive subcutaneous emphysema, pneumomediastinum, and pneumopericardium identified in an otherwise healthy U.S. Marine who was enrolled in the Marine Corps School of Infantry. His training regimen included prolonged periods of yelling and elevation changes during sustained hiking through hilly terrain. The patient presented to the Fast Track with normal vital signs but complained of dyspnea, cough, and subjective fevers. Although he lacked a history of trauma, he was found to have pneumopericardium, pneumomediastinum, and subcutaneous emphysema without pneumothorax. He was admitted to the general surgery service for observation and was ultimately released back to his unit after 24 hours. To our knowledge, pneumopericardium has never been attributed to persistent yelling in the setting of a lower respiratory tract infection and should be considered in the differential of atraumatic chest symptomatology in otherwise healthy military service members.

Macrophage reprogramming by negatively charged membrane phospholipids controls infection.

Extracellular vesicles (ECVs) are heterogeneous membrane-enclosed structures containing proteins, nucleic acids, and lipids that participate in intercellular communication by transferring their contents to recipient cells. Although most of the attention has been directed at the biologic effect of proteins and microRNA, the contribution of phospholipids present in ECVs on cellular activation has not been extensively addressed. We investigated the biologic effect of phosphatidylserine (PS) and phosphatidylcholine (PC), 2 phospholipids highly abundant in ECVs. A transcriptomic analysis revealed that ∼4700 genes were specifically modified by exposing peritoneal macrophages to PS or PC liposomes in vivo. Among them, the expression of several chemokines and cytokines was highly upregulated by PS liposome treatment, translating into a massive neutrophil infiltration of the peritoneum capable of neutralizing a septic polymicrobial insult. Both the l and d stereoisomers of PS induced the same response, suggesting that the effect was related to the negative charge of the phospholipid head. We concluded that an increase in the internal negative charge of the cell triggers a signaling cascade activating an innate immune response capable of controlling infection.-Cauvi, D. M., Hawisher, D., Dores-Silva, P. R., Lizardo, R. E., De Maio, A. Macrophage reprogramming by negatively charged membrane phospholipids controls infection.

Isolation and characterization of human urine extracellular vesicles.

Extracellular vesicles (ECV) reflect physiological or pathological conditions, emerging as potential biomarkers for disease. They can be obtained from a variety of body fluids, particularly urine that is an ideal source because it can be obtained in great quantities, recurrently and with minimal intervention. However, the characterization of urine ECV is challenging because the preparation is usually contaminated with soluble proteins, such as uromodulin (UMOD) or Tamm-Horsfall glycoprotein that forms large extracellular filaments co-sedimenting with ECV. We developed a method to obtain human urine ECV free of UMOD by the addition of ZnSO4 prior to vesicle isolation by differential centrifugation. Treatment with ZnSO4 did not affect the size and concentration of the vesicle preparation and preserved the storage of the samples at low temperatures. We did not observe a variation in the number of vesicles isolated during different times of the day or different days between different donors. The glycoprotein pattern of urine ECV was characterized by binding to concanavalin A (Con A) and mass spectroscopy. Several markers were found, including dipeptidyl peptidase IV (CD26), vacuolar protein sorting factor 4A (VPS4A) and dipeptidase 1 (DPEP1), and galectin 3 binding protein (G3-BP). The levels of VPS4A and DPEP1 were similar in ECV preparations obtained from several donors of both sexes. Con A binding pattern and monosaccharide composition were also comparable between subjects. In summary, our method for the isolation of highly pure ECV derived from human urine is likely to help in the use of these vesicles as potential biomarkers.

Why Antibiotic Treatment Is Not Enough for Sepsis Resolution: an Evaluation in an Experimental Animal Model.

Sepsis remains a major health problem at the levels of mortality, morbidity, and economic burden to the health care system, a condition that is aggravated by the development of secondary conditions such as septic shock and multiple-organ failure. Our current understanding of the etiology of human sepsis has advanced, at least in part, due to the use of experimental animal models, particularly the model of cecum ligation and puncture (CLP). Antibiotic treatment has been commonly used in this model to closely mirror the treatment of human septic patients. However, whether their use may obscure the elucidation of the cellular and molecular mechanisms involved in the septic response is questionable. The objective of the present study was to determine the effect of antibiotic treatment in the outcome of a fulminant model of CLP. Various dosing strategies were used for the administration of imipenem, which has broad-spectrum coverage of enteric bacteria. No statistically significant differences in the survival of mice were observed between the different antibiotic dosing strategies and no treatment, suggesting that live bacteria may not be the only factor inducing septic shock. To further investigate this hypothesis, mice were challenged with sterilized or unsterilized cecal contents. We found that exposure of mice to sterilized cecal contents also resulted in a high mortality rate. Therefore, it is possible that bacterial debris, apart from bacterial proliferation, triggers a septic response and contributes to mortality in this model, suggesting that additional factors are involved in the development of septic shock.

Ketorolac does not reduce effectiveness of pleurodesis in pediatric patients with spontaneous pneumothorax.

PURPOSE: Antiinflammatory medications are thought to reduce the effectiveness of pleurodesis performed for the treatment of spontaneous pneumothorax. We reviewed our experience with children undergoing video-assisted thorascopic surgery (VATS) with pleurodesis for pneumothorax to determine if ketorolac administration influences patient outcomes. METHODS: A retrospective review of patients who underwent VATS pleurodesis for spontaneous pneumothorax from 2009 to 2013 at a pediatric hospital was performed. Length of stay, radiographic pneumothorax resolution prior to discharge, and ipsilateral recurrence rates were compared in patients who did and did not receive perioperative ketorolac. RESULTS: Over a 50-month period, 51 patients underwent VATS with mechanical pleurodesis for spontaneous pneumothorax. The average age was 15.5years, and 76% were male. Ketorolac was administered to 26/51 patients. There were no differences in average length of stay (11.3 vs 10.9days, p=0.36), incidence of residual pneumothorax at discharge (22/41 vs 19/41, p=0.48), or ipsilateral recurrence (5/10 vs 5/10, p=1). CONCLUSIONS: Despite the intrinsic antiinflammatory properties of ketorolac, our data suggests that its use for patients undergoing pleurodesis for spontaneous pneumothorax does not detrimentally influence the outcomes of surgery. Therefore, we conclude that ketorolac can be used for pain control in this population. Large-scale studies are warranted to validate these findings.