Delphi Process for Validation of Fluid Treatment Algorithm for Critically Ill Pediatric Trauma Patients.

INTRODUCTION: While intravenous fluid therapy is essential to re-establishing volume status in children who have experienced trauma, aggressive resuscitation can lead to various complications. There remains a lack of consensus on whether pediatric trauma patients will benefit from a liberal or restrictive crystalloid resuscitation approach and how to optimally identify and transition between fluid phases. METHODS: A panel was comprised of physicians with expertise in pediatric trauma, critical care, and emergency medicine. A three-round Delphi process was conducted via an online survey, with each round being followed by a live video conference. Experts agreed or disagreed with each aspect of the proposed fluid management algorithm on a five-level Likert scale. The group opinion level defined an algorithm parameter's acceptance or rejection with greater than 75% agreement resulting in acceptance and greater than 50% disagreement resulting in rejection. The remaining were discussed and re-presented in the next round. RESULTS: Fourteen experts from five Level 1 pediatric trauma centers representing three subspecialties were included. Responses were received from 13/14 participants (93%). In round 1, 64% of the parameters were accepted, while the remaining 36% were discussed and re-presented. In round 2, 90% of the parameters were accepted. Following round 3, there was 100% acceptance by all the experts on the revised and final version of the algorithm. CONCLUSIONS: We present a validated algorithm for intavenous fluid management in pediatric trauma patients that focuses on the de-escalation of fluids. Focusing on this time point of fluid therapy will help minimize iatrogenic complications of crystalloid fluids within this patient population.

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae.

The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on inter- and intra-cellular crosstalk important in pulmonary immune responses.

A Novel Risk Score to Predict Post-Trauma Mortality in Nonagenarians.

BACKGROUND: Nonagenarians represent a rapidly growing age group who often have functional limitations and multiple comorbidities, predisposing them to trauma. AIMS: The purpose of this study was to identify patient characteristics, hospital complications, and comorbidities that predict in-hospital mortality in the nonagenarian population following trauma. We also sought to create a scoring system using these variables. SETTINGS AND DESIGN: This study was a retrospective chart review. METHODS: We reviewed the medical records of 548 nonagenarian trauma patients admitted to two Level I trauma centers from 2006 to 2015. Statistical analysis was performed using logistic regression and a machine learning model, which calculated significant variables and computed a scoring system. RESULTS: The in-hospital mortality rate was 7.1% (n = 39). Significant predictors of mortality were cardiac comorbidity, neuro-concussion, New Injury Severity Score (ISS) 16+, striking an object, ISS 25-75, and pulmonary and cardiac complications. Significant variables were assigned a numeric value. A score of 5+ carried a 41.1% mortality risk, 79% sensitivity, and 91% specificity. A score of 10+ had an associated 81.8% mortality risk with 31% specificity and 99% sensitivity. CONCLUSIONS: Our findings identified reliable predictors of mortality in nonagenarian population posttrauma. The scoring system performs with good specificity and sensitivity and incrementally correlates with mortality risk.

Clearing the cervical spine in patients with distracting injuries: An AAST multi-institutional trial.

BACKGROUND: Single institution studies have shown that clinical examination of the cervical spine (c-spine) is sensitive for clearance of the c-spine in blunt trauma patients with distracting injuries. Despite an unclear definition, most trauma centers still adhere to the notion that distracting injuries adversely affect the sensitivity of c-spine clinical examination. A prospective AAST multi-institutional trial was performed to assess the sensitivity of clinical examination screening of the c-spine in awake and alert blunt trauma patients with distracting injuries. METHODS: During the 42-month study period, blunt trauma patients 18 years and older were prospectively evaluated with a standard c-spine examination protocol at 8 Level 1 trauma centers. Clinical examination was performed regardless of the presence of distracting injuries. Patients without complaints of neck pain, tenderness or pain on range of motion were considered to have a negative c-spine clinical examination. All patients with positive or negative c-spine clinical examination underwent computed tomography (CT) scan of the entire c-spine. Clinical examination findings were documented prior to the CT scan. RESULTS: During the study period, 2929 patients were entered. At least one distracting injury was diagnosed in 70% of the patients. A c-spine injury was found on CT scan in 7.6% of the patients. There was no difference in the rate of missed injury when comparing patients with a distracting injury to those without a distracting injury (10.4% vs. 12.6%, p = 0.601). Only one injury missed by clinical examination underwent surgical intervention and none had a neurological complication. CONCLUSIONS: Negative clinical examination may be sufficient to clear the cervical spine in awake and alert blunt trauma patients, even in the presence of a distracting injury. These findings suggest a potential source for improvement in resource utilization. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Squamous cell carcinoma of cervix origin with rare metastasis to the colon.

We discuss the rare case of a 47-year-old female with a history of squamous cell carcinoma (SCC) in situ of the cervix, who presents with a bowel obstruction secondary to a sigmoid colon mass confirmed to be SCC of cervical origin. SCC is one of the rare malignancies of the gastrointestinal tract, and may occur as either a primary or secondary lesion. Metastasis from the cervix to the gastrointestinal tract is a rare occurrence, and has only been described in a handful of case reports. The treatment for colonic metastatic tumor arising from cervical SCC remains controversial. Surgery and debulking are the primary treatment modalities, while the role for radiotherapy and chemotherapy remain ambiguous. Further study is required to compare the efficacy of different treatment regimens.

Thoracoabdominal imaging of tuberous sclerosis.

Imaging of tuberous sclerosis complex has rapidly evolved over the last decade in association with increased understanding of the disease process and new treatment modalities. Tuberous sclerosis complex is best known for the neurological symptoms and the associated neuroimaging findings, and children with tuberous sclerosis complex require active surveillance of associated abnormalities in the chest, abdomen and pelvis. Common findings that require regular imaging surveillance are angiomyolipomas in the kidneys and lymphangioleiomyomatosis in the chest. However multiple rarer associations have been attributed to tuberous sclerosis complex and should be considered by radiologists reviewing any imaging in these children. In this review the authors discuss the spectrum of imaging findings in people with tuberous sclerosis complex, focusing on MR imaging findings in the chest, abdomen and pelvis.

Port site hernias following robotic colorectal surgery in people with obesity.

Port site hernias are a rare complication following robotic surgery that can result in disastrous outcomes. We describe incarcerated port site hernias in two patients with obesity. Both patients required laparoscopic reduction. Following laparoscopic reduction, one patient's postoperative course was complicated by pneumatosis intestinalis, requiring exploratory laparotomy and subsequent small bowel resection. It is standard practice to not close the fascia of port sites less than 12 mm in robotic surgery. However, this allows for the rare possibility of small bowel herniation through the port site. We suggest that our patients' history of obesity and metabolic dysfunction contributed to difficult port retention during the case, and longer operating times which caused an increased amount of torque at the port site. Additionally, compared with laparoscopic surgery, robotic surgery is associated with increased torque at port sites. The combination of these risk factors extended the fascial defect, ultimately leading to the incarceration of small bowel in the port site.

A Descriptive Analysis of EtOH Intoxication in our Latino Trauma Patients: An Indication for a Preventive Program.

We sought to determine patterns of injury in our Latino trauma community targeting alcohol (EtOH) intoxication as an influential variable. With the information gained in our culturally specific and culturally sensitive trauma community, we can use the information to fine-tune our trauma preventive medicine programs. Trauma injuries are the third largest contributor to racial disparities in the United States. Alcohol is involved in approximately half of all trauma admissions to trauma centers around the country. Some investigators have shown that Latinos have higher rates of high-risk drinking, and this factor is independently associated with mortality after trauma. This study is a retrospective review of 524 Latino blunt and penetrating trauma admissions for years (2012-2014). Electronic medical records with the hospital trauma registry charts were evaluated. The trauma registry database included age, gender, EtOH, mechanism of injury, location, insurance, and disposition. Statistical significance was used with chi-square test. Our results show a predominantly male population with falls being the primary mechanism of injury. Intoxicated injuries occurred mostly at bars/clubs, but a substantial amount occurred at the workplace. Despite having a majority of the injuries occurring with patients that have Medicaid or Charity Care insurance, a certain amount of the alcohol-related injuries had private insurance. Many of our Latino trauma patients are still suffering from trauma-related EtOH intoxication. With the information obtained from our project, we will be able to fine-tune and target our trauma preventive medicine program to provide education for our inner-city Latino community of EtOH intoxication-related trauma injuries.

Undiagnosed hypothyroidism presenting with sigmoid volvulus.

The incidence of hypothyroidism presenting with sigmoid volvulus, a phenomenon known as myxedema pseudovolvulus, is exceedingly rare. A male in his late thirties presented to our institution with a chief complaint of abdominal pain. The patient underwent CT scan, which was consistent with massive colonic dilatation with sigmoid volvulus. He was taken to the operating room for exploration and was found to have sigmoid volvulus and underwent a segmental resection. Postoperatively, the patient was newly diagnosed with severe hypothyroidism.

A multicenter outcomes analysis of children with severe rhino/enteroviral respiratory infection.

OBJECTIVES: To investigate the impact of human rhino/enteroviruses on morbidity and mortality outcomes in children with severe viral respiratory infection. DESIGN: Retrospective cohort study. SETTING: The ICU, either PICU or cardiac ICU, at three urban academic tertiary-care children's hospitals. PATIENTS: All patients with laboratory-confirmed human rhino/enteroviruses infection between January 2010 and June 2011. INTERVENTIONS: We captured demographic and clinical data and analyzed associated morbidity and mortality outcomes. MEASUREMENTS AND MAIN RESULTS: There were 519 patients included in our analysis. The median patient age was 2.7 years. The median hospital and ICU lengths of stay were 4 days and 2 days, respectively. Thirty-four percent of patients had a history of asthma, and 25% of patients had a chronic medical condition other than asthma. Thirty-two percent of patients required mechanical ventilation. Eleven patients (2.1%) did not survive to hospital discharge. The rate of viral coinfection was 12.5% and was not associated with mortality. Predisposing factors associated with increased mortality included immunocompromised state (p < 0.001), ICU admission severity of illness score (p < 0.001), and bacterial coinfection (p = 0.003). CONCLUSIONS: There is substantial morbidity associated with severe respiratory infection due to human rhino/enteroviruses in children. Mortality was less severe than reported in other respiratory viruses such as influenza and respiratory syncytial virus. The burden of illness from human rhino/enteroviruses in the ICU in terms of resource utilization may be considerable.

Characterization of the AggR regulon in enteroaggregative Escherichia coli.

AggR is a transcriptional regulator of enteroaggregative Escherichia coli (EAEC) and has been proposed as the defining factor for typical EAEC strains. Expression of multiple putative virulence factors, including the aggregative adherence fimbriae (AAF), dispersin, the dispersin translocator Aat, and the Aai type VI secretion system, have been found to be regulated by AggR. Here, we confirm the existence of at least 44 AggR-regulated genes using DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR); these genes include chromosomal and plasmid-borne loci and 19 previously unsuspected genes. Two previously uncharacterized virulence plasmid-encoded open reading frames (ORFs) (designated ORF3 and ORF4) exhibit significant identity with isoprenoid biosynthesis genes of Bacteria and Archaea. The predicted ORF4 product is closely related to isopentenyl isomerase (IDI) enzymes, whereas the predicted product of the adjacent ORF3 exhibits an aspartate-rich region that is common among trans-isoprenyl phosphate synthases. We show that mutations in these ORFs confer changes in bacterial surface properties. AggR coordinately controls expression of a large number of EAEC genes.

Autoactivation of the AggR regulator of enteroaggregative Escherichia coli in vitro and in vivo.

Enteroaggregative Escherichia coli (EAEC) causes diarrhea in diverse populations worldwide. The AraC-like regulator AggR is a key virulence regulator in EAEC. AggR-regulated genes include those encoding the Aggregative Adherence Fimbria, the dispersin protein, and a type VI secretion system. This study characterizes the regulation of the aggR promoter (P(aggR)). Using primer extension analysis, the transcriptional start site of the aggR promoter was located 40 nucleotides upstream of the translational start. P(aggR) was found to be autoregulated and DNA footprinting revealed the presence of two AggR-binding sites: one upstream of the transcriptional start site and one downstream. Additionally, P(aggR) was found to be positively regulated by the DNA-binding protein FIS and negatively regulated by the global regulator H-NS. To further understand this complex regulation scheme, a bacterial luciferase reporter system was used with a mouse model of EAEC colonization. This allowed for the in vivo measurement of P(aggR), P(fis), and P(hns) activity. EAEC present in the mouse intestine possessed relatively high levels of P(fis) and P(aggR) activity and a low level of P(hns) when compared with in vitro experiments. The data provide significant insights into the regulation cascade leading to aggR expression in the mammalian intestine during EAEC infection.

Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity.

OBJECTIVES: Diarrheal diseases remain a major human plague that still claim millions of lives every year. Probiotics, including Lactobacillus GG (LGG), are known to have a beneficial effect on diarrheal diseases, but their mechanism of action has not yet been completely established. Therefore, the main objective of this work was to identify and characterize moieties elaborated by LGG that exert antibacterial activity. MATERIALS AND METHODS: Lactobacillus GG conditional media was subjected to liquid chromatography/mass spectrometry. The identified peptides were synthesized by Symphony peptide synthesizer and purified by HPLC using Dynamax reverse-phase C18 column. Using A600 measurement and tested for their antibacterial activity. RESULTS: We identified 7 small peptides from LGG cultured media, 2 of which are NPSRQERR and PDENK, retained the antibacterial activity detected with LGG conditional media. The antibacterial activity was exerted against both Gram-negative (Escherichia coli EAEC 042 and Salmonella typhi) and, with less potency, Gram-positive (Staphylococcus aureus) bacteria. CONCLUSIONS: Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity. NPSRQERR showed the most potent antibacterial effect that was detected both in Gram-negative and Gram-positive microorganisms. These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.

The Escherichia coli biofilm-promoting protein Antigen 43 does not contribute to intestinal colonization.

Abstract Escherichia coli is a versatile organism capable of causing a variety of intestinal and extraintestinal diseases, as well as existing as part of the commensal flora. A variety of factors permit specific attachment to host receptors including fimbrial adhesins and outer membrane proteins such as autotransporters. One of the better characterized autotransporters is Antigen 43 (Ag43), the major phase-variable surface protein of E. coli. Ag43 is associated with bacterial cell-cell aggregation and biofilm formation. Nevertheless, the precise biological significance and contribution to intestinal colonization remain to be elucidated. Here we investigated the contribution of Ag43 to E. coli adherence to intestinal epithelial cells and colonization of the mouse intestine. These investigations revealed that Ag43 increased in vitro adherence of E. coli to epithelial cells by promoting bacterial cell-cell aggregation but that Ag43 did not promote specific interactions with the mammalian cells. Furthermore, Ag43 did not contribute significantly to colonization of the mouse intestine and expression of Ag43 was lost a few days after colonization of the mouse was established. Unexpectedly, considering its similarity to other adhesins, our findings suggest that Ag43 does not act as a direct colonization factor by binding to mammalian cells.

Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is defined by aggregative adherence (AA) to HEp-2 cells, where bacteria display adherence to cell surfaces and also to the intervening substratum in a stacked-brick configuration. We previously showed that an AraC homologue designated AggR is required for the expression of plasmid-encoded genes that mediate AA of EAEC strain 042. In this study, we hypothesized that AggR also controls the expression of other virulence determinants in EAEC 042. Using proteomic and microarray analysis, we identified for the first time that AggR activates the expression of chromosomal genes, including 25 contiguous genes (aaiA-Y), which are localized to a 117 kb pathogenicity island (PAI) inserted at pheU. Many of these genes have homologues in other Gram-negative bacteria and were recently proposed to constitute a type VI secretion system (T6SS). AaiC was identified as a secreted protein that has no apparent homologues within GenBank. EAEC strains carrying in-frame deletions of aaiB, aaiG, aaiO or aaiP still synthesized AaiC; however, AaiC secretion was abolished. Cloning of aai genes into E. coli HB101 suggested that aaiA-P are sufficient for AaiC secretion. A second T6SS was identified within the pheU PAI that secretes a protein unrelated by sequence identity to AaiC. Distribution studies indicated that aaiA and aaiC are commonly found in EAEC isolates worldwide, particularly in strains defined as typical EAEC. These data support the hypothesis that AggR is a global regulator of EAEC virulence determinants, and builds on the hypothesis that T6SS is an importance mediator of pathogenesis.