Costs of Clostridium difficile infection in pediatric operations: A propensity score-matching analysis.

BACKGROUND: The purpose of this analysis was to assess the burden of Clostridium difficile infection in the hospitalized pediatric surgical population and to characterize its influence on the costs of care. METHODS: There were 313,664 patients age 1-18 years who underwent a general thoracic or abdominal procedure in the Kids' Inpatient Database during 2003, 2006, 2009, and 2012. Logistic regression was used to model factors associated with the development of C difficile infection. A propensity score-matching analysis was performed to evaluate the influence of C difficile infection on mortality, duration of stay, and costs in similar patient cohorts. Population weights were used to estimate the national excess burden of C difficile infection on these outcomes. RESULTS: The overall prevalence of C difficile infection in the sampled cohort was 0.30%, with an increasing trend of C difficile infection over time in non-children's hospitals (P < .001). C difficile infection was associated with younger age, nonelective procedures, increasing comorbidities, and urban teaching hospital status (P < .001). An estimated 1,438 children developed C difficile infection after operation. After propensity score matching, the mean excess duration of stay and costs attributable to C difficile infection were 5.8 days and $12,801 (P < .001), accounting for 8,295 days spent in the hospital and $18.4 million (2012 USD) in spending annually. CONCLUSION: C difficile infection is a relatively uncommon but costly complication after pediatric operative procedures. Given the increasing trend of C difficile infection among hospitalized surgical patients, there is substantial opportunity for reduction of inpatient burden and associated costs in this potentially preventable nosocomial infection.

ZnT2-Mediated Zinc Import Into Paneth Cell Granules Is Necessary for Coordinated Secretion and Paneth Cell Function in Mice.

BACKGROUND & AIMS: Defects in Paneth cell (PC) function are associated with microbial dysbiosis and intestinal inflammation. PC granules contain antimicrobial peptides, cytokines, and substantial stores of zinc (Zn). We hypothesized that Zn, transported into the granule through the Zn transporter (ZnT)2, is critical for signature PC functions. METHODS: ZnT2 was localized to PC granules using immunofluorescence and sucrose gradient fractionation in wild-type (wt) mice, and consequences of ZnT2 loss were characterized in ZnT2 knockout (ZnT2ko) mice. Terminal ilea were harvested for immunofluorescence, electron microscopy, and fluorescent imaging with the Zn reporter Zinpyr-1. Alterations in fecal microbiota were characterized using 16s ribosomal RNA sequencing. PC degranulation, bacterial translocation, cytokine response to Escherichia coli endotoxin lipopolysaccharide, crypt viability after exposure to the oxidant monochloramine (NH2Cl), and bactericidal activity of luminal contents of terminal ilea against enteropathogenic E coli were assessed. RESULTS: ZnT2 was localized to the membrane of PC granules. In ZnT2ko mice, spontaneous degranulation was observed more frequently than among wt mice. Secretory granules were hypodense with less active lysozyme, and there was evidence of autophagosome accumulation and granule degradation in PCs from ZnT2ko mice. Gut microbiota of ZnT2ko mice were enriched in Bacteroidales S24-7 and relatively depleted of species commonly found in wt mice. Evidence of PC dysfunction in ZnT2ko mice included impaired granule secretion and increased inflammatory response to lipopolysaccharide, less bactericidal activity, and greater susceptibility to cell death from NH2Cl. CONCLUSIONS: ZnT2 is critical for Zn import into PC granules, and the inability to import Zn leads to profound defects in PC function and uncoordinated granule secretion.

Impaired recovery from peritoneal inflammation in a mouse model of mild dietary zinc restriction.

SCOPE: Mild dietary zinc (Zn) deficiency is wide-spread in human populations, but the effect on Zn-dependent processes of immune function and healing are not well understood. The consequences of mild dietary Zn restriction were examined in two mouse models of inflammation and recovery. METHODS AND RESULTS: Male C57BL/6 mice were fed a Zn adequate diet (ZA, 30 mg Zn/kg diet), or diets containing sub-optimal Zn levels (ZM, 15 mg Zn/kg diet; ZD, 10 mg Zn/kg diet) for 30 days before a thioglycollate peritonitis challenge. Plasma lipid profiles were distinct, with greater Zn restriction resulting in a greater impact on metabolites. The milder ZM diet was selected for immune studies. Peritoneal macrophages from ZM mice displayed increased phagocytosis and amplified pro-inflammatory cytokine (IL-1ß, IL-6, and TNFα) release compared to ZA, at baseline and after a secondary LPS challenge. Splenocytes isolated from ZM mice displayed an increase in IL-6 and a reduction in anti-inflammatory IL-4 compared to ZA. Cytokine levels in plasma were unaltered. Following mechanical manipulation of the intestines to induce ileus, ZM mice had delayed intestinal transit compared to ZA. CONCLUSION: Mild Zn deficiency enhances local inflammatory responses, amplifying macrophage functions and delaying recovery from acute insults within the peritoneum.

Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy.

INTRODUCTION: Fall risk for older adults is a multi-factorial public health problem as 90% of geriatric injuries are caused by traumatic falls. The CDC estimated 33% of adults >65 years incurred a fall in 2011, with 30% resulting in moderate injury. While much has been written about overall risk to trauma patients on oral anticoagulant (OAC) therapy, less has been reported on outcomes in the elderly trauma population. We used data from the National Trauma Data Bank (NTDB) to identify the types of injury and complications incurred, length of stay, and mortality associated with OACs in elderly patients sustaining a fall. METHODS: Using standard NTDB practices, data were collected on elderly patients (≥65 years) on OACs with diagnosis of fall as the primary mechanism of injury from 2007 to 2010. Univariate analysis was used to determine patient variables influencing risk of fall on OACs. Odds ratios were calculated for types of injury sustained and post-trauma complications. Logistic regression was used to determine mortality associated with type of injury incurred. RESULTS: Of 118,467 elderly patients sampled, OAC use was observed in 444. Predisposing risk factors for fall on OACs were >1 comorbidity (p<0.0001). Patients on OACs were 188% and 370% more likely to develop 2 and >3 complications (p<0.0001); the most significant being ARDS and ARF (p<0.0001). The mortality rate on OACs was 16%. Injuries to the GI tract, liver, spleen, and kidney (p<0.0002) were more likely to occur. However, if patients suffered a mortality, the most significant injuries were skull fractures and intracranial haemorrhage (p<0.0001). CONCLUSIONS: Risks of anticoagulation in elderly trauma patients are complex. While OAC use is a predictor of 30-day mortality after fall, the injuries sustained are markedly different between the elderly who die and those who do not. As a result there is a greater need for healthcare providers to identify preventable and non-preventable risks factors indicative of falls in the anti-coagulated elderly patient.

Endobronchial occlusion with one-way endobronchial valves: a novel technique for persistent air leaks in children.

PURPOSE: In children, persistent air leaks can result from pulmonary infection or barotrauma. Management strategies include surgery, prolonged pleural drainage, ventilator manipulation, and extracorporeal membrane oxygenation (ECMO). We report the use of endobronchial valve placement as an effective minimally invasive intervention for persistent air leaks in children. METHODS: Children with refractory prolonged air leaks were evaluated by a multidisciplinary team (pediatric surgery, interventional pulmonology, pediatric intensive care, and thoracic surgery) for endobronchial valve placement. Flexible bronchoscopy was performed, and air leak location was isolated with balloon occlusion. Retrievable one-way endobronchial valves were placed. RESULTS: Four children (16 months to 16 years) had prolonged air leaks following necrotizing pneumonia (2), lobectomy (1), and pneumatocele (1). Patients had 1-4 valves placed. Average time to air leak resolution was 12 days (range 0-39). Average duration to chest tube removal was 25 days (range 7-39). All four children had complete resolution of air leaks. All were discharged from the hospital. None required additional surgical interventions. CONCLUSION: Endobronchial valve placement for prolonged air leaks owing to a variety of etiologies was effective in these children for treating air leaks, and their use may result in resolution of fistulae and avoidance of the morbidity of pulmonary surgery.

Transumbilical laparoscopic-assisted appendectomy is associated with lower costs compared to multiport laparoscopic appendectomy.

BACKGROUND/PURPOSE: Single-incision laparoscopic appendectomy has been associated with improved cosmetic benefits, and decreased postoperative pain. Less is known about costs and other outcomes. Our aim was to evaluate the costs and outcomes between transumbilical laparoscopic-assisted appendectomy (TULAA) and multiport laparoscopic appendectomy (MLA). METHODS: IRB-approved retrospective review (September 2010-July 2013) of institutional medical records identified 372 pediatric patients undergoing laparoscopic appendectomy. Outcomes included costs, LOS and readmission. Costs were fully loaded operating costs from the hospital's cost accounting database. Generalized linear regression was used to assess costs of MLA and TULAA. A subgroup analysis was performed using only patients with non-perforated appendicitis. RESULTS: There were 132 patients (35.5%) that underwent TULAA while 240 patients (65.5%) underwent MLA. Compared to MLA, TULAA was associated with decreased operative time (0.6 vs. 1.0h, p<0.0001), used in comparable proportions of interval appendectomies, but was performed less often for perforated appendicitis (9.8% vs. 22.9%, p=0.002). Readmission and postoperative complications were similar between both groups. In the setting of non-perforated appendicitis, TULAA was associated with lower costs of $1378 relative to MLA (p=0.009). CONCLUSIONS: In non-perforated appendicitis, TULAA is associated with lower costs and comparable rates of readmission and postoperative complications.

Mannose-binding lectin serum levels are low in persons with clinically active coccidioidomycosis.

BACKGROUND: Mannose-binding lectin (MBL) is a circulating collectin that is part of the innate immune response. We explored the serum levels of MBL in persons with different forms of coccidioidomycosis. METHODS: Serum MBL was measured by ELISA from samples obtained from healthy donors with immunity to Coccidioides, and those with various forms of active coccidioidomycosis. Blood cell specimens from a subgroup of subjects with active coccidioidomycosis were examined for single nucleotide polymorphisms of the MBL gene and promoter regions. RESULTS: The control group comprised 29 healthy immune subjects. Patient groups with active coccidioidomycosis consisted of 20 patients with symptomatic primary pulmonary coccidioidomycosis, 26 with non-meningeal disseminated coccidioidomycosis, and nine with coccidioidal meningitis. The group with active coccidioidomycosis was significantly older and more likely to be male than the control group (for both, P < 0.001). The mean +/- SEM level of serum MBL in the healthy controls was 169.4 +/- 28.6 ng/ml, significantly higher than the 79.2 +/- 10.9 ng/ml for all active groups (P < 0.001). Moreover, the active coccidioidomycosis group was significantly more likely to have serum MBL level

Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation.

Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time- and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E2. Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.