Abigail B. Podany

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.

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 hospitals 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

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

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.

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

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

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.

Metabolism-related microRNAs in maternal breast milk are influenced by premature delivery

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-1β, 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.

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

BackgroundMaternal breast milk (MBM) is enriched in microRNAs, factors that regulate protein translation throughout the human body. MBM from mothers of term and preterm infants differs in nutrient, hormone, and bioactive-factor composition, but the microRNA differences between these groups have not been compared. We hypothesized that gestational age at delivery influences microRNA in MBM, particularly microRNAs involved in immunologic and metabolic regulation.MethodsMBM from mothers of premature infants (pMBM) obtained 3–4 weeks post delivery was compared with MBM from mothers of term infants obtained at birth (tColostrum) and 3–4 weeks post delivery (tMBM). The microRNA profile in lipid and skim fractions of each sample was evaluated with high-throughput sequencing.ResultsThe expression profiles of nine microRNAs in lipid and skim pMBM differed from those in tMBM. Gene targets of these microRNAs were functionally related to elemental metabolism and lipid biosynthesis. The microRNA profile of tColostrum was also distinct from that of pMBM, but it clustered closely with tMBM. Twenty-one microRNAs correlated with gestational age demonstrated limited relationships with method of delivery, but not other maternal–infant factors.ConclusionPremature delivery results in a unique MBM microRNA profile with metabolic targets. This suggests that preterm milk may have adaptive functions for growth in premature infants.