Preoperative Risk Factors and Postoperative Complications of COVID-Positive Children Requiring Urgent or Emergent Surgical Care.

BACKGROUND: Preoperative COVID-19 testing protocols were widely implemented for children requiring surgery, leading to increased resource consumption and many delayed or canceled operations or procedures. This study using multi-center data investigated the relationship between preoperative risk factors, COVID-positivity, and postoperative outcomes among children undergoing common urgent and emergent procedures. METHODS: Children (<18 years) who underwent common urgent and emergent procedures were identified in the 2021 National Surgical Quality Improvement Program Pediatric database. The outcomes of COVID-positive and non-COVID-positive (negative or untested) children were compared using simple and multivariable regression models. RESULTS: Among 40,628 children undergoing gastrointestinal surgery (appendectomy, cholecystectomy), long bone fracture fixation, cerebrospinal fluid shunt procedures, gonadal procedures (testicular detorsion, ovarian procedures), and pyloromyotomy, 576 (1.4%) were COVID-positive. COVID-positive children had higher American Society of Anesthesiologists scores (p ≤ 0.001) and more frequently had preoperative sepsis (p ≤ 0.016) compared to non-COVID-positive children; however, other preoperative risk factors, including comorbidities, were largely similar. COVID-positive children had a longer length of stay than non-COVID-positive children (median 1.0 [IQR 0.0-2.0] vs. 1.0 [IQR 0.0-1.0], p < 0.001). However, there were no associations between COVID-19 positivity and overall complications, pulmonary complications, infectious complications, or readmissions. CONCLUSIONS: Despite increased preoperative risk factors, COVID-positive children did not have an increased risk of postoperative complications after common urgent and emergent procedures. However, length of stay was greater for COVID-positive children, likely due to delays in surgery related to COVID-19 protocols. These findings may be applicable to future preoperative testing and surgical timing guidelines related to respiratory viral illnesses in children. LEVEL OF EVIDENCE: III.

Relationship between the COVID-19 pandemic and structural inequalities within the pediatric trauma population.

BACKGROUND: The COVID-19 pandemic disrupted social, political, and economic life across the world, shining a light on the vulnerability of many communities. The objective of this study was to assess injury patterns before and after implementation of stay-at-home orders (SHOs) between White children and children of color and across varying levels of vulnerability based upon children's home residence. METHODS: A multi-institutional retrospective study was conducted evaluating patients < 18 years with traumatic injuries. A "Control" cohort from an averaged March-September 2016-2019 time period was compared to patients injured after SHO initiation-September 2020 ("COVID" cohort). Interactions between race/ethnicity or social vulnerability index (SVI), a marker of neighborhood vulnerability and socioeconomic status, and the COVID-19 timeframe with regard to the outcomes of interest were assessed using likelihood ratio Chi-square tests. Differences in injury intent, type, and mechanism were then stratified and explored by race/ethnicity and SVI separately. RESULTS: A total of 47,385 patients met study inclusion. Significant interactions existed between race/ethnicity and the COVID-19 SHO period for intent (p < 0.001) and mechanism of injury (p < 0.001). There was also significant interaction between SVI and the COVID-19 SHO period for mechanism of injury (p = 0.01). Children of color experienced a significant increase in intentional (COVID 16.4% vs. Control 13.7%, p = 0.03) and firearm (COVID 9.0% vs. Control 5.2%, p < 0.001) injuries, but no change was seen among White children. Children from the most vulnerable neighborhoods suffered an increase in firearm injuries (COVID 11.1% vs. Control 6.1%, p = 0.001) with children from the least vulnerable neighborhoods having no change. All-terrain vehicle (ATV) and bicycle crashes increased for children of color (COVID 2.0% vs. Control 1.1%, p = 0.04 for ATV; COVID 6.7% vs. Control 4.8%, p = 0.02 for bicycle) and White children (COVID 9.6% vs. Control 6.2%, p < 0.001 for ATV; COVID 8.8% vs. Control 5.8%, p < 0.001 for bicycle). CONCLUSIONS: In contrast to White children and children from neighborhoods of lower vulnerability, children of color and children living in higher vulnerability neighborhoods experienced an increase in intentional and firearm-related injuries during the COVID-19 pandemic. Understanding inequities in trauma burden during times of stress is critical to directing resources and targeting intervention strategies.

Characteristics and neighborhood-level opportunity of assault-injured children in Milwaukee.

BACKGROUND: Multiple studies have explored demographic characteristics and social determinants of health in relation to the risk of pediatric assault-related injuries and reinjury. However, few have explored protective factors. The Child Opportunity Index (COI) uses neighborhood-level indicators to measure 'opportunity' based on factors such as education, social environment, and economic resources. We hypothesized that higher 'opportunity' would be associated with less risk of reinjury in assault-injured youth. METHODS: This was a single-institution, retrospective study at a Level 1 Pediatric Trauma Center. Trauma registry and electronic medical record data were queried for children ≤ 18 years old with assault-related injuries from 1/1/2016 to 5/31/2021. Reinjured children, defined as any child who sustained more than one assault injury, were compared to non-reinjured children. Area Deprivation Index (ADI), a marker of socioeconomic status, and COI were determined through census block and tract data, respectively. A post-hoc analysis examined COI between all assault-injured children, unintentionally injured children, and a state-based normative cohort representative of non-injured children. RESULTS: There were 55,862 traumatic injury encounters during the study period. Of those, 1224 (2.3%) assault injured children were identified, with 52 (4.2%) reinjured children and 1172 (95.8%) non-reinjured children. Reinjured children were significantly more likely to be older (median age 15.0 [IQR 13.8-17.0] vs. median age 14.0 [IQR 8.8-16.0], p < 0.001) and female (55.8% vs. 37.5%, p = 0.01) than non-reinjured children. COI was not associated with reinjury. There were also no significant differences in race, ethnicity, insurance status, ADI, or mechanism and severity of injury between cohorts. Post-hoc analysis revealed that assault-injured children were more likely to live in areas of lower COI than the other cohorts. CONCLUSIONS: Compared to children who sustained only one assault during the study period, children who experienced more than one assault were more likely to be older and female. Furthermore, living in an area with more or less opportunity did not influence the risk of reinjury. However, all assault-injured children were more likely to live in areas of lower COI compared to unintentionally injured and a state-based normative cohort. Identification of factors on a social or environmental level that leads to assaultive injury warrants further exploration.

Characterizing rural families' experiences receiving pediatric surgical care: A qualitative study.

PURPOSE: Access to pediatric surgical care is influenced by multiple factors, including proximity to care and financial resources. There is limited understanding regarding the process by which rural children acquire surgical care. We qualitatively explored rural families' experiences seeking surgical care for their children at a major children's hospital. METHODS: Parents or legal guardians ≥18 years of age with children who received general surgical care at a major children's hospital and who lived in rural areas were included. Operative logs from 2020 to 2021 and postoperative clinic visits were used to identify families. Semi-structured interviews explored rural families' experiences receiving surgical care. Interviews were inductively and deductively analyzed to create codes and identify thematic domains. Twelve interviews (with 15 individuals) were conducted before thematic saturation was reached. FINDINGS: Children were predominantly White (92%) and lived a median of 98.3 mi (interquartile range 49.4-147.0 mi) from the hospital. Four thematic domains were identified: (1) Accessing surgical care included difficulties with referral processes and travel/lodging burdens; (2) surgical care processes involved treatment details and provider/hospital expertise; (3) resources for navigating care encompassed families' employment status, financial burden, and technology use; and (4) social support included family situations, emotions and stress, and coping with diagnoses. CONCLUSIONS: Rural families experienced difficulties with obtaining referrals, challenges with travel and employment, and the benefits of technology use. These findings can be applied to the development of tools that can ease challenges faced by rural families whose children require surgical care.

The Effects of the COVID-19 Pandemic on Violent Injuries in Children: A Literature Review.

The SARS-CoV-2 (COVID-19) pandemic and implementation of stay-at-home orders led to changes in the daily lives of children. Subsequently, there have been reports of increases in pediatric violent traumatic injuries. This review summarizes the existing literature regarding pediatric violent injury temporally related to the COVID-19 pandemic, including demographic, injury, and hospital characteristics in addition to associated factors. Key findings include an increase in fatal and nonfatal firearm injuries, particularly in minority and socioeconomically disadvantaged populations. However, more comprehensive and long-term data are needed specific to pediatric violent injuries to fully understand how the COVID-19 pandemic impacted trends.

Association of Rural Residence With Surgical Outcomes Among Infants at US Children's Hospitals.

OBJECTIVES: Disparities in pediatric health outcomes are widespread. It is unclear whether rurality negatively impacts outcomes of infants with surgical congenital diseases. This study compared outcomes of rural versus urban infants requiring complex surgical care at children's hospitals in the United States. METHODS: Rural and urban infants (aged <1 year) receiving surgical care at children's hospitals from 2016 to 2019 for esophageal atresia, gastroschisis, Hirschsprung's disease, anorectal malformation, and congenital diaphragmatic hernia were compared over a 1-year postoperative period using the Pediatric Health Information System. Generalized linear mixed effects models compared outcomes of rural and urban infants. RESULTS: Among 5732 infants, 20.2% lived in rural areas. Rural infants were more frequently white, lived farther from the hospital, and lived in areas with lower median household income compared with urban infants (all P < .001). Rural infants with anorectal malformation and gastroschisis had lower adjusted hospital days over 1 year; rural infants with esophageal atresia had higher adjusted odds of 30-day hospital readmission. Adjusted mortality, hospital days, and readmissions were otherwise similar between the 2 groups. Outcomes remained similar when comparing urban infants to rural infant subgroups with the longest hospital travel distance (≥60 miles) and lowest median household income (<$35 000). CONCLUSIONS: Despite longer travel distances and lower financial resources, rural infants with congenital anomalies have similar postoperative outcomes to urban infants when treated at children's hospitals. Future work is needed to examine outcomes for infants treated outside children's hospitals and to determine whether efforts are necessary to increase access to children's hospitals.

Distribution of acute appendicitis care in children: A statewide assessment of the surgeons and facilities providing surgical care.

BACKGROUND: Pediatric appendicitis is managed by general and pediatric surgeons at both children's hospitals and non-children's hospitals. A statewide assessment of surgeons and facilities providing appendicitis care was performed to identify factors associated with location of surgical care. METHODS: Children aged <18 years undergoing appendectomy for appendicitis in Wisconsin from 2018-2020 were identified through the International Classification of Diseases, 10th revision, and Current Procedural Terminology codes using Wisconsin Hospital Association data. Patient residence and hospital locations were used to determine travel distance, rurality, and neighborhood-level socioeconomic status. RESULTS: Among 3,604 children with appendicitis, 36.0% and 12.8% had an appendectomy at 2 major children's hospitals and 4 other children's hospitals, respectively, and 51.2% had an appendectomy at 99 non-children's hospitals. Pediatric surgeons performed 76.1% of appendectomies at children's hospitals and 2.9% at non-children's hospitals. Only 32.2% of patients received care at the hospital closest to their homes. Non-children's hospitals disproportionally cared for older, non-Hispanic White, and privately insured children, those with uncomplicated appendicitis, and those living in rural areas, in mid-socioeconomic status neighborhoods, and greater distances from children's hospitals (all P < .001). After multivariable adjustment, receipt of care at children's hospitals was associated with younger age, minority race, complicated appendicitis, shorter distance to children's hospitals, and urban residence. CONCLUSION: Over half of surgical care for pediatric appendicitis occurred at non-children's hospitals, especially among older children and those living in rural areas far from children's hospitals. Future work is necessary to determine which children benefit most from care at children's hospitals and which can safely receive care at non-children's hospitals to avoid unnecessary time and resource utilization associated with travel to children's hospitals.

A Multi-institutional Study Evaluating Pediatric Burn Injuries During the COVID-19 Pandemic.

During the COVID-19 pandemic, children were out of school due to Stay-at-Home Orders. The objective of this study was to investigate how the COVID-19 pandemic may have impacted the incidence of burn injuries in children. Eight Level I Pediatric Trauma Centers participated in a retrospective study evaluating children <18 years old with traumatic injuries defined by the National Trauma Data Bank. Patients with burn injuries were identified by ICD-10 codes. Historical controls from March to September 2019 ("Control" cohort) were compared to patients injured after the start of the COVID-19 pandemic from March to September 2020 ("COVID" cohort). A total of 12,549 pediatric trauma patients were included, of which 916 patients had burn injuries. Burn injuries increased after the start of the pandemic (COVID 522/6711 [7.8%] vs Control 394/5838 [6.7%], P = .03). There were no significant differences in age, race, insurance status, burn severity, injury severity score, intent or location of injury, and occurrence on a weekday or weekend between cohorts. There was an increase in flame burns (COVID 140/522 [26.8%] vs Control 75/394 [19.0%], P = .01) and a decrease in contact burns (COVID 118/522 [22.6%] vs Control 112/394 [28.4%], P = .05). More patients were transferred from an outside institution (COVID 315/522 patients [60.3%] vs Control 208/394 patients [52.8%], P = .02), and intensive care unit length of stay increased (COVID median 3.5 days [interquartile range 2.0-11.0] vs Control median 3.0 days [interquartile range 1.0-4.0], P = .05). Pediatric burn injuries increased after the start of the COVID-19 pandemic despite Stay-at-Home Orders intended to optimize health and increase public safety.

Improved Mortality of Patients with Gastroschisis: A Historical Literature Review of Advances in Surgery and Critical Care from 1960-2020.

The improved survival of gastroschisis patients is a notable pediatric success story. Over the past 60 years, gastroschisis evolved from uniformly fatal to a treatable condition with over 95% survival. We explored the historical effect of four specific clinical innovations­mechanical ventilation, preformed silos, parenteral nutrition, and pulmonary surfactant­that contributed to mortality decline among gastroschisis infants. A literature review was performed to extract mortality rates from six decades of contemporary literature from 1960 to 2020. A total of 2417 publications were screened, and 162 published studies (98,090 patients with gastroschisis) were included. Mortality decreased over time and has largely been <10% since 1993. Mechanical ventilation was introduced in 1965, preformed silo implementation in 1967, parenteral nutrition in 1968, and pulmonary surfactant therapy in 1980. Gastroschisis infants now carry a mortality rate of <5% as a result of these interventions. Other factors, such as timing of delivery, complex gastroschisis, and management in low- and middle-income countries were also explored in relation to gastroschisis mortality. Overall, improved gastroschisis outcomes serve as an illustration of the benefits of clinical advances and multidisciplinary care, leading to a drastic decline in infant mortality among these patients.

Utilization and Adequacy of Telemedicine for Outpatient Pediatric Surgical Care.

INTRODUCTION: Telemedicine (TM) use accelerated out of necessity during the COVID-19 pandemic, but the utility of TM within the pediatric surgery population is unclear. This study measured utilization, adequacy, and disparities in uptake of TM in pediatric surgery during the COVID-19 pandemic. METHODS: Scheduled outpatient pediatric surgery clinic encounters at a large academic children's hospital from January 2020 through March 2021 were reviewed. Sub-group analysis examined post-operative (PO) visits after appendectomy and umbilical, epigastric, and inguinal hernia repairs. RESULTS: Of 9149 scheduled visits, 87.9% were in-person and 12.1% were TM. TM visits were scheduled for PO care (76.9%), new consultations (7.1%), and established patients (16.0%). Although TM visits were more frequently canceled or no shows (P < 0.001), most canceled TM visits were PO visits, of which 41.7% were canceled via electronic communication reporting the absence of any PO concerns. TM visits were adequate for accomplishing visit goals in 98.2%, 95.5%, and 96.2% of PO, new, and established patient visits, respectively. Patients utilizing TM visits were more frequently of white race, privately-insured, from less disadvantaged neighborhoods, and living a greater distance from clinic (P < 0.001 for all comparisons). CONCLUSIONS: TM was adequate for the majority of visits in which it was utilized, including the basic PO visits that occurred via TM. TM was used more by patients with greater travel and less by those of minority race, with public insurance, and from more disadvantaged neighborhoods. Future work is necessary to ensure broad access to this useful tool for all children requiring surgical care.

Precision medicine in trauma: a transformational frontier in patient care, education, and research.

PURPOSE: Trauma is the leading cause of death before the age of 45 in the United States. Precision medicine (PM) is the most advanced scientific form of medical practice and seeks to gather data from the genome, environmental interactions, and lifestyles. Relating to trauma, PM promises to significantly advance our understanding of the factors that contribute to the physiologic response to injury. METHODS: We review the status of PM-driven trauma care. Semantic-based methods were used to gather data on genetic/epigenetic variability previously linked to the principal causes of trauma-related outcomes. Data were curated to include human investigations involving genomics/epigenomics with clinical relevance identifiable early after injury. RESULTS: Most studies relevant to genomic/epigenomic differences in trauma are specific to traumatic brain injury and injury-related sepsis. Genomic/epigenomic differences rarely encompass other relevant factors, such as coagulability and pharmacogenomics. Few studies describe clinical use of genomics/epigenomics for therapeutic intervention in trauma care, and even fewer attempt to incorporate real-time genomic/epigenomic information to precisely guide clinical decision-making. CONCLUSION: Considering that genomics/epigenomics, environmental exposures, and lifestyles are most likely to be of significant medical relevance in advancing the field of trauma, the lack of application of concepts and methodologies from PM to trauma education, research, practice, and community wellness is underwhelming. We suggest that significant effort be given to incorporate the tools of what is becoming the "new medicine".

Iatrogenic vascular trauma and complications of vascular access in children.

Vascular access is frequently a critical component of the diagnostic and therapeutic procedures required to manage childhood illnesses, including many emergent conditions and critical illnesses. Vascular access in the pediatric population presents unique challenges, and many clinical and technical factors must be considered to avoid complications that can occur with vascular access procedures. This article reviews various aspects of vascular access and associated iatrogenic trauma in children, including risk factors, management of complications, and preventive measures to avoid complications. It is only with a comprehensive understanding of the topic that vascular access in children can be performed safely, effectively, and efficiently.

Primary Aortoduodenal Fistula: A Case Report and Current Literature Review.

Primary aortoduodenal fistula is a rare, life-threatening pathology that is difficult to diagnose and manage. We present the case of a 64-year-old male with a primary aortoduodenal fistula. Our patient initially underwent an endovascular aneurysm repair at an outside institution before being transferred to our tertiary care center, where he ultimately had definitive management with an extra-anatomic bypass, aortic ligation, duodenal resection with primary anastomosis, and gastrojejunostomy tube placement. His surgical cultures grew Candida albicans, and he was discharged with a 6-week course of intravenous antibiotics with subsequent antibiotic suppression for 1 year. He died 14 months postoperatively from tongue squamous cell carcinoma. We also review the current literature regarding epidemiology, pathology, diagnostics, management, and case reports from 2015 to present. Overall, timely diagnosis and treatment is imperative for reducing mortality from primary aortoduodenal fistula, and although formal consensus is lacking regarding most clinical aspects, an increasing number of case reports has helped describe options for management.

Venous thromboembolism prophylaxis after pediatric trauma.

In recent years, there has been an increased focus on developing and validating venous thromboprophylaxis guidelines in the pediatric trauma population. We review the current literature regarding the incidence of and risk factors for venous thromboembolism (VTE) and the use of prophylaxis in the pediatric trauma population. Risk factors such as age, injury severity, central venous catheters, mental status, injury type, surgery, and comorbidities can lead to a higher incidence of VTE. Risk stratification tools have been developed to determine whether mechanical and/or pharmacologic prophylaxis should be implemented depending on the degree of VTE risk. When VTE risk is high, pharmacologic prophylaxis, such as with low molecular weight heparin, is often initiated. However, the timing and duration of VTE prophylaxis is dependent on patient factors including ambulatory status and contraindications such as bleeding. In addition, the utility of screening ultrasound for VTE surveillance has been evaluated and though they are not widely recommended, no formal guidelines exist. While more research has been done in recent years to assess the most appropriate type, timing, and duration of VTE prophylaxis, further studies are warranted to create optimal guidelines for decreasing the risk of VTE after pediatric trauma.

STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer.

Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors.

Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between "malignant" and "benign" IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-73.2, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.

A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status. METHODOLOGY/PRINCIPAL FINDINGS: In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (P<10-3, area underneath the curve (AUC) = 87%). The same trend was observed in the validation phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic duct involvement (P = 0.021), and serum albumin levels were positively correlated with miR-99a (r = 0.52, P = 0.004) and miR-100 expression (r = 0.49, P = 0.008). Literature, validated miRNA:target gene interactions, and pathway enrichment analysis supported the candidate miRNAs as tumor suppressors and regulators of PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a (ATG2B, MEOX2), miR-342-3p (DNMT1), and miR-126 (IRS-1) were up-regulated in high- versus low-risk IPMNs (P<0.10). CONCLUSIONS: This pilot study highlights miRNAs that may aid in preoperative risk stratification of IPMNs and provides novel insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs identified here and in other recent investigations warrant evaluation in biofluids in a well-powered prospective cohort of individuals newly-diagnosed with IPMNs and other pancreatic cysts and those at increased genetic risk for these lesions.