Search

MALDI-IMS analysis of treated xenograft tissues.

Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation of cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by the gene CDKN2A, is a potent inhibitor of CDK4/6 and serves as a critical checkpoint of cell proliferation. Mutations in and subsequent loss of the p16 gene occur in PDAC at a rate higher than that reported in any other tumor type and results in Rb inactivation and unrestricted cellular growth. Therefore, strategies targeting downstream RAS pathway effectors combined with CDK4/6 inhibition (CDK4/6i) may have the potential to improve outcomes in this disease. Herein, we show that expression of p16 is markedly reduced in PDAC tumors compared with normal pancreatic or pre-neoplastic tissues. Combined MEK inhibition (MEKi) and CDK4/6i results in sustained downregulation of both ERK and Rb phosphorylation and a significant reduction in cell proliferation compared with monotherapy in human PDAC cells. MEKi with CDK4/6i reduces tumor cell proliferation by promoting senescence-mediated growth arrest, independent of apoptosis in vitro. We show that combined MEKi and CDK4/6i treatment attenuates tumor growth in xenograft models of PDAC and improves overall survival over 200% compared with treatment with vehicle or individual agents alone in Ptf1acre/+;LSL-KRASG12D/+;Tgfbr2flox/flox (PKT) mice. Histologic analysis of PKT tumor lysates reveal a significant decrease in markers of cell proliferation and an increase in senescence-associated markers without any significant change in apoptosis. These results demonstrate that combined targeting of both MEK and CDK4/6 represents a novel therapeutic strategy to synergistically reduce tumor growth through induction of cellular senescence in PDAC.

Weight of PKT mice during treatment regimen.

Primary antibodies used for immunohistochemistry and Western blot analysis.

Supplementary Figure Legends (S1-S3)

Combined Src and EGFR inhibition decreases collagen I content in PANC1 orthotopic xenograft models of PDAC.

Supplementary Tables S1-S3

Supplementary Figures

This study aims to determine postoperative outcomes and readmissions in pediatric cholecystectomy with routine intraoperative cholangiogram (IOC) utilization.The Nationwide Readmissions Database 2010-2014 was queried for all pediatric cholecystectomies. A propensity score-matched analysis (PSMA) with over 30 covariates was performed between cholecystectomy alone (CCY) versus those with routine IOC (CCY + IOC, no biliary obstruction, dilatation, or pancreatitis). χ34,390 cholecystectomies were performed: 92% were laparoscopic, most were teenage females (75%, 15 years [13-17]) and did not undergo IOC (75%). Postoperative mortality rate was 0.1%. The PSMA cohort comprised of 1412 CCY and 1453 CCY + IOC. Patients with CCY alone had higher rates of 30-day (7% vs 5%), 1-year readmissions (13% vs 11%) and had higher rates of overall complications (22% vs 12%) compared with CCY + IOC, all p 0.05. Although uncommon, bile duct injuries were more prevalent in CCY (2% vs 0%, p 0.001), while there was no difference in readmissions for retained stones. Resource utilization was increased in CCY patients, likely due to increased complication rates.This nationwide PSMA suggests pediatric CCY with routine IOC is associated with decreased readmissions, overall resource utilization, complications, and bile duct injuries.Retrospective Comparative Study.Level III.

This study aims to analyze the relative risks for total thyroidectomies by comparing complication rates for total versus partial thyroidectomy in the pediatric population.We queried the Kids' Inpatient Database (KID) 1997-2012 for all cases of total (n = 3253) or partial (n = 2380) thyroidectomy. We then designed a propensity score matching model and compared total versus partial thyroidectomy based on surgical complications and outcomes.In our cohort, the median age was 16 years and 79% were females. Those treated at a specialty pediatric hospital or pediatric unit in a general hospital comprised 73% of all patients. The most common indications for surgery were malignancy (46%) and goiter (42%). The most common complications were hypocalcemia and nerve injury with an unweighted incidence of 9% (n = 174) and 3% (n = 57) respectively. When compared to partial thyroidectomy, total thyroidectomy was associated with increased rates of postoperative complications. Additionally, the median length of stay was significantly higher for total thyroidectomy patients.This is the largest analysis to date comparing outcomes for total versus partial thyroidectomy in the pediatric population. Surgeons should consider the increased rates of hypocalcemia and nerve injury complications when selecting total compared to partial thyroidectomy in children.

Introduction: Surgery remains an important treatment modality for the management of pediatric Crohn's disease (CD). The objective of this study was to perform a comparative analysis of open right h...

The purpose of this study is to identify determinants of mortality and hospital readmission in infants born with esophageal atresia ± tracheoesophageal fistula.The Nationwide Readmissions Database (2010-2014) was queried for newborns with a diagnosis of esophageal atresia. Outcomes included mortality and readmissions at 30-day and 1-year.3157 patients were identified, of which 54% were male. 81% had an additional congenital anomaly, and 35% had VACTERL association. Overall mortality at index hospitalization was 11% (n = 360) and was significantly higher with additional congenital anomalies (13%), VACTERL (19%), and Spitz classification II/III (18%) vs. isolated esophageal atresia/tracheoesophageal fistula (4%), all p 0.001. After esophageal atresia repair (n = 2179), 10% (n = 212) were readmitted within 30 days and 26% (n = 563) within 1 year, with 17% admitted to different hospitals. Common diagnoses during readmission were GERD (54%), infections (42%), failure to thrive (17%), tracheomalacia (14%), and esophageal stricture (10%). Unplanned readmissions accounted for 85% of readmissions. A large number underwent operative procedures, most commonly esophageal dilation (17%) and fundoplication/gastrostomy (12%).Our study has uncovered a high likelihood of complications and unplanned readmission within the first year of life for newborns with esophageal atresia. Coordinated multidisciplinary care may help to decrease unnecessary readmissions and improve outcomes in this vulnerable population.Retrospective comparative analysis.Level III.

Lack of durable response to cytotoxic chemotherapy is a major contributor to the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder the delivery of chemotherapeutic drugs into PDAC tumors and mediate resistance to therapy. Previously, we have shown that STAT3 is a key biomarker of therapeutic resistance to gemcitabine treatment in PDAC, which can be overcome by combined inhibition of the Src and EGFR pathways. Although it is well-established that concurrent EGFR and Src inhibition exert these antineoplastic properties through direct inhibition of mitogenic pathways in tumor cells, the influence of this combined therapy on stromal constituents in PDAC tumors remains unknown. In this study, we demonstrate in both orthotopic tumor xenograft and Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mouse models that concurrent EGFR and Src inhibition abrogates STAT3 activation, increases microvessel density, and prevents tissue fibrosis in vivo. Furthermore, the stromal changes induced by parallel EGFR and Src pathway inhibition resulted in improved overall survival in PKT mice when combined with gemcitabine. As a phase I clinical trial utilizing concurrent EGFR and Src inhibition with gemcitabine has recently concluded, these data provide timely translational insight into the novel mechanism of action of this regimen and expand our understanding into the phenomenon of stromal-mediated therapeutic resistance. Implications: These findings demonstrate that Src/EGFR inhibition targets STAT3, remodels the tumor stroma, and results in enhanced delivery of gemcitabine to improve overall survival in a mouse model of PDAC.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality following distal pancreatectomy (DP). However, the influence of operative technique on VTE risk after DP is unknown. The purpose of this study was to examine the association between the MIS technique versus the open technique and the development of postoperative VTE after DP. Patients who underwent DP from 2014 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program pancreas-specific database. Multivariable logistic regression was then used to identify independent associations with the development of postoperative VTE after DP. A total of 3558 patients underwent DP during this time period. Of these cases, 47.8% (n = 1702) were performed via the MIS approach. After adjusting for significant covariates, the MIS approach was independently associated with the development of any VTE (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06–2.40; p = 0.025), as well as increasing the risk of developing a postdischarge VTE (OR 1.80, 95% CI 1.05–3.08; p = 0.033) when compared with the open approach. There was an association between VTE and the development of numerous postoperative complications, including pneumonia, unplanned intubation, need for prolonged mechanical ventilation, and cardiac arrest. Compared with the open approach, the MIS approach is associated with higher rates of postoperative VTE in patients undergoing DP. The majority of these events are diagnosed after hospital discharge.

Background Conjoined twins are rare developmental anomalies. There is a paucity of literature other than case reports and small case series. The aim of this study was to examine national outcomes and identify predictors of mortality in newborn conjoined twins. Methods We reviewed data on newborn conjoined twins from the Kids' Inpatient Database (1997–2012). Results A total of 240 patients were identified for a nationally weighted incidence of 1 per 100,000 live births. The majority of conjoined twins were female (n = 190 [81%]). The most commonly associated anomalies were cardiac (n = 87 [36%]), gastrointestinal (n = 41 [17%]), and abdominal wall (n = 32 [13%]) defects. Fifty-six (23%) patients underwent operative procedures, including 28 (12%) neonatal separation surgeries. The overall mortality rate was 61%; most deaths occurred within 24 hours (99 of 146 [68%]) to 48 hours (129 of 146 [88%]) after birth. Mortality was higher in female compared with male children (66% vs 38%, P = .025), premature compared with full-term children (72% vs 44%, P = .007), and in children with extremely low birth weight (95% vs 59%, P = .002). Congenital diaphragmatic hernias were seen in 15 (6%) patients and were uniformly fatal (100% vs 58%, P = .029). Mortality was highest in hospitals not designated as children’s hospitals (72%) compared with children’s hospitals (44%) (P = .007). Conclusion Conjoined twins are rare anomalies who are susceptible to extremely high perinatal mortality, especially in female children, those who are premature, or those who have low birth weight. These data support caring for these complex patients at hospitals equipped to care for this fragile population.

The purpose of this study was to identify the risk factors for hospital readmission for child maltreatment after trauma, including admissions across different hospitals nationwide. The Nationwide Readmissions Database for 2010–2014 was queried for all patients younger than 18 years admitted for trauma. The primary outcome was readmission for child maltreatment. The secondary outcome was readmission for maltreatment presenting to a hospital different than the index admission hospital. A subgroup analysis was performed on patients without a diagnosis of maltreatment during the index admission. Multivariable logistic regression was performed for each outcome. There were 608,744 admissions identified and 44,569 (7.32%) involved maltreatment at the index admission. Readmission for maltreatment was found in 1,948 (0.32%) patients and 368 (18.89%) presented to a different hospital. The highest risk for readmission for maltreatment was found in patients with maltreatment identified at the index admission (odds ratios (OR) 9.48 [8.35–10.76]). The strongest risk factor for presentation to a different hospital was found with the lowest median household income quartile (OR 3.50 [2.63–4.67]). The subgroup analysis identified 647 (0.11%) children with readmission for maltreatment that was missed during the index admission. The strongest risk factor for this outcome was Injury Severity Score > 15 (OR 3.29 [2.68–4.03]). This study demonstrates that a significant portion of admissions for trauma in children and teenagers could be misrepresented as not involving maltreatment. These index admissions could be the only chance for intervention for child maltreatment. Identifying these at-risk individuals is critical to prevention efforts.

The purpose of this study was to stratify fractures associated with child abuse in relation to the child's age.The Kids' Inpatient Database (1997-2012) was queried for all patients (18 years old) with a diagnosis of fracture and child abuse. The primary outcome was age-related determinants of fracture distribution. Chi-squared analysis was used for statistical analysis where appropriate, with significance set at p 0.05.More than 39,000 children were admitted for child abuse, and 26% sustained fractures. Most were infants (median age 0 year [IQR 0-1]). 28% sustained multiple fractures, and 27% had skull fractures. By age, infants had the highest rate of multiple fractures (33% vs 16% 1-4 years), and the highest rate of closed skull fractures (33% vs 21% ages 1-4), while adolescents had more facial fractures (43% vs 11% ages 9-12), all p 0.001. Multiple rib fractures were more commonly seen in infants (28% vs 8% ages 1-4), while children 5-8 years had the highest rates of clavicular fractures (7% vs 3% in infants), all p 0.001.Age-related fracture patterns exist and may be due to changing mechanism of abuse as a child grows. These age-related fracture patterns can help aid in healthcare detection of child abuse in hopes to thwart further abuse.Retrospective comparative study.Level III.

The dogma of early inguinal hernia repair in infants, especially those born prematurely, has dominated clinical practice owing to reports of a high frequency of incarceration and significant complications associated with untreated inguinal hernias. We aim to evaluate the frequency of complications after discharge with delayed surgery for inguinal hernia repair.The Nationwide Readmissions Database (2010-2014) was queried to identify infants diagnosed with inguinal hernia. We compared the frequency and characteristics of inguinal hernia repair performed during the index admission, discharge from the index admission without hernia repair, and unplanned readmissions.We identified 33,530 infants (16,624 preterm and 16,906 full-term) diagnosed with an inguinal hernia during an index admission. For those infants diagnosed with an inguinal hernia at birth, inguinal hernia repair was performed during the birth admission for only a minority of both preterm (35%) and full-term infants (18%; P.001). Of the infants discharged without hernia repair, 15% required nonelective readmission up to 1 year later, but only 2% of preterm and 1% of full-term infants actually underwent inguinal hernia repair during these unplanned readmissions. None of the readmitted infants underwent additional procedures suggestive of a strangulated hernia.Complications among infants awaiting inguinal hernia repair may be substantially less common than previously reported, and the occurrence of significant associated morbidity is quite rare.

Kasai portoenterostomy (KPE) remains the first-line operation for patients with biliary atresia (BA), but ultimately fails in up to 60% of cases. This study sought to identify factors contributing to hospital readmission and early liver transplant.The Nationwide Readmissions Database from 2010 to 2014 was used to identify patients with BA who underwent KPE on index admission. Patient factors, hospital characteristics, and complications of BA were compared by readmission rates and rate of liver transplant within 1 y. The results were weighted for national estimates.Nine hundred and sixty three patients were identified. The readmission rate within 30-d was 36% (n = 346) and within 1-y was 67% (n = 647). Only 9% (n = 90) received a liver transplant within a year. The most common complications after KPE were cholangitis in 58%, decompensated cirrhosis in 54%, and recurrent jaundice in 34%. Male patients (OR 1.5, P = 0.02) with comorbid gastrointestinal anomalies (OR 2.1, P 0.01) from lower income households (OR 4.6, P 0.01) and early development of cirrhosis (OR 3.0, P 0.01) were more likely to be readmitted. Liver transplant was more common in men (OR 4.0, P 0.01) and those from lower income households (OR 5.2, P 0.01) with decompensated cirrhosis (OR 8.6, P 0.01), cholangitis (OR 5.0, P 0.01), or sepsis (OR 5.7, P 0.01) on index admission.This is the first nationwide study to evaluate readmissions in patients with BA undergoing KPE. Although KPE is a lifesaving procedure, hospital readmission rates are high and complications are common. Cholangitis, early progression of cirrhosis, and infections are highly associated with readmission and failure of KPE.

Recurrent intussusception following successful nonoperative reduction has previously been reported with a frequency of 8%-12% based on data from individual institutions. Meanwhile, the timing of discharge after successful reduction continues to be debated. Here, we evaluate readmissions for recurrent intussusception in young children using a large-scale national database.The National Readmissions Database (2010-2014) was queried to identify young children (age 5 years) diagnosed with intussusception. We compared procedures performed during the index admission and frequency of readmissions for recurrent intussusception. Results were weighted for national estimates.We identified 8289 children diagnosed with intussusception during an index admission. These patients received definitive treatment with nonoperative reduction alone (43%), surgical reduction (42%), or bowel resection (15%). Readmission for recurrent intussusception was required for 3.7% of patients managed with nonoperative reduction alone, 2.3% of patients that underwent surgical reduction, and 0% of those that underwent bowel resection. Median time to readmission was 4 days after nonoperative reduction, and only 1.5% of these patients experienced recurrence within 48 h of discharge.Recurrent intussusception may be substantially less common than previously reported. Our findings support the practice of discharge shortly after successful nonoperative reduction.Retrospective, prognosis study.III.

No nationwide studies on hospital readmissions exist for children who have undergone pull-through operations for Hirschsprung disease. The study aim is to identify determinants of postoperative discharge outcomes and hospital readmissions in children with Hirschsprung disease.The Nationwide Readmissions Database for 2010-2014 was queried for children (18yo) with Hirschsprung disease and whom had undergone pull-through procedure, utilizing ICD-9 codes 751.3 and 48.40-69, respectively. Outcomes included complications and readmissions at 30-day and 1-year. Results were weighted for national estimates.The cohort consisted of 3635 patients, 75% male and 79% 1 year of age. Readmission rates at 30 days and 1-year were 20% and 36%, respectively. Overall, the most common diagnoses for readmission were gastrointestinal disorders (46%) and infections (39%). All age groups had a ≥ 10% readmission rate for gastrointestinal disorders. Infants were more likely to be admitted for enterocolitis and infections (16% and 15%), while children (1-6 years old) were most commonly readmitted for electrolyte disturbances (12%). Total hospitalization cost was over $162 million with $24 million from readmissions.Pull-through procedure for Hirschsprung disease is associated with high readmissions and associated economic burden. Age specific interventions to prevent unnecessary readmissions could improve outcomes and curtail healthcare spending.Retrospective Comparative Analysis.Level III.

Pediatric firearm injury is a national crisis that inflicts significant trauma. No studies have captured risk factors for readmissions after firearm injury, including cost analysis.Nationwide Readmissions Database (2010-2014) was queried for patients18 years admitted after acute firearm injury. Outcomes included mortality, length of stay, hospital costs, and readmission rates (30-day and 1-year). Multivariable logistic regression identified risk factors, significance set at p 0.05.There were 13,596 children admitted for firearm injury. Mortality rate was 6% (n = 797). Self-inflicted injury was the most lethal (37%, n = 218) followed by unintentional (5%, n = 186), and assault (4%, n = 340), all p 0.01. Readmission rates at 30 days and 1-year were 6% (12% to different hospital) and 12% (19% to different hospital), respectively. Medicaid patients were more frequently readmitted to the index hospital, whereas self-pay and/or high income were readmitted to a different hospital. The total hospitalizations cost was over $382 million, with $5.4 million due to readmission to a different hospital.While guns cause significant morbidity, disability, and premature mortality in children, they also have a substantial economic impact. This study quantifies the previously unreported national burden of readmission costs and discontinuity of care for this preventable public health crisis.Retrospective Comparative Study.Level III.

BACKGROUND: Laparoscopic approach for the surgical management of familial adenomatous polyposis (FAP) has become increasingly common for pediatric patients. The purpose of this study was to compare short-term outcomes and resource utilization between open and laparoscopic surgery for prophylactic colectomy in children with FAP. METHODS: The Kids’ Inpatient Database (2009 and 2012) was analyzed for children (age ≤20 years) with FAP that underwent prophylactic total colectomy or proctocolectomy. Patient demographics, treating hospital characteristics, hospital charges, and short-term outcomes were compared according to the surgical technique utilized (open versus laparoscopic). RESULTS: Overall, we identified 216 patients with FAP that underwent elective total colectomy, of which 95 cases were performed by open surgery and 121 were done laparoscopically. The majority of patients were treated at large, not-for-profit, urban teaching hospitals, and the median age was equal (16 years) in both groups. Complications that were more common for open procedures included accidental perforation or hemorrhage (4% vs. 0%, P=0.023), reopening of surgical site (3% vs. 0%, P=0.049), and pneumonia (3% vs. 0%, P=0.049). Simultaneous proctectomy was performed more commonly in the open cohort (91% vs. 71%, P

BACKGROUND: Ulcerative colitis (UC) is an aggressive disease in the pediatric population and a cause of significant, lifelong morbidity. The aim of this study is to compare surgical complications in pediatric patients undergoing laparoscopic vs. open surgical treatment for UC. METHODS: We queried the Kids’ Inpatient Database (KID) for all cases of UC undergoing surgical treatment in 2009 and 2012. We identified patients who received total colectomy without proctectomy (n=413) or total proctocolectomy (n=196) and performed univariate and multivariate analyses comparing laparoscopic vs. open procedures. RESULTS: In pediatric UC patients undergoing total colectomy without proctectomy, open procedures were associated with more complications than laparoscopic, including fluid and electrolyte disorders (40% vs. 28%), surgical wound dehiscence (6% vs. 2%), septicemia (18% vs. 2%), and gastrointestinal disorders (16% vs. 7%) among others, all P2.4; all P

Hospital readmission in trauma patients is associated with significant morbidity and increased healthcare costs. There is limited published data on early hospital readmission in pediatric trauma patients. As presently in healthcare outcomes and readmissions rates are increasingly used as hospital quality indicators, it is paramount to recognize risk factors for readmission. We sought to identify national readmission rates in pediatric assault victims and identify the most common readmission diagnoses among these patients.The Nationwide Readmission Database (NRD) for 2013 was queried for all patients under 18years of age with a non-elective admission with an E-code that is designed as assault using National Trauma Data Bank Standards. Multivariate logistic regression was implemented using 18 variables to determine the odds ratios (OR) for non-elective readmission within 30-days.There were 4050 pediatric victims of assault and 92 (2.27%) died during the initial admission. Of the surviving patients 128 (3.23%) were readmitted within 30days. Of these readmitted patients 24 (18.75%) were readmitted to a different hospital and 31 (24.22%) were readmitted for repeated assault. The variables associated with the highest risk for non-elective readmission within 30-days were: length of stay (LOS)7days (OR 3.028, p0.01, 95% CI 1.67-5.50), psychoses (OR 3.719, p0.01, 95% CI 1.70-8.17), and weight loss (OR 4.408, p0.01, 95% CI 1.92-10.10). The most common readmission diagnosis groups were bipolar disorders (8.2%), post-operative, posttraumatic, or other device infections (6.2%), or major depressive disorders and other/unspecified psychoses (5.2%).Readmission after pediatric assault represents a significant resource burden and almost a quarter of those patients are readmitted after a repeated assault. Understanding risk factors and reasons for readmission in pediatric trauma assault victims can improve discharge planning, family education, and outpatient support, thereby decreasing overall costs and resource burden. Psychoses, weight loss, and prolonged hospitalization are independent prognostic indicators of readmission in pediatric assault patients.Level IV - Prognostic and Epidemiological - Retrospective Study.

Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation of cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by the gene CDKN2A, is a potent inhibitor of CDK4/6 and serves as a critical checkpoint of cell proliferation. Mutations in and subsequent loss of the p16 gene occur in PDAC at a rate higher than that reported in any other tumor type and results in Rb inactivation and unrestricted cellular growth. Therefore, strategies targeting downstream RAS pathway effectors combined with CDK4/6 inhibition (CDK4/6i) may have the potential to improve outcomes in this disease. Herein, we show that expression of p16 is markedly reduced in PDAC tumors compared with normal pancreatic or pre-neoplastic tissues. Combined MEK inhibition (MEKi) and CDK4/6i results in sustained downregulation of both ERK and Rb phosphorylation and a significant reduction in cell proliferation compared with monotherapy in human PDAC cells. MEKi with CDK4/6i reduces tumor cell proliferation by promoting senescence-mediated growth arrest, independent of apoptosis in vitro. We show that combined MEKi and CDK4/6i treatment attenuates tumor growth in xenograft models of PDAC and improves overall survival over 200% compared with treatment with vehicle or individual agents alone in Ptf1acre/+;LSL-KRASG12D/+;Tgfbr2flox/flox (PKT) mice. Histologic analysis of PKT tumor lysates reveal a significant decrease in markers of cell proliferation and an increase in senescence-associated markers without any significant change in apoptosis. These results demonstrate that combined targeting of both MEK and CDK4/6 represents a novel therapeutic strategy to synergistically reduce tumor growth through induction of cellular senescence in PDAC.

PURPOSE: Child abuse is a national, often hidden, epidemic. The study objective was to determine at-risk populations that have been previously hospitalized prior to their admission for child abuse. METHODS: The Nationwide Readmissions Database (NRD) was queried for all children hospitalized for abuse. Outcomes were previous admissions and diagnoses. χ(2) analysis was used; significance equals p < 0.05. RESULTS: 31,153 children were hospitalized for abuse (half owing to physical abuse) during the study period. 11% (n = 3487) of these children had previous admissions (one in three to a different hospital), while 3% (n = 1069) had multiple hospitalizations. 60% of prior admissions had chronic conditions, and 12% had traumatic injuries. Children with chronic conditions were more likely to have sexual abuse (89% vs. 57%, p < 0. 001) and emotional abuse (75% vs. 60%, p < 0. 01). 25% of chronic diagnoses were psychiatric, who were also more likely to have sexual and emotional abuse (47% vs. 5.5% and 10% vs. 1%, all p < 0. 001). CONCLUSION: This study uncovers a hidden population of children with past admissions for chronic conditions, especially psychiatric diagnoses that are significantly associated with certain types of abuse. Improved measures to accurately identify at-risk children must be developed to prevent future childhood abuse and trauma.

The purpose of this study was to identify the risk factors for hospital readmission for child maltreatment after trauma, including admissions across different hospitals nationwide. The Nationwide Readmissions Database for 2010-2014 was queried for all patients younger than 18 years admitted for trauma. The primary outcome was readmission for child maltreatment. The secondary outcome was readmission for maltreatment presenting to a hospital different than the index admission hospital. A subgroup analysis was performed on patients without a diagnosis of maltreatment during the index admission. Multivariable logistic regression was performed for each outcome. There were 608,744 admissions identified and 44,569 (7.32%) involved maltreatment at the index admission. Readmission for maltreatment was found in 1,948 (0.32%) patients and 368 (18.89%) presented to a different hospital. The highest risk for readmission for maltreatment was found in patients with maltreatment identified at the index admission (odds ratios (OR) 9.48 [8.35-10.76]). The strongest risk factor for presentation to a different hospital was found with the lowest median household income quartile (OR 3.50 [2.63-4.67]). The subgroup analysis identified 647 (0.11%) children with readmission for maltreatment that was missed during the index admission. The strongest risk factor for this outcome was Injury Severity Score15 (OR 3.29 [2.68-4.03]). This study demonstrates that a significant portion of admissions for trauma in children and teenagers could be misrepresented as not involving maltreatment. These index admissions could be the only chance for intervention for child maltreatment. Identifying these at-risk individuals is critical to prevention efforts.

Importance Although margin-negative (R0) resection is the gold standard for surgical management of localized pancreatic ductal adenocarcinoma (PDAC), the question of how to manage the patient with a microscopically positive intraoperative neck margin (IONM) during pancreaticoduodenectomy remains controversial. Observations In the absence of randomized clinical trials, we critically evaluated high-quality retrospective studies examining the oncologic utility of re-resecting positive IONMs during pancreaticoduodenectomy for PDAC (2000-2019). Several studies have concluded that additional pancreatic resection to achieve an R0 margin in IONM-positive cases does not influence survival. The largest is a multi-institutional study of 1399 patients undergoing pancreaticoduodenectomy, which demonstrated that in comparison with patients undergoing R0 resection (n = 1196; median survival, 21 months), those with either final R1 resections (n = 131) or undergoing margin conversion from IONM-positive to R0 resection on permanent section (n = 72) demonstrated similar median survival times (13.7 and 11.9 months, respectively). Conversely, recent reports suggest that the conversion of IONM to R0 resection with additional resection or even total pancreatectomy may be associated with improved survival. The discordance between these conflicting studies could be explained in part by the influence of biologic and physiologic selection on the association of IONM re-resection and survival. Since most studies did not include patients receiving modern combination chemotherapy regimens, the intersection between margin status, tumor biology, and chemoresponsiveness remains unclear. Furthermore, there are no dedicated data to guide surgical management in IONM-positive pancreaticoduodenectomy for patients receiving neoadjuvant chemotherapy. Conclusions and Relevance Although data regarding the oncologic utility of additional resection to achieve a tumor-free margin following initial IONM positivity during pancreaticoduodenectomy for PDAC are conflicting, they suggest that IONM positivity may be a surrogate for biologic aggressiveness that is unlikely to be mitigated by the extent of surgical resection. The complex relationship between margin status and chemoresponsiveness warrants exploration in studies including patients receiving increasingly effective neoadjuvant chemotherapy.

Gastrointestinal stromal tumors are exceedingly rare tumors in the pediatric population, as a result many clinicians either may never see this diagnosis or will encounter it only a few times throughout their careers. It is imperative in the pediatric population to follow appropriate steps to ensure a swift diagnosis and referral to specialized centers that are equipped with the multidisciplinary teams accustomed to treating rare diseases. This review aims to discuss the most recent data available on the diagnostic modalities utilized in cases of suspected Pediatric GIST.

Gastrointestinal stromal tumors (GIST) are exceedingly rare tumors in the pediatric population. As a result, many clinicians either may never see this diagnosis or will encounter it only a few times throughout their careers. Additionally, the more we discover about this disease, it becomes evident that it represents a distinct clinical entity from adult GIST. Many of the treatments and strategies used to combat the adult tumor are either ineffective or may be harmful to the pediatric population with this disease. The unique tumor biology found in pediatric GIST necessitates unique approaches and treatment strategies in order to achieve the best clinical outcome. This review aims to discuss the most recent data available on the different therapeutic modalities utilized in cases of Pediatric GIST.

Experimental infections and field-collected lizards were used to investigate issues of transmission, host specificity, and seasonal occurrence in the nematode Cyrtosomum penneri (Cosmocercoidea: Atractidae). Anolis sagrei (87 males, 42 females) were captured from the Florida Southern College campus, Polk County, Florida, from October 2010 to September 2011, and 8,803 C. penneri were collected from their intestines. During the breeding season all sexually mature (SVL ≥ 34 mm) A. sagrei were infected, whereas juvenile lizards (SVL34 mm) were never infected. Experimental infections, using A. sagrei , found that worms were transferred to new hosts venereally, but not during oral exposures. Mating trials confirmed that worms were consistently transferred between hosts during copulation under natural conditions. Experimental exposures found that land snails and crickets do not serve as transport or intermediate hosts, which supports the idea that C. penneri is transferred only during host copulation. Experimental infections to test host specificity in C. penneri successfully infected A. sagrei , Hemidactylus turcicus , and Sceloporus undulatus , but not Anolis carolinensis or Plestiodon inexpectatus. Overall, this is the first study to fully elucidate the life cycle of any atractid nematode, and we suggest a venereal route of transmission for all atractid worms that infect reptilian hosts. Our findings also have implications for the host's reproductive and behavioral biology, e.g., support for covert or satellite males in the A. sagrei mating system.