Post-Procedural Opioid Prescribing in Children: A Survey of the American Academy of Pediatrics.

INTRODUCTION: North America is in the midst of an opioid epidemic. The role of pediatric surgeons and other procedural specialists in this public health crisis remains unclear. There is likely considerable variation in the use of opioid and non-opioid analgesics, but the spectrum of practice is still uncertain. METHODS: We performed an online survey in July 2018 of the 2086 pediatric surgeons and proceduralists who were active members in the American Academy of Pediatrics. The survey inquired about practice environment, use of opioid and non-opioid pain medications, and attitudes towards the opioid epidemic. RESULTS: 178 specialists completed the survey for a response rate of 8.5%. Most respondents utilize oral acetaminophen (86%) and ibuprofen (80%) after procedures >75% of the time. Self-reported opioid prescribing increases with age after both outpatient and inpatient procedures (P < 0.001). Pediatric general surgeons prescribe opioids less frequently than other specialists, particularly after inpatient procedures. The majority of respondents (81%) believe that the opioid epidemic is a major problem but only 31% indicated that they have a major role to play. CONCLUSIONS: There is significant variation in opioid prescribing patterns as reported by pediatric surgeons and proceduralists. Guidelines are needed to standardize the use of non-opioid analgesics and decrease reliance on opioids for outpatient and inpatient procedures.

Evaluation of Rhodiola crenulata on growth and metabolism of NB-1691, an MYCN-amplified neuroblastoma cell line.

Outcomes of children with high grade neuroblastoma remain poor despite multi-agent chemotherapy regimens. Rhodiola crenulata extracts display anti-neoplastic properties against several cancers including breast cancer, melanoma, and glioblastoma. In this study, we evaluated the anti-neoplastic potential of Rhodiola crenulata extracts on human neuroblastoma cells. Through this work, cell viability and proliferation were evaluated following treatments with ethanol (vehicle control) or Rhodiola crenulata extract in neuroblastoma, NB-1691 or SK-N-AS cells, in vitro. HIF-1 transcriptional activity was evaluated using a dual luciferase assay. Quantitative real-time polymerase chain reaction was utilized to assess the expression of HIF-1 targets. Selected metabolic intermediates were evaluated for their ability to rescue cells from Rhodiola crenulata extract-induced death. Lactate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase activities and NAD+/NADH levels were assayed in vehicle and Rhodiola crenulata extract-treated cells. The effects of Rhodiola crenulata extracts on metabolism were assessed by respirometry and metabolic phenotyping/fingerprinting. Our results revealed striking cytotoxic effects upon Rhodiola crenulata extract treatment, especially prominent in NB-1691 cells. As a greater response was observed in NB-1691 cells therefore it was used for remaining experiments. Upon Rhodiola crenulata extract treatment, HIF-1 transcriptional activity was increased. This increase in activity correlated with changes in HIF-1 targets involved in cellular metabolism. Serendipitously, we observed that addition of pyruvate protected against the cytotoxic effects of Rhodiola crenulata extracts. Therefore, we focused on the metabolic effects of Rhodiola crenulata extracts on NB-1691 cells. We observed that while the activities of pyruvate kinase and pyruvate dehydrogenase activities were increased, the activity of lactate dehydrogenase activity was decreased upon Rhodiola crenulata extract treatment. We also noted a decline in the total NAD pool following Rhodiola crenulata extract treatment. This correlated with decreased cellular respiration and suppressed utilization of carbon substrates. Through this work, we observed significant cytotoxic effects of Rhodiola crenulata extract treatment upon treatment on NB-1691 cells, a human neuroblastoma cell line with MYCN amplification. Our studies suggest that these cytotoxic effects could be secondary to metabolic effect induced by treatment with Rhodiola crenulata extract.

Pediatric Surgery from the Roads Less Traveled: Challenges, Communication, and Collaboration from a Community Nonteaching Hospital.

Unique challenges face pediatric surgeons at community-based nonteaching hospitals. Communication and collaboration among and between healthcare providers, hospital administrators, and quaternary referral programs is crucial for the success of these smaller hospitals as they care for children.

The impact of vesicoureteral reflux treatment on the incidence of urinary tract infection.

Vesicoureteral reflux (VUR) is a heterogeneous disease and its management remains one of the most controversial topics in pediatrics. Management options include surveillance, antibiotics, and surgery. The approval of dextranomer/hyaluronic acid (DHA) as a bulking agent by the Food and Drug Administration was followed by wide acceptance of endoscopic techniques as a major tool in the management of reflux. Pyelonephritis rather than VUR is the most common cause of kidney damage in children. It should be emphasized that the primary goal of diagnosing and treating VUR should be preventing this complication. There are no sufficient data in the literature to address the impact of the different treatment modalities on the incidence of febrile urinary tract infections (feb-UTIs) denoting pyelonephritis, with very few studies evaluating endoscopic treatment in light of this clear and well-defined outcome. The fact that we can correct the anatomy at the vesicoureteral junction with a simple and relatively safe outpatient procedure does not justify offering it to all patients. In this review, we attempt to critically evaluate the available literature pertaining to the impact of different treatment modalities on reducing the incidence of febrile UTIs and kidney damage, with a special emphasis on endoscopic treatment.

Missed opportunities in the treatment of pediatric appendicitis.

INTRODUCTION: This study sought to evaluate the outcomes of in-hospital delay and determine associated co-morbidities in the treatment of pediatric acute appendicitis. METHODS: This was a retrospective analysis of the national inpatient sample from 2000 to 2008. Immediate treatment was defined as treatment in hospital day 0 or 1. Delay in treatment was defined as treatment in hospital day 2 and beyond. RESULTS: During the study period, 683,016 pediatric appendicitis were identified. 17,737 (2.6%) experienced a delay in treatment. Multivariate analysis identified associated co-morbidities for delay in treatment: ALL (OR 12.84, CI 11.04-14.94), AML (OR 9.41, CI 7.58-11.68), neutropenia (OR 5.53, CI 4.60-6.65), and ovarian cyst without torsion (OR 3.17, CI 2.94-3.42). Surgical management included more than 13-fold increase in drainage procedures (5.5 vs. 0.4%), sixfold increase in cecectomy (1.2 vs. 0.2%), 14-fold increase in hemicolectomy (1.4 vs. 0.1%), 11-fold increase in small bowel laceration suture repair (1.1 vs. 0.1%), and 15-fold increase in small bowel resection (1.5 vs. 0.1%). CONCLUSIONS: In-hospital delay beyond 2 days is associated with significant negative outcomes with regard to complications, economic burden, and subsequent surgical management. Using the co-morbidity index, high-risk co-morbidities with associated delay in treatment were identified.

Is partial colectomy the operation of choice in pediatric Clostridium difficile colitis?

PURPOSE: This study examined the national trends in incidence and surgical management of pediatric Clostridium difficle colitis (CDC) hospitalizations. METHODS: This was a cross-sectional Nationwide Inpatient Sample (NIS) analysis of pediatric CDC from 2000 to 2008. Data analysis included patient demographics, procedures, length of stay (LOS), total hospital charges (THC), and in-hospital mortality. RESULTS: During the 9-year study period, the total number of CDC hospitalizations per year increased almost twofold, from 2,513 in 2000 to 4,817 in 2008. The rate per 100,000 discharges followed a similar trend, increasing from 38.08 in 2000 to 72.57 in 2008. Abdominal colectomy was performed in 0.35 %, with partial colectomy performed more often than total colectomy. Mortality, mean LOS, and mean THC were not statistically different between partial versus total colectomy. Children with ulcerative colitis were more likely to undergo total colectomy, (OR 35.700, CI 11.025-115.98, P < 0.001). Infants under the age of 1 year were less likely to undergo total colectomy (OR 0.568, 0.477-0.677, P < 0.001). CONCLUSION: Pediatric hospitalizations for CDC are on the rise. Partial colectomy is performed more often than total colectomy without statistical compromise of mortality, length of stay, and total hospital charges. Further studies are needed to determine the standard surgical management of pediatric CDC.

Subcutaneous Endoscopic-Assisted Ligation of the Internal Ring for Inguinal Hernia Repair in Neonates Under Spinal Anesthesia.

Introduction: While laparoscopy is now widely accepted for inguinal hernia repair in infants, it traditionally has required general anesthesia. We sought to evaluate the safety of laparoscopic inguinal hernia repair in infants under spinal anesthesia. Materials and Methods: We performed a retrospective cohort study of all inguinal hernia repairs at a single institution between December 2011 and June 2019 in patients younger than 6 months of age. Four groups were compared: laparoscopic under general anesthesia, laparoscopic with spinal anesthesia, open with spinal anesthesia, and open under general anesthesia. Main outcome measures include operative time, cost, and postoperative outcomes. These were assessed using Kruskal-Wallis median comparison. Results: Of the 226 patients meeting inclusion criteria, 54% (122/226) of patients underwent general anesthesia, while 46% (104/226) had spinal. When compared to general anesthesia, spinal anesthesia was associated with significantly shorter procedure times (P < .01) and lower cost (P < .01) for both open and laparoscopic approaches. Complications were few and underpowered to calculate significance across each group. Conclusions: Laparoscopic inguinal hernia repair can be safely performed in infants under spinal anesthesia without significant compromise of early perioperative outcomes. Advantages may include shorter procedure time and lower cost.

Surgeon perceptions of volume threshold and essential practices for pediatric thyroidectomy✰.

INTRODUCTION: The topics of sub-specialization and regionalization of care have garnered increased attention among pediatric surgeons. Thyroid surgeries are one such sub-specialty and are commonly concentrated within practices. A national survey was conducted examining current surgeon practices and beliefs surrounding pediatric thyroid surgery. METHODS: Non-resident members of the American Pediatric Surgical Association (APSA) were surveyed in October 2020. Respondents were stratified based on self-reported thyroid surgical experience. Those who performed thyroid surgery were asked about surgical technique and operative practices; those who did not were asked about referral patterns. All respondents were asked about perceptions surrounding the volume-outcome relationship for pediatric thyroid surgery. RESULTS: Among 1015 APSA members, 405 (40%) responded, with 79% (317/400) practicing at academic hospitals, 58% (232/401) practicing in major metropolitan area, and 41% (161/392) with over 10 years of attending pediatric surgery experience. Most respondents (88%, n = 356) agreed that thyroid surgery volume affects outcome, though wide variation was reported in the annual case threshold for "high volume" surgery. Eighty-four respondents (21%) reported performing ≥ 1 pediatric thyroid surgery in the past year. Of these, 82% routinely use recurrent laryngeal nerve monitoring, 32% routinely send hemithyroidectomy patients home the same day, and there was little consensus surrounding postoperative hypocalcemia management. The majority of respondents endorse performing thyroid procedures with a colleague. CONCLUSIONS: Pediatric thyroid surgery appears to be performed by a subset of active pediatric surgeons, most of whom endorse the use of a dual operating team. More evidence is needed to build consensus around additional perioperative practices.

Primary repair of facial dog bite injuries in children.

OBJECTIVES: The management of dog bite wounds is controversial, and current data on risk of infection are variable and inconsistent. Furthermore, the use of prophylactic or empiric antibiotics for the treatment of these wounds is debatable. We investigate the rate of wound infections and other complications after primary repair of pediatric facial dog bite injuries. METHODS: We reviewed 87 consecutive patients aged 18 years or younger who had facial dog bite injuries from January 2003 to December 2008. Variables examined were age, sex, setting of repair, number of sutures used for repair, whether surgical drains were used, and antibiotic administration. End points measured were incidence of wound infection, need for scar revision, and any wound complications. RESULTS: The mean age of patients was 6.8 years, and the majority were women (53%). All facial injuries were primarily repaired at the time of presentation either in the emergency department (ED; 46%), operating room (OR; 51%), or an outpatient setting (3%). All patients received an antibiotic course, none of the patients developed wound infection, and no subsequent scar revisions were performed. Three patients repaired in the OR underwent placement of a total of 4 closed-suction drains. The mean (SD) age of patients repaired in the OR was significantly younger than those repaired in the ED (5.7 [3.9] vs 8.0 [4.5] years, respectively; P < 0.01). The number of sutures used were greater for patients repaired in the OR than in the ED (66.4 [39.6] vs 21.7 [12.5], respectively; P < 0.01). CONCLUSIONS: Intuitively, younger patients and patients with greater severity injuries are more likely to undergo repair in the OR, and this was supported by our data. Overall, we found that primary repair of pediatric facial dog bite injuries, including complex soft-tissue injuries, is safe when performed in conjunction with antibiotic administration; however, further cross-specialty studies are needed to fully characterize these end points in a larger population.

Return of the Banana Knife: An Alternative Instrument for Laparoscopic Pyloromyotomy.

Background: When the disposable arthroscopic banana knife (Linvatec, Largo, FL) became unavailable, many pediatric surgeons adapted the use of spatula tip cautery for laparoscopic pyloromyotomy; however, reusable arthroscopic knives remain readily available and are well suited to the procedure. Methods: We compared laparoscopic pyloromyotomy with a reusable arthroscopic banana knife (Sklar, West Chester, PA; catalog no. 45-6050) to those using spatula tip cautery at a single institution between September 1, 2012, and December 31, 2019. Mann-Whitney U test was used to compare operative time, room time, and time to discharge between groups. Results: Overall, 109 patients underwent pyloromyotomy for hypertrophic pyloric stenosis during the study time period. Of these, 12 were open and one was undertaken with the Storz pyloromyotomy knife, so these were excluded. A total of 74 (77.1%) laparoscopic cases with spatula tip cautery and 22 (22.9%) with the banana knife were included. Mean age at the time of surgery was ∼37 days. The majority of patients in each group were white, male, and full term. The most common comorbid conditions were reactive airway disease and neonatal abstinence syndrome. There were no significant differences in operative time (P = .61), room time (P = .41), or time from surgery to discharge (P = .26) between procedures using the banana knife and those using the cautery spatula tip. There were no perforations or recurrences. Conclusion: Our findings suggest that the reusable banana knife is a safe and effective alternative to spatula tip cautery for laparoscopic pyloromyotomy, with no difference in operative time, time from surgery to discharge, or complications.

Defining the role of advanced care practitioners in pediatric surgery practice.

INTRODUCTION: The role of advanced care practitioners (ACPs) in pediatric surgery is increasingly important and not well described. METHODS: Electronic surveys were sent to pediatric surgery division chiefs within the Children's Hospital Association. RESULTS: We received 77/163 survey responses (47%). The median number of ACPs per service was 3.0 (range 0-35). ACP number correlated with inpatient census, surgeon number, case volume, trauma centers, intensive care unit status, and fellowship programs but not with presence of residents/hospitalists, hospital setting, or practice type. Nearly all programs incorporated nurse practitioners while almost half utilized physician assistants. Approximately one-third of ACPs were designated for subspecialties (35%) such as trauma and colorectal. Only 9% of centers had surgeon-specific ACPs. ACP responsibilities included both inpatient and outpatient tasks. Nearly all ACPs participated in procedures (89%), mostly bedside (80%). All ACPs worked daytime shifts, with less nights and weekends. Most ACPs billed for services (80%). Satisfaction with ACP coverage was widespread and did not correlate with ACP number. Most respondents felt that ACPs enhance, and not hinder, resident/fellow training (85%). CONCLUSION: ACPs are useful adjuncts in pediatric surgery. A better understanding of practice patterns may help optimize utilization to enhance patient care and can be used to advocate for appropriate resources.

Subspecialization in pediatric surgery: Results of a survey to the American Pediatric Surgical Association.

BACKGROUND: Current practice patterns and opinions regarding subspecialization within pediatric surgery are not well known. We aimed to characterize the prevalence of and attitudes surrounding subspecialization within pediatric surgery. METHODS: An anonymous survey regarding subspecialization was distributed to all nonresident members of the American Pediatric Surgical Association. RESULTS: Of 1118 surveys, we received 458 responses (41%). A majority of respondents labeled themselves 'general pediatric surgeons' (63%), while 34% considered themselves general surgeons with a specific clinical focus, and 3% reported practicing solely within a specific niche. Subspecialists commonly serve as consultants for relevant cases (52%). Common niches included oncology (10%) and anorectal malformations (9%). Subspecialists felt to be necessary included transplant (79%) and fetal (78%) surgeons. Opinions about subspecialization were variable: 41% felt subspecialization improves patient care while 39% believe it is detrimental to surgeon well-roundedness. Only 10% felt subspecialists should practice solely within their subspecialty. Practicing at an academic hospital or fellowship program correlated with subspecialization, while length of time in practice did not. CONCLUSION: While pediatric surgeons report that subspecialization may benefit patient care, concerns exist regarding the unfavorable effect it may have on the individual surgeon. A better understanding of how subspecialization affects quality and outcomes would help clarify its utility. TYPE OF STUDY: Review article. LEVEL OF EVIDENCE: Level V.

Clinical outcomes following identification of tip appendicitis on ultrasonography and CT scan.

BACKGROUND/PURPOSE: With recent improvements in imaging technology, subtler variations in the anatomy of the appendix can be appreciated. We hypothesized that radiographic findings of tip appendicitis may not correlate strongly with a pathologic diagnosis of appendicitis. METHODS: Our radiology database was searched for reports of a diagnosis of tip appendicitis between January 2013 and June 2017 for patients between the ages of 2 and 17. Retrospective chart review was performed for demographic and clinical data, including outcomes. For patients managed operatively, the pathology results were reviewed for evidence of acute appendicitis. Patients managed nonoperatively and those with negative pathology were considered to not have appendicitis. RESULTS: Fifty-five patients met inclusion criteria (31 boys and 24 girls); 46/55 patients with tip appendicitis on imaging ultimately did not have appendicitis. Twenty-one patients underwent appendectomy, and 9/21 had pathologic evidence of appendicitis. One patient had a ruptured appendix. No other pathology was identified in the negative appendectomies. Two patients managed nonoperatively required readmission, but not secondary to missed diagnosis of appendicitis. CONCLUSIONS: Ultrasound and CT findings of tip appendicitis may not accurately associate with a final diagnosis of acute appendicitis. Clinical judgment should ultimately dictate appropriate initial management, follow-up tests, and imaging. TYPE OF STUDY: Diagnostic Study. LEVEL OF EVIDENCE: Level III.

5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk).

A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure-activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.

Itk kinase inhibitors: initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead.

Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.

Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk).

A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK.