Peer Support to Promote Surgeon Well-being: The APSA Program Experience.

BACKGROUND: Peer support programs have evolved to train physicians to provide outreach and emotional first aid to their colleagues when they experience the inevitable challenge of a serious adverse event, whether or not it is related to a medical error. Most pediatric surgeons have experienced the trauma of a medical error, yet, in a survey of APSA membership, almost half said that no one reached out to them, and few were satisfied with their institution's response to the error. Thus, the APSA Wellness Committee developed an APSA-based peer support program to meet this need. METHODS: Peer supporters were nominated by fellow APSA members, and the group was vetted to ensure diversity in demographics, practice setting, and seniority. Formal virtual training was conducted before the program went live in 2020. Trained supporters were surveyed 6 months after the program launched to evaluate their experiences with providing peer support. RESULTS: 15 referrals were made in the first year, 60 % of which were self-initiated. Most referrals were for distress related to adverse events or toxic work environments (33 % each). While only about 25 % of trained supporters had provided formal support through the APSA program, more than 80 % reported using the skills to support colleagues and trainees within their own institutions. CONCLUSION: Our experience in the first year of the APSA peer support program demonstrates the feasibility of building and maintaining a national program to provide emotional first aid by a professional society to expand the safety net for surgeons who are suffering.

Preoperative platelet transfusions: A retrospective review of pediatric patients with thrombocytopenia, 2011-2016.

BACKGROUND: Thrombocytopenia is a common perioperative clinical problem and preoperative platelet transfusion prior to surgery is standard practice. Recent platelet trials and literature reviews have found no association between platelet count and bleeding incidence except when platelet count is extremely low. Our aim was to evaluate the bleeding risk and the overall platelet transfusion management among pediatric patients with severe thrombocytopenia based on whether they were preoperatively transfused versus transfused at time of incision. METHODS: This is a retrospective analysis of pediatric patients with a platelet count ≤50 × 109/L in the 12 h prior to surgery at a single tertiary pediatric hospital from 2011 to 2016. Eligible patients were ≤21 years old. Patients with necrotizing enterocolitis and neonates were excluded. The primary outcome was postoperative bleeding complications. Additional outcomes were preoperative platelet change and weight adjusted transfusion volumes. RESULTS: A total of 37 patients were included in this analysis of which 29 (78%) received preoperative platelet transfusions within 12 h prior to surgery. No postoperative bleeding complications occurred 30 days after operation, regardless of preoperative transfusion status. There was no significant difference in platelet change by preoperative transfusion status and preoperative transfusion volume was a poor predictor of change in preoperative platelet count (crude: r2=0.19, age/gender adjusted: r2=0.48). CONCLUSION: Patients transfused at time of surgical procedure did not have an increased risk of bleeding over those preoperatively transfused. This finding is in agreement with previous studies in adult populations, supporting the safety of deferring platelet transfusions until the time of incision for thrombocytopenic pediatric surgical patients. LEVEL OF EVIDENCE: III.

Ventricular tachycardia converts to sinus rhythm after administration of propofol.

Ventricular tachycardia (VT) is a major contributor to sudden cardiac death, and pharmacologic treatment options beyond antiarrhythmics are limited. Emerging data suggest sympathetic blocking agents such as propofol are a potential management option for VT refractory to first line antiarrhythmics. Previous literature has described fixed-dose propofol boluses and continuous infusions to convert ventricular arrhythmias; however, to our knowledge, there are no reports of a weight-based dosing strategy for VT. We present the case of a patient with amiodarone-refractory VT who received a 1 mg/kg propofol bolus in preparation for cardioversion and subsequently converted to normal sinus rhythm. The patient stabilized following these interventions, transferred to a tertiary care facility, and was discharged home with an implantable cardioverter defibrillator.

Accidental trauma of infancy: emergency department evaluation and management.

The common mechanisms and injury patterns of accidental trauma in infants differ from those of older children and adults, with falls representing the most common etiology. While the evaluation of traumatic injury in infants should follow an algorithm similar to that used for adults, the unique pediatric physiologic response to trauma must be taken into consideration. In addition, the utility of certain imaging studies in these patients is highly case specific, particularly with minor head injuries. This supplement reviews the evaluation and management of infants with accidental traumatic injury, including the most common circumstances and pathophysiology of injury, the differential diagnosis of the infant trauma victim, and the workup and management of accidental injuries in this patient population.

Treatment of Hypothermic Cardiac Arrest in the Pediatric Drowning Victim, a Case Report, and Systematic Review.

OBJECTIVES: Drowning is the second leading cause of death in children. Extracorporeal membrane oxygenation (ECMO) has become the criterion standard therapy to resuscitate the hypothermic drowning victim in cardiac arrest. We present our own experience treating 5 children with hypothermic cardiac arrest in conjunction with a systematic review to analyze clinical features predictive of survival. METHODS: Our search resulted in 55 articles. Inclusion criteria were as follows: (1) younger than 18 years, (2) ECMO therapy, and (3) drowning. Ten articles met our inclusion criteria. We included studies using both central and peripheral ECMO and salt or fresh water submersions. We compared clinical features of survivors to nonsurvivors. RESULTS: A total of 29 patients from the 10 different studies met our criteria. Data analyzed included presenting cardiac rhythm, time to initiation of ECMO, submersion time, pH, potassium, lactate, duration of chest compressions, and survival. There was a significant increase in mortality for presenting rhythm of asystole and with hyperkalemia (P < 0.05). CONCLUSIONS: Extracorporeal membrane oxygenation is an important resuscitation tool for the hypothermic drowning victim. Hyperkalemia and presenting cardiac rhythm correlate with survival although they are not reasons to end resuscitation. More studies are needed to compare the outcomes in using ECMO for the hypothermic drowning victim.

Change in cervical length and spontaneous preterm birth in nulliparous women with a history of loop electrosurgical excision procedure.

BACKGROUND: Prior studies have shown an association between history of loop electrode procedures (LEEP) and spontaneous preterm delivery (SPTD) independent of mid-trimester cervical length. These studies suggest that there may be other factors beyond an individual cervical length, which contribute to identifying at-risk pregnancies. OBJECTIVE: The objective of this study is to determine the association between change in cervical length and SPTD in women with a history of LEEP. STUDY DESIGN: This is a retrospective cohort study of singleton nulliparous women with a history of LEEP who received serial cervical length measurements at a single institution between 2012 and 2016. Women with serial cervical lengths and available outcome data were included. The cervical length at different gestational ages and the rate of change in length were compared with the risk for SPTD <37 weeks using Student's t-test. RESULTS: One-hundred-thirty subjects met the inclusion criteria for the study. The mean cervical length (35.3 versus 39.8 mm, p = .042 at 16 weeks; 32.2 versus 37.8 mm, p < .01 at 20 weeks; 29.9 versus 35.6 mm, p = .027 at 24 weeks; 21.6 versus 33.4 mm, p < .01 at 28 weeks) was significantly different between women who had an SPTD <37 weeks compared to women who did not. The average rate of change in transvaginal cervical length between 16 to 28 weeks was significantly different between women who had an SPTD <37 weeks compared to women who did not (-1.4 versus 0.4 mm/week, p < .01). CONCLUSION: Women with a history of LEEP who had an SPTD <37 weeks had a shorter cervical length at 16, 20, 24, and 28 weeks' gestation and a higher rate of change in cervical length between 16 and 28 weeks than women without a history of SPTD. Our findings support the concept of the preterm birth syndrome as an evolving biophysical process rather than a distinct event, suggesting improved prediction in the setting of prior history of a LEEP with serial imaging.

Salmonella enterica Typhimurium engineered for nontoxic systemic colonization of autochthonous tumors.

Much of the bacterial anticancer therapy being developed relies on the ability of bacteria to specifically colonise tumours. Initial attempts to translate promising Salmonella enterica Typhimurium (S. Typhimurium) preclinical results to the clinical setting failed, primarily due to lack of tumour colonisation and the significant toxicities from systemically administered Gram-negative bacteria. To address the difference in results between preclinical experiments performed in mice with transplant tumours and clinical trials in human volunteers with autochthonous tumours, a genetically engineered mouse model of breast cancer (BALB-neuT) was utilised to develop a strain of virulence-attenuated S. Typhimurium capable of robust colonisation of autochthonous tumours. Several genes that code for bacterial surface molecules, responsible for signalling a toxic immune response against the bacteria, were mutated. The resulting S. Typhimurium strain, BCT2, allowed non-toxic intravenous administration of 3 × 106 colony forming units of bacteria in tumour-burdened mice when combined with a vascular disruption agent to induce intratumoral necrotic space and facilitate bacterial colonisation.

Virulence-attenuated Salmonella engineered to secrete immunomodulators reduce tumour growth and increase survival in an autochthonous mouse model of breast cancer.

The ultimate goal of bacterial based cancer therapy is to achieve non-toxic penetration and colonisation of the tumour microenvironment. To overcome this efficacy-limiting toxicity of anticancer immunotherapy, we have tested a therapy comprised of systemic delivery of a vascular disrupting agent to induce intratumoral necrotic space, cannabidiol to temporarily inhibit angiogenesis and acute inflammation, and a strain of Salmonella Typhimurium that was engineered for non-toxic colonisation and expression of immunomodulators within the tumour microenvironment. This combination treatment strategy was administered to transgenic mice burdened with autochthonous mammary gland tumours and demonstrated a statistically significant 64% slower tumour growth and a 25% increase in mean survival time compared to control animals without treatment. These experiments were accomplished with minimal toxicity as measured by less than 7% weight loss and a return to normal weight gain within three days following intravenous administration of the bacteria. Thus, non-toxic, robust colonisation of the microenvironment was achieved to produce a significant antitumor effect.

A Phase I, Dose Escalation, Single Dose Trial of Oral Attenuated Salmonella typhimurium Containing Human IL-2 in Patients With Metastatic Gastrointestinal Cancers.

Salmonella has been shown to preferentially colonize solid tumors. It is known that toxicity limits the systemic administration of immunomodulatory cytokines that have a significant anticancer effect. Therefore, we tested a unique cancer treatment strategy comprised of oral delivery of Saltikva, an attenuated strain of Salmonella typhimurium that contain the human gene for interleukin-2. In preclinical experimentation, a significant antitumor effect without toxicity was observed. A dose escalation, single dose, Phase I trial was conducted. Dose escalation (10 to 10) while monitoring for dose limiting toxicity and response was performed. Flow cytometry was conducted to determine the immunologic effect. In total 22 patients were administered Saltikva. Eight patients did not complete the trial. No toxicity or adverse events were observed. There was no survival advantage. Flow cytometry demonstrated an increase in circulating natural killer (NK) cells and NK-T cells when comparing the prestudy period. The results of this phase I dose escalation study show that oral attenuated S. typhimurium containing the human interleukin-2 gene caused no significant toxicities up to doses of 10 colony forming unit. There was no evidence of partial or complete response. All patients had progressive disease and eventually succumbed to their illness. Although no survival advantage was seen in this single dose study, the statistically significant increase in circulating NK and NK-T cell demonstrates an immunologic effect from this treatment regimen and suggest that a multiple dose study should be undertaken.

Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening.

OBJECTIVES: The performance of noninvasive prenatal screening (NIPS) for fetal aneuploidy in twin pregnancies is dependent on the amount of placentally derived cell-free DNA, the "fetal fraction (FF)," present in maternal plasma. We report FF values in monozygotic (MZ) and dizygotic (DZ) pregnancies. METHODS: We reviewed FF in pregnancies at 10 to 20 completed weeks gestational age based on single-nucleotide polymorphism (SNP)-based NIPS where zygosity was routinely established in twin pregnancies. The cohort included 121 446 (96.3%) singleton, 1454 (1.2%) MZ, and 3161 (2.5%) DZ pregnancies. For DZ twins, individual FFs were measured. RESULTS: Combined FF for DZ and MZ fetuses were 35% and 26% greater than singletons, respectively. The individual FF contributions from each fetus in DZ twins were, on average, 32% less than singletons. FF in DZ twin pairs were moderately correlated (Pearson correlation coefficient.66). When a threshold of 2.8% FF was applied to define uninterpretable results, 1.7% (2102/121 446) of singletons, 0.8% (11/1454) of MZ pairs, and 5.6% (178/3161) of DZ pairs were uninterpretable. CONCLUSION: For optimal aneuploidy NIPS in twin pregnancies, zygosity should be established and in DZ twins FF for both fetuses should be determined to identify those cases where results can be reliably interpreted.

Use of virtual reality for pre-surgical planning in separation of conjoined twins: A case report.

We describe the use of virtual reality technology for surgical planning in the successful separation of thoracopagus conjoined twins. Three-dimensional models were created from computed tomography angiograms to simulate the patient's anatomy on a virtual stereoscopic display. Members of the surgical teams reviewed the anatomical models to localize an interatrial communication that allowed blood to flow between the two hearts. The surgical plan to close the 1-mm interatrial communication was significantly modified based on the pre-procedural spatial awareness of the anatomy presented in the virtual visualization. The virtual stereoscopic display was critical for the surgical team to successfully separate the twins and provides a useful case study for the use of virtual reality technology in surgical planning. Both twins survived the operation and were subsequently discharged from the hospital.

A systematic review of management options in pediatric rectal prolapse.

PURPOSE: Rectal prolapse is a relatively common condition in infants and young children with a multifactorial etiology. Despite its prevalence, there remains clinical equipoise with respect to secondary treatment in pediatric surgery literature. We conducted a systematic review to evaluate methods of secondary treatment currently used to treat rectal prolapse in children. METHODS: We searched Pubmed, Medline, and Scopus with the terms "rectal prolapse" and "children" for papers published from 1990 to April 2017. Papers satisfying strict criteria were analyzed for patient demographics, intervention, efficacy, and complications. Procedures were grouped by like type. Pooled success rates were calculated. RESULTS: Twenty-seven studies documenting 907 patients were included. Injection sclerotherapy had an overall initial success rate of 79.5%. Ethyl alcohol seemed the best sclerosing agent due to a high first-injection success rate, low complication rate, and ready accessibility. Several perineal repairs were found, with operative success rates ranging from 60.8%-100%. Laparoscopic rectopexy with mesh was the most commonly reported transabdominal procedure and had an overall success rate of 96.1%. Postoperative complications from all procedures were comparable. CONCLUSION: Though many secondary treatment options have been reported for rectal prolapse, sclerotherapy and laparoscopic rectopexy predominate in contemporary literature and appear to have high success and low complication rates. LEVEL OF EVIDENCE: IV.

Outcomes in patients with early-onset fetal growth restriction without fetal or genetic anomalies.

OBJECTIVE: Early-onset fetal growth restriction is associated with poor pregnancy outcomes, but frequently is due to fetal structural or chromosomal abnormalities. The objective of this study was to determine outcomes in patients with early-onset fetal growth restriction without diagnosed fetal or genetic anomalies and to identify additional risk factors for poor outcomes in these patients. METHODS: This was retrospective cohort study of singleton pregnancies in women with early-onset growth restriction defined as a sonographic estimated fetal weight <10% diagnosed between 16-28 weeks' gestation. We excluded all women with a fetal structural or chromosomal abnormality diagnosed prenatally. Data on pregnancy characteristics and outcomes were collected and analyzed for estimated fetal weight <10% and ≤5%. A nested case-control study within the cohort of patients with ongoing pregnancies was then performed to identify risk factors associated with poor pregnancy outcome using chi-squared test. RESULTS: One hundred forty-two patients were identified who met inclusion and exclusion criteria and 20 patients were found to have fetal structural or chromosomal abnormalities. In the remaining 122 patients, the incidence of intrauterine fetal demise was 5.7% and there were high rates of preterm birth <37 weeks (20%), birth weight <10% (59.3%), and gestational hypertension (14.1%). Later gestational age at diagnosis and the presence of echogenic bowel and abnormal initial umbilical artery Dopplers were associated with poor pregnancy outcome (22.56 versus 20.86 weeks, p = .046), (17.4 versus 2.2%, OR 9.68, 95%CI 1.65-56.73), and (35.3 versus 0%, OR 4.46, 95%CI 2.65-7.50) respectively. CONCLUSIONS: Patients with early-onset fetal growth restriction with no fetal structural or genetic abnormality have a high risk of poor pregnancy outcomes. Gestational age at diagnosis and certain ultrasound findings are associated with poor pregnancy outcome.

Standardized irrigation technique reduces intraabdominal abscess after appendectomy.

PURPOSE: The utility of irrigation at the time of appendectomy for acute appendicitis has been debated, with recent studies showing no benefit to irrigation. In our practice, two techniques have been used; one in which irrigation was at the discretion of the surgeon, and one in which irrigation was standardized. The standardized irrigation technique involved large volume (3-12 l) irrigation in small, focused, directed aliquots to achieve optimal dilution. We sought to retrospectively assess whether the standardized large volume irrigation technique was associated with measurably reduced intraabdominal infection. We hypothesized that there would be no difference in intraabdominal infection rate. METHODS: Medical records for cases of appendectomies performed for acute appendicitis, years 2007 through 2017, were reviewed (n = 432). Rate of subsequent abdominal infection was compared between patients who underwent the standardized large volume irrigation technique compared to those who did not using Fisher's exact test; p < 0.05 was considered significant. RESULTS: For patients that underwent the standardized large volume irrigation technique there were no (0/140) subsequent abdominal infections within the study period, compared with a rate of 6.2% (18/292) for all other patients (p value 0.001). Among cases that had a perforated appendix (n = 105), the rates were 0% (0/31) compared to 18.9% (14/74; p value 0.009). CONCLUSIONS: Utilization of a standardized large volume irrigation technique with the objective of serial dilution is associated with a significantly lower rate of subsequent abdominal infection, even among cases with a perforated appendix. Prospective studies are needed to evaluate this technique. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Treatment study.

Combined laparoscopic-fluoroscopic technique for primary gastrojejunostomy button tube placement.

BACKGROUND: Gastrojejunostomy (GJ) tubes are frequently used to provide pediatric enteral nutritional support for pediatric patients. Various placement methods have been described, each with attendant advantages and disadvantages. DESCRIPTION OF THE OPERATIVE TECHNIQUE: We present a technique for primary laparoscopic/fluoroscopic GJ button tube placement designed to avoid delay in placement of the jejunal limb, and difficulties associated with endoscopic-assisted and primary fluoroscopic placement. RESULTS: There were 52 gastrojejunostomy button tubes placed via this technique in patients ranging from 3.8 to 90.3 kg in weight. Three postoperative complications were identified; one bowel perforation on postoperative day two, and two tube dislodgements within 30 days. CONCLUSION: The described technique was uniformly effective and was associated with a low complication rate (5.8%).

Peritoneal dialysis catheter placement, outcomes and complications.

PURPOSE: Peritoneal dialysis (PD) is a commonly used method for renal support in pediatric patients and can be associated with the risk of post-surgical complications. We evaluated method of placement of PD catheters with regard to post-surgical complications. METHODS: PD catheters placed at two institutions between 2005 and 2017 were reviewed. Complication rates were evaluated based on method of placement, delayed usage, omentectomy, and patient age using Fisher's exact test, two-sided, with significance set at 0.05. Factors influencing complication were evaluated with multivariate logistic regression and Kaplan-Meier survival analysis. RESULTS: There were 130 patients with 157 catheters placed, ranging in age from 1 day to 23 years. There was no significant difference in complication rate by method of placement or delayed usage. Infants were significantly more likely to experience leakage (21% vs 8%, p 0.036) and hernias (15% vs 5%, p 0.030). Patients that underwent an omentectomy were less likely to require a catheter replacement (7% vs 27%, p 0.004), and the catheters had a significantly higher survival rate (p 0.009). We found that laparoscopic intervention resulted in catheter salvage. Lateral exit sites may be a risk factor for catheter migration in some patients. CONCLUSIONS: Omentectomy is associated with longer PD catheter survival. Laparoscopic salvage of dysfunctional catheters may be a valuable adjunct in management.

White paper on microbial anti-cancer therapy and prevention.

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.

Antenatal Testing for Women With Preexisting Medical Conditions Using Only the Ultrasonographic Portion of the Biophysical Profile.

OBJECTIVE: To report the utility of the ultrasonographic biophysical profile, which includes all the components of a biophysical profile minus the nonstress test, in women with maternal indications for antepartum surveillance. METHODS: We conducted a case series reviewing the records of all women at 32 weeks of gestation or greater with at least one indication for antenatal testing (per the American College of Obstetricians and Gynecologists) delivered by a single maternal-fetal medicine practice between 2006 and 2018. Indications included diabetes, hypertension, lupus, antiphospholipid syndrome, sickle cell disease, renal disease, heart disease, hyperthyroidism, isoimmunization, inherited thrombophilia, and prior intrauterine fetal demise. Weekly ultrasonographic biophysical profiles were initiated at 32 weeks of gestation. We calculated the test-positive rate, the percentage of women delivered for an abnormal ultrasonography biophysical profile, and the intrauterine fetal demise rate (false-negative rate). RESULTS: Nine hundred eighty-five women underwent 3,981 ultrasonographic biophysical profiles (four per woman; range 1-11). Sixteen women had an abnormal ultrasonographic biophysical profile, for a test positive rate of 1.6% (95% CI 1.0-2.6%) per woman, or 0.4% (95% CI 0.3-0.7%) per ultrasonographic biophysical profile. Of the 16 women with abnormal ultrasonographic biophysical profiles, 13 were delivered with good outcomes and three women had normal follow-up testing and uncomplicated deliveries at a later date. There were three women with intrauterine fetal demise (false-negative rate of 0.3%, 95% CI 0.1-0.9%). One woman with intrauterine fetal demise had a factor V Leiden mutation, fetal ventriculomegaly, and fetal growth restriction. The second woman with intrauterine fetal demise had advanced maternal age, a factor V Leiden mutation, and fetal growth restriction. The third woman with intrauterine fetal demise had class B diabetes. All three intrauterine fetal demises were diagnosed antepartum with an interval from normal ultrasonographic biophysical profile to intrauterine fetal demise of 7, 7, and 6 days, respectively. CONCLUSION: The use of ultrasonographic biophysical profile in a high-risk cohort is associated with a very low test-positive rate and a very low incidence of intrauterine fetal demise. In women with preexisting medical conditions that place them at higher risk for intrauterine fetal demise, ultrasonographic biophysical profile can be used for antenatal testing.

Necrotizing Enterocolitis in Two Siblings and an Unrelated Infant with Overlapping Chromosome 6q25 Deletions.

The pathogenesis of necrotizing enterocolitis (NEC) remains poorly understood but is thought to be multifactorial. There are no specific recurring chromosomal abnormalities previously associated with NEC. We report 3 cases of intestinal necrosis associated with large chromosome 6 deletions. The first patient was found to have a 7.9-Mb deletion of chromosome 6 encompassing over 40 genes, arr[GRCh37] 6q25.3q26(155699183_163554531)×1. The second patient had a 19.5-Mb deletion of chromosome 6 generated by an unbalanced translocation with chromosome 18, 46,XY,der(6)t (6;18)(q25.1;p11.23), arr[GRCh37] 6q25.1q27(151639526_ 171115067)×1, 18p11.32p11.23(131700_7694199)×3, which included the whole 7.9-Mb region deleted in the first patient. The third patient was the younger sibling of the second patient with an identical derivative chromosome 6. The shared abnormal chromosome 6 region includes multiple genes of interest, particularly EZR. Mouse models have demonstrated that Ezr is expressed in microvillar epithelium and helps regulate cell-cell adhesion in the gut. We hypothesize that deletion of this shared region of 6q leads to gastrointestinal vulnerability which may predispose patients to intestinal necrosis.