A Step Toward Personalized Surgical Decision Making: Machine Learning Predicts 1 Versus Numerous Melanoma Lymph Node Metastases Using RNA-sequencing.

OBJECTIVE: Develop a predictive model to identify patients with 1 pathologic lymph node (pLN) versus >1 pLN using machine learning applied to gene expression profiles and clinical data as input variables. BACKGROUND: Standard management for clinically detected melanoma lymph node metastases is complete therapeutic LN dissection (TLND). However, >40% of patients with a clinically detected melanoma lymph node will only have 1 pLN on final review. Recent data suggest that targeted excision of just the single enlarged LN may provide excellent regional control, with less morbidity than TLND. The selection of patients for less morbid surgery requires accurate identification of those with only 1 pLN. METHODS: The Cancer Genome Atlas database was used to identify patients who underwent TLND for melanoma. Pathology reports in The Cancer Genome Atlas were reviewed to identify the number of pLNs. Patients were included for machine learning analyses if RNA sequencing data were available from a pLN. After feature selection, the top 20 gene expression and clinical input features were used to train a ridge logistic regression model to predict patients with 1 pLN versus >1 pLN using 10-fold cross-validation on 80% of samples. The model was then tested on the remaining holdout samples. RESULTS: A total of 153 patients met inclusion criteria: 64 with one pLN (42%) and 89 with >1 pLNs (58%). Feature selection identified 1 clinical (extranodal extension) and 19 gene expression variables used to predict patients with 1 pLN versus >1 pLN. The ridge logistic regression model identified patient groups with an accuracy of 90% and an area under the receiver operating characteristic curve of 0.97. CONCLUSIONS: Gene expression profiles together with clinical variables can distinguish melanoma metastasis patients with 1 pLN versus >1 pLN. Future models trained using positron emission tomography/computed tomography imaging, gene expression, and relevant clinical variables may further improve accuracy and may predict patients who can be managed with a targeted LN excision rather than a complete TLND.

Cancer Screening and Treatment Delays During the COVID-19 Pandemic and the Role of Health Literacy in Care Re-engagement: Findings from an NCI-Designated Comprehensive Cancer Center sample.

The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. A total of 1,533 participants completed the survey, and nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cancer screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.

Standing Intravenous Acetaminophen Is Associated With a Reduction of Post-operative Opioid Use in Infants Aged Less Than 1 Year Treated on the Acute Care Floor.

INTRODUCTION: Given the negative clinical effects opiates can have, the search for alternative forms of analgesia to treat post-operative pain continues. We implemented an opiate reduction strategy using standing intravenous (IV) acetaminophen for infants aged less than 1 y who underwent abdominal or anorectal surgery and recovered on the acute care floor. MATERIALS AND METHODS: Infants were administered standing IV acetaminophen every 6 h for a minimum of 48 h as the main form of post-operative analgesia. Pain severity was objectively scored using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. A before-and-after retrospective cohort analysis was performed and process control charts were used to examine trends in post-operative opiate use in our pre-intervention (January 2012 to January 2016), roll-out (January 2016 to December 2016), and post-intervention (December 2016 to December 2020) cohorts. RESULTS: A total of 131 infants were included: 56 in the pre-intervention, 17 in the roll-out, and 58 in the post-intervention group. Patient demographics were equivalent. The intervention was associated with a 36-fold reduction in post-operative morphine equivalents (median 0.36 mg/kg in the pre-intervention group versus 0.0 mg/kg in the post-intervention group, P < 0.0001). The median and maximum FLACC pain scores along with clinical safety profiles were statistically equivalent between the groups. The intervention was associated with a 2-d reduction in post-operative length of stay (P < 0.0001). CONCLUSIONS: Standing IV acetaminophen is associated with a reduction of post-operative opioid use in infants being treated on the acute care floor while maintaining equivalent FLACC pain scores. Similar opiate reduction strategies may be of value at other institutions.

Gastrostomy tubes appear to be safe following pediatric orthotopic heart transplant.

BACKGROUND: Gastrostomy tube (GT) placement is a common pediatric surgical procedure typically indicated for oral aversion. This may develop in patients with congenital heart disease (CHD) who require an orthotopic heart transplant (OHT). The safety profile of GT placement in OHT patients who are immunosuppressed is unknown. Given the potential increased risk of wound site complications on a patient receiving immunosuppression, we sought to determine the safety profile of GT placement in pediatric patients with OHT. MATERIALS AND METHODS: We performed a retrospective case series of all pediatric OHT recipients who subsequently underwent GT placement from January 1, 2009, to August 1, 2018, at the University of Virginia Children's Hospital. Major GT complications of wound breakdown, wound infection, peristomal GT leakage, ileus, or persistent emesis, and minor GT complication including the presence of granulation tissue are reported. RESULTS: Six patients who had a pediatric OHT subsequently underwent GT placement over the study period. There were no major 30-day or 90-day GT complications. One patient had excessive granulation tissue at their GT site. There were no accounts of acute kidney injury, urinary tract infection, sepsis, or pneumonia. CONCLUSION: Gastrostomy tube (GT) placement appears to be safe in pediatric OHT patients who are on immunosuppressive medications and unable to feed orally. This is the first study documenting the safety profile of GTs in pediatric OHT patients and may aid clinicians to make decisions regarding this intervention.

Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?

Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members.

Post-operative Opioid Reduction Protocol Reduces Racial Disparity in Clinical Outcomes in Children.

INTRODUCTION: Racial disparities in health outcomes continue to exist for children requiring surgery. Previous investigations suggest that clinical protocols may reduce racial disparities. A post-operative opioid reduction protocol was implemented in children undergoing abdominal surgery who were less than 1 years old at a tertiary level hospital. The purpose of this investigation was to determine if the clinical protocol was associated with a reduction in racial disparity in post-operative opioid prescribing patterns and associated clinical outcomes. METHODS: A post-operative opioid reduction protocol based on standing intravenous acetaminophen, educational sessions with nursing staff, and standardized post-operative sign-out between the surgical and NICU teams was implemented in children under 1 year old in 2016. A time series and before and after analysis was conducted using a historical pre-intervention cohort (Jan 2011-Dec 2015) and prospectively collected post-intervention cohort (Jan 2016-Jan 2021). Primary outcomes included post-operative opioid use and post-operative pain scores stratified by race. Secondary outcomes included associated clinical outcomes also stratified by race. RESULTS: A total of 249 children were included in the investigation, 117 in the pre-intervention group and 132 in the post intervention group. The majority of patients in both cohorts were either White or Black. The two cohorts were equally matched in terms of pre-operative clinical variables. In the pre-intervention cohort, the median post-operative morphine equivalents in White children was 2.1 mg/kg (IQR 0.2, 11.1) while in Black children it was 13.1 mg/kg (IQR 2.4, 65.3), p-value = 0.0352. In the post-intervention cohort, the median value for White children and Black children was statistically identical (0.05 mg/kg (IQR 0, 0.5) and 0.0 mg/kg (IQR 0, 0.3), respectively, p-value = 0.237). This pattern was also demonstrated in clinical variables including length of stay, intubation length and total parenteral nutrition use. In the pre-intervention cohort, the total length of stay for white children was 16 days while for black children it was 45 days (p = 0.007). In the postintervention cohort the length of stay for both White and Black children were identical at 8 days (p = 0.748). CONCLUSION: The use of a clinical opioid reduction protocol implemented at a tertiary medical center was associated with a reduction in racial disparity in opioid prescribing habits in children. Prior to the protocol, there was a racial disparity in clinical variables associated with prolonged opioid use including length of stay, TPN use, and intubation length. The clinical protocol reduced variability in opioid prescribing patterns in all racial groups which was associated with a reduction in variability in associated clinical variables. LEVEL OF EVIDENCE: Level III.

Clinical Trials in Breast Cancer: Practice Changing, Landmark with a Focus on More Current Trials.

Randomized clinical trials have been essential in guiding the surgical and systemic treatment of breast cancer, with most focusing on de-escalation. Here, we discuss key clinical trials that have shaped the modern approach to the treatment of breast cancer, focusing on studies that are more recent.

Management of Nipple Discharge.

Nipple discharge is the third most common breast-related complaint but is rarely the presenting symptom of breast cancer. Distinguishing patients with physiologic versus pathologic nipple discharge, and treating the later according to the underlying pathologic condition is of utmost importance. Nipple discharge is categorized as lactational, physiologic, or pathologic. Physiologic nipple discharge (galactorrhea) is typically caused by hyperprolactinemia due to medications (ie, antipsychotics), pituitary tumors, and endocrine disorders. When a suspicious radiologic lesion is identified, pathologic assessment of the lesion is indicated. Patients with pathologic nipple discharge should be referred to a breast surgeon for definitive treatment and follow-up.

Reduction of post-operative opioid use in neonates following open congenital diaphragmatic hernia repairs: A quality improvement initiative.

BACKGROUND: A limited number of post-operative opioid reduction strategies have been implemented in the neonatal population. Given the potential neurodevelopment effects of prolonged opioid use, we created a quality improvement initiative to reduce opioids in our NICU and evaluated the intervention in our CDH population. METHODS: Our opioid reduction intervention was based on standing post-operative IV acetaminophen, standardizing post-surgical sign-out between the surgical, anesthesia and NICU teams and a series of education seminars with NICU providers on post-operative pain control management. A historical control was used to perform a retrospective cohort analysis of opioid prescribing patterns in addition to a utilizing process control charts to investigate time trends in prescribing patterns. RESULTS: Forty-five children with CDH underwent an operation were included in our investigation- 18 in our pre-intervention cohort, 6 in a roll-out cohort and 21 in our post-intervention cohort. Each cohort was clinically similar. The intervention reduced total post-operative opioid use (morphine equivalents) from 82.2 (mg/kg) to 2.9 (mg/kg) in our post-intervention group (p < 0.0001). Our maximum Neonatal Pain and Agitation Sedation Score over the first 48 post-operative hours were equivalent (p = 0.827). Safety profiles were statistically equivalent. The opioid reduction intervention reduced post-operative intubation length from 156 to 44 h (p = 0.021). CONCLUSION: A multi-tiered intervention can decrease opioid use in post-surgical neonates with complex surgical pathology including CDH. The intervention proposed in this investigation is safe and does not increase pain or sedation scores in neonates, while lessening post-operative intubation length. EVIDENCE LEVEL: Level II.

A Quality Improvement Intervention to Reduce Postoperative Opiate Use in Neonates.

BACKGROUND AND OBJECTIVES: Opiate use in neonates can affect clinical outcomes after surgery and may alter future neurodevelopment. We implemented a multimodal opioid reduction strategy in our NICU for infants undergoing nonemergent gastrointestinal surgery. METHODS: After multiple stakeholder's meetings, our opioid reduction intervention included giving neonates postoperative standing intravenous acetaminophen every 6 hours for 48 hours, a standardized postsurgical sign-out with the NICU team in which pain control was directly addressed, and a series of postsurgical pain education seminars with NICU providers. To assess the impact of our quality improvement project, we used process control charts to investigate trends in postoperative opioid use in our preintervention (January 2012 to April 2016) and postintervention (May 2016 to September 2019) cohorts. RESULTS: A total of 77 infants were included in the study (40 in the preintervention cohort and 37 in the postintervention cohort). Patient characteristics were equivalent. The intervention significantly reduced the trend in postoperative morphine equivalents (median: 7.96 mg/kg in preintervention cohort versus 0.095 mg/kg in postintervention cohort; P < .0001). The Neonatal Pain, Agitation, and Sedation Scale pain scores and safety profiles were equivalent in both groups. The intervention was also associated with a 24-hour reduction in postoperative ventilation time (P < .048) and a 7-day reduction in the use of total parenteral nutrition (P < .017). CONCLUSIONS: Standing intravenous acetaminophen coupled with provider education can successfully reduce opioid use in postsurgical neonates. Given the concern for opioid exposure in neonatal neurodevelopment as well as clinical benefits of reduced opioids, similar strategies for opioid reduction may prove useful at other institutions.

Sutureless closure: a versatile treatment for the diverse presentations of gastroschisis.

OBJECTIVE: Case series have demonstrated sutureless closures to be safe for the correction of gastroschisis. We hypothesize that sutureless closure is efficacious in patients requiring silo reduction without need for intubation. STUDY DESIGN: We conducted a retrospective case control study of infants who underwent gastroschisis repair at our institution (January 2011-August 2018). Patient characteristics and clinical outcomes were compared between sutureless closure and primary fascial repair groups. RESULTS: Seventeen patients in the sutureless group and 28 patients in the primary fascial repair group were included. Success of sutureless closure was 94%. Mechanical ventilation was reduced by 2.8 days in the sutureless group (P < 0.0001) and fewer patients required general anesthesia (29.4% vs. 100%, P < 0.0001). CONCLUSIONS: Sutureless closure is effective for the diverse presentations of gastroschisis. Given the concerns of effects of general anesthesia on the developing brain, sutureless closure should be strongly considered.

Clinical yield of fetal echocardiography for suboptimal cardiac visualization on obstetric ultrasound.

OBJECTIVE: Suboptimal cardiac imaging on obstetric ultrasound is a frequent referral indication for fetal echocardiography, even in the absence of typical risk factors for fetal cardiac disease. The clinical profile of patients and findings of examinations performed for such an indication are not well defined. Given the increased cost, time and resource utilization of fetal echocardiography, we sought to determine the clinical findings of such referrals. STUDY DESIGN: We performed a single-center review of such referrals from January 2010 to June 2016. Patients with commonly accepted indications for fetal echocardiography were excluded. Demographic variables and echocardiogram findings were collected. Findings were classified as (1) "normal," (2) "probably normal," if minor pathology could not confidently be excluded, or if minor findings were noted that were expected to resolve, or (3) "abnormal." Rates of pathology were determined with comparison of nonobese and obese populations. RESULTS: A total of 583 gestations in 562 women were included (median gestational age 23.3 weeks, range 19.0-38.4). The median body mass index (BMI) was 34.6 kg/m2 (range 17.2-66.3 kg/m2 ). The majority of women were obese (BMI ≥ 30 kg/m2 in 74.6%). Overall, 574 of 583 examinations (98.5%) were normal or "probably normal." Pathology was noted in 9 fetuses (1.5%), 3 of whom required intervention (0.5%). No ductal dependent lesions were diagnosed. There was no significant difference in pathology rates between nonobese and obese mothers. CONCLUSIONS: We found a low fetal cardiac anomaly rate in studies performed for suboptimal views on obstetric ultrasound. The majority of women referred for this indication were obese. The practice of routine referral for this indication deserves further evaluation.