Robot-Assisted-Minimally Invasive-Transhiatal Esophagectomy (RAMI-THE).

The authors review the development and steps of the robotic-assisted minimally invasive transhiatal esophagectomy. Key goals of the robot-assisted approach have been to address some of the concerns raised about the technical challenges with the traditional open transhiatal esophagectomy while keeping most of the steps consistent with the open approach.

Urinary Tract Infections in Children.

Despite the American Academy of Pediatrics guidelines for the evaluation, treatment, and management of urinary tract infections (UTIs), UTI diagnosis and management remains challenging for clinicians. Challenges with acute UTI management stem from vague presenting signs and symptoms, diagnostic uncertainty, limitations in laboratory testing, and selecting appropriate antibiotic therapy in an era with increasing rates of antibiotic-resistant uropathogens. Recurrent UTI management remains difficult due to an incomplete understanding of the factors contributing to UTI, when to assess a child with repeated infections for kidney and urinary tract anomalies, and limited prevention strategies. To help reduce these uncertainties, this review provides a comprehensive overview of UTI epidemiology, risk factors, diagnosis, treatment, and prevention strategies that may help pediatricians overcome the challenges associated with acute and recurrent UTI management.

Improving Adolescent Psychosocial Assessment through Standardized Patient Simulation: An Interdisciplinary Quality Improvement Initiative.

Adolescent suicide and mental illness have increased at alarming rates. Healthcare professionals report a lack of skill and confidence in obtaining adolescent histories and managing confidential care due to limited training in residency. Nursing professional development practitioners face challenges of adequately preparing interdisciplinary healthcare providers to assess, identify, and intervene at all points of contact with adolescents. To increase the confidence in clinical communication skills and clinical competency, and to increase the number of social work referrals related to modifiable risk factors for adolescent patients, a Texas pediatric tertiary care center utilized standardized patient (SP) methodology to supplement traditional clinical experiences with communication-focused education based on the Home, Education, Eating, Activities, Drugs, Sexuality, Suicidality, and Safety (HEEADSSS) interviewing. This quality improvement (QI) pilot demonstrated the benefits of utilizing standardized patient methodology in communication-focused education based on the HEEADSSS interviewing. Following the SP simulations, confidence in clinical communication skills increased by 13%, clinical competency in performing comprehensive psychosocial interviews increased by 11%, use of HEEADSSS increased by 64%, and social work referrals increased by 89%. This interdisciplinary SP interviewing simulation pilot was beneficial in improving the 36 physician and nursing residents' ability to conduct psychosocial assessments for risk factors of suicidality among adolescents.

Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs.

BACKGROUND: About 20% of breast cancers in humans are basal-like, a subtype that is often triple-negative and difficult to treat. An effective translational model for basal-like breast cancer is currently lacking and urgently needed. To determine whether spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog-human molecular homology at the subtype level. METHODS: We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We identified feature genes for human BLBC and luminal A subtypes via machine learning and used these genes to repeat canine-alone and cross-species tumor classifications. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog-human subtype comparison. RESULTS: Our independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 and feature gene classifications, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched in histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER-) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER-PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors and with the expression of T cell exhaustion markers (e.g., PDCD1) in ER-PR+ canine tumors. CONCLUSIONS: We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall and thus could serve as a vital translational model of this devastating breast cancer subtype. Our study also sheds light on the dog-human difference in the mammary tumor histology and the hormonal cycle.

Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics.

Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.

Preterm and Term Infants Evaluated for Sepsis: Differences in Management and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: To describe differences in practice patterns and outcomes of young preterm versus age-matched term infants evaluated for sepsis, because evaluation and management of this group are not well defined. METHODS: We conducted a retrospective single-center study at an academic, freestanding children's hospital of previously healthy preterm and term infants aged 0 to 60 days, who presented for initial evaluation of fever and/or hypothermia from 2014 to 2019. We classified infants by gestational age as preterm (32-36 6/7 weeks) and term (37-42 weeks) and compared diagnostic evaluation, management, and clinical outcomes. RESULTS: Out of 363 preterm infants evaluated for sepsis, 336 met inclusion criteria; within the same study period, 2331 term infants were evaluated for sepsis, of which 600 were randomly selected and 554 were included. Clinicians performed inflammatory marker testing and chest x-rays more frequently in preterm infants 31% vs 25% (P = .034) and 50% vs 32% (P < .001), respectively. Preterm infants had a higher rate of bacteremia 5.9% vs 2.5% (P = .035), were hospitalized more frequently 72% vs 63% (P = .006), and required ICU level of care more often 32% vs 5% (P < .001) than term infants. They had lower rates of viral infections 33% vs 42% (P = .015) and no significant increased return visits. Febrile preterm and term infants, and older hypothermic preterm infants had relatively higher rates of serious bacterial infections. Hypothermic preterm infants had the longest hospitalizations. CONCLUSIONS: Preterm infants had increased rates of bacteremia and required higher level of care compared with age-matched term infants, likely reflecting their increased risk for sepsis and other concomitant morbidities associated with preterm birth.

Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs.

Background: About 20% of breast cancers in humans are basal-like, a subtype that is often triple negative and difficult to treat. An effective translational model for basal-like breast cancer (BLBC) is currently lacking and urgently needed. To determine if spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog-human molecular homology at the subtype level. Methods: We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog-human subtype comparison. Results: Our independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 classification, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER-) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER-PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors, and with the expression of T cell exhaustion markers (e.g., PDCD1 ) in ER-PR+ canine tumors. Conclusions: We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall, and thus could serve as a vital spontaneous animal model of this devastating breast cancer subtype. Our study also sheds light on the dog-human difference in the mammary tumor histology and the hormonal cycle.

Implementation and Patient Outcomes of a Pediatric COVID-19 Monoclonal Antibody Program.

BACKGROUND: The severity and reach of the COVID-19 pandemic drove the development of various therapeutic approaches to combat SARS-CoV-2, including several neutralizing monoclonal antibody (mAb) therapies. A January 2021 pediatric consensus statement opposed routine use and recommended individualized risk assessments when considering COVID-19 mAb therapies in children and adolescents due to limited data. This report describes the implementation of a mAb referral process and the clinical outcomes of patients who received a mAb infusion in a pediatric hospital. METHODS: We developed a tiered allocation system based on underlying medical conditions and incorporated it into a standardized COVID-19 mAb referral and approval process. Demographics and clinical data were collected on all patients who received mAb therapy for treatment or post-exposure prophylaxis. Data recorded included sociodemographics, qualifying underlying medical conditions, clinical manifestations of infection, and overall course of treatment and disease. RESULTS: A total of 182 patients ≤21 years old received a COVID-19 mAb infusion between November 27, 2020 and January 26, 2022. Patient age ranged from 10 months to 21 years, with a median age of 15 years. In total, 7 patients (4%) had suspected adverse reactions during the infusion, and 15 (8%) patients required a COVID-19-related visit within 30 days of the mAb infusion. CONCLUSIONS: A tiered allocation process may provide the framework for the stratification and efficient distribution of mAb therapies. Future research must focus on the efficacy of these therapies in the pediatric population, standardized therapeutic prioritization, and the optimal timeframe for mAb delivery to prevent progression to severe disease.

Novel urine biomarkers to distinguish UTI from culture-negative pyuria.

BACKGROUND: Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. METHODS: In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. RESULTS: BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). CONCLUSIONS: BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI.

Increasing Adherence to Acute Otitis Media Treatment Duration Guidelines using a Quality Improvement Approach.

This quality improvement initiative aimed to improve American Academy of Pediatrics acute otitis media (AOM) guideline adherence in pediatric urgent care sites by increasing the percentage of patients 2 years and older with AOM who received a short duration (7 days or fewer) of antibiotics from a baseline of 7% to a goal of 50%. METHODS: This quality improvement initiative was conducted in a network of seven urgent care sites affiliated with a large academic children's hospital. The interventions focused on clinician and family education, clinical decision support, and a discharge template that defaulted to a 7-day duration of antibiotics for patients 2 years and older diagnosed with AOM. The outcome measure was the percentage of patients receiving 7 days or fewer of antibiotics. The process measure was the percentage of prescriptions originating from the new discharge template. A repeat visit for AOM within 30 days from the initial visit was the balancing measure. RESULTS: The percentage of patients diagnosed with AOM receiving a short antibiotic course increased from a baseline of 7% to a new centerline mean of 67%, which exceeded the goal. This project resulted in 10,138 antibiotic days being avoided. Eighty-two percent of short-course prescriptions originated from the discharge template. Repeat visits for AOM within 1 month of the initial visit did not increase. CONCLUSIONS: A quality improvement initiative combining education and clinical decision support improved adherence to AOM treatment duration guidelines and avoided unnecessary antibiotic exposure in a pediatric urgent care network without increasing treatment failures.

Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds.

Spontaneous canine cancers are valuable but relatively understudied and underutilized models. To enhance their usage, we reanalyze whole exome and genome sequencing data published for 684 cases of >7 common tumor types and >35 breeds, with rigorous quality control and breed validation. Our results indicate that canine tumor alteration landscape is tumor type-dependent, but likely breed-independent. Each tumor type harbors major pathway alterations also found in its human counterpart (e.g., PI3K in mammary tumor and p53 in osteosarcoma). Mammary tumor and glioma have lower tumor mutational burden (TMB) (median < 0.5 mutations per Mb), whereas oral melanoma, osteosarcoma and hemangiosarcoma have higher TMB (median ≥ 1 mutations per Mb). Across tumor types and breeds, TMB is associated with mutation of TP53 but not PIK3CA, the most mutated genes. Golden Retrievers harbor a TMB-associated and osteosarcoma-enriched mutation signature. Here, we provide a snapshot of canine mutations across major tumor types and breeds.

Empiric Vancomycin Reduction in a Pediatric Intensive Care Unit.

BACKGROUND: At our institution, empirical vancomycin is overused in children with suspected bacterial community-acquired infections (CAIs) admitted to the PICU because of high community rates of methicillin-resistant Staphylococcus aureus (MRSA). Our goal was to reduce unnecessary vancomycin use for CAIs in the PICU. METHODS: Empirical PICU vancomycin indications for suspected CAIs were developed by using epidemiological risk factors for MRSA. We aimed to reduce empirical PICU vancomycin use in CAIs by 30%. After retrospectively testing, the indications were implemented and monthly PICU empirical vancomycin use during baseline (May 2017-April 2018) and postintervention (May 2018-July 2019) periods. Education was provided to PICU providers, vancomycin indications were posted, and the antibiotic order set was revised. Statistical process control methods tracked improvement over time. Proven S aureus infections for which vancomycin was not empirically prescribed and linezolid or clindamycin use were balancing measures. RESULTS: We identified 1620 PICU patients with suspected bacterial CAIs. Empirical vancomycin decreased from a baseline of 73% to 45%, a 38% relative reduction. No patient not prescribed empirical vancomycin later required the addition of vancomycin or other MRSA-targeted antibiotics. There was no change in nephrotoxicity or in the balancing measures. CONCLUSIONS: Development of clear and concise recommendations, combined with clinician education and decision support via an order set, was an effective and safe strategy to reduce PICU vancomycin use. Retrospective validation of the recommendations with local data were key to obtaining PICU clinician buy in.

Implementation of a Pharmacist-Led Antimicrobial Time-Out for Medical-Surgery Services in an Academic Pediatric Hospital.

OBJECTIVE: This report describes a quality improvement initiative to implement a pharmacist-led antimicrobial time-out (ATO) in a large, freestanding pediatric hospital. Our goal was to reach 90% ATO completion and documentation for eligible patients hospitalized on general pediatric medicine or surgery services. METHODS: A multidisciplinary quality improvement team developed an ATO process and electronic documentation tool. Clinical pharmacists were responsible to initiate and document an ATO for pediatric medicine or surgery patients on or before the fifth calendar day of therapy. The quality improvement team educated pharmacists and physicians and provided ATO audit and feedback to the pharmacists. We used statistical process control methods to track monthly rates of ATO completion retrospectively from October 2017 through March 2018 and prospectively from April 2018 through April 2019. Additionally, we retrospectively evaluated the completion of 6 data elements in the ATO note over the final 12-month period of the study. RESULTS: Among 647 eligible antimicrobial courses over the 19-month study period, the mean monthly documentation rate increased from 54.6% to 83.5% (p < 0.001). The mean ATO documentation rate increased from 32.8% to 74.2% (p < 0.001) for the pediatric medicine service and from 65.0% to 88.1% for the pediatric surgery service (p = 0.006). Among 302 notes assessed for completeness, 35.8% had all the required data fields completed. A tentative antimicrobial stop date was the data element completed least often (49.3%). CONCLUSIONS: We implemented a pharmacist-led ATO, highlighting the role pharmacists play in antimicrobial stewardship. Additional efforts are needed to further increase ATO completion rates and to define treatment duration.

Surrogate testing of oral third-generation cephalosporin susceptibility to common uropathogens.

Cefazolin susceptibility of urine isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis predicts susceptibility to oral cephalosporins, but cefazolin-resistant isolates may be susceptible to oral third-generation cephalosporins. Among 194 urine isolates, we found >95% categorical agreement among oral third-generation cephalosporins. Surrogate testing of cefpodoxime for cefdinir, and vice versa, resulted in no major or very major errors, while combinations involving cefixime produced rare major and very major errors.

Lived experience of medical veterans transitioning from military service to civilian nursing education.

BACKGROUND: Many veterans take advantage of the educational benefits afforded them after service. As veterans, students in higher education are a special population with subsequent needs. PURPOSE: The purpose of this study was to explore the lived experience of medic student veterans attending a full-time Bachelor of Science in Nursing (BSN) program. METHOD: This study used the hermeneutic phenomenology research approach to explore the lived experiences of student veterans with military medic experience enrolled in a Bachelor of Science in Nursing (BSN) program. RESULTS: While our study revealed diverse student experiences among these veterans, common themes included staying true to military training, normal life, and fitting in as a university student. CONCLUSIONS: Findings in this study substantiate medic student veterans attending nursing school represent a unique cohort which can benefit from customized services from the university.

Overcoming barriers to the adoption and implementation of predictive modeling and machine learning in clinical care: what can we learn from US academic medical centers?

There is little known about how academic medical centers (AMCs) in the US develop, implement, and maintain predictive modeling and machine learning (PM and ML) models. We conducted semi-structured interviews with leaders from AMCs to assess their use of PM and ML in clinical care, understand associated challenges, and determine recommended best practices. Each transcribed interview was iteratively coded and reconciled by a minimum of 2 investigators to identify key barriers to and facilitators of PM and ML adoption and implementation in clinical care. Interviews were conducted with 33 individuals from 19 AMCs nationally. AMCs varied greatly in the use of PM and ML within clinical care, from some just beginning to explore their utility to others with multiple models integrated into clinical care. Informants identified 5 key barriers to the adoption and implementation of PM and ML in clinical care: (1) culture and personnel, (2) clinical utility of the PM and ML tool, (3) financing, (4) technology, and (5) data. Recommendation to the informatics community to overcome these barriers included: (1) development of robust evaluation methodologies, (2) partnership with vendors, and (3) development and dissemination of best practices. For institutions developing clinical PM and ML applications, they are advised to: (1) develop appropriate governance, (2) strengthen data access, integrity, and provenance, and (3) adhere to the 5 rights of clinical decision support. This article highlights key challenges of implementing PM and ML in clinical care at AMCs and suggests best practices for development, implementation, and maintenance at these institutions.

Relationship Between Clinical Factors and Duration of IV Antibiotic Treatment in Neonatal UTI.

OBJECTIVES: To describe practice patterns of intravenous (IV) antibiotic treatment duration in term neonates ≤28 days old with a urinary tract infection (UTI). METHODS: We performed a retrospective chart review of term neonates ≤28 days old hospitalized for UTI at 2 academic pediatric hospitals from 2012 to 2018. Neonates who were admitted to the PICU or with known preexisting renal and/or urologic anomalies or concomitant bacteremia were excluded. We examined clinical features, complications, and duration of IV antibiotic therapy. Univariate and multivariate analyses of long duration of IV antibiotics (>48 hours) were performed by using logistic regression. RESULTS: Of 310 neonates identified by diagnostic codes and chart review, 112 met criteria for inclusion. The median IV antibiotic duration was 49 hours (51% received IV antibiotics for >48 hours), and the median total antibiotic duration was 10 days. No demographic features or laboratory values correlated with IV antibiotic duration apart from age <7 days. The odds of long IV antibiotic duration increased if the neonate had a secondary diagnosis extending hospitalization (adjusted odds ratio [aOR] = 3.2; P = .002; 95% confidence interval [CI], 1.2-8.7), subspecialty consult (aOR = 4.79; P < .001; 95% CI, 1.87-12.3), or an abnormal renal ultrasound (aOR = 2.26; P = .02; 95% CI, 1.01-5.08). Only 1 neonate experienced treatment failure. CONCLUSIONS: Our study revealed the recent trend toward shorter IV antibiotic courses for healthy term neonates with UTI is inclusive of infants ≤28 days at these 2 sites. Few factors associated with neonates' initial clinical presentation appear to influence the length of IV antibiotic treatment.

Aptamer based proteomic pilot study reveals a urine signature indicative of pediatric urinary tract infections.

OBJECTIVE: Current urinary tract infection (UTI) diagnostic strategies that rely on leukocyte esterase have limited accuracy. We performed an aptamer-based proteomics pilot study to identify urine protein levels that could differentiate a culture proven UTI from culture negative samples, regardless of pyuria status. METHODS: We analyzed urine from 16 children with UTIs, 8 children with culture negative pyuria and 8 children with negative urine culture and no pyuria. The urine levels of 1,310 proteins were quantified using the Somascan™ platform and normalized to urine creatinine. Machine learning with support vector machine (SVM)-based feature selection was performed to determine the combination of urine biomarkers that optimized diagnostic accuracy. RESULTS: Eight candidate urine protein biomarkers met filtering criteria. B-cell lymphoma protein, C-X-C motif chemokine 6, C-X-C motif chemokine 13, cathepsin S, heat shock 70kDA protein 1A, mitogen activated protein kinase, protein E7 HPV18 and transgelin. AUCs ranged from 0.91 to 0.95. The best prediction was achieved by the SVMs with radial basis function kernel. CONCLUSIONS: Biomarkers panel can be identified by the emerging technologies of aptamer-based proteomics and machine learning that offer the potential to increase UTI diagnostic accuracy, thereby limiting unneeded antibiotics.