Exploring the Historical Context of American Indian/Alaska Native Intensive Care Inequities: A Narrative Review.

INTRODUCTION: This narrative review aims to frame the historical context of American Indian/Alaska Native (AI/AN) pediatric intensive care and offers suggestions for mitigating the impact of unique social drivers. METHODS: Recent literature was surveyed to determine pertinent studies describing intensive care outcomes in AI/AN children and was summarized in a narrative review. RESULTS: American Indian/Alaska Native people experience disproportionate health inequites due to unique social drivers of health, including settler colonialism, historical trauma, and systemic racism. These factors contribute to inequities in the pediatric intensive care experience, including rates of admission for injury and infectious diseases and mortality due to injuries and following cardiac surgery. DISCUSSION: These inequities are understudied and require dedicated evaluation. Institutions and providers are responsible for educating, modeling, and providing culturally competent care and aiming to achieve workforce equity to improve outcomes for AI/AN children receiving intensive care.

Recovery kinetics of dual AAV-mediated human otoferlin expression.

Deafness-causing deficiencies in otoferlin (OTOF) have been addressed preclinically using dual adeno-associated virus (AAV)-based approaches. However, timing of transduction, recombination of mRNA, and protein expression with dual hybrid AAV methods methods have not previously been characterized. Here, we have established an ex vivo assay to determine the kinetics of dual-AAV mediated expression of OTOF in hair cells of the mouse utricle. We utilized two different recombinant vectors that comprise DB-OTO, one containing the 5' portion of OTOF under the control of the hair cell-specific Myo15 promoter, and the other the 3' portion of OTOF. We explored specificity of the Myo15 promoter in hair cells of the mouse utricle, established dose response characteristics of DB-OTO ex vivo in an OTOF-deficient mouse model, and demonstrated tolerability of AAV1 in utricular hair cells. Furthermore, we established deviations from a one-to-one ratio of 5' to 3' vectors with little impact on recombined OTOF. Finally, we established a plateau in quantity of recombined OTOF mRNA and protein expression by 14 to 21 days ex vivo with comparable recovery timing to that in vivo model. These findings demonstrate the utility of an ex vivo model system for exploring expression kinetics and establish in vivo and ex vivo recovery timing of dual AAV-mediated OTOF expression.

High-Risk Anomalous Aortic Origin of the Left Coronary Artery: Consecutive Admissions Presenting With Sudden Cardiac Arrest.

Anomalous aortic origin of the left coronary artery (AAOLCA) confers high risk for sudden cardiac arrest (SCA). This series aims to describe consecutive admissions with interarterial AAOLCA presenting with SCA and distinct clinical trajectories. An eight-year-old boy collapsed at school and received 10-min of cardiopulmonary resuscitation (CPR) and defibrillation prior to return of spontaneous circulation. He had no end-organ dysfunction and underwent uneventful coronary unroofing. In contrast, a 14-year-old boy presented with collapse while jogging. He received 40-min of CPR prior to extracorporeal membranous oxygenation cannulation with multisystem dysfunction and persistent severely depressed left ventricular function. He is now rehabilitating following uneventful orthotropic heart transplantation. These cases illustrate the diverse outcomes of AAOLCA with SCA following exertional syncope.

Food insecurity in children with heart disease.

PURPOSE OF REVIEW: This review discusses the epidemiology of food insecurity (FI) and its consequences in children with congenital heart disease. We aimed to highlight current interventions to screen and address food insecurity in the context of pediatric cardiology and to offer strategies for providers to engage in this meaningful work. RECENT FINDINGS: Food insecurity is consistently associated with poor health outcomes in children. In the United States, 17.3% of households with children experience FI. Nonwhite and single-parent families are disproportionately affected. Interestingly, because of a low-quality diet, FI is associated with childhood obesity, putting affected children at increased risk for cardiovascular morbidity and mortality over time. Children with congenital heart disease are susceptible to poor outcomes due to unique altered metabolic demands, increased risk for growth impairment, frequent need for specialized feeding regimens, and additional morbidity associated with heart surgery in underweight children. SUMMARY: Today, the burden of screening for FI is most commonly placed on general pediatricians. Considering the importance of nutrition to cardiovascular health and general wellbeing, and the ease with which screening can be performed, pediatric cardiologists and other subspecialists should take a more active role in FI screening.

Analyzing interprofessional teamwork in the operating room: An exploratory observational study using conventional and alternative approaches.

Intraoperative teamwork is vital for patient safety. Conventional tools for studying intraoperative teamwork typically rely on behaviorally anchored rating scales applied at the individual or team level, while others capture narrative information across several units of analysis. This prospective observational study characterizes teamwork using two conventional tools (Operating Theatre Team Non-Technical Skills Assessment Tool [NOTECHS]; Team Emergency Assessment Measure [TEAM]), and one alternative approach (modified-Systems Engineering Initiative for Patient Safety [SEIPS] model). We aimed to explore the advantages and disadvantages of each for providing feedback to improve teamwork practice. Fifty consecutive surgical cases at a Canadian academic hospital were recorded with the OR Black Box®, analyzed by trained raters, and summarized descriptively. Teamwork performance was consistently high within and across cases rated with NOTECHS and TEAMS. For cases analyzed with the modified-SEIPS tool, both optimal and suboptimal teamwork behaviors were identified, and team resilience was frequently observed. NOTECHS and TEAM provided summative assessments and overall pattern descriptions, while SEIPS facilitated a deeper understanding of teamwork processes. As healthcare organizations continue to prioritize teamwork improvement, SEIPS may provide valuable insights regarding teamwork behavior and the broader context influencing performance. This may ultimately enhance the development and effectiveness of multi-level teamwork interventions.

Feeding Difficulties Following Vascular Ring Repair: A Contemporary Narrative Review.

Vascular rings are congenital abnormalities of the aortic arch vascular system that compress the trachea and esophagus. A review of long-term outcomes suggests that chronic feeding difficulties can persist following surgical repair of vascular rings. Previous reports of postoperative vascular ring division outcomes indicate that chronic esophageal symptoms may persist following repair, though most available data focuses on persistent respiratory symptoms. It is therefore the aim of this article to summarize and organize recent evidence reporting the frequency, presentation, and management of feeding difficulties following vascular ring repair in pediatric patients. Pathophysiologic mechanisms for postoperative esophageal symptoms may include residual compression from an unresected diverticulum of Kommerell or delayed repair leading to chronic esophageal dysmotility despite correction of esophageal compression. Guidance on the management of feeding difficulties following vascular ring repair is limited. The authors describe success in one case with nasogastric tube feeding and interdisciplinary evaluation. Consensus regarding the management of feeding difficulty following vascular ring repair is needed.

Diagnosis of EVALI in Adolescents During the COVID-19 Pandemic: A Case Series.

OBJECTIVE: Electronic-cigarette or vaping use-associated lung injury (EVALI) is an illness that requires further awareness for appropriate diagnosis and management. This series is a retrospective chart review of EVALI cases admitted from June to December 2020 at a large academic children's hospital in New York. METHODS: Notably during this time, the coronavirus disease 2019 (COVID-19) global pandemic rendered the world under strict quarantine mandates. We discuss 7 patients, all of whom were seen in a clinic, urgent care, or emergency department before presentation to our hospital. RESULTS: Patients presented with respiratory, gastroenterology, and constitutional complaints typically seen with EVALI and COVID-19. However, given their complex presentations in the setting of the COVID-19 pandemic, EVALI was not considered as pertinent history was not elicited. CONCLUSIONS: With the COVID-19 pandemic as a setting for these cases, we emphasize the importance of eliciting a complete psychosocial history for all adolescents because without vaping disclosure, EVALI will go undiagnosed. It is also imperative to ensure consistent outpatient follow-up, although difficult because of limited access or hesitation and fear of acquiring COVID-19 in health care settings during the pandemic, and to stress vaping cessation, both of which are crucial in preventing further complications.

Tranexamic acid for prevention of bleeding in cesarean delivery: An overview of systematic reviews.

BACKGROUND: Bleeding is the leading cause of maternal mortality in the world. Tranexamic acid reduces bleeding in trauma and surgery. Several systematic reviews of randomized trials have investigated tranexamic acid in the prevention of bleeding in cesarean delivery. However, the conclusions from systematic reviews are conflicting. This overview aims to summarize the evidence and explore the reasons for conflicting conclusions across the systematic reviews. METHODS: A comprehensive literature search of Medline, Embase, and Cochrane Database of Systematic Reviews was conducted from inception to April 2021. Screening, data extraction, and quality assessments were performed by two independent reviewers. A Measurement Tool to Assess Reviews 2 and the Risk of Bias Assessment Tool for Systematic Reviews were used for study appraisal. A qualitative synthesis of evidence is presented. RESULTS: In all, 14 systematic reviews were included in our analysis. Across these reviews, there were 32 relevant randomized trials. A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain. CONCLUSIONS: Systematic reviews investigating prophylactic tranexamic acid in cesarean delivery are heterogeneous in terms of methodological and reporting quality. Tranexamic acid may reduce blood transfusion and bleeding outcomes, but rigorous well-designed research is needed due to the limitations of the included studies. Data on safety and adverse effects are insufficient to draw conclusions.

How gender shapes interprofessional teamwork in the operating room: a qualitative secondary analysis.

BACKGROUND: Despite substantial implications for healthcare provider practice and patient outcomes, gender has yet to be systematically explored with regard to interprofessional operating room (OR) teamwork. We aimed to explore and describe how gender and additional social identity factors shape experiences and perceptions of teamwork in the OR. METHODS: This study was a qualitative secondary analysis of semi-structured interviews with OR team members conducted between November 2018 and July 2019. Participants were recruited across hospitals in Ontario, Canada. We conducted both purposive and snowball sampling until data saturation was reached. Transcripts were analyzed thematically by two independent research team members, moving from open to axial coding. RESULTS: Sixty-six interviews of OR healthcare professionals were completed: anesthesia (n=17), nursing (n=19), perfusion (n=2), and surgery (n=26). Traditional gender roles, norms, and stereotypes were perceived and experienced by both women and men, but with different consequences. Both women and men participants described challenges that women face in the OR, such as being perceived negatively for displaying leadership behaviours. Participants also reported that interactions and behaviours vary depending on the team gender composition, and that other social identities, such as age and race, often interact with gender. Nevertheless, participants indicated a belief that the influence of gender in the OR may be modified. CONCLUSIONS: The highly gendered reality of the OR creates an environment conducive to breakdowns in communuication and patient safety risks in addition to diminishing team morale, psychological safety, and provider well-being. Consequently, until teamwork interventions adequately account for gender, they are unlikely to be optimally effective or sustainable.

Mapping multicenter randomized controlled trials in anesthesiology: a scoping review.

BACKGROUND: Evidence suggests that there are substantial inconsistencies in the practice of anesthesia. There has not yet been a comprehensive summary of the anesthesia literature that can guide future knowledge translation interventions to move evidence into practice. As the first step toward identifying the most promising interventions for systematic implementation in anesthesia practice, this scoping review of multicentre RCTs aimed to explore and map the existing literature investigating perioperative anesthesia-related interventions and clinical patient outcomes. METHODS: Multicenter randomized controlled trials were eligible for inclusion if they involved a tested anesthesia-related intervention administered to adult surgical patients (≥ 16 years old), with a control group receiving either another anesthesia intervention or no intervention at all. The electronic databases Embase (via OVID), MEDLINE, and MEDLINE in Process (via OVID), and Cochrane Central Register of Control Trials (CENTRAL) were searched from inception to February 26, 2021. Studies were screened and data were extracted by pairs of independent reviewers in duplicate with disagreements resolved through consensus or a third reviewer. Data were summarized narratively. RESULTS: We included 638 multicentre randomized controlled trials (n patients = 615,907) that met the eligibility criteria. The most commonly identified anesthesia-related intervention theme across all studies was pharmacotherapy (n studies = 361 [56.6%]; n patients = 244,610 [39.7%]), followed by anesthetic technique (n studies = 80 [12.5%], n patients = 48,455 [7.9%]). Interventions were most often implemented intraoperatively (n studies = 233 [36.5%]; n patients = 175,974 [28.6%]). Studies typically involved multiple types of surgeries (n studies = 187 [29.2%]; n patients = 206 667 [33.5%]), followed by general surgery only (n studies = 115 [18.1%]; n patients = 201,028 [32.6%]) and orthopedic surgery only (n studies = 94 [14.7%]; n patients = 34,575 [5.6%]). Functional status was the most commonly investigated outcome (n studies = 272), followed by patient experience (n studies = 168), and mortality (n studies = 153). CONCLUSIONS: This scoping review provides a map of multicenter RCTs in anesthesia which can be used to optimize future research endeavors in the field. Specifically, we have identified key knowledge gaps in anesthesia that require further systematic assessment, as well as areas where additional research would likely not add value. These findings provide the foundation for streamlining knowledge translation in anesthesia in order to reduce practice variation and enhance patient outcomes.

The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-related neurologic complications have a diverse presentation in transplant recipients, creating diagnostic and therapeutic challenges for clinicians. In this case series, we report unique manifestations of EBV related neurologic complications following solid organ transplant and highlight pitfalls in management. CASE PRESENTATIONS: A retrospective search of the electronic medical record of all patients from January 2015 to December 2020 who underwent solid organ transplantation and had central nervous system complications as determined by ICD-10 codes were included. Three patients with unique manifestation of EBV-related neurologic complications after liver transplantation were identified. The first was a 52-year-old man with a live-donor liver transplant 11 years prior for Budd-Chiari syndrome presented with several weeks of headache and several lesions on brain MRI; he was diagnosed with primary central nervous system post-transplant lymphoproliferative disorder. The second patient was a 63-year-old man with a deceased-donor liver transplant 16 years prior for alpha-1-antitrypsin deficiency and was found to have a stroke; he was diagnosed with EBV encephalitis. The final patient was a 75-year-old woman with a deceased-donor liver transplant six years prior for primary biliary cirrhosis who presented with four months of gait instability; she was diagnosed with EBV myelitis. A review of the literature was performed to supplement description of the different diseases. CONCLUSIONS: EBV-related central nervous infection in post-transplant patients can manifest in a variety of neurologic syndromes, which can be challenging to diagnose. Careful correlation of clinical, pathologic, and radiologic findings and a high index of suspicion are crucial in identification and appropriate management.

Movement Disorder Emergencies.

Acute presentation of new movement disorders and acute decompensation of chronic movement disorders are uncommon but potentially life-threatening. Inadvertent or purposeful overdose of many psychiatric medications can result in acute life-threatening movement disorders including serotonin syndrome, neuroleptic malignant syndrome, and malignant catatonia. Early withdrawal of potentiating medications, treatment with benzodiazepines and other diagnosis-specific drugs, and providing appropriate supportive care including airway and breathing management, hemodynamic stabilization, fluid resuscitation, and renal support including possible hemodialysis are the mainstays of acute management. Many of these conditions require admission to the neurologic intensive care unit.

Arthroscopic Repair of Medium to Large Rotator Cuff Tears With a Triple-Loaded Medially Based Single-Row Technique Augmented With Marrow Vents.

PURPOSE: The primary purpose of this study was to evaluate the repair integrity on magnetic resonance imaging (MRI), and secondarily, clinical outcomes, of medium to large (2-4 cm) rotator cuff tears treated using an arthroscopic triple-loaded medially based single-row repair technique augmented laterally with bone marrow vents. METHODS: This is a retrospective outcomes study of patients with full-thickness medium to large (2-4 cm) rotator cuff tears repaired by 4 surgeons at a single institution over a 2-year period with a minimum of 24 months' follow-up. A single-row repair with tension-minimizing medially based triple-loaded anchors and laterally placed bone marrow vents was used. Patients completed a satisfaction and pain survey, the Western Ontario Rotator Cuff index questionnaire, and a Short Form-36 version 2 survey to evaluate clinical outcomes. MRI was obtained at a minimum of 24 months follow-up to assess repair integrity. RESULTS: A total of 64 males and 27 females with a mean age of 59.7 (range, 34-82) were included. The mean tear size was 2.6 cm in anteroposterior dimension, treated with a mean of 2.2 anchors. Eighty-three of 91 shoulders (91%) reported being completely satisfied with their result. The median Western Ontario Rotator Cuff score was 95.2% of normal, with a significant difference found between those with an intact repair and those with a full-thickness recurrent defect (median, 95.9% vs. 73.8%; P = .003). Postoperative MRI obtained at a median of 32 months (range, 24-48) demonstrated an intact repair in 84 of 91 shoulders (92%), with failure defined as a full-thickness defect of the tendon. CONCLUSIONS: Arthroscopic repair of medium to large rotator cuff tears using triple-loaded medially based single-row repair augmented with marrow vents resulted in a 92% healing rate by MRI and excellent patient-reported outcomes LEVEL OF EVIDENCE: Level IV, retrospective case series.

A structured curriculum and procedure clinic to help family medicine residents diagnose and treat skin cancer.

Melanoma is a potentially deadly type of skin cancer that has been increasing in incidence but is curable if found in the early stages. Family physicians are in an ideal situation to examine the skin during routine visits, but studies indicate they are not well trained to detect or treat skin cancers. We piloted a structured, longitudinal, hands-on procedural curriculum to improve family medicine residents' ability to identify and manage skin cancers. Family medicine residency programs wishing to improve the diagnosis and management of skin cancer by family physicians might consider trialing our structured curriculum and procedure clinic.

Le mélanome est un type de cancer de la peau potentiellement mortel qui est de plus en plus fréquent, mais qui est guérissable sous réserve d'une détection précoce. La visite de routine chez le médecin de famille est l'occasion idéale pour examiner la peau. Les études indiquent toutefois que les médecins de famille n'ont pas le niveau de formation nécessaire pour détecter et traiter les cancers de la peau. Nous avons piloté un programme structuré longitudinal axé sur la pratique visant à améliorer la capacité des résidents en médecine familiale à identifier et à traiter ce type de cancer. Nous invitons les responsables de programmes de résidence en médecine familiale qui souhaitent améliorer le diagnostic et la prise en charge des cancers cutanés par les médecins de famille à expérimenter notre programme structuré sur les procédures cliniques.

Evaluation of a unilateral neck mass in a 16-year-old female: Kikuchi-Fujimoto disease with superimposed bacterial lymphadenitis.

The evaluation of pediatric neck masses offers the opportunity for consideration of a diverse range of pathologies, from infectious to neoplastic. A 16-year-old female presented with 2 weeks of worsening swelling and pain of a left-sided neck mass. Findings were consistent with Epstein-Barr virus and cytomegalovirus coinfection, but considering profound lymphadenopathy of the supraclavicular, mammillary, and axillary chains, further investigations were undertaken. Hematopathologic examination demonstrated necrotizing lymphadenitis, consistent with Kikuchi-Fujimoto disease. A diagnosis of Kikuchi-Fujimoto disease alongside chronic bacterial lymphadenitis was made on the basis of her response to clindamycin, and the chronic course of her illness and subsequent persistence of the swelling managed on an outpatient basis. The case study describes the initial diagnostic considerations and management as well as a review of the disease pathology.

Toxin-Induced Subacute Encephalopathy.

Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize-in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide, antibiotics, antineoplastic agents, and psychiatric medications.

Sporadic activation of an oxidative stress-dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies.

Breast and mammary epithelial cells experience different local environments during tissue development and tumorigenesis. Microenvironmental heterogeneity gives rise to distinct cell regulatory states whose identity and importance are just beginning to be appreciated. Cellular states diversify when clonal three-dimensional (3D) spheroids are cultured in basement membrane, and one such state is associated with stress tolerance and poor response to anticancer therapeutics. Here, we found that this state was jointly coordinated by the NRF2 and p53 pathways, which were costabilized by spontaneous oxidative stress within 3D cultures. Inhibition of NRF2 or p53 individually disrupted some of the transcripts defining the regulatory state but did not yield a notable phenotype in nontransformed breast epithelial cells. In contrast, combined perturbation prevented 3D growth in an oxidative stress-dependent manner. By integrating systems models of NRF2 and p53 signaling in a single oxidative stress network, we recapitulated these observations and made predictions about oxidative stress profiles during 3D growth. NRF2 and p53 signaling were similarly coordinated in normal breast epithelial tissue and hormone-negative ductal carcinoma in situ lesions but were uncoupled in triple-negative breast cancer (TNBC), a subtype in which p53 is usually mutated. Using the integrated model, we correlated the extent of this uncoupling in TNBC cell lines with the importance of NRF2 in the 3D growth of these cell lines and their predicted handling of oxidative stress. Our results point to an oxidative stress tolerance network that is important for single cells during glandular development and the early stages of breast cancer.

Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis.

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). OBJECTIVE: To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.