Analysis of 20 Years of Ethics Consultations at a U.S. Children's Hospital.

AbstractEmpirical studies of pediatric clinical ethics cases are scant in the biomedical and bioethics literature. In this study, more than 100 detailed records of clinical ethics consultations spanning from 2000 to 2020 at a moderately sized U.S. Mid-Atlantic children's hospital were abstracted and analyzed. Findings of the analysis were generally consistent with other studies in pediatric clinical ethics, with additional insight into aspects of moral distress associated with cases, family engagement with consultations, and other characteristics of interest also documented. Over the 20-year time frame, ethics consults were completed on average twice a year, with a detectable upward trend. Consultations were requested across the spectrum of services and units within the hospital, with critical care environments represented most frequently and genetic and neurological conditions being the most common primary diagnoses. Ethical analysis most commonly related to questions around the principles of autonomy and beneficence.

Emergency Department Initiative to Decrease High-flow Nasal Cannula Use for Admitted Patients with Bronchiolitis.

Background: Despite limited evidence, a high-flow nasal cannula (HFNC) is often used to treat mild to moderate (m/m) bronchiolitis. We aimed to decrease the rate of HFNC use in the pediatric emergency department (PED) for m/m bronchiolitis from a baseline of 37% to less than 18.5%. Methods: A multidisciplinary team created a bronchiolitis pathway and implemented it in December 2019. A respiratory score (RS) in the electronic medical record objectively classified bronchiolitis severity as mild, moderate, or severe. We tracked HFNC utilization in the PED among patients with m/m bronchiolitis as our primary outcome measure between December 2019 and December 2021. We monitored the percentage of patients with an RS as a process measure. Interventions through four plan-do-study-act cycles included updating the hospital oxygen therapy policy, applying the RS to all patients in respiratory distress, modifying the bronchiolitis order set, and developing a bronchiolitis-specific HFNC order. Results: Three hundred twenty-five patients were admitted from the PED with m/m bronchiolitis during the 11-month baseline period and 600 patients during the 25-month intervention period. The mean rate of HFNC utilization decreased from 37% to 17%. Despite a decrease in bronchiolitis encounters after the pandemic, in the spring of 2021, when volumes returned, we had a sustained HFNC utilization rate of 17%. RS entry increased from 60% to 73% in the intervention period. Conclusions: A clinical pathway for bronchiolitis can lead to decreased use of HFNC for m/m bronchiolitis. Consistent RS, order set development with decision support, and education led to sustained improvement despite pandemic-related volumes.

Community Partnership to Co-Develop an Intervention to Promote Equitable Uptake of the COVID-19 Vaccine Among Pediatric Populations.

Objective: To describe the process of engaging community, caregiver, and youth partners in codeveloping an intervention to promote equitable uptake of the COVID-19 vaccine in non-Hispanic Black (Black) and Hispanic youth who experience higher rates of COVID-19 transmission, morbidity, and mortality but were less likely to receive the COVID-19 vaccine. Methods: A team of 11 Black and Hispanic community partners was assembled to codevelop intervention strategies with our interdisciplinary research team. We used a mixed-methods crowdsourcing approach with Black and Hispanic youth (n=15) and caregivers of Black and Hispanic youth (n=20) who had not yet been vaccinated against COVID-19, recruited from primary care clinics, to elicit perspectives on the acceptability of these intervention strategies. Results: We codeveloped five strategies: (1) community-tailored handouts and posters, (2) videos featuring local youth, (3) family-centered language to offer vaccines in the primary care clinic, (4) communication-skills training for primary care providers, and (5) use of community health workers to counsel families about the vaccine. The majority (56-96.9%) of youth and caregivers rated each of these strategies as acceptable, especially because they addressed common concerns and facilitated shared decision-making. Conclusions: Engaging community and family partners led to the co-development of culturally- and locally-tailored strategies to promote dialogue and shared decision-making about the COVID-19 vaccine. This process can be used to codevelop interventions to address other forms of public health disparities. Policy Implications: Intervention strategies that promote dialogues with trusted healthcare providers and support shared decision-making are acceptable strategies to promote COVID-19 vaccine uptake among youth from historically underserved communities. Stakeholder-engaged methods may also help in the development of interventions to address other forms of health disparities.

Transcriptome dataset of Caenorhabditis elegans responses to varied microbial pathogens.

Transcriptome analysis through next-generation sequencing (NGS) is an invaluable tool for investigating changes in gene expression across diverse organisms. The nematode Caenorhabditis elegans (C. elegans) serves as an excellent model organism for dissecting host responses to bacterial infections. Here, our dataset obtained from bulk RNA-sequencing (RNA-seq) can be used to provide in-depth characterization of the mRNA transcriptome profiles of wild-type N2 animals and null mutants of the cytoskeletal regulatory gene unc-53/Nav2 following exposure to distinct bacterial environments: their natural laboratory food source, Escherichia coli OP50, the human and nematode pathogen Pseudomonas aeruginosa PA14, and the emerging pathogen Elizabethkingia anophelis Ag1. As proof of the dataset quality, downstream differential gene expression analysis reveals significant shifts in gene expression patterns within N2 and unc-53 mutants under varying bacterial conditions that will be useful for our companion studies investigating these pathways. These data provide an effective methodological framework for future investigators to investigate the interplay between cytoskeletal proteins and the innate immune response. The raw FASTQ files generated from our transcriptome experiment is deposited in the publicly available NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA1010192, for further exploration and validation by the C. elegans research community.

OPTN/SRTR 2022 Annual Data Report: Pancreas.

The postpandemic recovery did not occur in pancreas transplantation as in other organs. The number of pancreas transplants in the United States decreased to 918 in 2022 from 963 in 2021. The number of simultaneous pancreas-kidney transplants decreased to 810 in 2022 from 820 in 2021, but the largest decrease was in pancreas transplant alone: 62 in 2022 compared with 92 in 2021. Pancreas-after-kidney transplants decreased to 46 in 2022 from 51 in 2021. The trend of increasing proportions of pancreas transplants in patients with type 2 diabetes seen over the past few years ended in 2022; there were 22.4% of such transplants in 2022 compared with 25.8% in 2021. The proportion of recipients older than 45 years decreased in 2022 as well. However, the proportions of candidates with type 2 diabetes and older candidates on the waiting list did not decrease. The number of pancreas donors decreased and the pancreas nonuse rate increased in 2022. Outcomes after pancreas transplant continued to improve, with an impressive 8.1% pancreas and 4.3% kidney graft failure rate for simultaneous pancreas-kidney transplant at 1 year in 2022. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants/year) returned to 37.2% in 2022 from a high of 48.3% in 2021, whereas the proportion of those done by large-volume centers (25 or more transplants/year) returned to 25.3% in 2022 from a low of 15.9% in 2021.

OPTN/SRTR 2022 Annual Data Report: Kidney.

The year 2022 had continued successes and challenges for the field of kidney transplantation, as the community adapted to ongoing surges of the COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 26,309, driven by continued growth in deceased donor kidney transplants (DDKTs). The total number of candidates listed for DDKT rose slightly in 2022 but remained below 2019 listing levels, with 12.4% of candidates having been waiting 5 years or longer. Following the height of the COVID-19 pandemic, pretransplant mortality in 2022 declined across age, race and ethnicity, sex, and blood type groups. Pretransplant mortality continued to vary substantially by donation service area. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 26.7% overall, with greater nonuse of biopsied kidneys (39.8%), kidneys from donors aged 55 years or older (54.7%), and kidneys with a kidney donor profile index (KDPI) of 85% or greater (71.3%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive rose to 30.2% but only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant (LDKT) persist, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 26.3% of adult kidney transplants in 2022. Five-year graft survival after LDKT compared with DDKT was 90.0% versus 81.4% for recipients aged 18-34 years and 80.8% versus 67.8% for recipients aged 65 years or older, respectively. The total number of pediatric kidney transplants performed in 2022 decreased to 705, its lowest point in the past decade; 502 (71.2%) were DDKTs and 203 (28.8%) were LDKTs. Among pediatric recipients, LDKT remains low, with continued racial disparities. The rate of DDKT among pediatric candidates has decreased by almost 25% since 2011. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates with a reported diagnosis. Most pediatric deceased donor recipients received a kidney from a donor with a KDPI of less than 35%. The rate of delayed graft function was 5.8% in 2022 and has been stable over the past decade. Long-term graft survival continues to improve, with superior outcomes for living donor transplant recipients.

OPTN/SRTR 2022 Annual Data Report: Deceased Organ Donation.

The Scientific Registry of Transplant Recipients uses data collected by the Organ Procurement and Transplantation Network to calculate metrics such as organs recovered per donor, organs transplanted per donor, and organs recovered for transplant but not transplanted (ie, nonuse). In 2022, there were 14,905 deceased donors, a 7.5% increase from 13,863 in 2021, and this number has been increasing since 2010. The number of deceased donor organs used for transplant increased to 37,334 in 2022, a 4.6% increase from 35,687 in 2021; this number has been increasing since 2012. The increase may be due in part to the rising number of deaths of young people amid the ongoing opioid epidemic. The number of organs transplanted included 10,130 left kidneys, 10,039 right kidneys, 298 en bloc kidneys, 922 pancreata, 8,847 livers, 83 intestines, 4,169 hearts, and 2,633 lungs. Compared with 2021, transplants of all organs except pancreata and intestines increased in 2022. In 2022, 3,563 left kidneys, 3,673 right kidneys, 156 en bloc kidneys, 366 pancreata, 965 livers, 4 intestines, 54 hearts, and 219 lungs were not used. These data suggest an opportunity to increase the number of transplants by reducing the number of unused organs. Despite the COVID-19 pandemic, there was no dramatic increase in the number of unused organs and there was an increase in the total numbers of donors and transplants.

OPTN/SRTR 2022 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2021 Annual Data Report with trends through November 12, 2022, and introduces trends in recovery and use of organs from donors with a positive COVID-19 test. Posttransplant mortality and graft failure, which remained a concern in all organs at the last report due to the Omicron variant wave, have returned to lower levels in the most recent available data through November 2022. Use of organs from donors with a positive COVID-19 test has grown, particularly after the first year of the pandemic. Mortality due to COVID-19 should continue to be monitored, but most other measures have sustained their recovery and may now be responding more to changes in policy than to ongoing concerns with COVID-19.

OPTN/SRTR 2022 Annual Data Report: Vascularized Composite Allograft.

This year's chapter on vascularized composite allograft (VCA) encompasses reviews of data collected from 2014 (when VCA was included in the Final Rule) through 2022. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and has remained consistent from the prior report. The data continue to be limited by sample size, with trends persistently demonstrating a predominance of White males in the young/middle-aged population as both donors and recipients for nonuterus VCA transplants, and White women younger than 35 years as the predominant recipients of uterus transplant. Similar to the 2021 report, there were only eight failed uterus grafts and one failed nonuterus VCA graft reported from 2014 through 2022. Standardization of definitions of success and failure as well as outcome measures for the different VCA types remain unmet needs in VCA transplantation.

Adjusting for race in metrics of organ procurement organization performance.

The Scientific Registry of Transplant Recipients has previously reported the effects of adjusting for demographic variables, including race, in the Centers for Medicare & Medicaid Services (CMS) organ procurement organization (OPO) performance metrics: donation rate and transplant rate. CMS chose not to adjust for most demographic variables other than age (for the transplant rate), arguing that there is no biological reason that these variables would affect the organ donation/utilization decision. However, organ donation is a process based on altruism and trust, not a simple biological phenomenon. Focusing only on biological impacts on health ignores other pathways through which demographic factors can influence OPO outcomes. In this study, we update analyses of demographic adjustment on the OPO metrics for 2020 with a specific focus on adjusting for race. We find that adjusting for race would lead to 8 OPOs changing their CMS tier rankings, including 2 OPOs that actually overperform the national rate among non-White donors improving from a tier 3 ranking (facing decertification without possibility of recompeting) to a tier 2 ranking (allowing the possibility of recompeting). Incorporation of stratified and risk-adjusted metrics in public reporting of OPO performance could help OPOs identify areas for improvement within specific demographic categories.

Improved Side-Effect Stimulation Thresholds and Postoperative Transient Confusion With Asleep, Image-Guided Deep Brain Stimulation.

BACKGROUND AND OBJECTIVES: Asleep, image-guided deep brain stimulation (DBS) is a modern alternative to awake, microelectrode recording (MER) guidance. Studies demonstrate comparable efficacy and complications between techniques, although some report lower stimulation thresholds for side effects with image guidance. In addition, few studies directly compare the risk of postoperative transient confusion (pTC) across techniques. The purpose of this study was to compare clinical efficacy, stimulation thresholds for side effects, and rates of pTC with MER-guided DBS vs intraoperative 3D-fluoroscopy (i3D-F) guidance in Parkinson's disease and essential tremor. METHODS: Consecutive patients from 2006 to 2021 were identified from the departmental database and grouped as having either MER-guided DBS or i3D-F-guided DBS insertion. Directional leads were used once commercially available. Changes in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, levodopa equivalent daily dose, Fahn-Tolosa-Marin scores, and stimulation thresholds were assessed, as were rates of complications including pTC. RESULTS: MER guidance was used to implant 487 electrodes (18 globus pallidus interna, GPi; 171 subthalamic nucleus; 76 ventrointermediate thalamus, VIM) in 265 patients. i3D-F guidance was used in 167 electrodes (19 GPi; 25 subthalamic nucleus; 41 VIM) in 85 patients. There were no significant differences in Unified Parkinson's Disease Rating III Scale, levodopa equivalent daily dose, or Fahn-Tolosa-Marin between groups. Stimulation thresholds for side effects were higher with i3D-F guidance in the subthalamic nucleus (MER, 2.80 mA ± 0.98; i3D-F, 3.46 mA ± 0.92; P = .002) and VIM (MER, 2.81 mA ± 1.00; i3D-F, 3.19 mA ± 1.03; P = .0018). Less pTC with i3D-F guidance (MER, 7.5%; i3D-F, 1.2%; P = .034) was also found. CONCLUSION: Although clinical efficacy between MER-guided and i3D-F-guided DBS was comparable, thresholds for stimulation side effects were higher with i3D-F guidance and the rate of pTC was lower. This suggests that image-guided DBS may affect long-term side effects and pose a decreased risk of pTC.

Impact of Centers for Medicare and Medicaid Services Final Rule on Organ Procurement Organization Metrics and Procedural Trends in the Procurement of Pancreata for Research.

OBJECTIVE: Pancreata recovered for research are included as a success (or positive) in the Centers for Medicare and Medicaid Services' (CMS) donation and organ transplantation rate metrics for recertification of organ procurement organizations (OPOs). MATERIALS AND METHODS: Given these metrics directly incentivize recovery of pancreata for research, this study tracks trends in recovery of pancreata for research across the implementation of the CMS metrics. RESULTS: In the 26 months before the December 2, 2020, publication of the CMS metrics, research pancreata as a percent of organs transplanted, including research pancreata, was 1.7% nationally, including as much as 10.8% of organs transplanted within any OPO. In the 26 months after the CMS metrics were published, research pancreata increased to 5.1% of organs counted as transplants nationally, including as much as 20.3% within any OPO. If research pancreata were excluded from the CMS metrics, 6 OPOs would change their CMS evaluation status for recertification purposes: 2 would move up a tier and 4 would move down a tier. CONCLUSIONS: Procurement of research pancreata has increased since the publication of the CMS performance metrics, OPOs vary in their recovery of pancreata for research, and recovery of pancreata for research can affect recertification of OPOs.

A Summer of Fevers and Fussiness: Eighteen Infants Admitted With Parechovirus Meningitis.

OBJECTIVE: To define the presentation, spectrum of illness, and outcomes in infants with parechovirus (PeV) meningitis admitted to our inpatient general pediatrics service during a spike in incidence of admissions in summer 2022. PATIENTS AND METHODS: This study is a retrospective case series of all patients aged 3 months and younger discharged from our institution with a CSF BioFire (BioFire Diagnostics, Salt Lake City, UT) FilmArray Polymerase Chain Reaction Meningitis/Encephalitis Panel result positive for PeV between January 1 and September 19, 2022. We collected and analyzed clinical and demographic data. RESULTS: Eighteen infants with PeV meningitis were admitted within our time frame, with 8 (44%) of the admissions occurring in July. Patients' mean age was 28.7 days and mean length of stay was 50.5 hours. Although all had a history of fever, only 72% were febrile on presentation. Laboratory findings showed a procalcitonin of less than 0.5 ng/mL in 86% of the 14 patients who had it drawn and no cerebrospinal fluid (CSF) pleocytosis in 83% of the patients who had CSF cell counts sent. Neutropenia was present in 17%. Although 89% of infants were given initial antibiotics, antibiotics were discontinued in 63% once their CSF panel returned positive for PeV, and in all by 48 hours. CONCLUSIONS: Infants hospitalized with PeV meningitis were febrile and fussy, but experienced uncomplicated hospital stays without neurological deficits. Parechovirus meningitis must be considered as a common cause of acute viral meningitis in young infants even without CSF pleocytosis. This study, although limited in scope and follow-up, can potentially assist in the diagnosis and treatment of PeV meningitis at other institutions.

Augmenting the Unites States transplant registry with external mortality data: A moving target ripe for further improvement.

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration After Tetraplegia.

BACKGROUND AND OBJECTIVES: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. METHODS: A 27-year-old right-handed man with AIS-B (motor-complete, sensory-incomplete) C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of using a brain-machine interface to read from and write to the brain for restoring motor and sensory functions of the participant's own arm and hand. RESULTS: Multiunit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions, resulting in functional movements that the participant was able to command under brain control to perform virtual and actual arm and hand movements. The system was well tolerated with no operative complications. CONCLUSION: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to create bidirectional restoration of motor and sensory functions of the arm and hand after neurological injury.

Digital ischaemia as a presenting feature in metastatic ovarian cancer.

A woman in her 50s presented with acute pain and discolouration in the fingertips of both hands, without other features of connective tissue disease. The history was otherwise significant for abdominal bloating, altered bowel habit, urinary urgency and fatigue. Inflammatory markers, antinuclear antibodies, serum protein electrophoresis and complement levels were all normal. The tumour marker CA125 was significantly elevated, prompting a CT abdomen and pelvis, which revealed a large right-sided adnexal mass with multiple enhancing peritoneal and omental nodules and moderate ascites, suggestive of disseminated primary ovarian cancer.Digital ischaemia (DI) can be associated with cancer in up to 15% of cases. An underlying cancer should be suspected in patients presenting with new or worsening symptoms of DI. Prompt treatment with anticancer therapies can achieve complete resolution of DI.

Transcriptome dataset of light-dependent expression in the early onset retinal degeneration model, Mcoln1-/- mouse.

Retinal degenerative diseases (RDDs) are a diverse group of retinal disorders that cause visual impairment. While RDD prevalence is high, little is known about the molecular mechanisms underlying the pathogenesis within many of these disorders. Here we use transcriptome analysis to elucidate the molecular mechanisms that drive early onset photoreceptor neuron function loss in the mouse model of the RDD Mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disorder resulting from loss of function mutations in the MCOLN1 gene. MCOLN1 encodes a lysosomal cation channel, the transient receptor potential channel mucolipin 1 (Trpml1). To identify changes in gene expression during onset in MLIV we used a genetic mouse model (Mcoln1-/-) which recapitulates clinical attributes of the human disease. We conducted transcriptome analysis in 6-week old control and Mcoln1-/- mice under normal 12:12 light cycle as well as low and high light stress conditions. These data will be valuable to the vision research community for identifying differentially expressed in early onset MLIV potentially leading to new insights into the pathophysiology of this RDD. Raw FASTQ files and processed counts files for the RNA-seq libraries are deposited in the NCBI Sequence Read Archive (SRA) and have been assigned BioProject accession PRJNA1002601 [1].

Space and time on the membrane: modelling Type VI secretion system dynamics as a state-dependent random walk.

The type six secretion system (T6SS) is a transmembrane protein complex that mediates bacterial cell killing. The T6SS comprises three main components (transmembrane, baseplate and sheath/tube complexes) that are sequentially assembled in order to enable an attacking cell to transport payloads into neighbouring cells. A T6SS attack disrupts the function of essential cellular components of target cells, typically resulting in their death. While the assembled T6SS adopts a fixed position in the cell membrane of the attacking cell, the location of the firing site varies between firing events. In Serratia marcescens, a post-translational regulatory network regulates the assembly and firing kinetics of the T6SS in a manner that affects the attacking cell's ability to kill target cells. Moreover, when the ability of membrane complexes to reorient is reduced, an attacking cell's competitiveness is also reduced. In this study, we will develop a mathematical model that describes both the spatial motion and assembly/disassembly of a firing T6SS. The model represents the motion of a T6SS on the cell membrane as a state-dependent random walk. Using the model, we will explore how both spatial and temporal effects can combine to give rise to different firing phenotypes. Using parameters inferred from the available literature, we show that variation in estimated diffusion coefficients is sufficient to give rise to either spatially local or global firers.