Children's & Women's Health Centre of British Columbia

To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8⁺ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in children with CKD stages 2–5, on dialysis and post-transplantation (CKD2-5D&T). The CPPs were developed and finalized using a Delphi consensus approach. We present six CPPs for vitamin management for children with CKD2-5D&T. We address assessment, intervention, and monitoring. We recommend avoiding supplementation of vitamin A and suggest water-soluble vitamin supplementation for those on dialysis. In the absence of evidence, a consistent structured approach to vitamin management that considers assessment and monitoring from dietary, physical, and biochemical viewpoints is needed. Careful consideration of the impact of accumulation, losses, comorbidities, and medications needs to be explored for the individual child and vitamin before supplementation can be considered. When supplementing, care needs to be taken not to over-prescribe. Research recommendations are suggested.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a “mature diet” high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a “pre-packaged” dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet–microbiota and microbiota–outcome associations may mediate this relationship.

Management of cancer during pregnancy requires careful consideration of risks and benefits from maternal and fetal perspectives. For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin–paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy. Considering this knowledge gap, we present a case of a young gravida 1 para 0 (G1P0) woman who continued alectinib 300 mg oral two times per day for ALK-rearranged metastatic lung adenocarcinoma throughout all 36 weeks of her pregnancy and delivered a healthy baby at term via caesarean section (C-section).

Posterior spinal fusion (PSF) is the current gold standard in surgical treatment for adolescent idiopathic scoliosis. Vertebral body tethering (VBT) is a fusionless alternative. Shoulder balance is an important metric for outcomes and patient satisfaction. Here we compare shoulder balance outcomes between PSF and VBT. In this retrospective review, the pre-operative and post-operative absolute radiographic shoulder height (|RSH|) of 45 PSF patients were compared to 46 VBT patients. Mean values were compared and then collapsed into discrete groups (|RSH| GROUP) and compared. Patients were propensity score matched. Regression models based on pretest–posttest designs were used to compare procedure type on post-operative outcomes. Pre-operatively there were no differences in |RSH| between PSF and VBT, however, at latest post-operative follow-up PSF maintained a larger |RSH| imbalance compared to VBT (0.91 cm vs 0.63 cm, p = 0.021). In an ANCOVA regression, PSF was associated with a larger |RSH| imbalance compared to VBT, F(1, 88) = 5.76, p = 0.019. An ordinal logistic regression found that the odds ratio of being in a worse |RSH| GROUP for PSF vs VBT is 2.788 (95% CI = 1.099 to 7.075), a statistically significant effect χ2(1) = 4.658, p = 0.031. Results were similar in subgroup analyses of Lenke 1 and Lenke 2 patients, though to less statistical significance. While PSF was found to be associated with worse |RSH| outcomes, the actual numbers (2–3 mm) are unlikely to be clinically meaningful. Thus, in this analysis, VBT can be said to show comparable shoulder balance outcomes to PSF.

Standardization of care seeks to improve patient outcomes and healthcare delivery by reducing unwanted variations in care as well as promoting the efficient and effective use of healthcare resources. There are many types of standardization, with clinical practice guidelines (CPGs), based on a stringent assessment of evidence and expert consensus, being the hallmark of high-quality care. This article outlines the history of CPGs, their benefits and shortcomings, with a specific focus on standardization efforts as it relates to congenital diaphragmatic hernia management.

Disasters can disrupt normal healthcare processes, with serious effects on children who depend upon regular access to the health care system. Children with medical complexity (CMC) are especially at risk. These children have chronic medical conditions, and may depend on medical technology, like feeding tubes. Without clear, evidence-based processes to connect with healthcare teams, families may struggle to access the services and supports they need during disasters. There is limited research about this topic, which has been pushed forward in importance as a result of the COVID-19 pandemic. The authors therefore conducted a rapid scoping review on this topic, with the intention to inform policy processes. Both the peer-reviewed and gray literatures on disaster, CMC, and communication were searched in summer 2020 and spring 2021. Twenty six relevant articles were identified, from which four main themes were extracted: 1. Cooperative and collaborative planning. 2. Proactive outreach, engagement, and response. 3. Use of existing social networks to connect with families. 4. Return to usual routines. Based on this review, good practices appear to involve including families, professionals, other stakeholders, and children themselves in pre-disaster planning; service providers using proactive outreach at the outset of a crisis event; working with existing peer and neighborhood networks for support; employing multiple and two-way communication channels, including social media, to connect with families; re-establishing care processes as soon as possible, which may include virtual connections; addressing mental health issues as well as physical functioning; and prioritizing the resumption of daily routines. Above all, a well-established and ongoing relationship among children, their caregivers, and healthcare teams could reduce disruptions when disaster strikes.

Short tandem repeats (STRs) are a class of repetitive elements, composed of tandem arrays of 1-6 base pair sequence motifs, that comprise a substantial fraction of the human genome. STR expansions can cause a wide range of neurological and neuromuscular conditions, known as repeat expansion disorders, whose age of onset, severity, penetrance and/or clinical phenotype are influenced by the length of the repeats and their sequence composition. The presence of non-canonical motifs, depending on the type, frequency and position within the repeat tract, can alter clinical outcomes by modifying somatic and intergenerational repeat stability, gene expression and mutant transcript-mediated and/or protein-mediated toxicities. Here, we review the diverse structural conformations of repeat expansions, technological advances for the characterization of changes in sequence composition, their clinical correlations and the impact on disease mechanisms.

PURPOSE Pediatric surgical care in low- and middle-income countries is often hindered by systemic gaps in healthcare resources, infrastructure, training, and organisation. This study aims to develop and validate the Global Assessment of Pediatric Surgery (GAPS) to appraise pediatric surgical capacity and discriminate between levels of care across diverse healthcare settings. METHODS The GAPS Version 1 was constructed through a synthesis of existing assessment tools and expert panel consultation. The resultant GAPS Version 2 underwent international pilot testing. Construct validation categorized institutions into providing Basic or Advanced Surgical Care. GAPS was further refined to Version 3 to include only questions with a > 75% response rate and those that significantly discriminated between Basic or Advanced Surgical settings. RESULTS GAPS Version 1 included 139 items, which, after expert panel feedback, was expanded to 168 items in Version 2. Pilot testing, in 65 institutions yielded a high response rate. Of the 168 questions in GAPS Version 2, 64 significantly discriminated between Basic and Advanced Surgical Care. The refined GAPS Version 3 tool comprises 64 questions: Human Resources (9), Material Resources (39), Outcomes (3), Accessibility (3), and Education (10). CONCLUSION The GAPS Version 3 tool presents a validated instrument for evaluating pediatric surgical capabilities in low-resource settings.

This cross-sectional study examines COVID-19 pandemic–related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

Objective: To use expert consensus to build a concrete and realistic framework and checklist to evaluate sustainability in Global Surgery Partnerships (GSPs). Summary background data: Partnerships between high- and low-resourced settings are often created to address the burden of unmet surgical need. Reflecting on the negative, unintended consequences of asymmetrical partnerships, global surgery community members have proposed frameworks and best practices to promote sustainable engagement between partners, though these frameworks lack consensus. This project proposes a cohesive, consensus-driven framework with accompanying evaluation metrics to guide sustainability in GSPs. Methods: A modified Delphi technique with purposive sampling was used to build consensus on the definitions and associated evaluation metrics of previously proposed pillars (Stakeholder Engagement, Multidisciplinary Collaboration, Context-Relevant Education and Training, Bilateral Authorship, Multisource Funding, Outcome Measurement) of sustainable GSPs. Results: Fifty global surgery experts from 34 countries with a median of 9.5 years of experience in the field of global surgery participated in three Delphi rounds. Consensus was achieved on the identity, definitions, and a 47-item checklist for the evaluation of the six pillars of sustainability in GSPs. 29% of items achieved consensus in the first round, whereas 100% achieved consensus in the second and third rounds. Conclusion: We present the first framework for building sustainable GSPs using the input of experts from all World Health Organization regions. We hope this tool will help the global surgery community to find non-colonial solutions to addressing the gap in access to quality surgical care in low-resource settings.

Purpose Emergency conditions such as the COVID-19 pandemic pose complex scientific and ethical challenges for researchers, which must be addressed to optimise efficiencies in trial conduct. Our purpose was to examine key factors essential to creating an agile system responsive to the rapidly changing research and clinical environment and to understand how we might learn from this unique experience to bolster research capacity in future pandemics. Methods Our evaluation employed robust qualitative descriptive methodology which comprises an approach for gathering information directly from those experiencing an event or process and flexible application of theoretical frameworks to assist in the analysis. Data was collected through individual interviews of key research stakeholders and our thematic analysis was informed by the Consolidated Framework for Implementation Research (CFIR). Results Over 17 months, we interviewed 64 participants across four research sites. Our findings uncovered key challenges in each of the 5 constructs of the CFIR: the outer setting, the inner setting, intervention characteristics, individual characteristics and rapid implantation processes which were put in place to allow crucial research to happen under extenuating circumstances. Conclusion Our data demonstrate the pandemic-magnified shortcomings of a precarious research infrastructure both in local ICUs and at the national level. Focusing investment on more efficient research platforms and administration, considering research and data sharing capacity and patient and family experience in protocol development, building a robust research workforce, and revamping the funding architecture at all levels are important lessons to promote seamless delivery of critical care research in pandemic conditions.

Aim Family Integrated Care (FICare) was developed in high‐income countries and has not been tested in resource‐poor settings. We aimed to identify the facilitators and constraints that informed the adaptation of FICare to a neonatal hospital unit in Uganda. Methods Maternal focus groups and healthcare provider interviews were conducted at Uganda's Jinja Regional Referral Hospital in 2020. Transcripts were analysed using inductive content analysis. An adaptation team developed Uganda FICare based on the identified facilitators and constraints. Results Participants included 10 mothers (median age 28 years) and eight healthcare providers (seven female, median age 41 years). Reducing healthcare provider workload, improving neonatal outcomes and empowering mothers were identified as facilitators. Maternal stress, maternal difficulties in learning new skills and mistrust of mothers by healthcare providers were cited as constraints. Uganda FICare focused on task‐shifting important but neglected patient care tasks from healthcare providers to mothers. Healthcare providers learned how to respond to maternal concerns. Intervention material was adapted to prioritise images over text. Mothers familiar with FICare provided peer‐to‐peer support to other mothers. Conclusion Uganda FICare shares the core values of FICare but was adapted to be feasible in low‐resource settings.

The increased size and enhanced compliance of the aortic bulb—the enlargement of the ascending aorta—are believed to maintain blood flow in pinnipeds during extended periods of diastole induced by diving bradycardia. The aortic bulb has been described ex vivo in several species of pinnipeds, but in vivo measurements are needed to investigate the relationship between structure and function. We obtained ultrasound images using electrocardiogram‐gated transesophageal echocardiography during anesthesia and after atropine administration to assess the relationship between aortic bulb anatomy and cardiac function (heart rate, stroke volume, cardiac output) in northern fur seals ( Callorhinus ursinus ) and Steller sea lions ( Eumetopias jubatus ). We observed that the aortic bulb in northern fur seals and Steller sea lions expands during systole and recoils over the entire diastolic period indicating that blood flow is maintained throughout the entire cardiac cycle as expected. The stroke volumes we measured in the fur seals and sea lions fit the values predicted based on body size in mammals and did not change with increased heart rates, suggesting that greater stroke volumes are not needed for aortic bulb function. Overall, our results suggest that peripheral vasoconstriction during diving is sufficient to modulate the volume of blood in the aortic bulb to ensure that flow lasts over the entire diastolic period. These results indicate that the shift of blood into the aortic bulb of pinnipeds is a fundamental mechanism caused by vasoconstriction while diving, highlighting the importance of this unique anatomical adaptation.

Background Reported rates of maternal mortality in the United States have been staggeringly high and increasing, and cardiovascular disease (CVD) is a chief contributor to such deaths. However, the impact of hypertensive disorders of pregnancy (HDP) on the short‐term risk of cardiovascular death is not well understood. Objectives To evaluate the association between HDP (chronic hypertension, gestational hypertension, preeclampsia, eclampsia, and superimposed preeclampsia) and pregnancy‐associated mortality rates (PMR) from all causes, CVD‐related causes both at delivery and within 1 year following delivery. Methods We used the Nationwide Readmissions Database (2010–2018) to examine PMRs for females 15–54 years old. International Classification of Disease 9 and 10 diagnosis codes were used to identify pregnancy‐associated deaths due to HDP and CVD. Discrete‐time Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality at delivery (0 days) and at <30, <60, <90, <180, and <365 days after delivery in relation to HDP. Results Of 33,417,736 hospital deliveries, the rate of HDP was 11.0% ( n = 3,688,967), and the PMR from CVD was 6.4 per 100,000 delivery hospitalisations ( n = 2141). Compared with normotensive patients, HRs for CVD‐related PMRs increased with HDP severity, reaching over 58‐fold for eclampsia patients. HRs were higher for stroke‐related (1.2 to 170.9) than heart disease (HD)‐related (0.99 to 39.8) mortality across all HDPs. Except for gestational hypertension, the increased risks of CVD mortality were evident at delivery and persisted 1 year postpartum for all HDPs. Conclusions HDPs are strong risk factors for pregnancy‐associated mortality due to CVD at delivery and within 1 year postpartum; the risks are stronger for stroke than HD‐related PMR. While absolute PMRs are low, this study supports the importance of extending postpartum care beyond the traditional 42‐day postpartum visit for people whose pregnancies are complicated by hypertension.

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity. Using genetically engineered monocytic U937 cells, we confirmed that DDIT4L overexpression altered mitochondrial dynamics, suppressing their activity, and blunted LPS-induced cytokine responses. We also showed that monocyte mitochondrial function is more restrictive in earlier gestation, resembling the phenotype of DDIT4L-overexpressing U937 cells. Gene expression analyses in neonatal granulocytes and lung macrophages in preterm infants confirmed upregulation of the DDIT4L gene in the early postnatal period and also suggested a potential protective role against inflammation-associated chronic neonatal lung disease. Taken together, these data show that DDIT4L regulates mitochondrial activity and provide what we believe to be the first direct evidence for its potential role supressing innate immune activity in myeloid cells during development.