Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy.

INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.

Disparities in postoperative complications and perioperative events based on insurance status following elective spine surgery: A systematic review and meta-analysis.

Background: Increasing evidence demonstrates disparities among patients with differing insurance statuses in the field of spine surgery. However, no pooled analyses have performed a robust review characterizing differences in postoperative outcomes among patients with varying insurance types. Methods: A comprehensive literature search of the PUBMED, MEDLINE(R), ERIC, and EMBASE was performed for studies comparing postoperative outcomes in patients with private insurance versus government insurance. Pooled incidence rates and odds ratios were calculated for each outcome and meta-analyses were conducted for 3 perioperative events and 2 types of complications. In addition to pooled analysis, sub-analyses were performed for each outcome in specific government payer statuses. Results: Thirty-eight studies (5,018,165 total patients) were included. Compared with patients with private insurance, patients with government insurance experienced greater risk of 90-day re-admission (OR 1.84, p<.0001), non-routine discharge (OR 4.40, p<.0001), extended LOS (OR 1.82, p<.0001), any postoperative complication (OR 1.61, p<.0001), and any medical complication (OR 1.93, p<.0001). These differences persisted across outcomes in sub-analyses comparing Medicare or Medicaid to private insurance. Similarly, across all examined outcomes, Medicare patients had a higher risk of experiencing an adverse event compared with non-Medicare patients. Compared with Medicaid patients, Medicare patients were only more likely to experience non-routine discharge (OR 2.68, p=.0007). Conclusions: Patients with government insurance experience greater likelihood of morbidity across several perioperative outcomes. Additionally, Medicare patients fare worse than non-Medicare patients across outcomes, potentially due to age-based discrimination. Based on these results, it is clear that directed measures should be taken to ensure that underinsured patients receive equal access to resources and quality care.

Problem-solving processes for central venous catheter occlusion within pediatric cancer care: A qualitative study.

PURPOSE: Central venous access devices play a crucial role in healthcare settings. However, there is concern regarding the high incidence of blockages occurring before the completion of treatments and existing guidelines for occlusion management are not consistently followed. To explore the decision-making and problem-solving process of occlusion management and identify enablers and barriers to implementing evidence for occlusion management in pediatric cancer care. METHODS: A qualitative design with individual semi-structured interviews. Participants were selected by purposeful sampling from a tertiary-referral pediatric facility, and semi-structured interviews were conducted. RESULTS: A total of 13 clinicians and 5 parents were interviewed. The thematic analysis revealed four main decision-making/problem-solving themes: 1) clinical reasoning and judgement for central venous access devices occlusion, 2) capability in central venous access devices occlusion management, 3) colleague collaboration in the escalation process and 4) lack of adequate support to manage the occlusion. This study identified positive and negative influences on the problem-solving process, including clinicians' psychological capabilities, social and physical resources, and beliefs about consequences. CONCLUSION: This study found that clinicians in pediatric cancer care were able to manage central venous access device occlusions using clinical reasoning and judgment skills, which may conflict with evidence-based practices. The study confirmed the importance of a team approach and prior experience in managing central venous access devices in pediatric oncology settings and identified potential conflicts between clinician decisions based on the patient's current and anticipated conditions and implementation of evidence-based practice. Improving documentation and providing visual aids could benefit clinicians' problem-solving processes.

An mHealth application for chronic vascular access: Consumer led co-creation.

PURPOSE: Children with chronic and complex health conditions frequently need intravenous devices. The current approach to intravenous device selection, insertion, and monitoring is inconsistent, and healthcare consumers are often negatively affected by siloed health information, and poor future planning. Despite child- and family-centred care being recognised as a pillar of paediatric nursing care, limited implementation for vascular access device planning and management is evident. DESIGN AND METHODS: To address this, we conducted a multi-phased approach to co-create, then evaluate, a mobile health (mHealth) application: IV Passport. Co-creation involved a prioritisation survey, followed by a Passport advisory panel consensus meeting. Following confirmation of the required content and features of the Passport, the mHealth application was designed and content validation achieved via survey. RESULTS: The prioritisation survey yielded recommendations for seven features (e.g., graphical presentations of current/past devices). Content for nine device types (e.g., totally implanted ports) was suggested, each with 10 related items (e.g., insertion site). Content items for device-associated complications, future vascular access plans, and educational resources were also suggested. Following design, the application was released through Apple and Android platforms; and adapted to a paper version. Content validation was established; 100% strongly agreed the application was easy to use; 80% agreed/strongly agreed that they would recommend the Passport to others. CONCLUSION: IV Passport embodies effective child- and family-centred care through consumer co-creation to empower patients and families manage vascular access devices. PRACTICE IMPLICATIONS: IV Passport remains active; and can be utilised across many healthcare settings and patient populations.

Silver Compounds for Caries Management.

Silver metal and compounds have antibacterial properties, although their action's mechanisms are not fully understood. Scientists generally consider that silver disrupts the bacterial cell wall. It causes a structural change in the bacterial cell membrane and cytoplasm. It also stops deoxyribonucleic acid replication, resulting in inactivating enzymatic activity and cell death. The antimicrobial effect of silver-containing compounds relies on the release of bioactive silver ions. Hence, silver metal and compounds have been used in medicine to prevent infection for hundreds of years. Silver metal and compounds are also used as antibacterial agents in dentistry. Studies have shown that silver compounds are effective in the management of dental caries. Fluoride-containing silver compounds have been found in experiments to be beneficial at remineralising dental cavities. Silver diamine fluoride (SDF) can assist in preventing and arresting tooth cavities. The World Health Organization included SDF in its Model List of Essential Medicine for both adults and children in 2021. Clinicians also use SDF to manage dentine hypersensitivity as well as to inhibit growth of periodontal pathogens. However, traditional silver compounds cause tooth discolouration because of the silver-staining effect. These side effects of their applications depend on the amount applied and the frequency of application. Researchers are developing nanosilver fluoride and silver nanoparticles to overcome the staining. This review gives an overview of the antibacterial mechanism of silver compounds, namely silver nitrate, silver fluoride, SDF, silver nanoparticles, and nano silver fluoride for caries management. The outlook for the future development of silver compounds will be discussed.

Gender disparities in postoperative outcomes following elective spine surgery: a systematic review and meta-analysis.

OBJECTIVE: Several studies have described disparities between male and female patients following spine surgery, but no pooled analyses have performed a robust review characterizing differences in postoperative outcomes based on gender. The purpose of this study was to broadly assess the effects of gender on postoperative outcomes following elective spine surgery. METHODS: Between November 2022 and March 2023, PubMed, MEDLINE, ERIC, and Embase were queried using artificial intelligence-assisted software for relevant cohort studies. Cohort studies with a minimum sample of 100 patients conducted in the United States since 2010 were eligible. Studies related to trauma, tumors, infections, and spinal cord pathology were excluded. Independent extraction by multiple reviewers was performed using Nested Knowledge software. A fixed- or random-effects model was used if heterogeneity among included studies in a meta-analysis was < 50% or ≥ 50%, respectively. Risk of bias was assessed independently by multiple reviewers using the Newcastle-Ottawa Scale. Pooled effect sizes were calculated for readmission, nonroutine discharge (NRD), length of stay (LOS), extended LOS, reoperation, mortality, all medical complications (individual analyses for cardiovascular, deep venous thrombosis/pulmonary embolism, genitourinary, neurological, respiratory, and systemic infection complications), and wound-related complications. For each outcome, two subanalyses were performed with studies that used either center-based (single- or multi-institution) or high-volume (national or state-wide) databases. RESULTS: Across 124 included studies, male patients had an increased incidence of mortality (OR 0.54, p < 0.0001) and all medical complications (OR 0.80, p = 0.0114), specifically cardiovascular (OR 0.68, p < 0.0001) and respiratory (OR 0.76, p = 0.0008) complications. Female patients were more likely to experience a wound-related surgical complication (OR 1.16, p = 0.0183). These findings persisted in the high-volume database subanalyses. Only center-based subanalyses showed that female patients were at greater odds of experiencing an NRD (OR 1.18, p = 0.0476), longer LOS (SMD 0.23, p = 0.0036), and extended LOS (OR 1.28, p < 0.0001). CONCLUSIONS: Males are more likely to experience death and medical complications, whereas females were more likely to face wound-related surgical complications. At the institution level, females more often experience NRD and longer hospital stays. These findings may better inform preoperative expectation management and provide more detailed postoperative risk assessments based on the patient's gender.

Optimized expression and purification of a human adenosine deaminase in E. coli and characterization of its Asp8Asn variant.

Homo sapiens adenosine deaminase isoform 1 (HsADA1) hydrolyzes adenosine and 2-deoxyadenosine as a key step in the purine nucleoside salvage pathway. Some HsADA1 mutations have severe deleterious effects, as is the case in a severe combined immunodeficiency resulting from loss of enzyme activity (ADA-SCID). Other mutations that reduce enzyme activity, for instance the Asp8Asn (D8N) variant, do not cause ADA-SCID but are correlated with other consequences to health. To ease further study of HsADA1 and its variants, we optimized an inexpensive, recombinant expression process in an Escherichia coli host through multiplexed parameter testing enabled by a lysate-based microtiter plate assay. We demonstrate the importance of gene codon usage, induction time and temperature, and alcohol supplementation towards improving enzyme yield to a final titer of 5 mg per liter of culture. We further show that use of a double-histidine-tag (his-tag) system greatly improves purity. We then utilize our expression and purification framework to produce the HsADA1 D8N variant, which had previously not been purified to homogeneity. We confirm that the D8N variant is ∼30% less active than the wildtype HsADA1 and show that it better retains its activity in human serum. Additionally, we show that both HsADA1 and the D8N variant have heightened activity in serum, driven in part by a previously undescribed phenomenon involving albumin. Therefore, this work presents a valuable process to produce HsADA1 that allows for insights into it and its variants' behavior. We also confirm the utility of lysate-based activity assays towards finding optimal E. coli expression conditions for enzymes and show how fusing his-tags in tandem can enhance product purity.

Infection Associated With Invasive Devices in Pediatric Health Care: A Meta-analysis.

CONTEXT: Indwelling invasive devices inserted into the body for extended are associated with infections. OBJECTIVE: This study aimed to estimate infection proportion and rates associated with invasive devices in pediatric healthcare. DATA SOURCES: Medline, CINAHL, Embase, Web of Science, Scopus, Cochrane CENTRAL, clinical trial registries, and unpublished study databases were searched. STUDY SELECTION: Cohort studies and trials published from January 2011 to June 2022, including (1) indwelling invasive devices, (2) pediatric participants admitted to a hospital, (3) postinsertion infection complications, and (4) published in English, were included. DATA EXTRACTION: Meta-analysis of observational studies in epidemiology guidelines for abstracting and assessing data quality and validity were used. MAIN OUTCOMES AND MEASURES: Device local, organ, and bloodstream infection (BSIs) pooled proportion and incidence rate (IR) per-1000-device-days per device type were reported. RESULTS: A total of 116 studies (61 554 devices and 3 632 364 device-days) were included. The highest number of studies were central venous access devices associated BSI (CVAD-BSI), which had a pooled proportion of 8% (95% confidence interval [CI], 6-11; 50 studies) and IR of 0.96 per-1000-device-days (95% CI, 0.78-1.14). This was followed by ventilator-associated pneumonia in respiratory devices, which was 19% (95% CI, 14-24) and IR of 14.08 per-1000-device-days (95%CI, 10.57-17.58). CONCLUSIONS: Although CVAD-BSI and ventilator associated pneumonia are well-documented, there is a scarcity of reporting on tissue and local organ infections. Standard guidelines and compliance initiatives similar to those dedicated to CVADs should be implemented in other devices in the future.

A disordered region controls cBAF activity via condensation and partner recruitment.

Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct "sequence grammars" underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are essential for chromatin localization and activity. Importantly, human disease-associated perturbations in ARID1B IDR sequence grammars disrupt cBAF function in cells. Together, these data identify IDR contributions to chromatin remodeling and explain how phase separation provides a mechanism through which both genomic localization and functional partner recruitment are achieved.

Overshadowed by shadowing: exploring how Canadian medical students experience shadowing.

Background: Preclinical medical students commonly perceive shadowing as beneficial for career exploration. However, research is sparse on the broader impact of shadowing as a learning strategy. We explored students' perceptions and lived experiences of shadowing to understand its role and impact on their personal and professional lives. Methods: Between 2020-2021, individual semi-structured video interviews were conducted with 15 Canadian medical students in this qualitative descriptive study. Inductive analysis proceeded concurrently with data collection until no new dominant concepts were identified. Data were iteratively coded and grouped into themes. Results: Participants described internal and external factors that moulded shadowing experiences, arising tensions between intended and perceived experiences, and how these lived experiences impacted their wellness. Internal factors associated with shadowing behaviour included: 1) aspiring to be the best and shadowing to demonstrate excellence, 2) shadowing for career exploration, 3) shadowing as learning opportunities for early clinical exposure and career preparedness, and 4) reaffirming and redefining professional identity through shadowing. External factors were: 1) unclear residency match processes which position shadowing as competitive leverage, 2) faculty messaging that perpetuates student confusion around the intended value of shadowing, and 3) social comparison in peer discourse, fuelling a competitive shadowing culture. Conclusions: The tension between balancing wellness with career ambitions and the unintended consequences of unclear messaging regarding shadowing in a competitive medical culture highlights issues inherent in shadowing culture.

Contexte: De manière générale, les étudiants en médecine préclinique considèrent que l'observation présente une occasion intéressante d'explorer les possibilités de carrière. Cependant, peu de recherches ont été menées sur l'impact plus large de l'observation comme stratégie d'apprentissage. Nous avons exploré les perceptions et les expériences vécues des étudiants en matière d'observation afin de comprendre son rôle et ses répercussions sur leur vie personnelle et professionnelle. Méthodes: Dans le cadre de cette étude qualitative descriptive, entre 2020 et 2021, des entretiens vidéo individuels semi-structurés ont été menés avec 15 étudiants en médecine canadiens. L'analyse inductive s'est déroulée simultanément à la collecte des données jusqu'à ce qu'aucun concept dominant nouveau n'apparaisse. Les données ont été codées de manière itérative et regroupées en thèmes. Résultats: Les participants ont décrit les facteurs internes et externes qui ont façonné leur expérience de l'observation et les tensions qui en ont découlé, ainsi que l'impact de ces expériences sur leur bien-être. Les facteurs internes associés au comportement d'observation sont les suivants : 1) vouloir être le meilleur et faire de l'observation pour montrer son excellence, 2) faire de l'observation dans le but d'explorer les débouchés de carrière, 3) faire de l'observation pour apprendre par l'exposition clinique précoce et pour se préparer à la carrière, et 4) réaffirmer et redéfinir l'identité professionnelle par l'observation. Les facteurs externes sont 1) le manque de clarté dans les processus de jumelage des résidents pouvant donner l'impression que l'observation est un atout, 2) le discours enseignant qui entretient la confusion des étudiants quant à la valeur de l'observation, et 3) la comparaison sociale dans le discours des pairs, alimentant une culture de l'observation compétitive. Conclusions: La difficulté de trouver un équilibre entre le bien-être et les ambitions professionnelles, et les conséquences involontaires d'un discours peu clair concernant l'observation dans le contexte d'un climat compétitif mettent en évidence les problèmes inhérents à la culture de l'observation.

Comprehension, Utility, and Acceptability of a Multidomain Physical Functioning Report for Systemic Lupus Erythematosus Patients and Their Providers.

OBJECTIVE: Patient-provider discussions about functioning are often outside the scope of usual care for systemic lupus erythematosus (SLE), and tools to facilitate such discussions are lacking. The present study was undertaken to assess the comprehension, utility, and acceptability of a novel, individualized functioning report, the purpose of which is to facilitate patient-provider communication about functioning, in a predominantly Black SLE patient population. METHODS: Individualized reports (including sections with pictorial representations of participants' measured activities of daily living, falls, physical performance, perceived physical functioning, and community mobility from a previous pilot study visit) and surveys were emailed or mailed to 59 SLE patients. Ease of interpretation was dichotomized ("very easy" versus all other responses). Utility and acceptability were assessed by items relating to usefulness for care planning and comfort with discussing the report. RESULTS: Among 47 (79.7%) SLE patients who completed the survey (78.7% Black, 91.5% female, mean age 49.6 years), the reported ease of interpretation ranged from 70.2% to 85.1% across the report sections. Ease of interpretation was lower among those who were older, Black, and female and who had lower cognitive scores (P > 0.05 for all). Most reported that physical functioning domains of the report were useful for treatment or other care planning (70.2-80.5%) and that they felt comfortable discussing the report with a health care provider (93.2-100%). CONCLUSION: We found that a novel functioning report for SLE patients was associated with high comprehension, utility, and acceptability. Future studies can help determine how an individualized functioning report could improve patient-provider communication in the clinic setting.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review. METHODS: We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges's g = -0.870, 95% confidence intervals (CI) = [-1.225 to -0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms. CONCLUSION: tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.

Testing surge capacity-A Canadian COVID-19 experience, Ontario's surge capacity for the first wave.

As of September 1st 2020, over 42 000 COVID-19 cases and 2 800 COVID-19-related deaths have been confirmed in Ontario, Canada. Testing enables quick identification of cases, which results in effective contact tracing and containment of virus spread. Faced with a lack of surge capacity in the public health laboratory system at the start, health officials implemented changes to testing and laboratory infrastructure to significantly expand testing capacity to include 1) the centralization of resources; and 2) the integration of private and independent labs into the COVID-19 testing program. With these changes, testing capacity has grown from approximately 4,000/day in March to 32,000/day by the end of August, 2020. Eligibility criteria for testing has expanded to increase sensitivity and include testing of asymptomatic individuals. Along with previous outbreaks, the COVID-19 pandemic has highlighted the need for integration of testing surge capacity in public health systems before outbreaks occur. This paper details the development and implementation of a COVID-19 testing program in Ontario from January 2020 to September 2020 during the first-wave of the pandemic. The goal of this analysis is to explore the historical precedence, present influences, and future implications of the program.

Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study.

Inflammatory biomarkers may be associated with disease severity and increased mortality in COVID-19 patients but have not been studied in North American populations. We sought to determine whether a set of commonly ordered inflammatory biomarkers can predict 28-day mortality. We analyzed a multi-centered (four) COVID-19 registry cohort from March 4th to December 7th, 2020. This cohort included COVID-19-positive patients admitted to medical wards or intensive care units. Patients presenting to the emergency department for COVID-19 symptoms and then subsequently discharged were also included. We performed Cox-regression analysis to measure whether commonly used biomarkers were associated with an increased 28-day mortality. Of 336 COVID-19-positive patients, 267 required hospital admission, and 69 were seen in the emergency room and discharged. The median age was 63 years (IQR 80-50) and the female-to-male ratio was 49:51. Derivation of internally validated cut-offs suggested that C-reactive protein ≥ 78.4 mg/L, neutrophil-to-lymphocyte ratio ≥ 6.1, lymphocyte-to-white blood cell ratio < 0.127, and a modified Glasgow prognostic score equal to 2 vs. 1 or 0 were associated with the highest increased risk of 28-day mortality. We provide early estimates of cut-off values for inflammatory biomarkers and indices measured at the time of admission that may be useful to clinicians for predicting 28-day mortality in North American COVID-19 patients.

Gender and Authorship in Pediatric Critical Care Randomized Control Trials.

OBJECTIVES: To examine the gender distribution of authorship of pediatric critical care randomized control trials. DATA SOURCES: The 415 randomized control trials in pediatric critical care published before 2019. STUDY SELECTION: We included all randomized control trials enrolling children in a PICU. We used PICUtrials.net, which uses comprehensive search strategies of multiple databases, to identify published randomized control trials. DATA EXTRACTION: We manually extracted the name and profession of each listed author from each publication and classified each author as male or female based on their name. RESULTS: We included 2,146 authors and were able to classify 1,888 (88%) as men or women. Overall, 38% of authors were women, this varied with the authorship position: 37% of first, 38% of middle, and 25% of last authors were women (p < 0.001). The three most common professions were physician (63%), nonclinician (11%), and nurse (6%)-of which 30%, 45%, and 97%, respectively, were women. The percentage of female authorship overall has increased from 28% in 1985-1989 to 39% in 2015-2018 (p for trend = 0.004). There were no significant differences in the characteristics of randomized control trials published with a female first or last author versus those with both male first and last authors with respect to the median number of children randomized (60 vs. 50; p = 0.41), multicentred trials (17% vs. 24%; p = 0.12), trials at low risk of bias (50% vs. 66%; p = 0.26), reporting any funding (55% vs. 51%; p = 0.66), or median number of citations per year (1.5 vs. 2.4; p = 0.09). CONCLUSIONS: Although increasing over time, the percentage of researchers publishing pediatric critical care randomized control trials who are women still lags behind the percentage clinicians who are women. Trials that female researchers publish are similar in characteristics and impact as male researchers. Further work should identify barriers to gender diversity and potential solutions in pediatric critical care research.

Research Collaboration in Pediatric Critical Care Randomized Controlled Trials: A Social Network Analysis of Coauthorship.

OBJECTIVES: Clinical research is a collaborative enterprise; researchers benefit from the expertise, experience, and resources of their collaborators. We sought to describe the extent and patterns of collaboration among pediatric critical care trialists, and to identify the most influential individuals, centers, and countries. DESIGN: Social network analysis of coauthorship. DATA SOURCES: Publications of pediatric critical care randomized controlled trials (1986-2018). DATA EXTRACTION: We manually extracted the names of all authors and their affiliations. We used productivity (number of randomized controlled trials), influence (number of citations), and four measures of prominence in the social network (degree, betweenness, closeness, and eigenvector centrality) to identify the most influential individuals. MEASUREMENTS AND MAIN RESULTS: From 415 randomized controlled trials in pediatric critical care, we identified 2,176 trialists from 377 centers in 43 countries. The coauthorship network is highly disconnected and dominated by a single large cluster of trialists publishing 142 (34%) of the randomized controlled trials. However, 119 (29%) of the randomized controlled trials were published by 28 smaller clusters-a median (interquartile range) of 3 (2-4) randomized controlled trials each. The remaining 154 (37%) randomized controlled trials were coauthored by researchers publishing a single randomized controlled trial each. This overall structure has remained constant with the publication of new randomized controlled trials over 33 years. The most influential trialists and centers varied according to the metric we used; only one trialist and three centers ranked in the top 10 for all measures of influence. Thirty-five of the 40 trialists (88%) ranking in the top 10 of any of the measures were from the United States, the United Kingdom, and Canada. CONCLUSIONS: Pediatric critical care has made considerable progress in the number of trialists and randomized controlled trials, but the research enterprise remains highly clustered and fragmented, particularly geographically. Efforts to further increase the quantity and quality of research in the field should include steps to increase the level and range of collaboration.

Iron Pathophysiology in Stroke.

Ischemic and hemorrhagic stroke are the common types of stroke that lead to brain injury neurological deficits and mortality. All forms of stroke remain a serious health issue, and there is little successful development of drugs for treating stroke. Incomplete understanding of stroke pathophysiology is considered the main barrier that limits this research progress. Besides mitochondria and free radical-producing enzymes, labile iron is an important contributor to oxidative stress. Although iron regulation and metabolism in cerebral stroke are not fully understood, much progress has been achieved in recent years. For example, hepcidin has recently been recognized as the principal regulator of systemic iron homeostasis and a bridge between inflammation and iron regulation. This review discusses recent research progress in iron pathophysiology following cerebral stroke, focusing molecular regulation of iron metabolism and potential treatment targets.

Link between Brugada phenocopy and myocardial ischemia: Results from the International Registry on Brugada Phenocopy.

BACKGROUND: Brugada phenocopies clinical entities that have indistinguishable electrocardiographic (ECG) patterns from true congenital Brugada syndrome. However, they are induced by other clinical circumstances such as myocardial ischemia. The purpose of our study was to examine the clinical features and pathogenesis of ischemia-induced Brugada phenocopy (BrP). METHODS: Data from 17 cases of ischemia-induced BrP were collected from the International Registry (www.brugadaphenocopy.com). Data were extracted from these publications and authors were contacted to provide further insight into each case. RESULTS: Of the patients included in this study, 71% were male. Mean age was 59 ± 11 years (range: 38-76). Type-1 Brugada ECG pattern occurred in 15/17 (88%) of the cases, while a type-2 Brugada ECG pattern was observed in the other 2/17 (12%). In all cases, the Brugada ECG pattern resolved upon correction of the ischemia, indicating ischemia as the inducing circumstance. No arrhythmic events have been detected acutely or during the follow-up. Reported time to resolution ranged from 2 minutes to 5 hours. Provocative challenges using sodium channel blocking agents were performed in 7/17 cases (41%), and all failed to induce a Brugada ECG pattern (BrP Class A). The remaining 10/17 cases (59%) did not undergo provocative testing due to various clinical reasons. CONCLUSIONS: Myocardial ischemia is a commonly reported etiology of BrP. Importantly, this study found no association between BrP induced by myocardial ischemia and sudden cardiac death or malignant ventricular arrhythmias.