The Integrative Cluster subtypes (IntClusts) provide a framework for the classification of breast cancer tumors into 10 distinct groups based on copy number and gene expression, each with unique ...biological drivers of disease and clinical prognoses. Gene expression data is often lacking, and accurate classification of samples into IntClusts with copy number data alone is essential. Current classification methods achieve low accuracy when gene expression data are absent, warranting the development of new approaches to IntClust classification. Copy number data from 1980 breast cancer samples from METABRIC was used to train multiclass XGBoost machine learning algorithms (CopyClust). A piecewise constant fit was applied to the average copy number profile of each IntClust and unique breakpoints across the 10 profiles were identified and converted into ~ 500 genomic regions used as features for CopyClust. These models consisted of two approaches: a 10-class model with the final IntClust label predicted by a single multiclass model and a 6-class model with binary reclassification in which four pairs of IntClusts were combined for initial multiclass classification. Performance was validated on the TCGA dataset, with copy number data generated from both SNP arrays and WES platforms. CopyClust achieved 81% and 79% overall accuracy with the TCGA SNP and WES datasets, respectively, a nine-percentage point or greater improvement in overall IntClust subtype classification accuracy. CopyClust achieves a significant improvement over current methods in classification accuracy of IntClust subtypes for samples without available gene expression data and is an easily implementable algorithm for IntClust classification of breast cancer samples with copy number data.
Biological systems overwhelmingly comprise charged entities generating electrical activity that can have significant impact on biological structure and function. This intrinsic bio-electrical ...activity can also be harnessed for overcoming the tissue matrix and cell membrane barriers, which have been outstanding challenges for targeted drug delivery, by using rationally designed cationic carriers. The weak and reversible long-range electrostatic interactions with fixed negatively charged groups facilitate electro-diffusive transport of cationic therapeutics through full-tissue thickness to effectively reach intra-tissue, cellular, and intracellular target sites. This article presents a perspective on the promise of using rationally designed cationic biomaterials in targeted drug delivery, the underlying charge-based mechanisms, and bio-transport phenomena while addressing outstanding concerns around toxicity and methods to mitigate them. We also discuss electrically charged drugs that are currently being evaluated in clinical trials and identify areas of further development that have the potential to usher in new treatments.
Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers ...with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19.
Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients >7 days to <1 year old hospitalized with symptomatic acute COVID-19.
We report 232 infants >7 days to <1 year of age hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients >7 days to <18 years old, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died.
Infants accounted for over a fifth of children <18 years of age hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.
Pacific young people living in Aotearoa New Zealand experience disparities in their sexual and reproductive health outcomes, thought to stem from cultural differences and educational inequities. ...Although these barriers have been characterised in literature, their influence on Pacific youth’s understandings of sexual and reproductive health have been relatively unexplored. This study investigated the sexual and reproductive health knowledge of Pacific students enrolled at a university in Aotearoa New Zealand in 2020 and where they gained this knowledge. The study used the theoretical framework of the (revitalised) Fonofale health model and was guided by the Kakala research methodology. Data were collected by means of an online survey comprised of open-ended questions and Likert scales, completed by eighty-one eligible students. Open-ended questions were analysed for general themes and responses to Likert scale items are reported using descriptive statistical analysis. The study found that Pacific youth have strong foundations of health knowledge that is heavily influenced by Polynesian cultural beliefs. Both formal and non-formal learning environments were important in developing participants’ health knowledge of these topics and for encouraging independent help-seeking behaviours. This is the first reported study to investigate the sexual and reproductive health knowledges of a pan-Pacific tertiary cohort of young people.
Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in ...patients with multisystem inflammatory syndrome were rare (7/2,086 0.3%). However, they required the need for additional therapy and/or readmission.
Objective
Evidence regarding effectiveness of interleukin‐1 receptor antagonism in multisystem inflammatory syndrome in children (MIS‐C) is lacking. We characterized variation in initial treatment ...with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy.
Methods
We conducted a retrospective cohort study of MIS‐C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0–1) were identified. We compared cases in patients ages 2–20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0–1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3–4. The secondary outcome was 50% reduction in C‐reactive protein on day 3.
Results
Among 1,516 MIS‐C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0–74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio RR 1.27 95% confidence interval (95% CI) 0.88–1.84), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 95% CI 0.98–1.75), or C‐reactive protein reduction.
Conclusion
We identified substantial variation in initial anakinra use in a real‐world population of children with MIS‐C, but no average short‐term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.
Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure ...refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed.
Case series of patients from the Overcoming COVID-19 public health surveillance registry.
Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021.
Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19.
None.
The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 2.4% requiring ECMO) or acute COVID-19 ( n = 1,203; 71 5.9% requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period.
ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.
Background Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are ...less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 range, 10.4–17.4 versus 10.0 range, 5.4–14.8 years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.
Maintaining an ample supply of personal protective equipment continues to be a challenge for the healthcare industry, especially during emergency situations and times of strain on the supply chain. ...Most critically, healthcare workers exposed to potential airborne hazards require sufficient respiratory protection. Respirators are the only type of personal protective equipment able to provide adequate respiratory protection. However, their ability to shield hazards depends on design, material, proper fit, and environmental conditions. As a result, not all respirators may be adequate for all scenarios. Additionally, factors including user comfort, ease of use, and cost contribute to respirator effectiveness. Therefore, a careful consideration of these parameters is essential for ensuring respiratory protection for those working in the healthcare industry. Here respirator design and material characteristics are reviewed, as well as properties of airborne hazards and potential filtration mechanisms, regulatory standards of governmental agencies, respirator efficacy in the clinical setting, attitude of healthcare personnel toward respiratory protection, and environmental and economic considerations of respirator manufacturing and distribution.
Healthcare workers exposed to potential airborne hazards require sufficient respiratory protection. The ability of respirators to shield hazards depends on design, material, proper fit, and environmental conditions. Here respirator design and material characteristics are reviewed, as well as properties of airborne hazards and filtration mechanisms, regulatory standards, respirator efficacy in clinical settings, attitudes toward respiratory protection, and environmental and economic considerations.
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