Gene Expression Studies in Down Syndrome: What Do They Tell Us about Disease Phenotypes?

Down syndrome is a well-studied aneuploidy condition in humans, which is associated with various disease phenotypes including cardiovascular, neurological, haematological and immunological disease processes. This review paper aims to discuss the research conducted on gene expression studies during fetal development. A descriptive review was conducted, encompassing all papers published on the PubMed database between September 1960 and September 2022. We found that in amniotic fluid, certain genes such as COL6A1 and DSCR1 were found to be affected, resulting in phenotypical craniofacial changes. Additionally, other genes such as GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1 were also identified to be affected in the amniotic fluid. In the placenta, dysregulation of genes like MEST, SNF1LK and LOX was observed, which in turn affected nervous system development. In the brain, dysregulation of genes DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 has been shown to contribute to intellectual disability. In the cardiac tissues, dysregulated expression of genes GART, ETS2 and ERG was found to cause abnormalities. Furthermore, dysregulation of XIST, RUNX1, SON, ERG and STAT1 was observed, contributing to myeloproliferative disorders. Understanding the differential expression of genes provides insights into the genetic consequences of DS. A better understanding of these processes could potentially pave the way for the development of genetic and pharmacological therapies.

Rethinking Blood Testing in Pediatric Cancer Patients: A Quality Improvement Approach.

Introduction: The overuse of blood tests burdens the healthcare system and can detrimentally impact patient care. Risks of frequent blood sampling include infection and clinician-induced anemia, which can negatively impact patients and their families. Pediatric cancer patients are particularly vulnerable as they are immunocompromised with a small blood volume. Four blood tests had become a daily practice. Therefore, we aimed to reduce the number of blood tests taken per bed day within the inpatient pediatric cancer unit by 15% within 8 months. Methods: This quality improvement project combined several strategies to reduce test frequency and empower clinicians on the rationale for blood test ordering. Recommendations were developed collaboratively presented in a summary table. Targeted behavior-change methodology built engagement and momentum for the change. All clinicians were challenged to STOP and THINK about why a test is necessary for each patient. The primary outcome measure was the frequency of the tests taken per bed day. Frequency was compared between pre- and postimplementation plus follow-up periods across 2019-2021. Results: 26,941 blood tests were captured in 1,558 admissions. The intervention led to an overall blood test reduction of 37% over 8 months. Liver Function Tests were the standout, with a 52% decrease in test frequency. Conclusions: A strategy incorporating education and culture change, combined with clear guidance on testing frequency, significantly reduced the ordering frequency of blood tests without increased patient harm.

Engraftment syndrome following hematopoietic stem cell transplant: A review of the literature.

Engraftment syndrome (ES) is a poorly understood condition which continues to present a significant cause of morbidity following haematopoietic stem cell transplantation (HSCT). Yet a standard approach to diagnosis and treatment of ES remains elusive and has the potential to impact patient outcomes. A literature search was performed using the databases ProQuest Health, PubMed, Medline and Embase. Included studies were published in English from 2001-2019 that reported on engraftment syndrome following HSCT. Articles were organized by study design, ES diagnostic criteria, symptom classification and treatment. The review consolidated an array of literature relating to all types of HSCT. Timing of ES onset, risk factors and outcomes were compared within the literature. Signs and symptoms of reported ES were collated to establish a concise set of diagnostic criteria that can provide rapid recognition. The use of a standard approach to ES diagnosis has the potential to improve patient outcomes and provide a uniform approach to future research.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

A Novel Pupillometric Method for Indexing Word Difficulty in Individuals With and Without Aphasia.

PURPOSE: Cognitive effort is a clinically important facet of linguistic processing that is often overlooked in the assessment and treatment of people with aphasia (PWA). Furthermore, there is a paucity of valid ways to index cognitive effort in PWA. The construct of cognitive effort has been indexed for decades via pupillometry (measurement of pupil dilation and constriction during a cognitive task), yet pupillometry has not been implemented in studies including PWA. In the present study, we tested a novel method for indexing cognitive effort during linguistic processing in people with and without aphasia. METHOD: Forty control participants and 39 PWA listened to semantically easy and difficult single nouns and looked at images while their pupillary responses were monitored. Mean pupil dilation in response to easy versus difficult nouns was calculated to index cognitive effort. RESULTS: Larger mean pupil dilation values were obtained for difficult compared with easy nouns for both groups. CONCLUSION: Results provide preliminary evidence that pupillometry can be used to index cognitive effort during linguistic processing of single nouns in people with and without aphasia. Methods for indexing cognitive effort will be a valuable addition to existing assessment methods. Suggestions for further research are offered.