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Fulltext DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia

Szoltysek K, Ciardullo C, Zhou P, Walaszczyk A, Willmore E, Rand V, et al.

Int J Mol Sci, 2020 Oct 16;21(20).
PMID: 33081245 DOI: 10.3390/ijms21207663

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.
Hypertension in Adults With Diabetes in Southeast Asia: A Systematic Review

Wong WJ, Nguyen TV, Ahmad F, Vu HTT, Koh AS, Tan KM, et al.

J Clin Hypertens (Greenwich), 2024 Nov 15.
PMID: 39545715 DOI: 10.1111/jch.14936

Diabetes is one of the most pressing health issues in the Southeast Asian region, and hypertension has been commonly reported as a comorbidity in adults with diabetes. This systematic review aimed to synthesize evidence on the prevalence and management of hypertension in adults with diabetes in Southeast Asian countries. A literature search was conducted in Ovid MEDLINE and Embase Classic + Embase from database inception until March 15, 2024. Studies were included if (1) they were conducted in Southeast Asian countries, (2) the study populations were adults with diabetes, and (3) there was information related to hypertension or blood pressure (BP) in the study results. Of the 7486 abstracts found, 90 studies qualified for this review. Most studies reported a hypertension prevalence of 70% or higher (ranging from 29.4% to 93.4%). Despite this high prevalence, a substantial proportion of these populations did not receive adequate BP control, with most studies indicating a control rate of less than 40%. There was limited evidence on the prescription of antihypertensive therapies and medication adherence. There was a lack of studies from 4 of the 11 countries in the region. This review highlights that BP control in adults with diabetes remains a significant challenge in Southeast Asia. Given the ongoing epidemiological transition, and the increasing older population in this region who are likely to accumulate multiple chronic conditions complicating medication strategies, this review highlights the urgent need to improve BP management in those with diabetes.
Fulltext SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry

Liew J, Gianfrancesco M, Harrison C, Izadi Z, Rush S, Lawson-Tovey S, et al.

RMD Open, 2022 Apr;8(1).
PMID: 35387864 DOI: 10.1136/rmdopen-2021-002187

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2.
METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes.
RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died.
CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

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