Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis.

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis.

Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities.

Diabetes is a chronic disease that induces many comorbidities, including cardiovascular disease, nephropathy, and liver damage. Many mechanisms have been suggested as to how diabetes leads to these comorbidities, of which increased oxidative stress in diabetic patients has been strongly implicated. Limited knowledge of antioxidative antidiabetic drugs and substances that can address diabetic comorbidities through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway calls for detailed investigation. This review will describe how diabetes increases oxidative stress, the general impact of that oxidative stress, and how oxidative stress primarily contributes to diabetic comorbidities. It will also address how treatments for diabetes, especially focusing on their effects on the Nrf2 antioxidative pathway, have been shown to similarly affect the Nrf2 pathway of the heart, kidney, and liver systems. This review demonstrates that the Nrf2 pathway is a common pathogenic component of diabetes and its associated comorbidities, potentially identifying this pathway as a target to guide future treatments.

Warfarin and aspirin versus warfarin alone for prevention of bleeding and thrombotic events in patients with a HeartMate 3™ left ventricular assist device.

BACKGROUND: We conducted a single-center, retrospective comparison of adult patients who received warfarin and ASA or warfarin alone after HeartMate 3 (HM3) LVAD placement. METHODS: The primary outcome was a composite of bleeding and thrombotic events. RESULTS: Of 81 patients, 53 patients received warfarin and ASA, and 28 patients received warfarin alone. A primary outcome event occurred in 22 of 53 patients (41.4%) in the warfarin and ASA group and in 2 of 28 patients (7.1%) in the warfarin alone group (p = 0.0533). The odds of a bleeding event occurring were higher in the warfarin and ASA group (32.1% vs. 7.1%, p = 0.01309). The odds of a thrombotic event occurring were not significantly different between the warfarin and ASA group and the warfarin alone group (9.4% vs. 0%, respectively, p = 0.1582). CONCLUSION: The complete omission of ASA from the antithrombotic regimen of patients with a HM3 LVAD was associated with less bleeding events without an increase in thrombotic events.

A scoping review on the factors associated with the lost to follow-up (LTFU) amongst patients with chronic disease in ambulatory care of high-income countries (HIC).

BACKGROUND: Despite the importance of long term follow-up care for patients with chronic disease, many patients fail to adhere to their follow-ups, which increase their risk of further health complications. Therefore, the purpose of this scoping review was to find out the factors associated with lost to follow-up (LTFU) amongst patients with chronic disease in the ambulatory care setting of high-income countries (HICs) to gain insights for better quality of care. Understanding the definition of LTFU is imperative in informing patients, health professionals and researchers for clinical and research purposes. This review also provided an overview of the terms and definitions used to describe LTFU. METHODS: The following databases: CINAHL, EMBASE, Medline, PsycINFO and Web of Science were searched for studies investigating the factors associated to LTFU from the date of inception until 07 January 2022. RESULTS: Five thousand one hundred and seven records were obtained across the databases and 3,416 articles were screened after removing the duplicates. 25 articles met the inclusion criteria, of which 17 were cohort studies, five were cross-sectional studies and three were case-control studies. A total of 32 factors were found to be associated with LTFU and they were categorised into patient factors, clinical factors and healthcare provider factors. CONCLUSION: Overall, the factors associated with LTFU were generally inconsistent across studies. However, some factors such as financial factors (i.e., no insurance coverage) and low accessibility of care were consistently associated with LTFU for both mental and physical chronic conditions. The operational definitions of LTFU also varied greatly across studies. Given the mixed findings, future research using qualitative aproaches would be pivotal in understanding LTFU for specific chronic diseases and the development of targeted interventions. Additionally, there is a need to standardise the operational definition of LTFU for research as well as clinical practice purposes.

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529).

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1-28.7%) and 23.4% (95%CI: 13.5-33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1-37.1%) at three months to 3.9% (95%CI: -24.8-32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8-58.3%) and 57.3% (95%CI: 54.0-60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8-48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5-69.7%) at three months, decreased to 49% (95%CI: 35.7-63.4%) within six months, and increased to 86% after the first or second booster dose.

Healthcare Professional Experiences of Clinical Incident in Hong Kong: A Qualitative Study.

BACKGROUND: Studies showed that adverse events within health care settings can lead to two victims. The first victim is the patient and family and the second victim is the involved healthcare professionals. However, there is a lack of research studying the experiences of healthcare professionals encountering clinical incidents in Hong Kong. This paper reports a qualitative study in exploring the healthcare professional experiences of clinical incident, their impacts and needs. METHODS: This study is the second part of the mixed research method with two studies conducted in a cluster of hospitals in Hong Kong. Study 1 was a quantitative questionnaire survey and Study 2 was a qualitative In-Depth Interview. In study 2, a semi-interview guide was used. RESULTS: Results showed that symptoms experienced after the clinical incident were mostly from psychological, physical, then social and lastly spiritual aspects which were consistent with those found in study 1 and other studies. Using content analysis for analyzing the impacts, four themes were identified. Concerning the impacts immediately from the clinical incident, two themes emerged were 1) facing emotion distress and 2) maintaining rationality. Regarding the impacts after the clinical incident, another two themes were 3) managing further emotional distress 4) restoring personal wellness. With regard to the needs after clinical incidents, three themes emerged were 1) self-recovery; 2) senior good mentoring and 3) positive organization climate with emphasis on enhancement of training and development of a positive practice culture. CONCLUSION: Great impacts are found with healthcare professionals encountering clinical incidents from a holistic perspective. They need time for self-recovery with support from good supervisors, peers and a caring environment. Some recommendations based on the findings of the study are made.

Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients.

UNLABELLED: Belinostat is a hydroxamate class HDAC inhibitor that has demonstrated activity in peripheral T-cell lymphoma and is undergoing clinical trials for non-hematologic malignancies. We studied the pharmacokinetics of belinostat in hepatocellular carcinoma patients to determine the main pathway of metabolism of belinostat. The pharmacokinetics of belinostat in liver cancer patients were characterized by rapid plasma clearance of belinostat with extensive metabolism with more than 4-fold greater relative systemic exposure of major metabolite, belinostat glucuronide than that of belinostat. There was significant interindividual variability of belinostat glucuronidation. The major pathway of metabolism involves UGT1A1-mediated glucuronidation and a good correlation has been identified between belinostat glucuronide formation and glucuronidation of known UGT1A1 substrates. In addition, liver microsomes harboring UGT1A1*28 alleles have lower glucuronidation activity for belinostat compared to those with wildtype UGT1A1. The main metabolic pathway of belinostat is through glucuronidation mediated primarily by UGT1A1, a highly polymorphic enzyme. The clinical significance of this finding remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov NCT00321594.