Publications by authors named "Karen J Ho"

Introduction: As a chronic and incurable condition, lower extremity peripheral artery disease (PAD) and its optimal self-management requires patient participation in treatment. Patient activation (knowledge, skills, and confidence to manage one's health) is known to improve chronic disease outcomes. We aimed to identify factors associated with activation in patients with PAD.

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Sympathetic innervation plays a critical role in regulating vascular function, yet its influence on vascular regeneration and reinnervation following ischemic injury remains poorly understood. This study develops and validates murine models of localized sympathetic denervation using 6-hydroxydopamine (6-OHDA) to enable study of the sympathetic nervous system's impact on vascular systems during tissue repair. Two methods of 6-OHDA administration were employed: a single topical application during open surgery and minimally invasive weekly subcutaneous injections.

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Neointimal hyperplasia, a pathological response to arterial interventions or injury, often leads to restenosis and recurrent narrowing or occlusion, particularly in the peripheral vasculature. Its prevalence and negative impact on the long-term success of vascular interventions have driven extensive research aimed at better understanding the condition and developing effective therapies. This review provides a comprehensive overview of emerging bioengineering strategies for treating neointimal hyperplasia in peripheral vessels.

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Article Synopsis
  • Patients with systemic sclerosis (SSc) show significant alterations in gut microbiota, particularly with higher levels of trimethylamine oxide (TMAO), which is linked to fibrosis and vascular issues common in SSc.
  • This study involved a case-control setup with 200 SSc patients and 400 matched controls, measuring various metabolites, including TMAO, using advanced techniques to accurately assess differences.
  • Results indicated that SSc patients had higher TMAO levels, especially among males and those who are obese, suggesting TMAO could be a potentially modifiable factor worth investigating further in relation to SSc severity and progression.
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Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. This objective of this study was to describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD.

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Background: Tissue fibrosis is a common pathway to failure in many organ systems and is the cellular and molecular driver of myriad chronic diseases that are incompletely understood and lack effective treatment. Recent studies suggest that gut microbe-dependent metabolites might be involved in the initiation and progression of fibrosis in multiple organ systems.

Main Body Of The Manuscript: In a meta-organismal pathway that begins in the gut, gut microbiota convert dietary precursors such as choline, phosphatidylcholine, and L-carnitine into trimethylamine (TMA), which is absorbed and subsequently converted to trimethylamine N-oxide (TMAO) via the host enzyme flavin-containing monooxygenase 3 (FMO3) in the liver.

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The factors associated with unplanned higher-level re-amputation (UHRA) and one-year mortality among patients with chronic limb-threatening ischemia (CLTI) after lower extremity amputation are poorly understood. This was a single-center retrospective study of patients who underwent amputations for CLTI between 2014 and 2017. Unadjusted bivariate analyses and adjusted odds ratios (AOR) from logistic regression models were used to assess associations between pre-amputation risk factors and outcomes (UHRA and one-year mortality).

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Objective: To model the volume of water used and wasted during wet scrubs at operating room (OR) scrub sinks and identify factors for reducing water waste.

Background: Wasteful consumption of water by US healthcare systems has not been well characterized.

Methods: This is a two-component observational study.

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People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans.

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Aim: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia).

Methods: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate.

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Article Synopsis
  • - The 2024 guideline focuses on managing lower extremity peripheral artery disease, providing recommendations for different patient conditions, including asymptomatic and acute limb ischemia.
  • - A thorough literature review from October 2020 to June 2022 was conducted, analyzing studies published in English, with further updates considered through May 2023.
  • - The updated guideline enhances the previous 2016 recommendations and introduces new strategies to ensure comprehensive care for patients suffering from peripheral artery disease.
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Article Synopsis
  • The study investigates how cocoa flavanols, particularly epicatechin (EPI), can help improve muscle function in patients with peripheral artery disease (PAD) by enhancing antioxidant defenses and reducing muscle damage.
  • In a clinical trial, participants consuming a cocoa-flavanol drink showed better walking performance and muscle health compared to those who received a placebo, with notable increases in key antioxidants linked to muscle repair.
  • Analysis revealed that cocoa flavanols activate Nrf2, a protein that boosts antioxidant production, which may protect against oxidative stress and improve mitochondrial function in muscle cells affected by PAD.
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Objective: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown.

Methods: A total of 1289 participants were included.

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Disparities by sex, race, socioeconomic status, and geography exist in diagnosis, treatment, and outcomes for people with lower extremity peripheral artery disease (PAD). PAD prevalence is similar in men and women, but women have more atypical symptoms and undergo lower extremity revascularization at older ages compared to men. People who are Black have an approximately 2-fold higher prevalence of PAD, compared to people who are White and have more atypical symptoms, greater mobility loss, less optimal medical care, and higher amputation rates.

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Importance: Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear.

Objective: To study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.

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An acute inflammatory response following arterial surgery for atherosclerosis, such as balloon angioplasty, stenting, and surgical bypass, is an important driver of neointimal hyperplasia after arterial injury, which leads to recurrent ischemia. However, a comprehensive understanding of the dynamics of the inflammatory infiltrate in the remodeling artery is difficult to attain due to the shortcomings of conventional methods such as immunofluorescence. We developed a 15-parameter flow cytometry method to quantitate leukocytes and 13 leukocyte subtypes in murine arteries at 4 time points after femoral artery wire injury.

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Malperfusion is a complication of acute aortic dissection associated with substantially increased morbidity and mortality. Although endovascular treatment of the dissection with a stent graft to cover the intimal tear and reexpand the true lumen will often be sufficient to treat distal malperfusion, persistent or delayed malperfusion will necessitate additional interventions. Endovascular strategies to increase true lumen expansion include bare metal dissection stent placement and percutaneous fenestration.

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Calcification in prosthetic vascular conduits is a major challenge in cardiac and vascular surgery that compromises the long-term performance of these devices. Significant research efforts have been made to understand the etiology of calcification in the cardiovascular system and to combat calcification in various cardiovascular devices. Novel biomaterial design and tissue engineering strategies have shown promise in preventing or delaying calcification in prosthetic vascular grafts.

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Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.

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Intestinal dysbiosis is prominent in systemic sclerosis (SSc), but it remains unknown how it contributes to microvascular injury and fibrosis that are hallmarks of this disease. Trimethylamine (TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. Using cell culture systems and patient biopsies, we now show that TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative TMAO receptor protein R-like endoplasmic reticulum kinase (PERK).

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Traumatic brain injury (TBI) has a bimodal age distribution with peak incidence at age 24 and age 65 with worse outcomes developing in aged populations. Few studies have specifically addressed age at the time of injury as an independent biologic variable in TBI-associated secondary pathology. Within the framework of our published work, identifying age related effects of TBI on neuropathology, cognition, memory and motor function we analyzed fecal pellets collected from young and aged TBI animals to assess for age-induced effects in TBI induced dysbiosis.

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Objective: An individual's understanding of disease risk factors and outcomes is important for the ability to make healthy lifestyle choices and decisions about disease treatment. Peripheral artery disease (PAD) is a condition with increasing global prevalence and high risk of adverse patient outcomes. This study seeks to understand the adequacy of disease understanding in patients with PAD.

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Background: Limb ischemia is a major complication of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Use of ankle-brachial index (ABI) to monitor limb perfusion in VA-ECMO has not been described. We report our experience monitoring femoral VA-ECMO patients with serial ABI and the relationships between ABI and near infrared spectroscopy (NIRS).

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