Publications by authors named "Dennedy M"

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis, treated primarily through surgery and chemotherapy. Other treatments like radiation or thermal ablation for metastases have limited success, and recurrence is common. More effective management options are needed.

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Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex that is associated with a poor prognosis. Developing effective treatment options for ACC is challenging owing to the current lack of representative preclinical models. This study addressed this limitation by developing and characterizing 3-dimensional (3D) cell cultures incorporating the ACC cell lines, MUC-1, HAC15, and H295R in a type I collagen matrix.

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Background: Despite growing use, questions remain surrounding the utility, acceptability and feasibility of chemical adherence testing (CAT) as part of hypertension management in clinical practice.

Objectives: This scoping review aimed to (i) identify and summarise studies using CAT in hypertension management, and (ii) describe and critically evaluate how CAT is currently being used in the clinical management of hypertension.

Eligibility Criteria: Peer-reviewed and published studies in English, reporting original research in any setting, with any study design, were included.

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Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach.

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Introduction: Aldosterone-producing adenoma (APA) is the most common cause of endocrine-related hypertension but surgery is not always feasible. Current medical interventions are associated with significant side effects and poor patient compliance. New APA animal models that replicate basic characteristics of APA and give physical and biochemical feedback are needed to test new non-surgical treatment methods, such as image-guided thermal ablation.

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Article Synopsis
  • Endocrine hypertension (EHT) is associated with various hormonal conditions like pheochromocytoma, Cushing's syndrome, and primary aldosteronism, leading to unique metabolic changes compared to primary hypertension (PHT).
  • A multicenter study of 263 patients analyzed the relationship between adrenal steroid levels and metabolomic alterations, revealing significant associations among different hormone levels and specific metabolites.
  • The findings suggest that elevated cortisol, cortisone, and catecholamines are linked to distinct metabolic profiles in EHT, with catecholamines being particularly important in pheochromocytoma cases.
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Aplasia cutis congenita (ACC) is one of several congenital malformations associated with antithyroid/thiourylene drug use in pregnancy. While uncommon among the general population (1-3/100 000 cases), the risk among those on thiourylenes is between 1.6% and 3%.

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Objectives: A knowledge gap exists around the costs and budget impact of specialist hypertension clinics. This study reports on the cost of providing care in a multidisciplinary hypertension clinic staffed by nephrologist, endocrinologist and cardiologist, which manages patients with suspected secondary hypertension and/or apparent treatment-resistant hypertension. The aim of this study is to provide the evidence required to inform policy and planning care pathways for this patient group.

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Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care.

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Primary aldosteronism is the most common cause of secondary hypertension. The first-line treatment adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone-producing adenomas, while preserving adjacent normal adrenal cortex.

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Significance Statement: CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function.

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Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.

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Purpose: To assess the feasibility of delivering microwave ablation for targeted treatment of aldosterone producing adenomas using image-based computational models.

Methods: We curated an anonymized dataset of diagnostic C-metomidate PET/CT images of 14 patients with aldosterone producing adenomas (APA). A semi-automated approach was developed to segment the APA, adrenal gland, and adjacent organs within 2 cm of the APA boundary.

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Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to 20% depending on the population studied.

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Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics.

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Introduction: Adrenocortical carcinoma (ACC) is a rare aggressive cancer with low overall survival. Adjuvant mitotane improves survival but is limited by poor response rates and resistance. Mitotane's efficacy is attributed to the accumulation of toxic free cholesterol, predominantly through cholesterol storage inhibition.

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Purpose: Bio-effects following thermal treatments are a function of the achieved temperature profile in tissue, which can be estimated across tumor volumes with real-time MRI thermometry (MRIT). Here, we report on expansion of a previously developed small-animal microwave hyperthermia system integrated with MRIT for delivering thermal ablation to subcutaneously implanted tumors in mice.

Methods: Computational models were employed to assess suitability of the 2.

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Aim: Many challenges exist in determining true rates of adherence to antihypertensive medications among individuals in a clinic setting. For the first time, we aimed to compare patient-reported antihypertensive adherence with objective evidence using mass spectrometry spot urinalysis in a tertiary referral clinic setting.

Methods: A prospective observational single-centre cohort study was performed in a tertiary referral hypertension clinic, encompassing antihypertensive initiation and persistence.

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Background: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined.

Objective: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS.

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Purpose Of Review: To summarise the emerging role of thermal ablation as a therapeutic modality in the management of functioning adrenal tumours and metastases to the adrenal gland.

Recent Findings: Observational evidence has demonstrated the benefit of thermal ablation in (i) resolving adrenal endocrinopathy arising from benign adenomas, (ii) treating solitary metastases to the adrenal and (iii) controlling metastatic adrenocortical carcinoma and phaeochromocytoma/paraganglioma.

Summary: Microwave thermal ablation offers a promising, minimally invasive therapeutic modality for the management of functioning adrenocortical adenomas and adrenal metastases.

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Context: Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL], and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension.

Objective: Use TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability.

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Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit.

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Background: Measurement of late night salivary cortisol (LNSF) is useful in the identification of cyclical Cushing's syndrome (CS); the usefulness of its metabolite cortisone (late night salivary cortisone, LNSE) is less well described.

Aim: The aim of this study was to determine the utility of measuring LNSE in patients with confirmed CS compared with other diagnostic tests and to analyse serial LNSF measurements for evidence of variable hormonogenesis.

Methods: This was a retrospective observational study including patients with confirmed CS in whom LNSF and LNSE were measured.

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Background: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC.

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