Heart and Blood Diseases

All Conditions

Immune System Diseases

Neoplasms

Symptoms and General Pathology

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Hypertension

Essential Hypertension

Hypersensitivity

Adenoma

Hyperplasia

Hyperaldosteronism

Adrenal Hyperplasia, Congenital

Adrenogenital Syndrome

Adrenocortical Adenoma

Syndrome

Vascular Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Disorders of Sex Development

Congenital Abnormalities

Urogenital Abnormalities

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Genetic Diseases, Inborn

Metabolism, Inborn Errors

Steroid Metabolism, Inborn Errors

Metabolic Diseases

Gonadal Disorders

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Congenital Adrenal Hyperplasia

21-hydroxylase Deficiency

Adenoma of the Adrenal Gland

Hyperadrenalism

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Epinephrine

Racepinephrine

Epinephryl borate

conclusive diagnosis of unilateral PA by the "four corners" criteria:

1. Biochemical evidence of PA
2. Lateralization of aldosterone secretion at adrenal venous sampling.
3. Correction of biochemical values and fall of blood pressure after adrenalectomy.
4. Immunohistochemical demonstration of CYP11B2 positive nodule(s)

Presumed diagnosis of bilateral PA, defined as above but without evidence of lateralized aldosterone excess.

Primary (essential) Hypertension (PH): conclusively ascertained high blood pressure and exclusion of secondary hypertension

comprising patients submitted to surgery but free of hypertension

Skin biopsies were obtained in all recruited patients.

Skin Biopsy

Video-laparoscopic adrenalectomy in those with unilateral PA. (PA group 1)

Video-laparoscopic adrenalectomy

Gian Paolo Rossi, Prof.

WHYSKI is a prospective within-patient observational clinical study designed to test the hypothesis that alterations of Na+, K+, water, and the lympho-angiogenetic transcription factor Tonicity Enhancing Binding Protein (TonEBP) mRNA take place in the interstitium of the skin compartment of patients with arterial hypertension due to primary aldosteronism in whom hypertension can be surgically cured.

Background. Given the key role of Na+ in the pathophysiology of HT, this study will test the hypothesis that in PA, which is the paradigm of salt-dependent hypertension, the skin, Na+, K+ and water content is altered and these alterations are corrected by surgical cure of PA with video-laparoscopic adrenalectomy. The investigators will use skin biopsies to directly examine the content of Na+, K+, water, and the lympho-angiogenetic transcription factor Tonicity Enhancing Binding Protein (TonEBP) mRNA in the skin, an important reservoir of body Na+, in primary aldosteronism (PA), the prototype of salt-dependent hypertension.

Methods. The investigators will measure Na+, K+, and water content (by chemical-physical methods) and TonEBP mRNA copy number (by droplet digital PCR) in skin biopsies from a sex-mixed cohort of consecutive consenting patients with unilateral PA treated with a mineralocorticoid receptor antagonist (MRA), before surgery, at doses that correct hypokalemia and HT in order to refer them for surgery with normokalemia and controlled high blood pressure, as per protocol at our institution. The participants will be reassessed in an identical way again after surgical cure.

The investigators expect the dry weight (DW) of the skin specimen obtained at surgery to be significantly higher than at follow-up and to correlate positively with skin Na+, K+, and water content. Hence, if these predictions will be verified, the skin cations and water content will need to be DW-adjusted in order to provide meaningful comparisons across specimen obtained at different time points. The investigators expect the TonEBP mRNA copy number to be markedly overexpressed compared to healthy subjects.

The WHYSKI study will provide solid knowledge of the skin Na+, K+ and water content in patients with arterial salt-dependent hypertension due to PA, PH, and on the effect of cure of the hyperaldosteronism on these variables. The investigators also expect to gather novel knowledge on the molecular and cellular mechanisms involved in the regulation of the content on Na+, K+ and water in a compartment as the skin interstitium that has been largely neglected thus far.

Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn

The Water and Electrolytes Content in Salt-dependent Human HYpertension (WHYSKI) in the SKIn Before and After Surgical Cure of Primary Aldosteronism

IPD available on reasonable request but if consistent with the ongoing privacy legislation.

With validated chemical physical methods, we will measure the Na+, K+ and water content in the skin of patients with primary aldosteronism (PA, PA Group), primary (essential) hypertension HT patients (PH Group) and in normotensive patients (Control Group). The skin biopsy will be performed during adrenalectomy in consecutive patients with confirmed unilateral PA (PA Group) and in parallel in the same anatomical region in the PH group and in the Control Group, during surgery for benign diseases.

To verify if the cure of PA improves Na+, K+ and water skin clearance in the PA Group the skin biopsy obtained during adrenalectomy will be within-patient compared to that obtained one month after adrenalectomy (PA Group 1). In PA patients found not to have unilateral PA (PA Group 2), the biopsy will be obtained after one month of target medical treatment with canrenone, a mineralocorticoid receptor antagonist.

While the measurement of skin Na+, K+ and water is the main study outcome, an additional important goal will be to determine the molecular mechanisms driven by "skin sodium storage" that underlie the crosstalk between skin cells, macrophages and lymphatic vessels in the interstitium of the patient with PA (PA group 1) and essential hypertensive patients (EH Group) compared with the normotensive patient (Control Group). To this end we will explore the mRNA content of Tonicity-Enhancing Binding Protein TonEBP (also known as NFAT5), a transcription factor known to activate neo-lymphoangiogenesis, using molecular biology techniques.

University Hospital Padova

Full Professor of Internal Medicine, MD, FAHA, FACC

Francesco Gatto, PhD

Francesco Gatto

LEVANTIS-0093A (LEV93A) is a prospective cohort observational clinical study to validate the plasma free GAGome MCED test in adults at high risk of developing cancer ("high-risk adults"), specifically in 55-80-year-old adults with significant smoking history.

LEV93A will use plasma biospecimens collected within the Yorkshire Lung Screening Trial Biomarker sub-study and corresponding participant data prospectively collected within the Yorkshire Lung Screening Trial (YLST) and the Yorkshire Kidney Screening Trial (YKST) all of which are sponsored by the University of Leeds and funded by Yorkshire Cancer Research (Award references: L403, L403B L403C), in collaboration with the University of Leeds, with the University of Manchester and with the Leeds Teaching Hospitals.

Prospectively collected blood samples sourced from patients enrolled in study

LEVANTIS-0093A: GAGomes for Multi-Cancer Early Detection in High-Risk Adults (LEV93A)

Indicative of any-type cancer vs. no cancer diagnosis

Accuracy to the "putative cancer location" (PCL) model among cases (confirmed cancer diagnosis)

Indicative of any-type cancer vs. no cancer diagnosis in combination with LDCT

Elypta

Adults \>= 18 years old with cancer or imminent cancer diagnosis (cases) versus cancer-free and no imminent cancer diagnosis (controls).

Sub-Study 1 is intended for the development of 3 free GAGome MCED tests.

Adults between 35 - 80 years old asymptomatic for cancer and with no recent history of cancer (\> 5 years since curative-intent treatment for cancer).

Sub-Study 2 is intended for the validation of the combined free GAGome MCED test (primary endpoint) and the plasma and urine free GAGome MCED tests (secondary endpoints).

The combined free GAGome MCED test aggregates measurements of plasma and urine GAGomes (the exhaustive human glycosaminoglycan profile) into a diagnostic score, the combined free GAGome MCED score. The measurements are performed using MIRAM MCED Kits (Elypta AB) and the scores are computed using Elypta SKY Software (Elypta AB)

Combined free GAGome MCED test

LEVANTIS-0087A (LEV87A) is a retrospective in vitro diagnostics clinical validation population cohort-based case-control study to validate the diagnostic performance of free GAGome-based tests for multi-cancer early detection (MCED) in adults asymptomatic for cancer and with no recent history of cancer.

Multi-cancer early detection (MCED) could prevent 26% of all cancer-related deaths - an effect larger than averting all deaths from breast cancer alone. However, a societal program to implement MCED requires a practical, noninvasive, and affordable diagnostic modality that is sensitive and specific to all forms of cancers. Liquid biopsies represent front-runner modalities to this end but virtually all of them rely on genomics biomarkers, typically circulating free DNA (cfDNA), which capture \<20% of cancers in stage I. In addition, they miss certain cancer types that shed little cfDNA, like brain or genitourinary tumors. Pilot studies show that free glycosaminoglycan profiles in plasma and urine, or free GAGomes, were promising noninvasive biomarkers of cancer metabolism that detected over a third of stage I cancers across 14 types, including brain and genitourinary tumors.

LEVANTIS-0087A (LEV87A) is a retrospective in vitro diagnostics clinical validation population cohort-based case-control study to develop free GAGome-based tests for multi-cancer early detection in adults asymptomatic for cancer and with no recent history of cancer (Sub-Study 1) and to validate their diagnostic performance in the target population (Sub-Study 2).

LEV87A uses retrospectively collected biospecimens from one or more population-based biobanks representative of the target population.

Biobanked plasma and urine biospecimens, originally collected by the selected biobank(s).

LEVANTIS-0087A: GAGomes for Multi-Cancer Early Detection in Asymptomatic Adults (LEV87A)

Accuracy to the "putative cancer location" (PCL) model in the case (cancer) arm

Overall survival (OS) in the case (cancer) arm

Carcinoma

Carcinoma, Renal Cell

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Patients with pathologically confirmed diagnosis of RCC

A score was calculated using a formula that factors in measurements of plasma glycosaminoglycan. A score higher than a here-determined threshold is deemed diagnostic of RCC.

Glycosaminoglycan plasma score

In this study, the investigators profiled plasma glycosaminoglycans (GAGs) in a retrospective consecutive series of patients with a radiographic finding of renal mass referred to primary surgery for renal cell carcinoma (RCC). A control group was formed by measuring plasma GAGs in healthy volunteers. The primary endpoints were the specificity and sensitivity of plasma GAGs in the detection of early stage RCC in pre-surgical samples versus healthy individuals. The investigators further analyzed how plasma GAGs varied according to stage, grade, RCC histology, other renal masses, and after surgery. Finally, the investigators estimated whether plasma GAGs could be used for prediction and surveillance of RCC recurrence.

Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma

The shift is the absolute difference plasma GAG score, which is measured in arbitrary units in the range 0 to +Inf with higher values associated with RCC versus healthy status.

The dichotomized plasma GAG score is a categorical binary variable based on a post-hoc cut-off value for the plasma GAG score, which is measured in arbitrary units in the range 0 to +Inf with higher values associated with RCC versus healthy status.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn	NCT06090617	Hyperaldosteron... Hypertension Aldosterone-pro... Aldosteronism Aldosterone Dis... Essential Hyper... Bilateral Adren... Conn Adenoma	Skin Biopsy Video-laparosco...	18 Years - 75 Years	University Hospital Padova
LEVANTIS-0093A: GAGomes for Multi-Cancer Early Detection in High-Risk Adults (LEV93A)	NCT05295017	Cancer		55 Years - 80 Years	Elypta
LEVANTIS-0087A: GAGomes for Multi-Cancer Early Detection in Asymptomatic Adults (LEV87A)	NCT05235009	Cancer	Combined free G...	18 Years - 80 Years	Elypta
LEVANTIS-0093A: GAGomes for Multi-Cancer Early Detection in High-Risk Adults (LEV93A)	NCT05295017	Cancer		55 Years - 80 Years	Elypta
Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma	NCT03471897	Renal Cell Carc...	Glycosaminoglyc...	18 Years -	Chalmers University of Technology

Spots Global Cancer Trial Database for glycosaminoglycans