Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

First Clinical Feasibility and Safety Study of a Novel Multimodality Fallopian Tube Imaging Endoscope.

Study Objective: We present the results of the first feasibility and safety study of a novel multi-modality falloposcope, in 19 volunteers. The falloposcope incorporated multispectral fluorescence imaging (MFI) and optical coherence tomography (OCT) for evaluation of the fallopian tubes (FT).

Methods: Nineteen females undergoing elective salpingectomy were recruited in this IRB-approved study.

Generation of TWO iPSC lines (CRICKi009-A; CRICKi010-A) from patients with type 1 von Hippel-Lindau (VHL) and histopathologically confirmed renal cell carcinoma (RCC).

VHL disease is an inherited and autosomal dominant disorder affecting 1 in 36,0000 individuals worldwide. It is caused by von Hippel-Lindau (VHL) gene mutations and can affect both genders and all ethnic backgrounds (Nordstrom-O'Brien et al., 2009; Maher, 2004).

Qualitative Exploration of the "Guilt Gap" Among Physician-Faculty with Caregiving Responsibilities.

Differences in time commitments and resources contribute to the difficulties of work-life integration for many physician-scientists, particularly for women with family caregiving responsibilities. Understanding the challenges faced by this population is critical for the retention of these critical members of the workforce. We conducted semi-structured telephone interviews with recipients of the 2017 Doris Duke Charitable Foundation's Fund to Retain Clinical Scientists (FRCS) and reviewed application narratives from the 2020 award recipients.

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1).

Understanding the Added Value of High-Resolution CT Beyond Chest X-Ray in Determining Extent of Physiologic Impairment.

Background: Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use.

Research Question: Whether standardized chest CT scan assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study.

Study Design And Methods: We used National Heart, Lung, and Blood Institute study Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) cases of sarcoidosis (n = 351) with Scadding stage and chest CT scans obtained in a standardized manner.

Infectious and non-infectious precipitants of sarcoidosis.

Sarcoidosis is a chronic inflammatory disease that can affect any organ in the body. Its exact cause remains unknown, but it is believed to result from a combination of genetic and environmental factors. Some potential causes of sarcoidosis include genetics, environmental triggers, immune system dysfunction, the gut microbiome, sex, and race/ethnicity.

Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism.

Background: Clinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure.

Methods: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation.

VHL: Trends and Insight into a Multi-Modality, Interdisciplinary Approach for Management of Central Nervous System Hemangioblastoma.

Von Hippel-Lindau (VHL) is a multi-system disease which results in significant morbidity from central nervous system (CNS) involvement as well as ocular, renal and neuro-endocrine effects. Haemangioblastomas of the CNS present a number of challenges. The natural history of these lesions is varied, as is the size and location within the CNS.

Resolution of dysglycaemia after treatment of monoclonal gammopathy of endocrine significance.

In very rare cases of monoclonal gammopathy, insulin-binding paraprotein can cause disabling hypoglycaemia. We report a 67-year-old man re-evaluated for hyperinsulinaemic hypoglycaemia that persisted despite distal pancreatectomy. He had no medical history of diabetes mellitus or autoimmune disease but was being monitored for an IgG kappa monoclonal gammopathy of undetermined significance.

Primary aldosteronism: molecular medicine meets public health.

Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s.

Iterative prototyping based on lessons learned from the falloposcope pilot study experience.

Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in FT and ovaries with good sensitivity and specificity.

Radiofrequency Ablation in Primary Aldosteronism.

The radiofrequency ablation (RFA) technique has been extensively used in the treatment of primary malignancies and metastases and has been recently deployed for the treatment of unilateral primary aldosteronism (PA) as an alternative to whole unilateral adrenalectomy.Current evidence comparing RFA with unilateral adrenalectomy in the treatment of PA so far has been variable, with studies being retrospective and small-scale, but it remains a very attractive option as a potentially less invasive treatment option compared to adrenalectomy.This review article describes the procedure, and provides evidence and the possible future direction of RFA in the treatment of unilateral PA.

Idiopathic subglottic stenosis arises at the epithelial interface of host and pathogen.

Background: Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Disease rarity and wide geographic patient distribution has previously limited substantive mechanistic investigation into iSGS pathogenesis.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1.

Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression.

Introduction: Sarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk stratification tools for important clinical outcomes in sarcoidosis, such as progressive lung disease. This study will address two clinical practice needs: (1) development of a risk calculator that provides an estimate of the likelihood of pulmonary progression in sarcoidosis patients during the follow-up period and (2) determine the optimal interval for serial clinical monitoring (eg, 6, 12, 18 months) using these risk prediction tools.

Low Gut Microbial Diversity Augments Estrogen-Driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines, such as IL-17A and TGF-β1, have been implicated in the pathogenesis of interstitial lung disease (ILD), the interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as the phosphorylation of STAT3, have not been defined. Here, through chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells, we show that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

Low Gut Microbial Diversity Augments Estrogen-driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines such as IL-17A and TGF-β1 have been implicated in interstitial lung disease (ILD) pathogenesis, interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as phosphorylation of STAT3, have not been defined. Here we show by chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells that regions within the locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

The clinical outcomes of imaging modalities for surgical management Cushing's disease - A systematic review and meta-analysis.

Introduction: Cushing's disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing's disease.

The road to systemic therapy in von Hippel-Lindau (VHL) disease: Are we there yet?

Pathogenic germline mutations in VHL gene cause von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary cancer syndrome associated with high penetrance of benign and malignant neoplasms, including clear cell renal cell carcinoma (ccRCC), central nervous system haemangioblastomas (CNS-HB), retinal angiomas, phaeochromocytomas and pancreatic neuroendocrine tumours (pNET). Management of VHL disease involves lifelong radiological and biochemical surveillance, often leading to repeat surgical intervention causing significant morbidity and mortality. Systemic therapy that prevents or reduces the need for surgical intervention could improve clinical outcomes and quality of life for affected individuals.