Mitochondrial dysfunction and lipid alterations in primary sclerosing cholangitis.

Objectives: Indications of mitochondrial dysfunction are commonly seen in liver diseases, but data are scarce in primary sclerosing cholangitis (PSC). Analyzing circulating and liver-resident molecules indirectly reflecting mitochondrial dysfunction, we aimed to comprehensively characterize this deficit in PSC, and whether this was PSC specific or associated with cholestasis.

Materials And Methods: We retrospectively included plasma from 191 non-transplant patients with large-duct PSC and 100 healthy controls and explanted liver tissue extracts from 24 PSC patients and 18 non-cholestatic liver disease controls.

Extended-release hydrocortisone formulations - Is there a clinically meaningful benefit?

Despite best practice replacement therapy with corticosteroids, patients with adrenal insufficiency report diminished quality of life and face increased mortality and morbidity. Conventional formulations of hydrocortisone have short half-lives (about 90 minutes) requiring multiple dosing during the day. Extended-release hydrocortisone (ER-HC) formulations have since 2011 been available enabling once, sometimes twice daily dosing.

Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease.

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. In vitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects.

Gunshot Injury With Bone Defect of the First Metatarsal Bone A Presentation of 2 Cases Treated With an Iliac Crest Structural Graft, Internal Fixation, and Bone Morphogenic Protein 2.

Gunshot injuries to the foot with segmental bone defects can be challenging to treat. When the vascularity is intact and the soft tissues allows, the goal should be to reconstruct the bony defect. We present 2 cases of a gunshot injury to the foot with a defect of the first metatarsal bone.

Corticosteroid rhythms in hypoparathyroid patients.

Objective: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns.

Design: Crossover interventional study.

Utility of salivary cortisol and cortisone in the diagnostics of adrenal insufficiency.

Background: Salivary cortisol (sa-cortisol) and salivary cortisone (sa-cortisone) correlate well with serum cortisol (s-cortisol) but validated reference ranges for healthy individuals are lacking.

Objective: To establish cutoff levels for sa-cortisol and cortisone following cosyntropin testing, and assess their diagnostic utility in adrenal insufficiency (AI).

Methods: Steroids in saliva were assayed using liquid-chromatography tandem-mass-spectrometry (LCMS/MS) before and after administration of 250µg cosyntropin test in 128 healthy subjects (16 on oral estrogens) and 59 patients with suspected AI, of whom 26 were diagnosed with AI with conventional serum cortisol criteria.

A multi-component intervention increased access to smoking cessation treatment after hospitalization for atherosclerotic cardiovascular disease: a randomized trial.

Aims: To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months.

Methods And Results: A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021.

Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event.

Background And Aims: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event.

Methods: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later.

Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.

Immune tolerance fails in autoimmune polyendocrine syndrome type 1 (APS-1) because of mutations. We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from expanded Tregs in APS-1 patients compared to healthy controls. We revealed only CD52 and LTB (down) and TXNIP (up) as consistently differentially expressed genes in the datasets.

Rare copy number variation in autoimmune Addison's disease.

Autoimmune Addison's disease (AAD) is a rare but life-threatening endocrine disorder caused by an autoimmune destruction of the adrenal cortex. A previous genome-wide association study (GWAS) has shown that common variants near immune-related genes, which mostly encode proteins participating in the immune response, affect the risk of developing this condition. However, little is known about the contribution of copy number variations (CNVs) to AAD susceptibility.

The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study.

Background And Aims: Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS.

Validation of a novel direct method to determine reduced adherence to atorvastatin therapy.

Aims: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in the blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values.

Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease.

Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta.

Frailty, health literacy and self-care in patients admitted with acute heart failure.

Background: There is limited knowledge from Norway on clinical characteristics, self-care and health literacy in patients admitted to hospital with acute heart failure. Our aim was to identify these factors in this group.

Material And Method: We included patients admitted with acute heart failure over a period of six months (2022/2023) at Drammen Hospital and Vestfold Hospital Trust.

Improving diagnostic precision in primary ovarian insufficiency using comprehensive genetic and autoantibody testing.

Study Question: Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening?

Summary Answer: Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11% to 41%.

What Is Known Already: POI affects ∼1% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases.

A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1.

Autoimmune polyendocrine syndrome type 1 (APS-1) is caused by mutations in the autoimmune regulator (AIRE) gene. Most patients present with severe chronic mucocutaneous candidiasis and organ-specific autoimmunity from early childhood, but the clinical picture is highly variable. AIRE is crucial for negative selection of T cells, and scrutiny of different patient mutations has previously highlighted many of its molecular mechanisms.

Outcomes After Proximal Medial Gastrocnemius Recession and Stretching vs Stretching as Treatment of Chronic Plantar Fasciitis at 6-Year Follow-up.

Background: Evidence from prospective short-term studies suggest that proximal medial gastrocnemius recession is a safe and efficient procedure to treat chronic plantar fasciitis resistant to nonoperative treatment. The aim of this study was to evaluate the long-term clinical outcomes of proximal medial gastrocnemius recession and stretching compared to a stretching exercise protocol for patients with chronic plantar fasciitis and an isolated gastrocnemius contracture (IGC).

Methods: Forty patients with plantar fasciitis lasting more than 1 year were prospectively randomized to a home stretching exercise program only, or to proximal medial gastrocnemius recession in addition to the stretching program.

Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study.

Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.

Design: Cross-sectional study.

Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex.

Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy.

Context: Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing.

Objective: This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life.

Prevalence, Risk Factors, and Clinical and Biochemical Characteristics of Alemtuzumab-Induced Graves Disease.

Objective: Atypical Graves disease (GD) is a common complication in multiple sclerosis (MS) patients treated with alemtuzumab. We present epidemiological, clinical, and biochemical characteristics of alemtuzumab-induced GD.

Methods: Retrospective follow-up study of MS patients treated with alemtuzumab from 2014 to 2020, including clinical course of GD, pregnancy outcome, and thyroid eye disease (TED).

Regulatory T cells in autoimmune primary adrenal insufficiency.

Primary adrenal insufficiency (PAI) is most often caused by an autoimmune destruction of the adrenal cortex resulting in failure to produce cortisol and aldosterone. The aetiology is thought to be a combination of genetic and environmental risk factors, leading to breakdown of immunological tolerance. Regulatory T cells (Tregs) are deficient in many autoimmune disorders, but it is not known whether they contribute to development of PAI.