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Background: Survivors of childhood brain tumours (SCBT) and teenage and young adult cancer survivors have an adverse cardiovascular risk profile, which translates into an increased vascular mortality. Data on cardiovascular risk profile in SCBT are limited and furthermore there are no data in adult-onset brain tumours.

Patients and Methods: Fasting lipids, glucose, insulin, 24-hour blood pressure, and body composition were measured in 36 brain tumours survivors [20 adult-onset (AO); 16 childhood-onset (CO)] and 36 age- and gender-matched controls.

Results: Compared with controls, patients had elevated total cholesterol (5.3±1.1 Vs. 4.6±1.0mmol/l, p=0.007), LDL-C (3.1±0.8 Vs. 2.7±0.9mmol/l, p=0.011), insulin (13.4±13.1 Vs. 7.6±3.3miu/l, p=0.014) and increased insulin resistance (HOMA-IR 2.90±2.84 Vs. 1.66±0.73, p=0.016). Patients showed adverse body composition, with increased total body fat mass (FM) (24.0±12.2 Vs. 15.7±6.6kg, p<0.001) and truncal FM (13.0±6.7 Vs. 8.2±3.7kg, p<0.001). After stratification by timing of onset, CO survivors showed significantly increased LDL-C, insulin, and HOMA-IR compared with controls. Body composition was characterized by increased total body and truncal FM. Truncal fat mass was increased by 84.1% compared with controls. AO survivors showed similar adverse cardiovascular risk profile, with increased total cholesterol and HOMA-IR. Truncal fat mass was increased by 41.0% compared with matched controls (p=0.029). No difference in mean 24hr BP was noted between patients and controls irrespective of timing of cancer diagnosis.

Conclusion: The phenotype of both CO and AO brain tumour survivors is characterized by an adverse metabolic profile and body composition, putatively placing long-term survivors at increased risk of vascular morbidity and mortality.

Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition.

Objectives: To conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant.

Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD and ABraOM), in silico prediction of pathogenicity, and gene expression in pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing.

Results: One female patient with deficiencies in GH, TSH, ACTH, LH, and FSH and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wild type CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected.

Conclusion: A homozygous CDH2 allelic variant was found in 1 hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations.

Objective: Patients with primary adrenal insufficiency (PAI) are thought to be particularly vulnerable to COVID-19; however, little is known about its true impact on this group. We assessed morbidity and health promotion attitudes during the pandemic amongst a large cohort of patients with PAI.

Design: Cross-sectional, single-centre study.

Methods: In May 2020, COVID-19 advice on social distancing and sick-day rules was distributed to all patients with PAI registered with a large secondary/tertiary care centre. A semi-structured questionnaire was used to survey patients in early 2021.

Results: Of 207 contacted patients, 162 responded (82/111 with Addison’s disease, AD; 80/96 with congenital adrenal hyperplasia, CAH). Patients with AD were older than those with CAH (median age 51 vs. 39 years; p<0.001) and had more comorbidities (Charlson comorbidity index ≥2 47.6% vs. 10.0%; p<0.001). By the time of the survey, 47 patients (29.0%) had been diagnosed with COVID-19, the second commonest cause of sick-day dosing during the study and the leading trigger of adrenal crises (4/18 cases). Patients with CAH had a higher risk of COVID-19 compared to AD (adjusted odds ratio 2.53 [95% CI 1.07-6.16], p=0.036), were less inclined to have the COVID-19 vaccine (80.0% vs. 96.3%; p=0.001), and were less likely to have undergone hydrocortisone self-injection training (80.0% vs. 91.5%; p=0.044) or wear medical alert jewellery (36.3% vs. 64.6%; p=0.001).

Conclusions: COVID-19 was a principal trigger for adrenal crises and sick-day dosing in patients with PAI. Despite a higher risk of COVID-19, patients with CAH showed less engagement with self-protective attitudes.

Skeletal muscle is the main metabolic tissue responsible for glucose homeostasis in the body. It is surrounded by the extracellular matrix (ECM) consisting of three layers: epimysium, perimysium, and endomysium. ECM plays an important role in the muscle, as it provides integrity and scaffolding cells. The observed disturbances in this structure are related to the abnormal remodeling of the ECM (through an increase in the concentration of its components). ECM rearrangement may impair insulin action by increasing the physical barrier to insulin transport and reducing insulin transport into muscle cells as well as by directly inhibiting insulin action through integrin signaling. Thus, improper ECM remodeling may contribute to the development of insulin resistance (IR) and related comorbidities. In turn, IR-associated conditions may further aggravate disturbances of ECM in skeletal muscle. This review describes the major components of the ECM that are necessary for its proper function. Particular attention was also paid to receptors (integrins) involved in the signaling of metabolic pathways. Finally, changes in ECM components in the context of clinical and animal studies are discussed. This article will help the reader to systematize knowledge related to the ECM and to better understand the relationship between ECM remodeling and IR, and its role in the pathogenesis of T2DM. The information in this article presents the concept of the role of ECM and its remodeling in the pathogenesis of IR, which may contribute to developing new therapeutic solutions.