Background: Emapticap pegol (NOX-E36) is a Spiegelmer® that specifically binds and inhibits the pro-inflammatory chemokine C-C motif-ligand 2 (CCL2) (also called monocyte-chemotactic protein 1). The objective of this exploratory study was to evaluate the safety and tolerability as well as the renoprotective and anti-diabetic potential of emapticap in type 2 diabetic patients with albuminuria. Methods: A randomized, double-blind, placebo-controlled Phase IIa study was initiated in 75 albuminuric type 2 diabetics. Emapticap at 0.5 mg/kg and placebo were administered subcutaneously twice weekly for 12 weeks to 50 and 25 patients, respectively, followed by a treatment-free phase of 12 weeks. Results: Twice weekly subcutaneous treatment with emapticap over 3 months was generally safe and well tolerated and reduced the urinary albumin/creatinine ratio (ACR) from baseline to Week 12 by 29% (P < 0.05); versus placebo a non-significant ACR reduction of 15% was observed (P = 0.221). The maximum difference, 26% (P = 0.064) between emapticap and placebo, was seen 8 weeks after discontinuation of treatment. At Week 12, the HbA1c changed by −0.31% in the emapticap versus +0.05% in the placebo group (P = 0.146). The maximum difference for HbA1c was observed 4 weeks after the last dose with −0.35% for emapticap versus +0.12% for placebo (P = 0.026). No relevant change in blood pressure or estimated glomerular filtration rate was seen between the treatment groups throughout the study. A post hoc analysis with exclusion of patients with major protocol violations, dual RAS blockade or haematuria increased the ACR difference between the two treatment arms to 32% at Week 12 (P = 0.014) and 39% at Week 20 (P = 0.010). Conclusions: Inhibition of the CCL2/CCL2 receptor axis with emapticap pegol was generally safe and well tolerated. Beneficial effects on ACR and HbA1c were observed in this exploratory study, which were maintained after cessation of treatment. Taken together, emapticap may have disease-modifying effects that warrant further investigation in adequately powered confirmatory studies.

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Introduction Acromegaly is a chronic and disfiguring hormonal disease caused by a benign growth hormone‐secreting pituitary adenoma in most of the cases. The objective of this study was to investigate three‐dimensional (3D) speckle tracking echocardiography (3DSTE)‐derived left atrial (LA) volumetric and functional properties in patients with acromegaly. It was also examined whether the activity of acromegaly is associated with further alterations in these LA parameters. Methods A total of 23 patients with acromegaly were involved in this study. Due to inadequate image quality, 4 patients were excluded from the 3DSTE analysis. The mean age of the remaining acromegalic subjects was 58.5 ± 13.1 years (7 males). The control group consisted of 21 age‐ and gender‐matched healthy subjects (mean age 51.8 ± 10.3 years, 10 males). Results Maximum (44.8 ± 12.7 mL vs 78.7 ± 25.4 mL, P < .05), minimum (24.1 ± 9.0 mL vs 44.5 ± 15.5 mL, P < .05), and preatrial contraction (35.5 ± 11.2 mL vs 66.0 ± 22.8 mL, P < .05) LA volumes were significantly different between all acromegaly patients compared with controls. Increased peak global and mean segmental radial and 3D strains and decreased LA circumferential strain (CS) could be detected in all acromegaly patients as compared to healthy subjects. Significant correlation could be detected between insulin‐like growth factor 1 (IGF‐1) index and peak superior LA‐CS (r = .49, P = .05) in acromegaly. Conclusion Acromegaly is associated with increased LA volumes and changes in LA functional properties.

Acromegaly is associated with impaired LV rotation and twist as assessed by 3-dimensional speckle tracking echocardiography. LV-RBR is a frequent phenomenon in acromegaly.

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.

A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Endoscopic ultrasound is the most accurate imaging modality for the diagnosis of pancreatic cancer, and endoscopic ultrasound-guided fine needle injection has already been used for palliative interventions. Surgical resection is currently the standard treatment for pancreatic insulinoma. Medical treatment may be necessary for symptomatic patients with unresectable disease. Case reports have been published about the success of endoscopic ultrasound-guided alcoholic ablation, but it has not been reported previously in Hungarian literature. The authors present the history of an 83-year-old woman who was evaluated because of repeated hypoglycemic coma occurring during the night. Endosonographic image and laboratory findings (elevated serum insulin and chromogranin A) revealed pancreatic insulinoma. Because of severe comorbidities and high risk of surgical resection, the decision was made to ablate the insulinoma by endoscopic ultrasound-guided alcohol injection. A total of 3 mL 95% ethanol was injected into the tumor. Despite the discontinuation of the diazoxide therapy the hypoglycemic episodes disappeared. This case history confirms that endoscopic ultrasound-guided alcoholic ablation is a novel, minimal invasive alternative treatment for patients with pancreatic neuroendocrine tumors in whom surgery is not feasible.

Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, P<0.0001). There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6±5.4 mm vs 48.0±3.9 mm, left ventricular end systolic diameter: 32.3±5.2 mm vs 29.1±4.4 mm, interventricular septum: 11.1±2.2 mm vs 8.8±0.7 mm, posterior wall of left ventricle: 10.8±1.4 mm vs 8.9±0.7 mm, P<0.05, respectively). Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia.