Background: The treatment of acromegaly resistant to first generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. Methods: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (1) resistant to high dose first generation SRLs and (2) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. Results: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4 %) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (p=0.004, HR:1.6, 95%CI:1.2-4.6), with a Ki67-Li>4% (p=0.004, HR:3.49, 95%CI:1.4-3.9) and with pre-treatment IGF-I>3.3xULN (p=0.03, HR:1.3, 95%CI:1.1-6.0). A poor Pasireotide Lar response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (p=0.025, HR:1.6 95%CI:1.4-3.4), pre-treatment IGF-I>2.3xULN (p=0.049, HR:2.4, 95%CI:1.4-8.0), SST5 membranous expression (p=0.023 HR:5.6 95%CI:1.3-6.4) and in patients carried the d3-delated GHR isoform (p=0.005, HR:11.37, 95%CI:1.3-20.0). Conclusion: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR

Purpose Osteopathy is an emerging complication of acromegaly. In somatostatin receptor ligands (SRL)-resistant patients, pegvisomant (PegV) and pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined. Methods In a longitudinal retrospective international study, we evaluated incidence of radiological vertebral fractures (VFs) in 55 patients with acromegaly resistant to first-generation SRL. Results At study entry, prevalent VFs occurred in 23 patients (41.8%). Biochemical acromegaly control was reached in 66.7% of patients on PegV and in 66.7% of patients on Pasi. During the follow-up, incident VFs (iVFs) were detected in 16 patients (29.1%). Occurrence of iVFs was associated with prevalent VFs (P = .002), persistence of active acromegaly (P = .01) and higher value of insulin-like growth factor 1 (IGF-1) during follow-up (P = .03). Among patients with active disease at last visit, iVFs occurred less frequently in patients on treatment with Pasi (25%) compared to PegV (77.8% P = .04), independently of the IGF-1 values (P = .90). In patients who reached biochemical control, 22.7% on PegV and 12.5% on Pasi had iVFs (P = .40). Among both treatment groups, the presence of pre-existent VFs was the main determinant for iVFs. Conclusion Our data show for the first time that patients with biochemically active disease treated with Pasi had lower risk of iVFs versus those treated with PegV. It also confirms that the presence of pre-existent VFs was the main determinant for iVFs. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings.

: Acromegaly and Growth Hormone (GHD) deficiency are associated with skeletal fragility and with an increased prevalence of vertebral fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

: Photocatalytic oxidation is a promising tool for waste water treatment and decomposition of biologically non digestible substances. Immersed nanoscale catalyst particles from semiconductor materials such as TiO2 and ZnO can be excited by absorbed UV radiation, leading to hydroxyl-ion formation at the surface of the semiconductor and oxidative degradation of pollutants. This contribution deals with reactors equipped with catalyst coated light guides to combine the advantages of immobilized catalysts with nearly homogeneous irradiation. With experimental and theoretical methods the coupling and decoupling of radiation were investigated and the performance of catalyst coated light guides was tested by means of methylene-blue degradation. Radiation models, known from the recent literature, use single ray, parallel ray or multi ray models to approximate the light transmission. These models neglect Fresnel reflection and consider only coupling into the light guide. In this study, the LED was simulated as a Lambertian radiator using 104 rays with angle dependent intensities. This well-known model was extended with Fresnel-reflection, which predicted the measured coupling efficiencies accurately. The simulations predict the decoupling and catalyst activation at the lateral surface of the light guide for two boundary cases, ideal matt and ideal reflective surfaces. To generate matt surfaces, the light guides were either scratched or coated with TiO2 p25 nanopowder. Sol-gel coating methods were used, to create reflective surfaces. When using matt surfaces, the decoupling rate is very high: 80% of the radiant flux exits the light guide in less than 10 cm. If light guides with reflective surfaces are used, the radiant flux leaving the light guide is low: less than 10% of the radiation exited the light conductor in the first 10 cm. Methylene-blue degradation, seen as a model reaction, was used to determine the reactor performance by comparing the pseudo first order reaction coefficients. Due to the uniform light distribution along the length of the light guides and the resulting even formation of reactive radicals, the quantum yield was increased by a factor of 3, using sol-gel coated light guides, rather than powder coated light guides.