Consensus on acromegaly therapeutic outcomes: an update.

The 15th Acromegaly Consensus Conference in September 2023 updated recommendations on therapeutic outcomes for acromegaly. Since the publication of medical management guidelines in 2018, new pharmacological agents and new treatment approaches have been developed. Fifty-two experts in the management of acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and management.

Novel applications of liquid Biopsy: Comprehensive methodology for circulating biomarker exploration in peripheral blood.

The liquid biopsy (LB) represents a minimally invasive method for cancer screening that has been introduced in clinical practice for over a decade and that can accelerate treatment response assessment. LB allows the analysis of tumor cells or tumor-derived products (e.g.

Impact of pasireotide on lipid and glucose metabolism in patients with acromegaly: a systematic review and meta-analysis.

Background: Pasireotide long-acting release (PasiLAR), a somatostatin multireceptor ligand, is effective in achieving biochemical control but can increase the risk of hyperglycemia in acromegaly. However, the impact of PasiLAR on lipid and glucose metabolism in patients with acromegaly has not been systematically studied. This systematic review aimed at synthesizing evidence on PasiLAR effects (as monotherapy or combination therapy with pegvisomant) on lipid and glucose metabolism in patients with acromegaly.

AP1-mediated reprogramming of EGFR expression triggers resistance to BLU-667 and LOXO-292 in RET-rearranged tumors.

Background: Non-small cell lung cancer (NSCLC) is a significant global health challenge, with 2% of cases fuelled by RET rearrangements. RET inhibitors (RETi) have revolutionized treatment for these patients, but resistance remains an important clinical challenge limiting therapy effectiveness. This study investigated the mechanisms underlying resistance to RETi.

Long-term clinical outcome of 103 patients with acromegaly after pituitary surgery.

Purpose: Acromegaly is a rare disease that can be challenging to treat due to residual pituitary adenoma after surgery or variable response to medical treatments. The primary aim of the study was to evaluate the path of treatment and long-term outcome of acromegaly after pituitary surgery.

Methods: Patients with acromegaly who had undergone surgery for a growth hormone-producing pituitary neuroendocrine tumor also known as a pituitary adenoma, at Sahlgrenska University Hospital between 1994 and 2019 were included in the study.

Differential Impact of Medical Therapies for Acromegaly on Glucose Metabolism.

Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, due, in the vast majority of cases, to the presence of a GH-secreting pituitary tumour. The chronic elevation of GH and the resulting high circulating levels of insulin-like growth factor-1 (IGF-1) cause the characteristic tissue overgrowth and a number of associated comorbidities, including several metabolic changes, such as glucose intolerance and overt diabetes mellitus (DM). Elevated GH concentrations directly attenuate insulin signalling and stimulate lipolysis, decreasing glucose uptake in peripheral tissues, thus leading to the development of impaired glucose tolerance and DM.

Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma.

Purpose: Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.

Experimental Design: In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients.

Systemic inflammatory markers and volume of enhancing tissue on post-contrast T1w MRI images in differentiating true tumor progression from pseudoprogression in high-grade glioma.

Background: High-grade glioma (HGG) patients post-radiotherapy often face challenges distinguishing true tumor progression (TTP) from pseudoprogression (PsP). This study evaluates the effectiveness of systemic inflammatory markers and volume of enhancing tissue on post-contrast T1 weighted (T1WCE) MRI images for this differentiation within the first six months after treatment.

Material And Methods: We conducted a retrospective analysis on a cohort of HGG patients from 2015 to 2021, categorized per WHO 2016 and 2021 criteria.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed.

The Impact of Growing Area on the Expression of Fruit Traits Related to Sensory Perception in Two Tomato Cultivars.

Environmental conditions greatly influence the quality of tomato fruit by affecting the expression of genes, the abundance of metabolites, and the perception of sensorial attributes. In this study, a fruit transcriptome investigation, a sensory test, and a metabolomic analysis were performed to evaluate the impact of the environment on two popular tomato cultivars grown in two Italian regions. The transcriptional profile of each cultivar, cultivated in two different areas, highlighted differential expression in genes involved in pathways related to cell wall components such as pectin, lignin, and hemicellulose and sugars as well as in amino acids, phenylpropanoids, and pigment synthesis.

Thyroid dysfunction in Hashimoto's thyroiditis: a pilot study on the putative role of miR-29a and TGFβ1.

Purpose: Hashimoto's thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFβ1) in HT patients with different patterns of thyroid function.

Methods: A total of 29 HT patients, with a median age of 52 years (21-68) were included.

-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R).

Cannabinoid receptor subtype 2 (CB2R) is emerging as a pivotal biomarker to identify the first steps of inflammation-based diseases such as cancer and neurodegeneration. There is an urgent need to find specific probes that may result in green and safe alternatives to the commonly used radiative technologies, to deepen the knowledge of the CB2R pathways impacting the onset of the above-mentioned pathologies. Therefore, based on one of the CB2R pharmacophores, we developed a class of fluorescent -adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives spanning from the green to the near-infrared (NIR) regions of the light spectrum.

EGFR and HER2 hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer.

In patients with ER + metastatic breast cancer (mBC), the first-line treatment involves the combination of endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i). However, a significant group of patients experiences disease progression, emphasizing the urgent clinical need to identify novel anti-tumor therapies. We previously generated breast cancer cells resistant to the combination of fulvestrant (ER downregulator) and abemaciclib (CDK4/6 inhibitor) from MCF7 and T47D (MCF7-FAR and T47D-FAR).

Mortality in patients with adrenal insufficiency: a protocol for a systematic review and meta-analysis.

Introduction: Adrenal insufficiency (AI) is a rare disorder characterised by an impaired secretion of glucocorticoids from the adrenal glands. Treatment strategies for AI have developed over time with reduced glucocorticoid replacement doses and improved circadian exposure regimens, but whether this has resulted in better survival is unknown. The main purpose of this systematic review is to gather and synthesise available evidence on long-term mortality in patients with AI.

Androgen deficiency in hypopituitary women: its consequences and management.

Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited.

Safety of Subcutaneous Daratumumab in Anti-CD38 Monoclonal Antibody-Naïve Patients with Plasma Cell Disorders: A Multicenter Real-Life Experience.

Background: Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few.

Objective: In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders.

Combined blockade of mTOR and p21-activated kinases pathways prevents tumour growth in KRAS-mutated colorectal cancer.

Background: The identification of novel therapeutic strategies for metastatic colorectal cancer (mCRC) patients harbouring KRAS mutations represents an unmet clinical need. In this study, we aimed to clarify the role of p21-activated kinases (Paks) as therapeutic target for KRAS-mutated CRC.

Methods: Paks expression and activation levels were evaluated in a cohort of KRAS-WT or -mutated CRC patients by immunohistochemistry.

Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis.

Introduction: Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated.

Objectives: The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA.

The effect of the alpha-specific PI3K inhibitor alpelisib combined with anti-HER2 therapy in HER2+/PIK3CA mutant breast cancer.

Background: HER2 is amplified or overexpressed in around 20% of breast cancers (BC). HER2-targeted therapies have significantly improved the prognosis of patients with HER2+ BC, however, and acquired resistance to anti-HER2 treatment is common. Activating mutations in the gene are reported in ∼30% of HER2+ BC and are associated with resistance to anti-HER2 therapies and a poor prognosis.

Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have been approved in combination with endocrine therapy (ET) to treat estrogen receptor-positive (ER+) metastatic breast cancer (BC). However, drug resistance represents the leading cause of breast cancer patients mortality. This study aimed to identify novel resistance mechanisms to ER antagonists in combination with CDK4/6 inhibitors.

Increased prevalence of nodular thyroid disease in patients with Klinefelter syndrome.

Purpose: Thyroid dysfunction in patients with Klinefelter syndrome (KS) remains an unresolved issue. Although low free thyroxine (FT4) levels within the normal range and normal thyroid stimulating hormone (TSH) levels have been reported, there is currently no data on nodular thyroid disease in this population. This study aims to evaluate the results of thyroid ultrasound (US) examinations in KS patients compared with healthy controls.

Role of FGFR3 in bladder cancer: Treatment landscape and future challenges.

Bladder cancer is a heterogeneous malignancy and is responsible for approximately 3.2% of new diagnoses of cancer per year (Sung et al., 2021).