Evolution in endoscopic endonasal approach for the management of hypothalamic–pituitary region metastasis: A single-institution experience

IntroductionEndonasal endoscopic surgery has changed the treatment perspectives for different lesions of the hypothalamic–pituitary region. The metastases of the hypothalamic–pituitary region represent 0.4% of all intracranial metastatic tumors and account for only 1.8% of surgically managed pituitary lesions. The aim of tshis study is to describe a single-center institutional experience with 13 cases of hypothalamic–pituitary metastasis focused on presurgical workup, the evolution of the surgical technique, and postsurgical management according to our protocols, showing effects on progression-free and overall survival rates for this relatively uncommon location.Material and MethodsWe retrospectively reviewed the whole series of patients that received the endoscopic endonasal approach at the Division of Neurosurgery at the University of Naples “Federico II” undergoing surgery from January 1997 to December 2021. We identified 13 cases whose pathology reports revealed a metastatic lesion. Statistical analysis was performed to determine the Kaplan–Meier survival function and assess for log-rank differences in survival based on gender, surgical treatment, and postoperative therapy (p-value < 0.02*).ResultsThe pathology report disclosed lung adenocarcinoma (six cases, 46%), breast adenocarcinoma (two cases, 15.4%), clear cell renal carcinoma (one case, 7%), melanoma (one case, 7%), colorectal adenocarcinoma (one case, 7%), uterine cervix carcinoma (one case, 7%), and follicular thyroid carcinoma (one case, 7%). A standard endoscopic endonasal approach was performed in 10 patients (76.9%), while an extended endonasal procedure was performed in only three cases (23%). Biopsy was the surgical choice in five patients with infiltrative and invasive lesions and a poor performance status (38%), while in the cases where neurovascular decompression was necessary, a subtotal resection was achieved in five patients (38%) and partial resection in three patients (23%). Recovery of visual field defect was observed in six of seven patients with visual loss (85.7%), improvement of oculomotor nerve palsy occurred in four of seven patients with this defect (57.1%), while the impairment of oculomotor palsy was observed in three patients (42.9%). Visual function was stable in the other patients. The median progression-free survival and overall survival were 14 and 18 months, respectively. There were statistically significant differences in PFS and OS in patients who underwent adjuvant radiotherapy (p=0.019 is referred to OS and p=0.017 to PFS, respectively; p-value = 0.02).ConclusionsThe endoscopic endonasal approach is a viable approach for the management of hypothalamic–pituitary metastases as this surgery provides an adequate opportunity to obtain tissue sample and neurovascular decompression, both being crucial for continuing the integrated adjuvant therapy protocols

NutriLive: An Integrated Nutritional Approach as a Sustainable Tool to Prevent Malnutrition in Older People and Promote Active and Healthy Ageing—The EIP-AHA Nutrition Action Group

The present document describes a nutritional approach that is nested in the European Innovation Partnership for Active and Healthy Aging (EIP-AHA) and aims to provide the first common European program translating an integrated approach to nutritional frailty in terms of a multidimensional and transnational methodology. The document has been developed by the A3 Nutrition Action Area of the EIP-AHA and aims at providing a stepwise approach to malnutrition in older citizens, identifying adequate interventions based on a unified assessment and ICT-supported solutions. "NutriLive" is an integrated nutritional approach, represented by a structured Screening-Assessment-Monitoring-Action-Pyramid-Model (SAM-AP). Its core concept is the stratification of the nutritional needs, considered by the working group as the key for targeted, effective, and sustainable interventions. "NutriLive" tries to close gaps in epidemiological data within an aging population, creating a unified language to deal with the topic of nutrition and malnutrition in Europe. By assembling all the validated screening, assessment, and monitoring tools on malnutrition in a first pyramid, which is interrelated to a second intervention pyramid, the A3 Nutrition WG identifies a common, integrated vision on the nutritional approach to frailty, which applies to the various health care settings

The Utility of Pyrogenic Cytokine (IL-1β, TNF-α and IL-6) Detection In Risk Stratification of Critically lll Febrile Patients in Emergency Department

Objective: Aim of our study was to evaluate the prognostic value of pyrogenic cytokines (IL-1β, TNF-α and IL-6) detection associated with Mid regional pro-Amedullin (MR-proADM) and the APACHE II score in febrile patients admitted to the Emergency Department (ED). Material: 64 patients in the Emergency Room (ER) during a period of 12 months with body temperature >37°C were recruited for this study. In order to compare MR-proADM and cytokine values, a control group of 40 healthy volunteers was enrolled. For each subject, the APACHE II score was calculated. Result: MR-proADM and cytokines were significantly higher in patients compared to controls (p<0.0001). When APACHE II score was correlated to MR-proADM and cytokines and grouped into quartile, it showed a significant increase in TNF-α and IL-6 levels (p<0.0001). A significant stepwise increase in MR-proADM in accordance with IL-6 quartile levels was observed (p<0.0001). The receiver operating characteristic (ROC) curve showed the abil

IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro and its plasma levels correlate with B-type natriuretic peptide in non-overloaded acute heart failure patients

Background: An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown tobe of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic,and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulatecardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptidesynthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients.Methods and Results: We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line toexpress the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction,and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-typenatriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patientswith diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levelsthan patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels.Conclusions: This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesisin vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status

Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS) causes distress in caregivers. The present study aims to examine the association between coping strategies and psychological distress in caregivers of ALS patients. Methods: Coping strategies were assessed in 96 ALS informal caregivers by means of the Coping Inventory for Stressful Situations. Data about caregivers’ demographic characteristics, levels of burden, depression and anxiety (psychological distress) were also gathered by standardised questionnaires. Patients’ clinical, cognitive and behavioural disturbances were evaluated by ALS specific assessment tools. Results: Sequential logistic regression analysis showed that emotion-oriented coping strategy was significantly associated with high levels of depressive (p < 0.01) and anxiety (p < 0.05) symptoms and high levels of burden (p < 0.05), after controlling for all other variables. Moreover, a significant relationship of patients’ functional dependence levels with burden experienced by caregivers was observed. No relationships were detected between task-oriented and avoidance-oriented coping strategies and caregivers’ levels of psychological distress. Conclusions: The present study supported the mediating effects of coping strategies on intensity of burden, depression and anxiety experienced by ALS caregivers. These findings suggest that interventions aimed at reducing utilisation of maladaptive coping strategies may improve well-being in ALS caregivers, and, possibly, management of symptoms in ALS patients

Somatotropin replacement therapy in normotensive adults does not elevate blood pressure after 1-year follow-up: the HypoCCS experience in Italy

none9noneValle D.; Aimaretti G.; Ambrosio M.R.; Scaroni C.; Di Somma C.; Giampietro A.; Lanzi R.; degli Uberti E. C.; Mantero F.Valle, D.; Aimaretti, G.; Ambrosio, Maria Rosaria; Scaroni, C.; Di Somma, C.; Giampietro, A.; Lanzi, R.; DEGLI UBERTI, Ettore; Mantero, F

Targeting G-quadruplex motifs interferes with differentiation of adipose-derived mesenchymal stem cells

Abstract Background G-quadruplex (G4) motifs are nucleic acid secondary structures observed in mammalian genomes and transcriptomes able to regulate various cellular processes. Several small molecules have been developed so far to modulate G4 stability, frequently associated with anticancer activity. However, how G4 structures are regulated over homeostatic conditions is mostly unexplored. Here, we used human adipose-derived mesenchymal stem cells (ASCs) to address the role of G4 motifs during adipogenic differentiation. Methods Adipocyte differentiation of ASCs was investigated in the presence or absence of a well-known G4 ligand, Braco-19. Cell viability was determined by sulforhodamine B assay. Cell dimension and granularity, DNA G4 motifs and cell cycle were detected by flow cytometry. Lipid droplet accumulation was assessed by Oil Red O staining. Cell senescence was evaluated by β-galactosidase staining. Gene expression was measured by qPCR. Protein release in the extracellular medium was quantified by ELISA. Results Braco-19 used at non-cytotoxic concentrations induced morphological changes in mature adipocytes partially restoring an undifferentiated-like status. Braco-19 reduced lipid vacuolization and PPARG, AP2, LEP and TNFA mRNA levels in terminally differentiated cells. No effect was observed in cell senescence, fibrotic markers, IL-6 and IL-8 production, while the secretion of VEGF was dose-dependently reduced. Interestingly, G4 structures were increased in differentiated adipocytes compared to their precursors. Braco-19 treatment reduced G4 content in mature adipocytes. Conclusions Our data highlight a new role of G4 motifs as genomic structural elements related to human ASC differentiation into mature adipocytes, with potential implications in physio-pathological processes

GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity

GM-CSF and IL-3 are hematopoietic cytokines that also modulate the effector functions of several immune cell subsets. In particular, GM-CSF and IL-3 exert a significant control on monocyte and macrophage effector functions, as assessed in experimental models of inflammatory and autoimmune diseases and also in human studies. Here, we sought to investigate the mechanisms and the extent to which GM-CSF and IL-3 modulate the pro-inflammatory, LPS-mediated, activation of human CD14(+) monocytes taking into account the new concept of trained immunity (i.e., the priming stimulus modulates the response to subsequent stimuli mainly by inducing chromatin remodeling and increased transcription at relevant genetic loci). We demonstrate that GM-CSF and IL-3 priming enhances TNF-α production upon subsequent LPS stimulation (short-term model of trained immunity) in a p38- and SIRT2-dependent manner without increasing TNF primary transcript levels (a more direct measure of transcription), thus supporting a posttranscriptional regulation of TNF-α in primed monocytes. GM-CSF and IL-3 priming followed by 6 days of resting also results in increased TNF-α production upon LPS stimulation (long-term model of trained immunity). In this case, however, GM-CSF and IL-3 priming induces a c-Myc-dependent monocyte renewal and increase in cell number that is in turn responsible for heightened TNF-α production. Overall, our results provide insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity

Current Water Conditions in Massachusetts (2011-01-13)

BACKGROUND: Neutrophil functions have long been regarded as limited to acute inflammation and the defense against microbes. The role(s) of neutrophils in cancer remain poorly understood. Neutrophils infiltrate tumors and are key effector cells in the orchestration of inflammatory responses. Thyroid cancer (TC) is the most recurrent endocrine malignant tumor and is responsible for 70% of deaths due to endocrine cancers. No studies are so far available on the role of neutrophils in TC. OBJECTIVE: Our purpose was to study the involvement of tumor-associated neutrophils in TC. METHODS: Highly purified human neutrophils (>99%) from healthy donors were stimulated in vitro with conditioned media derived from TC cell lines TPC1 and 8505c (TC-CMs). Neutrophil functions (e.g., chemotaxis, activation, plasticity, survival, gene expression, and protein release) were evaluated. RESULTS: TC-derived soluble factors promoted neutrophil chemotaxis and survival. Neutrophil chemotaxis toward a TC-CM was mediated, at least in part, by CXCL8/IL-8, and survival was mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, each TC-CM induced morphological changes and activation of neutrophils (e.g., CD11b and CD66b upregulation and CD62L shedding) and modified neutrophils' kinetic properties. Furthermore, each TC-CM induced production of reactive oxygen species, expression of proinflammatory and angiogenic mediators (CXCL8/IL-8, VEGF-A, and TNF-α), and a release of matrix metalloproteinase 9 (MMP-9). Moreover, in TC patients, tumor-associated neutrophils correlated with larger tumor size. CONCLUSIONS: TC cell lines produce soluble factors able to "educate" neutrophils toward an activated functional state. These data will advance the understanding of the molecular and cellular mechanisms of innate immunity in TC

Position paper sulle politiche per la cronicità e sugli interventi per la gestione dello scompenso cardiaco

The work represents a position paper on chronic diseases policies and management models. It is the result of a Consensus Conference with 14 stakeholders that took place between October and November 2018. After an analysis of chronic diseases policies in 10 Italian regions, the paper focuses on management models for one specific chronic disease, heart failure, around which the regional intervention has centred. This paper aims at: 1) ascertain the state of the art of Italian policies on chronic diseases by mapping regional plans, programs and projects; 2) understand the main trends affecting policies on chronic diseases and heart failure, through a compared analysis of the mapped legislation; 3) identify the characteristics of regional projects related to chronic disease management and, where available, to hearth failure management through the selection of those representing regional tendencies. Our findings show that chronic diseases are developing according to some trends including demand management, comorbidity and frailty management and management of service usage. The paper ends with 8 statements representing the point of view of the expert panel group who took part to the Consensus Conference