25 research outputs found
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the articleâs Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the articleâs Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-ÎșB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio
Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study
Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men
Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study
Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care
La misura dellâattaccamento materno prenatale: un confronto psicometrico di tre strumenti di valutazione
RIASSUNTO: Obiettivi: Questo studio confronta le proprietĂ psicometriche dei rating di attaccamento
prenatale, misurati dalle scale Maternal Foetal Attachment Scale (MFAS), Prenatal Attachment Scale (PAI) e
Maternal Antenatal Attachment Scale (MAAS), tenendo in considerazione lâetĂ gestazionale. Metodo: 254
donne (età 31±5 anni; età gestazionale 24±11 settimane) hanno compilato i tre strumenti presentati in ordine
casuale. LâattendibilitĂ e la validitĂ dei punteggi totali e parziali Ăš stata valutata in funzione dellâetĂ gestazionale.
Risultati: I punteggi totali, in particolare quelli di MFAS e PAI, raggiungono gli standard di attendibilitĂ ,
specialmente se i rating sono stati raccolti entro la 20-esima settimana. I punteggi parziali hanno
una buona validitĂ convergente, ma la loro attendibilitĂ Ăš minacciata dal ridotto numero di item, specialmente
per i rating raccolti oltre la 21-esima settimana. Tutti i punteggi correlano con lâetĂ gestazionale, mentre
quelli del PAI erano i piĂč correlati con le caratteristiche del campione. Conclusioni: I punteggi totali sono
piĂč attendibili dei punteggi parziali, ma essi colgono meno aspetti specifici del costrutto. Le proprietĂ
psicometriche tendono a peggiorare nella seconda metĂ della gravidanza, presumibilmente a causa di un
âeffetto tettoâ nella valutazione materna. Lâanalisi fattoriale confermativa ha dimostrato che nessuno dei modelli ipotizzati nella letteratura raggiunge un fit accettabile. Ulteriori studi dovranno indagare la caratteristiche strutturali dei rating di attaccamento, per distinguere fattori comuni e specifici utili per le applicazioni cliniche e di ricerca
Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review
Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life
Patterns of practice and survival in a retrospective analysis of 1722 adult astrocytoma patients treated between 1985 and 2001 in twelve italian radiation oncology centers
Purpose: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated
in 12 Italian radiotherapy centers.
Methods and Materials: A total of 1722 patients were treated with postoperative radiotherapy (90% World
Health Organization [WHO] Grade 3â4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits,
44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in
the clinicalâtherapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with
overall survival for the different subgroups.
Results: The proportion of women, of older patients, of those with worse neurologic performance status (NPS),
with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with
radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging
procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex,
neurologic performance status, WHO grade, extent of surgery, and radiation dose.
Conclusions: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques,
smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are
treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The
accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for
the individual patient is chosen