Archivio istituzionale della Ricerca - Università degli Studi di Parma
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Effectiveness of nivolumab-based immunotherapy and prognostic stratification by the Meet-URO score in real-world older patients with metastatic renal cell carcinoma
No full textIntroduction: The incidence of renal cell carcinoma (RCC) increases with age, yet older patients (≥70 years) are underrepresented in clinical trials. Evidence on the efficacy of immune checkpoint inhibitors (ICIs) and on reliable prognostic tools for this population remains limited. We aimed to evaluate the effectiveness of nivolumab-based immunotherapy in older patients with metastatic RCC (mRCC) and assess the prognostic accuracy of the International Metastatic RCC Database Consortium (IMDC) and Meet-URO scores.
Materials and Methods: This multicenter study included 889 patients with mRCC treated with nivolumab alone or in combination with ipilimumab, using data from the Meet-URO 15 study and the Italian Expanded Access Program. Progression-free survival (PFS), overall survival (OS), and prognostic factors were analyzed by age group (<70 and ≥ 70 years) using Kaplan-Meier curves and multivariate models.
Results: Median OS and PFS were similar between younger and older patients (mOS: 23.5 vs. 25.1 months, HR: 1.02, p = 0.82; mPFS: 6.28 vs. 7.82 months, HR: 0.93, p = 0.40). The Meet-URO score outperformed the IMDC score in prognostic accuracy (p < 0.001), particularly in older patients. Non-clear cell histology was linked to shorter PFS (HR: 1.37, p = 0.05), while prior nephrectomy improved OS (HR: 0.55, p = 0.001). Limitations include the retrospective design and treatment heterogeneity. Prospective validation is needed.
Discussion: In this large real-world cohort, outcomes in older patients with mRCC receiving nivolumab-based immunotherapy were comparable to those in younger patients. The Meet-URO score improved prognostic stratification and supported clinical decision-making
Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review
No full textBackground: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being
COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID
No full textBackground: The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF. Methods: This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV1 recorded 6 months after acute infection was also evaluated. Results: A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1 % of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV1 after 6 months from the infection was +1.8 % (95 % CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8 %, 95 % CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1 %, 95 % CI: 0.6-1.9). Conclusions: In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults
Reflective Writing to Support Nursing Students' Ethical Understanding of End-of-Life Care: A Phenomenological Study
No full textEnd-of-life care requires nurses to integrate ethical sensitivity, emotional presence, and effective communication. Reflective writing, a key component of Narrative Medicine, offers nursing students a structured method to process complex emotional experiences and deepen their ethical understanding. This study investigated how third-year nursing students reflected on ethical issues and emotional responses related to end-of-life care through a structured reflective writing activity conducted after a film-based educational session. A qualitative phenomenological approach was applied to analyze 55 written reflections produced by Italian nursing students. The reflections were collected following a classroom screening of a film portraying terminal illness and decision-making at the end of life. Data were examined thematically using Braun and Clarke method. Four key themes emerged: emotional responses to death; relational and ethical dynamics; communication and connection; and temporal-spiritual meaning-making. Students’ reflections revealed an emerging awareness of ethical dimensions such as patient autonomy, vulnerability, and the value of nonverbal communication. Through reflective writing, participants articulated emotions including fear, anger, and guilt and engaged in personal meaning-making related to self-determination and compassionate care. Overall, reflective writing facilitated the development of ethical awareness and emotional resilience among students preparing for palliative care practice. The integration of structured reflection into hospice and palliative nursing education may enhance students’ readiness to deliver empathetic, person-centered care
Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy
No full textAberrant O-glycosylation of the IgA1 hinge region is a characteristic finding in patients with IgA nephropathy (IgAN) and is thought to contribute to immune-complex formation and kidney injury. Other studies have suggested that abnormalities in mucosal immunity and lymphocyte homing are major contributors to disease. We identified a family with IgAN segregating a heterozygous predicted loss-of-function (LOF) variant in GALNT14, the gene encoding N-acetylgalactosaminyltransferase 14, one of the enzymes involved in mucin-type protein O-glycosylation. While GALNT14 is expressed in IgA1-producing cells, carriers of the LOF variant did not have altered levels of poorly glycosylated IgA1, suggesting other disease mechanisms. Investigation of Galnt14-null mice revealed elevated serum IgA levels and ex vivo IgA production by B cells. These mice developed glomerular IgA deposition with aging and after induction of sterile colitis. Galnt14-null mice also displayed an attenuated mucin layer in the colon and redistribution of IgA-producing cells from mucosal to systemic sites. Adoptive-transfer experiments indicated impaired homing of spleen-derived Galnt14-deficient B lymphocytes, resulting in increased retention in peripheral blood. These findings suggest that abnormalities in O-glycosylation alter mucosal immunity and B lymphocyte homing, pointing to an expanded role of aberrant O-glycosylation in the pathogenesis of IgAN
Perchè e cosa ha ancora senso insegnare a scrivere nell’epoca della GenAI: alcune riflessioni
No full textEvolution of perianal extramammary Paget disease from an erythematous patch to an achromic patch
No full textUnmet needs of Italian centers for pediatric diabetes care: analysis of a survey among pediatric diabetologists facing the national screening program for Type 1 Diabetes
No full textBackgrounds: The incidence of Type 1 Diabetes (T1D) in children and adolescents is increasing by 3–4% per year. Children and adolescents with T1D (CwD) should receive person-centered, specialized treatment from a multidisciplinary team to ensure appropriate care. Italy is the first to implement a countrywide T1D screening program, which will raise the need for funding for specialized pediatric care. The study aims to update the organization of the Italian Centers for pediatric diabetes care. Methods: In 2022, members of the 59 Italian Centers following CwD were invited to complete an email survey regarding the Centers’ organization, characteristics, and activities. The questionnaire included information on responders, department organization, team composition, activities, and the organizational structures: department, ambulatory care services (AC), simple operational units (UOS), simple departmental operational units (UOSd), and complex operational units (UOC). Results: The data collected referred to the year 2022. According to the results, 21,318 people with diabetes were treated. Of these, 19,643 subjects (92.1%) have T1D (16,672 were CwD), 387 (1,8%) have Type 2 Diabetes, and 1,288 (6,1%) have other forms of diabetes. Compared to the 2012 survey, a 13% decrease (from 68 to 59 Centers) in the number of pediatric Centers caring for CwD was observed with a parallel increase of total (+ 6.6%) and average (+ 22%) number of CwD per Center. The estimated prevalence of T1D has increased (1.4 vs. 1.7 per 1,000 CwD—2012 vs. 2022). A reduction in numbers for AC (-22%) and UOS (-35%) was observed, whereas UOSd/UOC increased by 50%. Almost 35% of the dietitians and 40% of the psychologists were not permanent members of the multidisciplinary diabetes team. Conclusions: The observed decrease in the overall number of pediatric diabetes Centers, the reduction in specialized and dedicated HCPs, and the concurrent increase in the number of treated CwD in the last ten years indicate an alarming situation for pediatric diabetes treatment in Italy. Furthermore, the projected rise in CwD due to the National T1D screening program emphasizes the need for increased resources for specialized pediatric care of CwD at all stages