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Recently, there has been a growing interest in epidemiological and clinical studies supporting a pathogenetic role of fructose in cardio-metabolic diseases, especially in children and adolescents. In the present review, we summarize experimental data on the potential biological mechanisms linking fructose and uric acid in the development of insulin resistance, metabolic syndrome, obesity, diabetes, hypertension, non-alcoholic fatty liver disease and chronic renal disease, thereby contributing to an increase in cardiovascular risk at pediatric age.

Epidemiological studies show that hyperuricemia independently predicts the development of chronic kidney disease (CKD) in individuals with normal kidney function both in the general population and in subjects with diabetes. As a matter of fact, an unfavorable role of uric acid may somewhat be harder to identify in the context of multiple risk factors and pathogenetic mechanisms typical of overt CKD such as proteinuria and high blood pressure. Although the discrepancy in clinical results could mean that urate lowering treatment does not provide a constant benefit in all patients with hyperuricemia and CKD, we believe that the inconsistency in the results from available meta-analysis is mainly due to inadequate sample size, short follow-up times and heterogeneity in study design characterizing the randomized controlled trials included in the analyses. Therefore, available data support the view that hyperuricemia has a damaging impact on kidney function, while preliminary evidence suggests that treatment of so-called asymptomatic hyperuricemia may be helpful to slow or delay the progression of chronic kidney.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2–12, p  = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p  = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6–27.3, p  = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients.

Acute Kidney Injury (AKI) is a common condition with significant impact on morbidity, mortality, and healthcare costs. This study explores the epidemiology of AKI, highlighting key factors and outcomes. In a retrospective study we evaluated patients admitted to hospital from 2016 to 2019, excluding those with pre-existing chronic kidney disease (CKD) stages 4–5. Data were extracted from hospital databases, with AKI defined by changes in serum creatinine (sCr) according to KDIGO criteria. Additionally, AKI was classified as “de novo” or as AKI on CKD in the subgroup of patients with available pre-hospital eGFR. Outcomes included mortality, hospital stay duration (LOS), AKI recovery, and persistent AKI. Of 87,087 patients, 17,946 (20.6%) developed AKI. AKI patients were older, with more comorbidities, and had significantly higher mortality (17.7% vs. 4.3%, p < 0.001). AKI was associated with in-hospital mortality (HR 1.23, 95% CI 1.16–1.30), longer LOS, and ICU admission. Mortality increased with AKI severity. Considering the 34,285 patients (39% of the total cohort) with pre-hospital eGFR, AKI occurred in 17.3% patients without previous CKD and in 31.1% of patients with previous CKD. These patients presented higher incidence of ICU admission and mortality. Additionally, 17.6% of AKI patients had persistent kidney dysfunction at discharge, often requiring extended hospitalization and ICU care. The substantial impact of AKI on both short- and potentially long-term health emphasizes the importance of early detection, personalized management, and structured follow-up to enhance outcomes and reduce CKD progression risk.

Abstract Background: Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary: Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines – molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation. Key Messages: The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic.

ABSTRACT Anti-aging therapy is the latest frontier in the world of medical science, especially for widespread diseases such as chronic kidney disease (CKD). Both renal aging and CKD are characterized by increased cellular senescence, inflammation and oxidative stress. A variety of cellular signalling mechanisms are involved in these processes, which provide new potential targets for therapeutic strategies aimed at counteracting the onset and progression of CKD. At the same time, sodium–glucose co-transporter 2 inhibitors (SGLT2is) continuously demonstrate large beneficial effects at all stages of the cardiorenal metabolic continuum. The broad-spectrum benefits of SGLT2is have led to changes in several treatment guidelines and to growing scientific interest in the underlying working principles. Multiple mechanisms have been studied to explain these great renal benefits, but many things remain to be solved. With this in mind, we provide an overview of the experimental evidence for the effects of SGLT2is on the molecular pathway’s ability to modulate senescence, aging and parenchymal damage, especially at the kidney level. We propose to shed some light on the role of SGLT2is in kidney care by focusing on their potential to reduce the progression of kidney disease across the spectrum of aging and dysregulation of senescence.

In the last few months, the coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and has provoked an exceptional effort from the scientific community to understand the disease. Clinical evidence suggests that severe COVID-19 is associated with both dysregulation of damage tolerance caused by pulmonary immunopathology and high viral load. In this review article, we describe and discuss clinical studies that show advances in the understanding of mild and severe illness and we highlight major points that are critical for improving the comprehension of different clinical outcomes. The understanding of pulmonary immunopathology will contribute to the identification of biomarkers in an attempt to classify mild, moderate, severe and critical COVID-19 illness. The interface of pulmonary immunopathology and the identification of biomarkers are critical for the development of new therapeutic strategies aimed to reduce the systemic and pulmonary hyperinflammation in severe COVID-19.

Background: Hemophilia A is a bleeding disorder caused by deficiency in coagulation factor VIII. Recombinant factor VIII (rFVIII) is an alternative to plasma-derived FVIII for the treatment of hemophilia A. However, commercial manufacturing of rFVIII products is inefficient and costly and is associated to high prices and product shortage, even in economically privileged countries. This situation may be solved by adopting more efficient production methods. Here, we evaluated the potential of transient transfection in producing rFVIII in serum-free suspension HEK 293 cell cultures and investigated the effects of different DNA concentration (0.4, 0.6 and 0.8 μg/106 cells) and repeated transfections done at 34° and 37°C. Results: We observed a decrease in cell growth when high DNA concentrations were used, but no significant differences in transfection efficiency and in the biological activity of the rFVIII were noticed. The best condition for rFVIII production was obtained with repeated transfections at 34°C using 0.4 μg DNA/106 cells through which almost 50 IU of active rFVIII was produced six days post-transfection. Conclusion: Serum-free suspension transient transfection is thus a viable option for high-yield-rFVIII production. Work is in progress to further optimize the process and validate its scalability.

Chronic kidney disease (CKD) is a prevalent global health concern affecting approximately 850 million people worldwide, with a significant and rising mortality rate. CKD often coexists with hyperuricemia (HSUA), which is also increasingly common due to its association with hypertension, obesity, and diabetes. The interplay between hyperuricemia and CKD is complex; while in vitro studies and animal models support a role for uric acid mediating glomerular and tubule-interstitial damage, and HSUA has been shown to predict the onset and progression of CKD, the expectations of renal protection by the use of urate lowering treatment (ULT) are inconsistent. A significant challenge in managing asymptomatic HSUA in CKD patients lies in determining the appropriate SUA threshold values. Recent research, including the URRAH project, has sought to identify SUA cut-offs predictive of cardiovascular mortality, but these thresholds may vary depending on the severity of CKD. This variability complicates the establishment of universal guidelines for treating asymptomatic HSUA, leading to a lack of specific recommendations in clinical practice. In conclusion, while hyperuricemia is recognized as a prognostic factor for CKD and cardiovascular risk, more research is needed to refine the threshold values for SUA and to identify which patients may benefit from ULT. Stratification based on glomerular filtration rate may be necessary to tailor the treatments and improve outcomes in this population.

The aim of this study is to investigate the bodily-self in Restrictive Anorexia, focusing on two basic aspects related to the bodily self: autonomic strategies in social behavior, in which others' social desirability features, and social cues (e.g., gaze) are modulated, and interoception (i.e., the sensitivity to stimuli originating inside the body). Furthermore, since previous studies carried out on healthy individuals found that interoception seems to contribute to the autonomic regulation of social behavior, as measured by Respiratory Sinus Arrhythmia (RSA), we aimed to explore this link in anorexia patients, whose ability to perceive their bodily signal seems to be impaired. To this purpose, we compared a group of anorexia patients (ANg; restrictive type) with a group of Healthy Controls (HCg) for RSA responses during both a resting state and a social proxemics task, for their explicit judgments of comfort in social distances during a behavioral proxemics task, and for their Interoceptive Accuracy (IA). The results showed that ANg displayed significantly lower social disposition and a flattened autonomic reactivity during the proxemics task, irrespective of the presence of others' socially desirable features or social cues. Moreover, unlike HCg, the autonomic arousal of ANg did not guide behavioral judgments of social distances. Finally, IA was strictly related to social disposition in both groups, but with opposite trends in ANg. We conclude that autonomic imbalance and its altered relationship with interoception might have a crucial role in anorexia disturbances.