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BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Background and purpose: The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) remains controversial. Limited studies have indicated a high prevalence of obstructive sleep apnoea (OSA) amongst iNPH patients. The aim was to investigate the clinical correlates of OSA in iNPH patients. Methods: In this cross‐sectional observational study, consecutive iNPH patients were prospectively enrolled. Evaluations included the iNPH Rating Scale, the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the time and number of steps to walk 10 m, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, a complete neuropsychological evaluation, 3‐T brain MRI, full‐night video‐polysomnography, tap test and cerebrospinal fluid (CSF) neurodegeneration biomarkers. Results: Fifty‐one patients were screened, of whom 38 met the inclusion criteria. Amongst the recruited patients, 19/38 (50%) exhibited OSA, with 12/19 (63.2%) presenting moderate to severe disorder. OSA+ iNPH patients required more time (p = 0.02) and more steps (p = 0.04) to complete the 10‐m walking test, had lower scores on the gait subitem of the iNPH Rating Scale (p = 0.04) and demonstrated poorer performance on specific neuropsychological tests (Rey Auditory Verbal Learning Test immediate recall, p = 0.03, and Rey–Osterrieth Complex Figure, p = 0.01). Additionally, OSA+ iNPH patients had higher levels of total tau (p = 0.02) and phospho‐tau (p = 0.03) in their CSF but no statistically significant differences in beta‐amyloid (1–42) levels compared to OSA− iNPH patients. Conclusion: Obstructive sleep apnoea is highly prevalent in iNPH patients, particularly at moderate to severe levels. OSA is associated with worse motor and cognitive performance in iNPH. The CSF neurodegeneration biomarker profile observed in OSA+ iNPH patients may reflect OSA‐induced impairment of cerebral fluid dynamics. [ABSTRACT FROM AUTHOR]

Background: The prognostic role of imaging with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in oropharynx cancer (OPC) has been demonstrated in the past. The aim of this study was to assess the prognostic impact of both baseline and post-treatment PET/CT in patients with OPC and treated with chemo- and/or radiotherapy. Methods: The PET/CT parameters of scans performed before and after therapy were collected and analyzed to find significant prognosticators for progression-free survival (PFS) and overall survival (OS). Human papillomavirus (HPV) infection's influence on the prognosis was also taken into account. Results: A total of 66 patients were included in the study. The staging volumetric parameters of PET/CT were significant prognosticators for OS, while the same parameters were affordable predictors for PFS at the restaging evaluation. No significant correlations between HPV infection and PET/CT parameters were reported. Conclusion: The prognostic role of volumetric [18F]FDG PET/CT parameters in patients with OPC was reported. [ABSTRACT FROM AUTHOR]

Fabry Registry data were analyzed among 83 agalsidase beta‐treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein‐creatinine ratio [UPCR], plasma globotriaosylceramide [GL‐3], plasma globotriaosylsphingosine [lyso‐GL‐3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre‐ and postswitch periods. eGFR decreased throughout both periods (preswitch: −0.85 mL/min/1.73 m2/year; postswitch: −1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late‐onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late‐onset patients. GL‐3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late‐onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (−0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late‐onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late‐onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL‐3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late‐onset patients. These findings indicate variability in long‐term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring. [ABSTRACT FROM AUTHOR]

This comprehensive review explores the pivotal role of radiotherapy in cancer treatment, emphasizing the diverse applications of genetic profiling. The review highlights genetic markers for predicting radiation toxicity, enabling personalized treatment planning. It delves into the impact of genetic profiling on radiotherapy strategies across various cancer types, discussing research findings related to treatment response, prognosis, and therapeutic resistance. The integration of genetic profiling is shown to transform cancer treatment paradigms, offering insights into personalized radiotherapy regimens and guiding decisions in cases where standard protocols may fall short. Ultimately, the review underscores the potential of genetic profiling to enhance patient outcomes and advance precision medicine in oncology. [ABSTRACT FROM AUTHOR]

The etiology of Inflammatory Bowel Disease (IBD) is not fully understood but is believed to involve a dysregulated immune response to intestinal microbiota in genetically susceptible individuals. Individuals with IBD are at increased risk of infections due to immunosuppressive treatments, comorbidities, and advanced age. Current evidence indicates that IBD patients are not at higher risk of SARS-CoV-2 infection compared to the general population, though the risk of severe outcomes remains debated. A retrospective observational study was conducted using Apulian regional health data from 2020 to 2022. This study included 1029 IBD patients and 3075 controls, matched by age and sex. COVID-19 incidence, hospitalization, and case fatality rates were analyzed alongside vaccination coverage. No significant differences in COVID-19 incidence (IRR = 0.97), hospitalization (p = 0.218), or lethality (p = 0.271) were evidenced between IBD patients and the general population. Vaccination rates were high in both groups, with slightly higher uptake in IBD patients. Multivariate analysis identified age and male sex as risk factors for severe COVID-19 outcomes, while vaccination significantly reduced hospitalization and lethality risks. IBD patients in Apulia do not have an increased risk of COVID-19 infection or severe outcomes compared to the general population. Vaccination is crucial in protecting IBD patients, and ongoing efforts to promote vaccination within this population are essential. Future research should focus on the impact of specific IBD treatments on COVID-19 outcomes and the long-term effectiveness of vaccines. [ABSTRACT FROM AUTHOR]

Key Clinical Message: PET‐driven SBRT plus pembrolizumab as first‐line therapy against pleomorphic Pancoast cancer appears beneficial, probably due to high equivalent doses of SBRT on photopenic necrotic core and synergic immune system stimulation of immunoradiotherapy. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is caused by mutations in the galactosidase alpha (GLA) gene which lead to the accumulation of globotriaosylceramide (Gb-3). Enzyme replacement therapy (ERT) and oral chaperone therapy are the current pharmacological treatments for this condition. However, in the literature, there is a growing emphasis on exploring non-pharmacological therapeutic strategies to improve the quality of life of patients with FD. In particular, the nutritional approach to FD has been marginally addressed in the scientific literature, although specific dietary interventions may be useful for the management of nephropathy and gastrointestinal complications, which are often present in patients with FD. Especially in cases of confirmed diagnosis of irritable bowel syndrome (IBS), a low-FODMAP diet can represent an effective approach to improving intestinal manifestations. Furthermore, it is known that some food components, such as polyphenols, may be able to modulate some pathogenetic mechanisms underlying the disease, such as inflammation and oxidative stress. Therefore, the use of healthy dietary patterns should be encouraged in this patient group. Sports practice can be useful for patients with multi-organ involvement, particularly in cardiovascular, renal, and neurological aspects. Therefore, the aim of this review is to summarize current knowledge on the role of nutrition and physical activity in FD patients. [ABSTRACT FROM AUTHOR]

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain‐age paradigm to assess whether FD patients' brains appear older than normal and to validate brain‐predicted age difference (brain‐PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1‐weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4–86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain‐age predictions in the internal cohort. Within a linear modeling framework, brain‐PAD was tested for age/sex‐adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel‐level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain‐age model achieved accurate out‐of‐sample performance (mean absolute error = 4.01 years, R2 =.90). FD patients had significantly higher brain‐PAD than HC (estimated marginal means: 3.1 vs. −0.1, p =.01). Brain‐PAD was associated with FASTEX score (B = 0.10, p =.02), brain parenchymal fraction (B = −153.50, p =.001), white matter hyperintensities load (B = 0.85, p =.01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain‐PAD correlates with FD‐related multi‐organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity. [ABSTRACT FROM AUTHOR]

This document discusses the investigational role of cytoreductive stereotactic ablative radiation therapy (SABR) in the treatment of metastatic kidney cancer. The article highlights the increasing incidence of renal cell carcinoma (RCC) in the older population and the challenges of offering invasive therapies to elderly patients. SABR has emerged as a noninvasive alternative, with studies showing promising results in terms of oncologic outcomes and renal function preservation. The document also mentions ongoing clinical trials investigating the combination of SABR with immune checkpoint inhibitors and tyrosine kinase inhibitors. The authors emphasize the advancements in radiation oncology and radiobiology that have made precise delivery of high-dose radiation possible, and they anticipate the availability of new radiotracers and treatment modalities in this field. [Extracted from the article]

Background: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is associated with prodromal Parkinson's disease (PD), but the mechanisms linking phenoconversion of iRBD to PD have not yet been clarified. Considering the association between mitochondrial dysfunction and sleep disturbances in PD, we explored mitochondrial activity in fibroblasts derived from iRBD patients to identify a biochemical profile that could mark the presence of impending neurodegeneration. Methods: The study involved 28 participants, divided into three groups: patients diagnosed with iRBD, PD patients converted from iRBD (RBD‐PD), and healthy controls. We performed a comprehensive assessment of mitochondrial function, including an examination of mitochondrial morphology, analysis of mitochondrial protein expression levels by western blot, and measurement of mitochondrial respiration using the Seahorse XFe24 analyzer. Results: In basal conditions, mitochondrial respiration did not differ between iRBD and control fibroblasts, but when cells were challenged with a higher energy demand, iRBD fibroblasts exhibited a significant (P = 0.006) drop in maximal and spare respiration compared to controls. Interestingly, RBD‐PD patients showed the same alterations with a further significant reduction in oxygen consumption linked to adenosine triphosphate production (P = 0.032). Moreover, RBD‐PD patients exhibited a significant decrease in protein levels of complexes III (P = 0.02) and V (P = 0.002) compared to controls, along with fragmentation of the mitochondrial network. iRBD patients showed similar, but milder alterations. Conclusions: Altogether, these findings suggest that mitochondrial dysfunctions in individuals with iRBD might predispose to worsening of the bioenergetic profile observed in RBD‐PD patients, highlighting these alterations as potential predictors of phenoconversion to PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

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Background: Infection of Cardiac Implantable Electronic Devices (CIEDI) is a real public health problem. The main aim of this study was to determine the diagnostic performance of 18F-FDG PET/CT in the diagnosis of CIEDI. Methods: A total of 48 patients, who performed 18F-FDG PET/CT for the clinical suspicion of CIEDI were retrospectively analyzed; all patients were provided with a model with procedural recommendations before the exam. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of 18F-FDG PET/CT were calculated; the reproducibility of qualitative analysis was assessed with Cohen's κ test. The semi-quantitative parameters (SUVmax, SQR and TBR) were evaluated in CIEDI+ and CIEDI− patients using the Student' t-test; ROC curves were elaborated to detect cut-off values. The trend of image quality with regards to procedural recommendation adherence was evaluated. Results: Se, Sp, PPV, NPV and DA were respectively 96.2%, 81.8%, 86.2%, 94.7% and 89.6%. The reproducibility of qualitative analysis was excellent (K = 0.89). Semiquantitative parameters resulted statistically different in CIEDI+ and CIEDI− patients. Cut-off values were SUVmax = 2.625, SQR = 3.766 and TBR = 1.29. Trend curves showed increasing image quality due to adherence to procedural recommendations. Conclusions: 18F-FDG-PET/CT is a valid tool in the management of patients suspected of CIEDI and adherence to procedural recommendations improves its image quality. [ABSTRACT FROM AUTHOR]

Different insights into the connection between kidney [18F]fluorodesoxyglucose ([18F]FDG) uptake at positron emission tomography/computed tomography (PET/CT) and renal function have been proposed in the past. The aim of this study was therefore to assess the presence of a correlation between these two parameters. Kidney uptakes were assessed and compared to the creatinine (Cr) values and estimated glomerular filtration rate (EGFR) among different classes of renal functional impairment or kidney status. A total of 339 patients and 385 different PET/CT scans were included in this study. Significant correlations between kidney uptakes and renal function parameters were reported in most of the groups studied, with the exception of patients with Cr < 1.2 mg/dL and subjects with a kidney transplantation. Strong concordance in the assessment of renal parenchymal uptakes between the different readers was reported. To conclude, strong correlations for renal [18F]FDG uptake with Cr levels and the EGFR were reported, with the exception of the group of patients with a Cr value < 1.2 mg/dL and for the group with a kidney transplantation. [ABSTRACT FROM AUTHOR]