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Comparative study of the glistening between four intraocular lens models assessed by OCT and deep learning.
To evaluate the glistening in 4 different models of intraocular lenses (IOLs) using optical coherence tomography (OCT) and deep learning (DL). Centro Internacional de Oftalmología Avanzada (Madrid, Spain). Cross-sectional study. 325 eyes were assessed for the presence and severity of glistening in 4 IOL models: ReSTOR+3 SN6AD1 (n = 41), SN60WF (n = 110), PanOptix TFNT (n = 128) and Vivity DFT015 (n = 46). The presence of glistening was analyzed using OCT, identifying the presence of hyperreflective foci (HRF) in the central area of the IOL. A manual and an original DL-based quantification algorithm designed for this purpose was applied. Glistening was detected in 22 (53.7%) ReSTOR SN6AD1, 44 (40%) SN60WF, 49 (38.3%) PanOptix TFNT, and 4 (8.7%) Vivity DFT015 IOLs, when any grade was considered. In the comparison of the different types of IOLs, global glistening measured as total HRF was 17.3 ± 25.9 for the ReSTOR+3; 9.3 ± 15.7 for the SN60WF; 6.9 ± 10.5 for the PanOptix; and 1.2 ± 2.6 for the Vivity ( P It is possible to quantify, classify and compare the glistening severity in different IOL models using OCT images in a simple and objective manner with a DL algorithm. In the comparative study, the Vivity presented the lowest severity of glistening
The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.
20.500.12530/87908MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice
Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.
20.500.12530/87908The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL
How Can We Improve Patient-Clinician Communication for Men Diagnosed with Prostate Cancer?
20.500.12530/87907The ability of health care professionals to communicate with patients compassionately and effectively is crucial for shared decision-making, but little research has investigated patient-clinician communication. As part of PIONEER-an international Big Data Consortium led by the European Association of Urology to answer key questions for men with prostate cancer (PCa), funded through the IMI2 Joint Undertaking under grant agreement 777492- we investigated communication between men diagnosed with PCa and the health care professional(s) treating them across Europe. We used the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Communication 26, which was shared via the PIONEER and patient organisations on March 11, 2022. We sought men who spoke French, Italian, Spanish, German, Dutch, or English who were diagnosed with PCa and were undergoing or had already received treatment for their PCa. A total of 372 men reported that they communicated with their clinician during either the diagnostic or the treatment period. Overall, the majority of participants reported positive experiences. However, important opportunities to enhance communication were identified, particularly with regard to correcting misunderstandings, understanding the patient's preferred approach to information presentation, addressing challenging questions, supporting the patient's comprehension of information, attending to the patient's emotional needs, and assessing what information had already been given to patients about their disease and treatment, and how much of it was understood. These results help us to identify gaps and barriers to shared treatment decision making. This knowledge will help devise measures to improve patient-health care professional communication in the PCa setting. As part of the PIONEER initiative, we investigated the communication between men diagnosed with prostate cancer and their health care professionals across Europe. A total of 372 men from six different countries participated in the study. Most participants reported positive experiences, but areas where communication could be improved were identified. These included addressing misunderstandings, tailoring the presentation of information to the patient's preferences, handling difficult questions, supporting emotional needs, and assessing the patient's understanding of their diagnosis and treatment
Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice
20.500.12530/87854Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years + 8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75 mg + 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects. (c) 2021 Sociedad Espanola de Neurolog & imath;a. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Loss-of-function of the Zinc Finger Homeobox 4 (ZFHX4) gene underlies a neurodevelopmental disorder.
20.500.12530/879138q21.11 microdeletions encompassing the gene encoding transcription factor ZFHX4, have previously been associated by us with a syndromic form of intellectual disability, hypotonia, decreased balance and hearing loss. Here, we report on 57 individuals, 52 probands and 5 affected family members, with protein truncating variants (n=36), (micro)deletions (n=20) or an inversion (n=1) affecting ZFHX4 with variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis. The phenotypes associated with 8q21.11 microdeletions and ZFHX4 intragenic loss-of-function variants largely overlap, identifying ZFHX4 as the main driver for the microdeletion syndrome, although leukocyte-derived DNA shows a mild common methylation profile for (micro)deletions only. We identify ZFHX4 as a transcription factor that is increasingly expressed during human brain development and neuronal differentiation. Furthermore, ZFHX4 interacting factors identified via IP-MS in neural progenitor cells, suggest an important role for ZFHX4 in cellular and developmental pathways, especially during histone modifications, cytosolic transport and development. Additionally, using CUT&RUN, we observed that ZFHX4 binds with the promoter regions of genes with crucial roles in embryonic, neuron and axon development. Since loss-of-function variants in ZFHX4 are found with consistent dysmorphic facial features, we investigated whether the disruption of zfhx4 causes craniofacial abnormalities in zebrafish. First-generation (F0) zfhx4 crispant zebrafish, (mosaic) mutant for zfhx4 loss-of-function variants, have significantly shorter Meckel's cartilages and smaller ethmoid plates compared to control zebrafish. Furthermore, behavioral assays show a decreased movement frequency in the zfhx4 crispant zebrafish in comparison with control zebrafish larvae. Although further research is needed, our in vivo work suggests a role for zfhx4 in facial skeleton patterning, palatal development and behavior
Cutaneous reactions during Helicobacter pylori eradication therapy referred to an allergy department.
Natural history of Wolcott-Rallison syndrome: A systematic review and follow-up study.
20.500.12530/87910To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival
Practice patterns and clinical outcomes in acute appendicitis differ in the elderly patient.
Appendicitis is the most frequent global abdominal surgical emergency. An ageing population, who often exhibit atypical symptoms and delayed presentations, challenge conventional diagnostic and treatment paradigms. This study aims to delineate disparities in presentation, management, and outcomes between elderly patients and younger adults suffering from acute appendicitis. This subgroup analysis forms part of ESTES SnapAppy, a time-bound multi-center prospective, observational cohort study. It includes patients aged 15 years and above who underwent laparoscopic appendectomy during a defined 90-day observational period across multiple centers. Statistical comparisons were performed using appropriate tests with significance set at p The study cohort comprised 521 elderly patients (≥65 years) and 4,092 younger adults (18-64 years). Elderly patients presented later (mean duration of symptoms: 7.88 vs. 3.56 days; p Our findings highlight significant differences in the clinical course and outcomes of acute appendicitis in the elderly compared to younger patients, suggesting a need for age-adapted diagnostic pathways and treatment strategies to improve outcomes in this vulnerable population