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Initial Experience With Aeson Total Artificial Heart in Cardiogenic Shock Patients on Extracorporeal Life Support
No full textPolymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization
No full textPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10−6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10−8 and OR = 1.16, p = 2.74 × 10−5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10−4 and p = 1.56 × 10−3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10−4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC
Correction: Current state-of-the-art of adrenal surgery in Italy: the cancer risk in surgical adrenal lesions (CRISAL) survey
No full textCurrent state-of-the-art of adrenal surgery in Italy: the cancer risk in surgical adrenal lesions (CRISAL) survey
No full textAdrenalectomies are growing worldwide because of the frequent diagnosis of incidentaloma and the use of minimally invasive surgery (MIS). The factors used to identify a malignant lesion and the best surgical technique are uncertain. In this context, the definition of high-volume center and expert surgeon is under debate. The Italian Society of Endoscopic Surgery and New Technologies (SICE) developed a nationwide survey to investigate the state-of-the-art of adrenal surgery in Italy. A web-based survey comprising 37 questions was developed and distributed to Italian surgeons involved in adrenal surgery. Two hundred forty-eight answers were analyzed. Consensus was reached among the survey participants regarding local infiltration (83%) and rapid growth of the lesion (81%) as markers of malignancy. Nearly 30% of the participants used MIS in case of malignant adrenal lesions. The lateral (50%) and anterior transperitoneal (44%) approaches were the most common among Italian surgeons. Approximately 40% of participants believe that 20–40 adrenalectomies/year are needed to define an expert surgeon and at least 20 procedures/year to define a high-volume center. Approximately half of participants performed < 10 adrenalectomies/year in centers with a median volume < 10 procedures/year. Based on participant feedback, this survey highlights local infiltration and rapid growth as the most significant markers of malignant adrenal lesions. While open adrenalectomy remains the gold standard for suspected malignant lesions, nearly 30% of the participants practice MIS even in these cases. The lateral and anterior transperitoneal approaches emerge as the most familiar for Italian surgeons. A substantial proportion of Italian patients with adrenal lesions undergo surgery performed by surgeons with an annual case volume < 10 procedures, at centers with a low annual volume of adrenalectomies. Moreover, there is a lack of standardized definitions for ‘expert surgeon’ and ‘high-volume center’ in this context.Adrenalectomies are growing worldwide because of the frequent diagnosis of incidentaloma and the use of minimally invasive surgery (MIS). The factors used to identify a malignant lesion and the best surgical technique are uncertain. In this context, the definition of high-volume center and expert surgeon is under debate. The Italian Society of Endoscopic Surgery and New Technologies (SICE) developed a nationwide survey to investigate the state-of-the-art of adrenal surgery in Italy. A web-based survey comprising 37 questions was developed and distributed to Italian surgeons involved in adrenal surgery. Two hundred forty-eight answers were analyzed. Consensus was reached among the survey participants regarding local infiltration (83%) and rapid growth of the lesion (81%) as markers of malignancy. Nearly 30% of the participants used MIS in case of malignant adrenal lesions. The lateral (50%) and anterior transperitoneal (44%) approaches were the most common among Italian surgeons. Approximately 40% of participants believe that 20–40 adrenalectomies/year are needed to define an expert surgeon and at least 20 procedures/year to define a high-volume center. Approximately half of participants performed < 10 adrenalectomies/year in centers with a median volume < 10 procedures/year. Based on participant feedback, this survey highlights local infiltration and rapid growth as the most significant markers of malignant adrenal lesions. While open adrenalectomy remains the gold standard for suspected malignant lesions, nearly 30% of the participants practice MIS even in these cases. The lateral and anterior transperitoneal approaches emerge as the most familiar for Italian surgeons. A substantial proportion of Italian patients with adrenal lesions undergo surgery performed by surgeons with an annual case volume < 10 procedures, at centers with a low annual volume of adrenalectomies. Moreover, there is a lack of standardized definitions for ‘expert surgeon’ and ‘high-volume center’ in this context
CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF HIGH-GRADE B-CELL LYMPHOMAS TRANSFORMED FROM INDOLENT LYMPHOMAS IN HIV-NEGATIVE AND HIV-POSITIVE PATIENTS
No full textAssessing the diagnostic accuracy of ChatGPT-4 in the histopathological evaluation of liver fibrosis in MASH
Get PDFBackground: Large language models like ChatGPT have demonstrated potential in medical image interpretation, but their efficacy in liver histopathological analysis remains largely unexplored. This study aims to assess ChatGPT-4-vision's diagnostic accuracy, compared to liver pathologists' performance, in evaluating liver fibrosis (stage) in metabolic dysfunction–associated steatohepatitis. Methods: Digitized Sirius Red-stained images for 59 metabolic dysfunction–associated steatohepatitis tissue biopsy specimens were evaluated by ChatGPT-4 and 4 pathologists using the NASH-CRN staging system. Fields of view at increasing magnification levels, extracted by a senior pathologist or randomly selected, were shown to ChatGPT-4, asking for fibrosis staging. The diagnostic accuracy of ChatGPT-4 was compared with pathologists' evaluations and correlated to the collagen proportionate area for additional insights. All cases were further analyzed by an in-context learning approach, where the model learns from exemplary images provided during prompting. Results: ChatGPT-4's diagnostic accuracy was 81% when using images selected by a pathologist, while it decreased to 54% with randomly cropped fields of view. By employing an in-context learning approach, the accuracy increased to 88% and 77% for selected and random fields of view, respectively. This method enabled the model to fully and correctly identify the tissue structures characteristic of F4 stages, previously misclassified. The study also highlighted a moderate to strong correlation between ChatGPT-4's fibrosis staging and collagen proportionate area. Conclusions: ChatGPT-4 showed remarkable results with a diagnostic accuracy overlapping those of expert liver pathologists. The in-context learning analysis, applied here for the first time to assess fibrosis deposition in metabolic dysfunction–associated steatohepatitis samples, was crucial in accurately identifying the key features of F4 cases, critical for early therapeutic decision-making. These findings suggest the potential for integrating large language models as supportive tools in diagnostic pathology
Usefulness of a hub and spoke TDM-guided expert clinical pharmacological advice program of dalbavancin for optimizing very long-term curative or suppressive treatment of chronic staphylococcal infections
No full textA hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97–43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29–57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists
The genetic architecture of primary lateral sclerosis in a cohort of Italian patients
No full textBackground and purpose: Recent studies suggest that primary lateral sclerosis (PLS) may have a genetic component. In this work, we performed a next-generation sequencing (NGS) analysis in order to explore the genetic architecture of PLS in a cohort of Italian patients. Methods: NGS was conducted to analyze 228 genes associated with amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), and parkinsonian syndromes (PS) in a cohort of PLS patients diagnosed between 2003 and 2021 at our center. All patients were also screened for C9orf72 hexanucleotide repeat expansion (C9orf72-HRE) by repeat-primed PCR. Genetic variants were classified according to the ACMG criteria. Results: In our study, including 47 PLS patients, we detected 22 rare variants in 17 patients, including 8 likely pathogenic or pathogenic variants and 14 variants of uncertain significance. Four patients carried more than one variant. Among the variants identified, 18 (81.8%) were found in ALS-associated genes. Variants in TBK1 were associated with extra-motor involvement. Conclusions: Although the majority of the PLS patients in our cohort tested negative for an expanded panel of genes associated with ALS, HSP and PS, in 36.2% of the cases, a genetic variant was identified and it mostly belongs to genes associated with ALS, including a C9orf72 expansion and a rare SOD1 variant. Based on these results, we emphasize the need for genetic screening in PLS patients. Further studies on the genetic background are necessary to better understand the complex pathomechanism of each phenotype within the MND-FTD spectrum disorder
Imaging of Migraine and Vestibular Migraine
No full textRecent advancements in neuroimaging have improved our understanding of migraine pathophysiology. Migraine patients exhibit abnormal function and structure in key cortical, subcortical, and brainstem regions involved in multisensory processing, including pain, during both acute attacks and interictal periods. Neuroimaging studies of vestibular migraine, although limited in number, provide preliminary insights into its underlying mechanisms. Notably, functional and structural alterations observed in vestibular migraine patients show a striking resemblance to those reported in migraine. Additionally, brain regions crucial for vestibular control exhibit abnormalities in both structure and function in vestibular migraine patients. These findings suggest that vestibular migraine may represent a convergence between migraine pathophysiology and dysfunction within the vestibular pathways. However, further research is necessary to elucidate the complexities of vestibular migraine pathophysiology