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Aims: Heterogeneity in the rate of β‐cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease‐modifying clinical trials. Integrative analyses of baseline multi‐omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis. Methods: We collected samples in a pan‐European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi‐Omics Factor Analysis to identify molecular signatures correlating with post‐diagnosis decline in β‐cell mass measured as fasting C‐peptide. Results: Two molecular signatures were significantly correlated with fasting C‐peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non‐lymphoid cell interactions and G‐protein coupled receptor signalling events that were inversely associated with a rapid decline in β‐cell function. The second signature was related to translation and viral infection was inversely associated with change in β‐cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β‐cell decline. Conclusions: Features that differ between individuals with slow and rapid decline in β‐cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify single nucleotide polymorphisms (SNPs) that could be associated with back fat thickness (BFT) in pigs. To achieve this goal, we evaluated the potential and limits of an experimental design that combined several methodologies. DNA samples from two groups of Italian Large White pigs with divergent estimating breeding value (EBV) for BFT were separately pooled and sequenced, after preparation of reduced representation libraries (RRLs), on the Ion Torrent technology. Taking advantage from SNAPE for SNPs calling in sequenced DNA pools, 39,165 SNPs were identified; 1/4 of them were novel variants not reported in dbSNP. Combining sequencing data with Illumina PorcineSNP60 BeadChip genotyping results on the same animals, 661 genomic positions overlapped with a good approximation of minor allele frequency estimation. A total of 54 SNPs showing enriched alleles in one or in the other RRLs might be potential markers associated with BFT. Some of these SNPs were close to genes involved in obesity related phenotypes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the accuracy of intra-operative ultrasound (IOUS) imaging in detecting liver secondaries at the time of primary colorectal surgery and to evaluate the impact of IOUS on patient management. Methods: Data from 167 patients with primary colorectal cancer who were admitted for elective surgery between January 1995 and December 2003 were prospectively evaluated and analysed. All patients underwent pre-operative abdominal ultrasonography (US) and computed tomography (CT), as well as IOUS. The final diagnosis of liver metastases was made by means of histological examination of either biopsy or surgical specimens. The sensitivities of pre-operative US and CT were compared with the sensitivity of IOUS, referred to histology. Changes in surgical management owing to IOUS findings were noted. Results: IOUS supplied additional information in the case of 31 patients. In 28 of these patients, this information had a major impact on the intra-operative strategy, in that the procedure was altered. Conclusions: IOUS is safe, simple to perform and more accurate than pre-operative imaging. It reduces the number of patients subjected to superfluous surgery. The use of IOUS is therefore encouraged during colorectal cancer surgery. [ABSTRACT FROM AUTHOR]

Background: Bronchobiliary fistula (BBF) is an uncommon but severe complication of hydatid disease of the liver. Operation is considered the treatment of choice but the most appropriate operation is uncertain. The aim of this study was to evaluate the early and long-term outcomes following different surgical procedures. Methods: A retrospective evaluation of 31 patients with BBF was performed. Surgical access consisted of laparotomy, thoracotomy or a thoracoabdominal (TA) incision. Surgical procedures for the treatment of the cyst were classified as conservative or radical. Results: Radical treatment including lung resection and pericystectomy was performed in all patients in whom the surgical exposure was obtained by either thoracotomy or TA. Of the patients treated by laparotomy, two had a pericystectomy, and four had drainage of the cyst. There were two deaths among the seven thoracotomy patients and one among the 18 TA patients. Pleural effusion was observed in six of the TA, two of the thoracotomy, and three of the laparotomy patients. Biliary fistula occurred in two of the five thoracotomy patients surviving operation and in two laparotomy patients (2/6). Progression of the lung disease was observed in four laparotomy patients and in one thoracotomy patient. Conclusions: The better outcome achieved in TA patients is the result of the simultaneous radical treatment of all the pathological aspects of BBF. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Increased growth differentiation factor 15 (GDF15) may reflect impaired metabolic health and an inflammatory state in metabolic dysfunction‐associated steatotic liver disease (MASLD). We investigated the role of GDF15 in histologically verified MASLD in a meal test (discovery) cohort (n = 20) and a prospective (validation) cohort with 2 years of follow‐up (n = 276).Participants were evaluated clinically and histologically in both cohorts. Fibrosis severity was classified as no/mild (F0/F1) or significant (F2–4). Plasma GDF15 was measured by enzyme‐linked immunosorbent assays and the SOMAScan platform. Hepatic GDF15 mRNA expression was analyzed by RNA in situ hybridization and bulk RNA‐sequencing. In addition, we used data from public single‐nucleus RNA‐sequencing datasets.In both cohorts, plasma GDF15 was increased in MASLD compared with healthy controls (p < 0.0001) with the highest levels in patients with significant fibrosis (area under the curve 0.83; 95% confidence interval [CI], 0.76–0.91). The GDF15 levels were unaffected by a standardized meal and there was no difference in peripheral or hepatic venous concentrations. After 2 years, the increase in GDF15 levels was reduced in patients treated with glucagon‐like peptide receptor agonists (GLP‐1‐RA) compared to patients receiving lifestyle advice (−28%; 95% CI, −44 to −8; p = 0.01). Plasma GDF15 was associated with circulating insulin‐like growth factor 1 and related proteins. Hepatic GDF15 mRNA was mainly expressed in hepatocytes and in cholangiocytes in fibrotic areas and was increased in MASLD (p = 0.02) with the highest expression in the group with steatohepatitis (p = 0.009).Increased hepatic and circulating GDF15 are found in MASLD. Treatment with GLP‐1‐RA may reduce GDF15, possibly reflecting beneficial metabolic and inflammatory effects. [ABSTRACT FROM AUTHOR]