Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery

To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery

Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor.

BACKGROUND: Health assessment of the transplanted organ is very important due to the relationship of long-term survival of organ transplant recipients and health organ maintenance. Nowadays, the measurement of cell-free DNA from grafts in the circulation of transplant recipients has been considered a potential biomarker of organ rejection or transplant associated complications in an attempt to replace or reduce liver biopsy. However, methods developed to date are expensive and extremely time-consuming. Our approach was to measure the SRY gene, as a male organ biomarker, in a setting of sex-mismatched female recipients of male donor organs. METHODS: Cell-free DNA quantization of the SRY gene was performed by real-time quantitative PCR beforehand, at the moment of transplantation during reperfusion (day 0) and during the stay at the intensive care unit. Beta-globin cell-free DNA levels, a general cellular damage marker, were also quantified. RESULTS: Beta-globin mean values of patients, who accepted the graft without any complications during the first week after surgery, diminished from day 0 until patient stabilization. This decrease was not so evident in patients who suffered some kind of post-transplantation complications. All patients showed an increase in SRY levels at day 0, which decreased during hospitalization. Different complications that did not compromise donated organs showed increased beta-globin levels but no SRY gene levels. However, when a donated organ was damaged the patients exhibited high levels of both genes. CONCLUSION: Determination of a SRY gene in a female recipient's serum is a clear and specific biomarker of donated organs and may give us important information about graft health in a short period of time by a non-expensive technique. This approach may permit clinicians to maintain a close follow up of the transplanted patient

Characteristics of patients.

<p>Characteristics of patients.</p

Serum SRY gene and beta-globin gene circulating levels in two re-transplanted female patients.

<p>Concentration of serum SRY gene and beta-globin gene circulating levels in two female patients who underwent two consecutive transplantations, one sex-mismatched donor–recipient and the other sex-matched. A) woman who underwent a liver transplantation from a male donor and re-transplanted from a female donor due to hepatic veins thrombosis complication. B) woman who underwent a liver transplantation from a woman donor and re-transplanted from a male donor due to a hepatic artery thrombosis. PT: pre-transplantation sample before organ reperfusion.</p

Concentration of serum beta-globin levels in patients without complications.

<p>Mean concentration of serum beta-globin circulating levels from patients who accepted transplanted livers without any complications during the first week of stay at ICU (patient 1 to 6, mean <u>+</u>SEM). (*) Kruskall Wallis test, p<0.05; Dunn's Multiple Comparison Test, p<0.05 vs day 0.</p

Profile of SRY and beta-globin genes circulating levels of two patients with severe complications after transplantation.

<p>A) Patient 7 was transplanted due to a co-infection of HBV and delta virus and after arterial thrombosis was urgently re-transplanted. B) Patient 8 suffered sustained a biliary complication after transplantation that ended in cholestasis. Patient was discharged on day 23 but she was re-admitted to the ICU and suffered a multi-organic failure (MF) on day 37. Patient died on day 70 after transplantation.</p

Comparison of serum beta-globin levels in patients with and without complications.

<p>Early mean concentration of serum beta-globin circulating levels from patients who accepted transplanted livers without any complications (white bars; n = 6) and patients suffering any kind of post-transplantation complications during their stay at ICU (shadow bars; n = 4).</p

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Dietary palmitic acid promotes a prometastatic memory via Schwann cells

Fatty acid uptake and altered metabolism constitute hallmarks of metastasis(1,2), yet evidence of the underlying biology, as well as whether all dietary fatty acids are prometastatic, is lacking. Here we show that dietary palmitic acid (PA), but not oleic acid or linoleic acid, promotes metastasis in oral carcinomas and melanoma in mice. Tumours from mice that were fed a short-term palm-oil-rich diet (PA), or tumour cells that were briefly exposed to PA in vitro, remained highly metastatic even after being serially transplanted (without further exposure to high levels of PA). This PA-induced prometastatic memory requires the fatty acid transporter CD36 and is associated with the stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A (as part of the COMPASS complex (Set1A/COMPASS)). Bulk, single-cell and positional RNA-sequencing analyses indicate that genes with this prometastatic memory predominantly relate to a neural signature that stimulates intratumoural Schwann cells and innervation, two parameters that are strongly correlated with metastasis but are aetiologically poorly understood(3,4). Mechanistically, tumour-associated Schwann cells secrete a specialized proregenerative extracellular matrix, the ablation of which inhibits metastasis initiation. Both the PA-induced memory of this proneural signature and its long-term boost in metastasis require the transcription factor EGR2 and the glial-cell-stimulating peptide galanin. In summary, we provide evidence that a dietary metabolite induces stable transcriptional and chromatin changes that lead to a long-term stimulation of metastasis, and that this is related to a proregenerative state of tumour-activated Schwann cells