35 research outputs found

    Agree on much, except it is time for change

    Full text link
    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149742/1/ajt15362_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149742/2/ajt15362.pd

    Urinary-Cell mRNA Profile and Acute Cellular Rejection in Kidney Allografts

    Get PDF
    Background—The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. Methods—We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. Results—A three-gene signature of 18S ribosomal (rRNA)–normalized measures of CD3Δ mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operatingcharacteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer–Lemeshow test indicated good fit (P = 0.77). In an externalvalidation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P = 0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti–interleukin-2 receptor antibodies from those who received T-cell–depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P = 0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). Conclusions—A molecular signature of CD3Δ mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts

    Embryonic Pig Pancreatic Tissue Transplantation for the Treatment of Diabetes

    Get PDF
    BACKGROUND: Transplantation of embryonic pig pancreatic tissue as a source of insulin has been suggested for the cure of diabetes. However, previous limited clinical trials failed in their attempts to treat diabetic patients by transplantation of advanced gestational age porcine embryonic pancreas. In the present study we examined growth potential, functionality, and immunogenicity of pig embryonic pancreatic tissue harvested at different gestational ages. METHODS AND FINDINGS: Implantation of embryonic pig pancreatic tissues of different gestational ages in SCID mice reveals that embryonic day 42 (E42) pig pancreas can enable a massive growth of pig islets for prolonged periods and restore normoglycemia in diabetic mice. Furthermore, both direct and indirect T cell rejection responses to the xenogeneic tissue demonstrated that E42 tissue, in comparison to E56 or later embryonic tissues, exhibits markedly reduced immunogenicity. Finally, fully immunocompetent diabetic mice grafted with the E42 pig pancreatic tissue and treated with an immunosuppression protocol comprising CTLA4-Ig and anti–CD40 ligand (anti-CD40L) attained normal blood glucose levels, eliminating the need for insulin. CONCLUSIONS: These results emphasize the importance of selecting embryonic tissue of the correct gestational age for optimal growth and function and for reduced immunogenicity, and provide a proof of principle for the therapeutic potential of E42 embryonic pig pancreatic tissue transplantation in diabetes

    Rare Histological Variants of Liver Cancer and Their Management: A Single-Institution Experience

    No full text
    Primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma, are a major cause of cancer-related morbidity and mortality worldwide. There are several histologically and biologically distinct subtypes of liver cancer that have previously been reported. However, literature regarding the nonsurgical management of these patients upon disease recurrence remains limited. These variants include combined HCC-cholangiocarcinoma (cHCC-CC), Epstein–Barr virus- (EBV-) associated carcinoma, undifferentiated carcinoma, and clear cell or thyroid-like variants of HCC. Here, we aim to highlight the pathologic features, clinical course, and outcomes of five patients with these unusual hepatic tumors and explain the rationale behind the choice of their systemic therapies upon disease recurrence. All patients underwent surgical resection as the standard of care for localized disease, and upon relapse, they were treated with either chemotherapy, targeted therapy, immunotherapy, or active surveillance based on the clinical context and tumor histology. These rare variants are important to recognize as they have prognostic and therapeutic implications, and there are currently insufficient data in the literature to guide further therapy

    Delayed Gastric Emptying after Living Donor Hepatectomy for Liver Transplantation

    No full text
    Delayed gastric emptying is a significant postoperative complication of living donor hepatectomy for liver transplantation and may require endoscopic or surgical intervention in severe cases. Although the mechanism of posthepatectomy delayed gastric emptying remains unknown, vagal nerve injury during intraoperative dissection and adhesion formation postoperatively between the stomach and cut liver surface are possible explanations. Here, we present the first reported case of delayed gastric emptying following fully laparoscopic hepatectomy for living donor liver transplantation. Additionally, we also present a case in which symptoms developed after open right hepatectomy, but for which dissection for left hepatectomy was first performed. Through our experience and these two specific cases, we favor a neurovascular etiology for delayed gastric emptying after hepatectomy

    Case Report Delayed Gastric Emptying after Living Donor Hepatectomy for Liver Transplantation

    No full text
    Delayed gastric emptying is a significant postoperative complication of living donor hepatectomy for liver transplantation and may require endoscopic or surgical intervention in severe cases. Although the mechanism of posthepatectomy delayed gastric emptying remains unknown, vagal nerve injury during intraoperative dissection and adhesion formation postoperatively between the stomach and cut liver surface are possible explanations. Here, we present the first reported case of delayed gastric emptying following fully laparoscopic hepatectomy for living donor liver transplantation. Additionally, we also present a case in which symptoms developed after open right hepatectomy, but for which dissection for left hepatectomy was first performed. Through our experience and these two specific cases, we favor a neurovascular etiology for delayed gastric emptying after hepatectomy
    corecore