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Frontiers in Immunology 2024Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising...
INTRODUCTION
Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3 T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3 T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3 T-lymphocytes.
METHODS
A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3 T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included.
RESULTS
Total lymphocyte counts below 0.3 x 10/L had a high sensitivity (86%) as a surrogate marker of CD3 T-lymphocytes below 0.05 x 10/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 10/L as a surrogate marker for CD3 T-lymphocytes above 0.05 x 10/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3 T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3 T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment.
DISCUSSION
Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 10/L whereas the CD3 T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.
Topics: Humans; Antilymphocyte Serum; Lymphocyte Count; Retrospective Studies; Male; Female; Middle Aged; Adult; Graft Rejection; Immunosuppressive Agents; T-Lymphocytes; Kidney Transplantation; Aged; Pancreas Transplantation; CD3 Complex; Organ Transplantation
PubMed: 38933271
DOI: 10.3389/fimmu.2024.1419726 -
Simultaneous Pancreas and Kidney Transplantation from Donors after Circulatory Death in Switzerland.Journal of Clinical Medicine Jun 2024Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after...
Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after circulatory death (DCD) is one important measure to expand the organ pool for pancreas transplantation (PT). After initial doubts due to higher complications, DCD SPK is now considered safe and equivalent to donation after brain death in terms of survival and graft function. We assessed pancreas and kidney graft function, as well as complications of the first three patients who underwent a DCD SPK in Switzerland. Two transplantations were after rapid procurement, one following normothermic regional perfusion (NRP). Intra- and postoperative courses were uneventful and without major complications in all patients. In the two SPK after rapid procurement, pancreas graft function was excellent, with 100% insulin-free survival, and hemoglobin A1C dropped from 7.9 and 7.5 before SPK and to 5.1 and 4.3 after three years, respectively. Kidney graft function was excellent in the first year, followed by a gradual decline due to recurrent infections. The patient, after NRP SPK, experienced short-term delayed pancreatic graft function requiring low-dose insulin treatment for 5 days post-transplant, most likely due to increased peripheral insulin resistance in obesity. During follow-up, there was persistent euglycemia and excellent kidney function. We report on the first series of DCD SPK ever performed in Switzerland. Results were promising, with low complication rates and sustained graft survival. With almost half of all donors in Switzerland currently being DCD, we see great potential for the expansion of DCD PT.
PubMed: 38930054
DOI: 10.3390/jcm13123525 -
Medicina (Kaunas, Lithuania) May 2024: The pancreatic solid pseudopapillary neoplasm (SPN), a rare tumor predominantly affecting young women, has seen an increased incidence due to improved imaging and...
: The pancreatic solid pseudopapillary neoplasm (SPN), a rare tumor predominantly affecting young women, has seen an increased incidence due to improved imaging and epidemiological knowledge. This study aimed to understand the outcomes of different interventions, possible complications, and associated risk factors. : This study retrospectively analyzed 24 patients who underwent pancreatic surgery for SPNs between September 1998 and July 2020. : Surgical intervention, typically required for symptomatic cases or pathological confirmation, yielded favorable outcomes with a 5-year survival rate of up to 97%. Despite challenges in standardizing preoperative evaluation and follow-up protocols, aggressive complete resection showed promising long-term survival and good oncological outcomes. Notably, no significant differences were found between conventional and minimally invasive (MI) surgery in perioperative outcomes. Histopathological correlations were lacking in prognosis and locations. Among the patients, one developed diffuse liver metastases 41 months postoperatively but responded well to chemotherapy and transcatheter arterial chemoembolization, with disease stability observed at 159 postoperative months. Another patient developed nonalcoholic steatohepatitis after surgery and underwent liver transplantation, succumbing to poor medication adherence 115 months after surgery. : These findings underscore the importance of surgical intervention in managing SPNs and suggest the MI approach as a viable option with comparable outcomes to conventional surgery.
Topics: Humans; Female; Pancreatic Neoplasms; Adult; Retrospective Studies; Male; Middle Aged; Treatment Outcome; Pancreatectomy; Young Adult; Carcinoma, Papillary; Adolescent; Aged
PubMed: 38929506
DOI: 10.3390/medicina60060889 -
Antioxidants (Basel, Switzerland) May 2024Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular... (Review)
Review
The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect.
Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson-Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions.
PubMed: 38929116
DOI: 10.3390/antiox13060678 -
Antioxidants (Basel, Switzerland) May 2024The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative... (Review)
Review
The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included ( = 41 MP; = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.
PubMed: 38929081
DOI: 10.3390/antiox13060642 -
BMC Cancer Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression.
METHODS
We reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised.
RESULTS
In total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082-2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68 macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm and 1812 ± 1008 µm for the SARIFA-negative and -positive cases, respectively (p < 0.001).
CONCLUSIONS
SARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.
Topics: Humans; Carcinoma, Pancreatic Ductal; Female; Male; Biomarkers, Tumor; Prognosis; Pancreatic Neoplasms; Aged; Middle Aged; Fatty Acid-Binding Proteins; Neoplasm Invasiveness; Tumor Microenvironment; Lipid Metabolism; Antigens, Differentiation, Myelomonocytic; Antigens, CD; Stromal Cells; CD36 Antigens; Adipocytes; Adult; Aged, 80 and over; CD68 Molecule
PubMed: 38926671
DOI: 10.1186/s12885-024-12519-9 -
Surgery Jun 2024
Corrigendum to "The 2016 update of the International Study Group (ISGPF) definition and grading of postoperative pancreatic fistula: eleven years after." Surgery 2017. Mar; 161 (3):584-591. Epub Dec 28, 2016.
PubMed: 38926000
DOI: 10.1016/j.surg.2024.05.043 -
Biosensors & Bioelectronics Jun 2024The quest to reduce kidney transplant rejection has emphasized the urgent requirement for the development of non-invasive, precise diagnostic technologies. These...
The quest to reduce kidney transplant rejection has emphasized the urgent requirement for the development of non-invasive, precise diagnostic technologies. These technologies aim to detect antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR), which are asymptomatic and pose a risk of potential kidney damage. The protocols for managing rejection caused by ABMR and TCMR differ, and diagnosis has traditionally relied on invasive biopsy procedures. Therefore, a convergence system using a nano-sensing chip, Raman spectroscopy, and AI technology was introduced to facilitate diagnosis using serum samples obtained from patients with no major abnormality, ABMR, and TCMR after kidney transplantation. Tissue biopsy and Banff score analysis were performed across the groups for validation, and 5 μL of serum obtained at the same time was added onto the Au-ZnO nanorod-based Surface-Enhanced Raman Scattering sensing chip to obtain Raman spectroscopy signals. The accuracy of machine learning algorithms for principal component-linear discriminant analysis and principal component-partial least squares discriminant analysis was 93.53% and 98.82%, respectively. The collagen (an indicative of kidney injury), creatinine, and amino acid-derived signals (markers of kidney function) contributed to this accuracy; however, the high accuracy was primarily due to the ability of the system to analyze a broad spectrum of various biomarkers.
PubMed: 38924813
DOI: 10.1016/j.bios.2024.116523 -
International Journal of Cancer Jun 2024Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in...
Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.
PubMed: 38924078
DOI: 10.1002/ijc.35046 -
Transplant International : Official... 2024In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their...
In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.
Topics: Humans; Netherlands; Male; Female; Tissue and Organ Procurement; Pancreas Transplantation; Kidney Transplantation; Retrospective Studies; Liver Transplantation; Graft Survival; Middle Aged; Adult; Risk Factors; Tissue Donors
PubMed: 38919904
DOI: 10.3389/ti.2024.12989