-
Stem Cell Reviews and Reports Jun 2024Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This...
Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This study investigated changes in the secretome of perirenal ASC (prASC) under different conditions: normoxia, cytokine exposure, high glucose, hypoxia, and hypoxia with high glucose. Using mass spectrometry and enrichment clustering analysis, we found that normoxia enriched pathways related to extracellular matrix (ECM) organization, platelet degranulation, and insulin-like growth factor (IGF) transport and uptake. Cytokine exposure influenced metabolism, vascular development, and protein processing pathways. High glucose affected the immune system, metabolic processes, and IGF transport and uptake. Hypoxia impacted immune and metabolic processes and protein processing. Combined hypoxia and high glucose influenced the immune system, IGF transport and uptake, and ECM organization. Our findings highlight the potential of manipulating culturing conditions to produce secretomes with distinct protein and functional profiles, tailoring therapeutic strategies accordingly.
PubMed: 38922529
DOI: 10.1007/s12015-024-10748-w -
International Ophthalmology Jun 2024The purpose of this study was to analyse the contamination rate of corneal samples stored in OCM at Lions Eye Bank of Western Australia over a 12-year period.
PURPOSE
The purpose of this study was to analyse the contamination rate of corneal samples stored in OCM at Lions Eye Bank of Western Australia over a 12-year period.
METHODS
All OCM samples used to preserve corneas from 2011 to 2022 (inclusive) underwent microbiological testing. Samples were collected into aerobic and anaerobic culture bottles on day 3-5 of corneal preservation and 24 h after transfer to thinning medium. Samples were tested for 7 days using the BACTEC FX system. Corneas remained in quarantine until clearance was obtained.
RESULTS
From 2011 to 2022, 3009 corneas were retrieved and 2756 corneas were stored in OCM. Thirty one (1.1%) positive samples were reported, with 20 growths of bacterial origin and 11 fungal. Microbial contamination was mostly identified on day 1 of culture (77.5%). Donors of contaminated samples had a mean age of 55 years, with 17 male and 14 female donors. The highest incidence of contamination came from donors whose cause of death was cancer. Death to enucleation times of contaminated samples ranged from 3.5 to 25.5 h (mean = 13.5 ± 7.3) and death to preservation time ranged from 4.1 to 27.5 h (mean = 14.8 ± 7.2). These did not significantly differ from the average time from death to enucleation (mean = 13.9 ± 3) and death to preservation (mean = 16.3 ± 4.2) of non-contaminated samples.
CONCLUSION
Microbiological screening of corneas stored in OCM at LEBWA showed a very low rate of positive cultures with no predictive donor characteristics.
Topics: Eye Banks; Humans; Cornea; Female; Male; Middle Aged; Western Australia; Organ Preservation; Tissue Donors; Adult; Aged; Bacteria; Organ Culture Techniques; Corneal Transplantation; Aged, 80 and over; Retrospective Studies; Fungi; Young Adult
PubMed: 38922477
DOI: 10.1007/s10792-024-03223-5 -
Metabolites Jun 2024High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction...
High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], < 0.001 and HR 1.25 [1.09-1.45], < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.
PubMed: 38921458
DOI: 10.3390/metabo14060323 -
Healthcare (Basel, Switzerland) Jun 2024Cardiovascular disease is the leading cause of mortality among nonalcoholic steatohepatitis (NASH) patients who undergo liver transplants. In the present study, machine...
Cardiovascular disease is the leading cause of mortality among nonalcoholic steatohepatitis (NASH) patients who undergo liver transplants. In the present study, machine learning algorithms were used to identify important risk factors for cardiovascular death and to develop a prediction model. The Standard Transplant Analysis and Research data were gathered from the Organ Procurement and Transplantation Network. After cleaning and preprocessing, the dataset comprised 10,871 patients and 92 features. Recursive feature elimination (RFE) and select from model (SFM) were applied to select relevant features from the dataset and avoid overfitting. Multiple machine learning algorithms, including logistic regression, random forest, decision tree, and XGBoost, were used with RFE and SFM. Additionally, prediction models were developed using a support vector machine, Gaussian naïve Bayes, K-nearest neighbors, random forest, and XGBoost algorithms. Finally, SHapley Additive exPlanations (SHAP) were used to increase interpretability. The findings showed that the best feature selection method was RFE with a random forest estimator, and the most critical features were recipient and donor blood type, body mass index, recipient and donor state of residence, serum creatinine, and year of transplantation. Furthermore, among all the outcomes, the XGBoost model had the highest performance, with an accuracy value of 0.6909 and an area under the curve value of 0.86. The findings also revealed a predictive relationship between features and cardiovascular death after liver transplant among NASH patients. These insights may assist clinical decision-makers in devising strategies to prevent cardiovascular complications in post-liver transplant NASH patients.
PubMed: 38921280
DOI: 10.3390/healthcare12121165 -
Gels (Basel, Switzerland) May 2024Vascularized organs hold potential for various applications, such as organ transplantation, drug screening, and pathological model establishment. Nevertheless, the in...
Vascularized organs hold potential for various applications, such as organ transplantation, drug screening, and pathological model establishment. Nevertheless, the in vitro construction of such organs encounters many challenges, including the incorporation of intricate vascular networks, the regulation of blood vessel connectivity, and the degree of endothelialization within the inner cavities. Natural polymeric hydrogels, such as gelatin and alginate, have been widely used in three-dimensional (3D) bioprinting since 2005. However, a significant disparity exists between the mechanical properties of the hydrogel materials and those of human soft tissues, necessitating the enhancement of their mechanical properties through modifications or crosslinking. In this study, we aim to enhance the structural stability of gelatin-alginate hydrogels by crosslinking gelatin molecules with oxidized pullulan (i.e., a polysaccharide) and alginate molecules with calcium chloride (CaCl). A continuous small-diameter vascular network with an average outer diameter of 1 mm and an endothelialized inner surface is constructed by printing the cell-laden hydrogels as bioinks using a coaxial 3D bioprinter. The findings demonstrate that the single oxidized pullulan crosslinked gelatin and oxidized pullulan/CaCl double-crosslinked gelatin-alginate hydrogels both exhibit a superior structural stability compared to their origins and CaCl solely crosslinked gelatin-alginate hydrogels. Moreover, the innovative gelatin and gelatin-alginate hydrogels, which have excellent biocompatibilities and very low prices compared with other hydrogels, can be used directly for tissue/organ construction, tissue/organ repairment, and cell/drug transportation.
PubMed: 38920913
DOI: 10.3390/gels10060366 -
Current Oncology (Toronto, Ont.) May 2024Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to... (Review)
Review
Oncologic Outcomes of Interventions to Decrease Allograft Ischemia-Reperfusion Injury within Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review.
Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to evaluate interventions to reduce IRI during liver transplantation for HCC and their impact on oncologic outcomes. A comprehensive literature search retrieved four retrospective studies involving 938 HCC patients, utilising interventions such as post-operative prostaglandin administration, hypothermic machine perfusion, and normothermic machine perfusion. Overall, treated patients exhibited reduced post-operative hepatocellular injury and inflammation and significantly enhanced recurrence-free survival. Despite these promising results, the impact of these interventions on overall survival remains unclear. This underscores the imperative for further prospective research to comprehensively understand the efficacy of these interventions in HCC patients undergoing transplantation. The findings highlight the potential benefits of these strategies while emphasising the need for continued investigation into their overall impact.
Topics: Humans; Reperfusion Injury; Liver Transplantation; Carcinoma, Hepatocellular; Liver Neoplasms; Treatment Outcome; Allografts
PubMed: 38920705
DOI: 10.3390/curroncol31060221 -
Annals of the Academy of Medicine,... Dec 2023
Topics: Humans; Kidney Transplantation; COVID-19; Renal Dialysis; Male; Female; Middle Aged; Aged; Singapore; Kidney Failure, Chronic; SARS-CoV-2; Medical Audit; Adult; Retrospective Studies; Transplant Recipients
PubMed: 38920163
DOI: 10.47102/annals-acadmedsg.2023272 -
Annals of the Academy of Medicine,... Dec 2023This systematic review and meta-analysis investigated the impact of intraoperative goal-directed therapy (GDT) compared with conventional fluid therapy on postoperative... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This systematic review and meta-analysis investigated the impact of intraoperative goal-directed therapy (GDT) compared with conventional fluid therapy on postoperative outcomes in renal transplantation recipients, addressing this gap in current literature.
METHOD
A systematic search of patients aged ≥18 years who have undergone single-organ primary renal transplantations up to June 2022 in PubMed, Embase, Scopus and CINAHL Plus was performed. Primary outcome examined was postoperative renal function. Secondary outcomes assessed were mean arterial pressure at graft reperfusion, intraoperative fluid volume and other postoperative complications. Heterogeneity was tested using I² test. The study protocol was registered on PROSPERO.
RESULTS
A total of 2459 studies were identified. Seven eligible studies on 607 patients were included. Subgroup assessments revealed potential renal protective benefits of GDT, with patients receiving cadaveric grafts showing lower serum creatinine on postoperative days 1 and 3, and patients monitored with arterial waveform analysis devices experiencing lower incidences of postoperative haemodialysis. Overall analysis found GDT resulted in lower incidence of tissue oedema (risk ratio [RR] 0.34, 95% CI 0.15-0.78, P=0.01) and respiratory complications (RR 0.39, 95% CI 0.17-0.90, P=0.03). However, quality of data was deemed low given inclusion of non-randomised studies, presence of heterogeneities and inconsistencies in defining outcomes measures.
CONCLUSION
While no definitive conclusions can be ascertained given current limitations, this review highlights potential benefits of using GDT in renal transplantation recipients. It prompts the need for further standardised studies to address limitations discussed in this review.
Topics: Humans; Kidney Transplantation; Fluid Therapy; Postoperative Complications; Edema; Creatinine; Renal Dialysis; Intraoperative Care
PubMed: 38920161
DOI: 10.47102/annals-acadmedsg.202367 -
Annals of the Academy of Medicine,... Dec 2023
Topics: Humans; Kidney Transplantation; Fluid Therapy; Goals
PubMed: 38920157
DOI: 10.47102/annals-acadmedsg.2023398 -
Annals of the Academy of Medicine,... Nov 2023AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical... (Review)
Review
AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Dexamethasone; Singapore; Bortezomib; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Consensus; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation
PubMed: 38920149
DOI: 10.47102/annals-acadmedsg.2023101