Biomarkers of biological aging in recipients of solid organ transplantation and clinical outcomes: A scoping review.

INTRODUCTION: Biological aging is the accumulation of cellular and molecular damage within an individual over time. The biological age of a donor organ is known to influence clinical outcomes of solid organ transplantation, including delayed graft function and frequency of rejection episodes. While much research has focused on the biological age of donor organs, the recipient's biological age may also influence transplantation outcomes. The aim of this scoping review was to identify and provide an overview of the existing evidence regarding biological aging in solid organ transplant recipients and the impact on patient outcomes post-transplant. METHODS: Literature searches were carried out on PubMed, Web of Science, Google Scholar, Embase and TRIP using the phrases 'solid organ transplant', 'cell senescence', 'cell aging' and 'outcomes', using boolean 'and/or' phrases and MeSH terms. Duplicates were removed and abstracts were reviewed by two independent reviewers. Full papers were then screened for inclusion by two reviewers. Data extraction was carried out using a standardised proforma agreed on prior to starting. RESULTS: 32 studies, including data on a total of 7760 patients, were identified for inclusion in this review; 23 relating to kidney transplant recipients, three to liver transplant, five to lung transplant and one to heart transplantation. A wide range of biomarkers of biological aging have been assessed in kidney transplant recipients, whereas studies of liver, lung and heart transplant have predominantly assessed recipient telomere length. The most robust associations with clinical outcomes are observed in kidney transplant recipients, possibly influenced by the larger number of studies and the use of a wider range of biomarkers of biological aging. In kidney transplant recipients reduced thymic function and accumulation of terminally differentiated T cell populations was associated with reduced risk of acute rejection but increased risk of infection and mortality. CONCLUSION: Studies to date on biological aging in transplant recipients have been heavily biased to kidney transplant recipients. The results from these studies suggest recipient biological age can influence clinical outcomes and future research is needed to prioritise robust biomarkers of biological aging in transplant recipients.

The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson's disease.

Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.

Relatedness of medically important strains of Saccharomyces cerevisiae as revealed by phylogenetics and metabolomics.

Ten medically important Saccharomyces strains, comprising six clinical isolates of Saccharomyces cerevisiae and four probiotic strains of Saccharomyces boulardii, were characterized at the genetic and metabolic level and compared with non-medical, commercial yeast strains used in baking and wine-making. Strains were compared by genetic fingerprinting using amplified fragment length polymorphism (AFLP) analysis, by ribosomal DNA ITS1 sequencing and by metabolic footprinting using both direct injection mass spectrometry (DIMS) and gas chromatography-time of flight-mass spectrometry (GC-ToF-MS). Overall, the clinical isolates fell into different groupings when compared with the non-medical strains, with good but not perfect correlation amongst strains at both the genetic and metabolic levels. Probiotic strains of S. boulardii that are used therapeutically to treat human gastro-intestinal tract disorders showed tight clustering both genetically and metabolically. Metabolomics was found to be of value both as a taxonomic tool and as a means to investigate anomalous links between genotype and phenotype. Key discriminatory metabolites were identified when comparing the three main groups of clinical, probiotic and non-medical strains and included molecules such as trehalose, myo-inositol, lactic acid, fumaric acid and glycerol 3-phosphate. This study confirmed the link between a subset of clinical isolates and baking or probiotic strains but also highlighted that in general the clinical strains were more diverse at both the genomic and metabolic levels.

Utility of the Wang 18-gauge transbronchial histology needle in the staging of bronchogenic carcinoma.

Use of the Wang 18-gauge histology needle in TBNA was employed as a staging procedure in 29 patients with bronchogenic carcinoma and mediastinal adenopathy demonstrated on chest CT. Twenty patients had malignant aspirates; 12 had both histologic and cytologic specimens demonstrating malignancy; six patients had malignant histologic specimens; two had cancerous cytologic specimens as their only evidence of mediastinal disease. Of the nine negative aspirates, four were true negative at surgery. Five patients had false-negative aspirates. Overall sensitivity of the Wang 18-gauge histology needle in the mediastinal staging of patients with bronchogenic carcinoma was 80 percent. When patients with small cell carcinoma were excluded, sensitivity was 82 percent. The enhanced yield of the 18-gauge histology needle warrants its use in mediastinal staging of bronchogenic carcinoma. We conclude that all patients with bronchogenic carcinoma and mediastinal adenopathy demonstrated on chest CT accessible via TBNA should undergo histology needle aspiration as an initial staging procedure.

Hypermagnesemia. A potential complication during treatment of theophylline intoxication with oral activated charcoal and magnesium-containing cathartics.

Toxic reaction to theophylline compounds is common. Oral activated charcoal (OAC) is a widely accepted mode of therapy for management of moderate to severe cases of theophylline toxicity. Magnesium-containing cathartics are generally recommended in conjunction with OAC in the treatment of drug or toxin ingestions. We report two cases of hypermagnesemia complicating the treatment of theophylline toxicity with OAC and magnesium citrate. In both patients, the hypermagnesemia contributed significantly to morbidity or mortality. In light of these cases and after review of the literature, we suggest that sorbitol be considered the cathartic agent of choice in the treatment of theophylline toxicity with OAC.

Respiratory muscle weakness and ventilatory failure in AL amyloidosis with muscular pseudohypertrophy.

Generalized muscle weakness culminating in ventilatory failure developed in a 59-year-old man with kappa light chain multiple myeloma. Physical examination demonstrated skeletal muscle enlargement, severe proximal muscle weakness, and macroglossia, consistent with amyloid-associated muscle pseudohypertrophy. Pulmonary function studies revealed a severe restrictive abnormality with a low maximal inspiratory pressure and maximal voluntary ventilation. Arterial blood gas values and chest radiographic results were normal. There was no clinical evidence of cardiac or central nervous system disease. At autopsy, skeletal muscles and diaphragm were diffusely infiltrated by amyloid. There was also multifocal deposition of amyloid in alveolar septae, esophagus, and subendocardium. This report suggests that ventilatory failure may occur as a complication of myeloma-associated (AL) amyloidosis involving the respiratory muscles.