Risk Factors of Serious Adverse Events for Geriatric Hip Fractures: Is it the Frailty or the Timing?

Objective: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization. Methods: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes. Results: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities (P < .001), lower surgical rates (P = .002), and delayed surgical times (P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications. Conclusions: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.

What role do extracellular vesicles play in developing physical frailty and sarcopenia? : A systematic review.

BACKGROUND: Frailty and sarcopenia are typical geriatric conditions with a complex pathophysiology. Extracellular vesicles (EVs) are key regulators of age-related diseases, but the mechanisms underlying physical frailty, sarcopenia, and EVs are not well understood. METHODS: A systematic literature review was conducted to examine the evidence supporting an association between EVs and physical frailty and/or sarcopenia by searching the electronic databases, including the Cochrane Library, PubMed, and Embase, from January 2000 to January 2021. RESULTS: A total of 216 cross-sectional studies were retrieved, and after the removal of 43 duplicate records, the title and abstract of 167 articles were screened, identifying 6 relevant articles for full-text review. Of the studies five met the inclusion criteria, and heterogeneity among studies was high. There is controversy regarding whether frailty and/or sarcopenia are related to circulating EV levels; however, the cargo of EVs has been associated with frailty and sarcopenia in various ways, such as microRNAs, mitochondrial-derived vesicles (MDVs), and protein cargoes. CONCLUSION: Recent studies, although limited, depicted that EVs could be one of the underlying mechanisms of frailty and/or sarcopenia. There is a possibility that physical frailty and sarcopenia may have specific EV concentrations and cargo profiles; however, further research is required to fully understand the mechanisms and identify potential biomarkers and early preventative strategies for physical frailty and sarcopenia.

Proteomic analysis reveals aberrant expression of CALR and HSPA5 in thyroid tissues of Graves' disease.

OBJECTIVES: To explore the proteomic changes in thyroid tissue from GD patients and find new biomarkers for the prevention, diagnosis as well as the treatment of GD. DESIGN AND METHODS: Group1 included five thyroid specimens of GD cases and 5 normal thyroid tissue samples which were removed surgically and collected. The proteins were extracted from these thyroid tissues and then the differentially expressed protein spots were identified by MALDI-TOF-MS. The interested proteins were further validated in more specimens (group2: 11 pathological thyroid specimens and 7 normal thyroid tissue samples). RESULTS: A total of 34 differentially expressed proteins were observed, and the majority of these proteins were involved in endoplasmic reticulum stress (ER-stress), oxidative stress, energy metabolism, cytoskeleton and movement. The overexpression of calreticulin(CALR) and heat shock 70kDa protein 5(HSPA5) was further validated. CONCLUSION: Alltogether, abundant new candidate molecules, especially proteins related to ER-stress, were found to be involved in the pathogenesis of GD.

Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves' disease.

BACKGROUND AND AIMS: Abnormal microRNA (miRNA) expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. METHODS: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls) were also collected for further validation by quantitative real-time PCR ( qRT-PCR ). RESULTS: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC ≥ 1.3 or ≤ 0.77 and p<0.05). In addition, the transcription of 1271 mRNAs was up-regulated, while the expression of 777 mRNAs transcripts was down-regulated (FC ≥ 2.0 or ≤ 0.5 and p<0.05). Furthermore, integrated analysis of differentially expressed miRNA and their target mRNAs demonstrated that 2 miRNA (miR-22 and miR-183) were increased while their potential target mRNAs were decreased. 3 miRNA (miR-101, miR-197 and miR-660) were decreased while their potential target mRNAs were increased. The above findings from microarray screening were confirmed by qRT-PCR in more samples. The results were consistent with those observed in the microarray assays. CONCLUSION: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.

Increased IL-21/IL-21R expression and its proinflammatory effects in autoimmune thyroid disease.

To determine the potential role of interleukin-21 (IL-21) / IL-21 receptor (IL-21R) in the pathogenesis of autoimmune thyroid disease (AITD) mainly known as Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL-21 and IL-21R of peripheral blood samples and/or thyroid tissues from AITD patients and healthy controls were analyzed by ELISA, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and immunohistochemistry. In vitro, the mRNA and protein of inflammatory cytokines of cultured peripheral blood mononuclear cells (PBMCs) upon recombinant human IL-21 (rhIL-21) stimulation were detected. There was an increased serum concentration of IL-21 in untreated GD and HT patients, and IL-21(+)CD3(+)CD8(-)T cells were significantly increased in PBMCs of HT patients compared with healthy volunteers. The IL-21 mRNA expression in PBMCs increased dramatically in GD and HT patients, and marked augmentations of IL-21 and IL-21R mRNA in thyroid tissues of HT patients were observed. Immunohistochemical staining confirmed the expression of IL-21R protein in HT thyroid cells and lymphocytes. In vitro, PBMCs from GD cultured with rhIL-21 induced increased IL-17A but decreased IL-4 production, while from HT stimulated by rhIL-21 induced augmented production of IFN-γ. In conclusion, the expression of IL-21 and IL-21R were up-regulated in AITD and may be involved in the pathogenesis of the disease through augmenting aberrant immune cascade.

Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population.

Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic susceptibility and environmental factors. The thyroid stimulating hormone receptor gene (TSHR) which is expressed on the surface of the thyroid epithelial cell is thought to be the main auto-antigen and a significant candidate for genetic susceptibility to AITD. This case-control study aimed at evaluating the association between single nucleotide polymorphisms (SNP) of TSHR and AITD in a Chinese Han population. We recruited 404 patients with Graves' disease (GD), 230 patients with Hashimoto's thyroiditis (HT) and 242 healthy controls. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was used to detect five SNPs (rs179247, rs12101255, rs2268475, rs1990595, and rs3783938) in TSHR gene. The frequencies of allele T and TT genotype of rs12101255 in GD patients were significantly increased compared with those of the controls (P=0.004/0.015, OR=1.408/1.446). The allele A frequency of rs3783938 was greater in HT patients than in the controls (P=0.025, OR=1.427). The AT haplotype (rs179247-rs12101255) was associated with an increased risk of GD (P=0.010, OR=1.368). The allele A of rs179247 was associated with ophthalmopathy in GD patients. These data suggest that the polymorphisms of rs12101255 and rs3783938 are associated with GD and HT, respectively.