Biomedicines最新文献

Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([¹⁸F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [¹⁸F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [¹⁸F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [¹⁸F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [¹⁸F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [¹⁸F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [¹⁸F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland-Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [¹⁸F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [¹⁸F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [¹⁸F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUV_peak are recommended for quantitative assessment. High [¹⁸F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles.

Background: Since the discovery of successful direct-acting antiviral (DAA) treatment, kidneys from hepatitis C virus (HCV) RNA-positive donors represent a new opportunity to expand the organ donor pool for HCV-negative recipients. Case presentation: In this paper, we describe a unique case of transplantation of an HCV genotype 3a-infected kidney into an HCV-negative recipient who was highly sensitized, with a virtual panel-reactive antibody level of 99.96%. Prior to the kidney transplantation, the recipient received DAA treatment with glecaprevir/pibrentasvir as a viable prophylactic strategy. Post-transplant, the recipient received a triple-combination DAA regimen with glecaprevir/pibrentasvir/sofosbuvir, which continued for 12 weeks. Subsequently, viral load was undetectable at 12 and 24 weeks after treatment, with no significant adverse events associated with DAA therapy. A 12-month post-transplantation biopsy revealed mixed rejection requiring treatment. The 19-month follow-up showed a favorable outcome regarding the function of the kidney allograft and the recipient's quality of life. HCV-positive transplantation allowed our recipient to receive a kidney from an immunologically compatible donor without donor-specific antibodies and the need for desensitization strategies. Conclusions: Each transplant center should decide on the selection of candidates for kidney transplantation from HCV RNA-positive donors to HCV-negative recipients, the availability and choice of DAA treatment, and post-transplant follow-up. Our case emphasizes the need for early DAA treatment based on viral load and HCV genotyping, as well as for careful post-transplant surveillance including protocol biopsies.

Sepsis remains a leading cause of morbidity and mortality worldwide, representing a substantial burden on healthcare systems [...].

Diabetes is a chronic disease that affects many people, with both its incidence and prevalence rising globally. Diabetes can lead to various complications, among which cognitive impairment in diabetic patients significantly impacts their daily life and blood glucose management, complicating treatment and worsening prognosis. Therefore, the early diagnosis and treatment of cognitive impairment are essential to ensure the health of diabetic patients. However, there is currently no widely accepted and effective method for the early diagnosis of diabetes-related cognitive impairment. This review aims to summarize potential screening and diagnostic methods, as well as biomarkers, for cognitive impairment in diabetes, including retinal structure and function examination, brain imaging, and peripheral blood biomarkers, providing valuable information and support for clinical decision making and future research.

Background: Total hip replacement replaces the femoral head, which cannot heal, with an artificial femoral shaft to ensure the patient's normal life. However, due to the stress-masking effect of the proximal femur loaded with the artificial femur stem, the implant bears a large part of the load, resulting in insufficient stress stimulation of the proximal femur and bone waste remodeling. In turn, it is easy to lose bone, resulting in loosening. As a new treatment method, electrical stimulation has been widely used for bone loss, nonunion, and other diseases, and it has achieved good therapeutic effects. Methods: Therefore, in this work, electrical stimulation was introduced for postoperative density assessment, and a new disuse remodeling model was established to simulate density loss after remodeling and the resistance effect of electrical stimulation. The effects of various parameters on density loss in the model are discussed. Results: The simulation results revealed significant stress masking and density loss in the neck of the femur after hip replacement, and electrical stimulation placed in the neck of the femur may resist this density loss to a certain extent. The rate of bone mineral density reduction decreased after the addition of electrical stimulation, indicating that electrical stimulation can have a certain resistance to the density reduction caused by stress shielding, and this result is helpful for the rehabilitation of hip arthroplasty.

Background: Coronary artery bypass grafting (CABG) is one of the main treatments for coronary heart disease (CHD). Gut microbiota, including bacteria, fungi, archaea, and virus, has been reported to be associated with CHD. However, the changes in the multi-kingdom gut microbiota after CABG are not yet clear. This study aimed to explore the changes in multi-kingdom gut microbiota during the early postoperative period of CABG. Methods: We collected fecal samples from 40 patients before and 1 week after CABG surgery. Metagenomic sequencing was used to detect the microbial spectrum and gene functions in the patients' fecal samples. Results: Post-CABG patients exhibited significant changes in the composition of multi-kingdom gut microbiota and gene functions. Among bacteria, beneficial species such as Bifidobacterium, Bacteroides, and Blautia were significantly reduced after CABG, while the harmful species Enterococcus was significantly increased. In fungi, Schizosaccharomyces pombe was significantly decreased in the postoperative group, while Saccharomyces cerevisiae and Aspergillus chevalieri were significantly increased postoperatively. Spearman correlation analysis indicated that Schizosaccharomyces pombe had positive interactions with beneficial bacteria such as Lachnospiraceae, Ruminococcus, and Blautia. Among archaea, the preoperatively enriched Methanomethylovorans-SGB40959 was significantly reduced postoperatively, and Spearman correlation analysis showed a significant positive interaction with probiotics Ruminococcus and Dorea. In viruses, the phage Enterococcus virus EFP01, which infects Enterococcus, was significantly increased postoperatively and showed a significant positive interaction with Enterococcus. Additionally, postoperative dysregulation of gene functions such as the Phosphoenolpyruvate-dependent Sugar Phosphotransferase System (PTS), Transposition, DNA-mediated, and Transposase Activity was observed, and Spearman correlation analysis indicated significant correlations between the dysregulated gene functions and the microbial communities. Conclusions: This study comprehensively revealed the changes in multi-kingdom species post-CABG. The reduction of beneficial microorganisms and the increase of harmful microorganisms after surgery are of significant clinical importance for understanding the overall health status of post-CABG patients and for optimizing postoperative treatment plans. Future research needs to further explore how to improve the prognosis of post-CABG patients by modulating the gut microbiota.

Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased pain sensitivity, and vascular changes that could contribute to headache development and progression. The bidirectional nature of this relationship creates a vicious cycle, with recurrent headaches becoming a source of additional stress. Dysregulation of the HPA axis and ANS imbalance could amplify susceptibility to headaches, intensifying their frequency and severity. While pharmacological interventions remain common, non-pharmacological approaches targeting stress reduction, such as cognitive-behavioral therapy, biofeedback, and relaxation techniques, offer promising avenues for comprehensive headache management. By addressing the underlying stress-related mechanisms, these approaches provide a sustainable strategy to reduce headache frequency and improve patients' quality of life.

Inflammation mechanisms play a critical role in muscle homeostasis, and in Muscular Dystrophies (MDs), the myofiber damage triggers chronic inflammation which significantly controls the disease progression. Immunomodulatory strategies able to target inflammatory pathways and mitigate the immune-mediated damage in MDs may provide new therapeutic options. Owing to its capacity of influencing the immune response and enhancing tissue repair, stem cells' secretome has been proposed as an adjunct or standalone treatment for MDs. In this review study, we discuss the challenging points related to the inflammation condition characterizing MD pathology and provide a concise summary of the literature supporting the potential of perinatal stem cells in targeting and modulating the MD inflammation.

Background/Objectives: Vedolizumab (VDZ) is the new monoclonal drug targeting α4β7 integrin for patients with moderate/severe IBD. Between 30 and 45% of patients fail to respond to VDZ after 14-16 weeks of treatment. The aim of the study was to explore the genetic profile of vedolizumab-treated Arab IBD patients in Saudi Arabia to identify the potential biomarkers to differentiate the responders from non-responders. Methods: A cohort of 16 patients with IBD, including 4 with Crohn's disease and 12 with ulcerative colitis, were recruited. Following 16 weeks of VDZ treatment, nine were found to be responders and seven non-responders. Blood samples were collected for the whole exome sequencing of DNA from all patients. The variants in the whole-exome sequencing data were analyzed with a variety of bioinformatics tools and databases, such as Polyphen2, Mutation Taster, CADD, FATHMM, Open Target Platform, TOPPFun, STRING, and GTEx. Results: More than 1.6 million variants from 16 samples were analyzed. The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders. NOD2, IL23, IL10, IL27, and TRAF1 were found to be the significant IBD risk factors in multiple genome-wide association studies, and their pro-inflammatory activity might contribute to the inherent resistance to VDZ. Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects. Conclusions: This investigation is the first to apply whole-exome sequencing to identify the potential drug response biomarkers for the IBD drug VDZ in Saudi Arabia.

Background: Previous studies have established a general understanding of the association between risky sexual behavior, genetic risk, and cervical carcinoma. However, these studies were conducted several years ago and lack systematic analysis using high-quality and population-based data. Methods: We conducted a prospective nested case-control study to identify risky behaviors and developed a behavior score. Combining the behavior score and genetic risk, we evaluated the effect of sexual and reproductive behavior and PRS on cervical carcinoma through the developed conditional logistic regression models. Results: We verified increased carcinoma risk in individuals with early sexual intercourse (OR: 1.41 [95% CI 1.09 to 1.83], p = 0.0083), non-monogamous sexual partners (OR: 3.13 [95% CI 2.15 to 4.57], p < 0.0001), three or more live births (OR: 1.44 [95% CI 1.12 to 1.84], p = 0.0040), and high PRS (polygenic risk score) (top 25% of PRS, OR: 1.58 [95% CI 1.15 to 2.16], p = 0.0044). The unfavorable sexual and reproductive behavior score we developed was linked to a 151% increased risk (OR: 2.51 [95% CI 1.79 to 3.52], p < 0.0001) after adjusting for PRS. Women with both unfavorable behavior and high genetic risk had a 5.5-fold increased cervical carcinoma risk (OR: 5.45 [95% CI 2.72 to 10.95], p < 0.0001) compared to individuals with favorable behavior and low genetic risk. Conclusions: Unfavorable sexual and reproductive behavior increases the risk of cervical carcinoma, especially in those with a high genetic risk. These findings encourage us to adhere to a healthy sexual and reproductive pattern.