Arabi, Tarek Ziad

Poststenotic dilatation in renal artery stenosis, evaluated at abdominal CT, might be related to stenotic kidney damage and inflammation, particularly to monocyte chemoattractant protein-1 release.

Abstract Renal artery stenosis (RAS) is the leading cause of secondary hypertension worldwide. However, current medical and surgical treatment modalities provide minimal benefits for kidney injury. Recent preclinical RAS models have demonstrated promising potential of human mesenchymal stem cells (MSC) and their daughter extracellular vesicles (EV) in improving murine renal function and attenuating inflammation. However, the extent and mechanisms underlying immune rejection of xenogeneic MSCs or EVs are yet undetermined. Therefore, adipose tissue was harvested from adult healthy patients. Adipose-derived MSCs were extracted and cultured, and EVs were isolated from their supernatants via ultra-centrifugation. Then, mice randomly assigned to RAS or sham surgery were divided into 6 groups: sham surgery, RAS, sham + MSC, RAS + MSC, sham + EV, and RAS + EV. Two weeks after intra-aortic injection of MSCs (5 × 105) or EVs (20 µg protein), we compared the intrarenal T-cell and macrophage accumulation, splenic B-cell numbers, circulating cytokines and anti-human antibodies levels among the groups. MSCs and EVs did not influence intrarenal immune cell infiltrations. However, MSCs significantly increased circulating anti-human antibodies. In the spleen, RAS + EV mice showed higher memory IgM+ B-cells but reduced CD19+ B-cells compared to RAS + MSC. In vitro T-cell recall assay showed that both MSCs and EVs exhibited reduced IFN-γ release upon re-stimulation, indicating an immunosuppressive effect. Therefore, xenogeneic MSCs induced a greater humoral response in mice, while EVs triggered a splenic cellular response, but neither elicits discernible kidney rejection. Our results provide key insights into the immunomodulatory mechanisms of MSCs and EVs and immune mechanisms underlying xenograft rejection.

Purpose: To systematically review the literature on the effectiveness, safety, and long-term outcomes of genicular artery embolization (GAE) for knee joint osteoarthritis (OA) associated pain. Materials and Methods: After registering the protocol with the PROSPERO database, a search was conducted from inception until July 31, 2023, in MEDLINE, Cochrane Central Register of Controlled Trials, and ScienceDirect databases to gather studies evaluating GAE’s safety and efficacy in knee OA. A total of 4979 studies were identified and evaluated against the inclusion criteria. Data on study characteristics, success parameters, and adverse events were collected and synthesized. Results: Twenty-three studies, primarily single-center prospective studies with a total of 657 patients, were included. Most studies reported a 100% technical success rates, except one study reporting a rate of 84.2%. Clinical success rates, defined variably across studies, ranged from 30% to 100%, depending on the study’s follow-up period and outcome measures. The most frequent adverse events included skin discoloration without an ulcer (15.6%, n = 98) and transient post-procedural knee pain (10.2%, n = 64). Most studies were rated as fair in terms of quality, but the lack of robust randomized controlled trials highlighted the need for further comparative studies to standardize outcome reporting. Conclusion: GAE appears to be a promising option for knee OA pain, particularly for patients unresponsive to conservative treatments or ineligible for surgery. High-quality studies are needed to confirm long-term effectiveness and standardize outcome measures. Clinical Impact This study highlights the safety and efficacy of genicular artery embolization as a minimally invasive treatment for knee osteoarthritis, particularly in patients who are unresponsive to conservative treatments or unsuitable for surgery. By targeting neovascularization and reducing inflammation, genicular artery embolization provides pain relief and functional improvement. Clinicians can consider genicular artery embolization as an alternative to surgery for mild-to-moderate OA, offering a lower adverse event rate and faster recovery.

Cardiac amyloidosis (CA) is a progressive condition resulting from the deposition of amyloid fibrils in the heart, which leads to severe diastolic dysfunction and restrictive cardiomyopathy. The disease has two main subtypes: light-chain and transthyretin (TTR) CA, with the latter subdivided into wild-type and hereditary forms. Despite advances in diagnostic imaging, early detection remains a challenge due to non-specific symptoms that mimic other cardiac conditions. Treatment has evolved significantly with targeted therapies like TTR stabilizers, gene silencers, and RNA interference, showing promise in altering disease progression. However, barriers such as high costs, limited availability of genetic testing, and inadequate multidisciplinary care continue to impede comprehensive management. Future strategies should focus on integrating novel gene-editing therapies, expanding access to diagnostics, and enhancing multidisciplinary care models to improve outcomes. Overall, early diagnosis, equitable access to therapies, and personalized management plans are crucial to advancing care for CA patients.

To address the ongoing shortage of organs available for replacement, xenotransplantation of hearts, corneas, skin, and kidneys has been attempted. However, a major obstacle facing xenotransplants is rejection due to a cycle of immune reactions to the graft. Both adaptive and innate immune systems contribute to this cycle, in which natural killer cells, macrophages, and T-cells play a significant role. While advancements in the field of genetic editing can circumvent some of these obstacles, biomarkers to identify and predict xenograft rejection remain to be standardized. Several T-cell markers, such as CD3, CD4, and CD8, are useful in both the diagnosis and prediction of xenograft rejection. Furthermore, an increase in the levels of various circulating DNA markers and microRNAs is also predictive of xenograft rejection. In this review, we summarize recent findings on the advancements in xenotransplantation, with a focus on pig-to-human, the role of immunity in xenograft rejection, and its biomarkers.