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Aim: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs). Materials and Methods: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2‐week intervals. Patients were monitored for any possible adverse effects and wound improvement. Results: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12‐week treatment phase, with complete closure in two patients at 24 weeks. Conclusions: The application of a bi‐layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing. [ABSTRACT FROM AUTHOR]

Objective: Kienböck disease is a rare condition characterized by severe pain and restricted wrist movement. Various palliative methods have been proposed as therapeutic strategies for alleviating symptoms. Mesenchymal stromal cell transplantation has been suggested as an innovative and promising approach due to its potential for inducing regeneration and immunomodulation in the necrotic tissue. This study aims to evaluate the safety of autologous bone marrow derived mesenchymal stromal cells (BM-MSCs) transplantation after core decompression in Kienböck disease. Materials and Methods: In this phase I of an open-label clinical trial, three patients (one female and two males) with stage 2 Kienböck disease underwent autologous BM-MSCs transplantation following lunate core decompression. The patients were followed up for six months to assess safety as well as secondary clinical outcomes, including pain level, range of motion (ROM), and functional disability. Results: Safety of BM-MSCs injection following the core decompression was evaluated by recording post-treatment complications during the six-month follow-up. No adverse events (AEs) or severe AEs (SAEs) were reported, indicating that BM-MSCs injection after core decompression is a safe intervention. All patients showed a remarkable reduction in visual analog scale (VAS) scores and "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire scores, suggesting the therapeutic potential of this intervention. Moreover, an increase in the ROM indicated that BM-MSCs transplantation can improve wrist functionality. Additionally, radiographic assessments before and after cell infusion demonstrated a reduction in lunate sclerosis after six months of follow-up. Conclusion: The transplantation of autologous BM-MSCs following lunate core decompression seems to be a safe clinical intervention and may lead to pain relief in patients with Kienböck disease. Furthermore, this procedure may help prevent disease progression during the follow-up period (registration number: NCT02646007). [ABSTRACT FROM AUTHOR]

Background and Aims Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients. Methods For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595. Results From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31–3.68%; I 2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1–30.2%; I 2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47–1.88%; I 2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6–4.7%; I 2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26–0.75%]; I 2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08–0.33%]; I 2: 97.95%) are considered as rare manifestations. Conclusion This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients. [ABSTRACT FROM AUTHOR]

The article focuses on targeted immunotherapy approaches for intraductal papillary neoplasm of the bile duct (IPNB). Topics include the significance of subclassifying IPNBs to tailor treatment strategies, the role of genetic mutations in guiding personalized therapies, and the potential of targeted and immune-based treatments to improve patient outcomes.

Background: Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). Methods: Total number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage. Results: Forty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively. Conclusion: Inter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group. Trial registration: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46), IRCT20080728001031N23. Registered 24 April 2018. [ABSTRACT FROM AUTHOR]

The rapid development of knowledge on healthy nutrition, and hygiene practices, as well as the advent of antibiotics and vaccines, has led to increased life expectancy in the recent century. The extended lifespan has brought new challenges for healthcare professionals, including the management of chronic degenerative diseases, malignancies, and autoimmune disorders. Advanced therapeutic medicinal products (ATMPs) have emerged as a promising frontier alongside conventional therapeutic modalities, offering innovative solutions through cell-based therapies, gene therapy, and tissue engineering. Recent years have witnessed remarkable advancements in regenerative medicine and the launching of innovative ATMPs. Numerous ATMPs have been registered and approved by regulatory agencies for the management of different diseases in 2023. The approval of groundbreaking therapies around the world has made 2023 an exceptional year. Novel ATMPs and the development of artificial intelligence (AI) in 2023 will pave the way for the integration of ATMPs and advanced technologies in personalized medicine, early diagnosis and targeted treatments. [ABSTRACT FROM AUTHOR]

Objective: Perianal fistulas in Crohn’s disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD. Materials and Methods: This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points. Results: In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening. Conclusion: Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD. [ABSTRACT FROM AUTHOR]

Background and Aims: Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients., Methods: For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595., Results: From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31-3.68%; I2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1-30.2%; I2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47-1.88%; I2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6-4.7%; I2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26-0.75%]; I2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08-0.33%]; I2: 97.95%) are considered as rare manifestations., Conclusion: This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Layered-graphene reinforced-metal matrix nanocomposites with excellent mechanical properties and low density are a new class of advanced materials for a broad range of applications. A facile three-step approach based on ultra-sonication for dispersion of graphene nanosheets (GNSs), ball milling for Al-powder mixing with different weight percentages of GNSs, and equal-channel angular pressing for powders' consolidation at 200 °C was applied for nanocomposite fabrication. The Raman analysis revealed that the GNSs in the sample with 0.25 wt.% GNSs were exfoliated by the creation of some defects and disordering. X-ray diffraction and microstructural analysis confirmed that the interaction of the GNSs and the matrix was almost mechanical, interfacial bonding. The density test demonstrated that all samples except the 1 wt.% GNSs were fully densified due to the formation of microvoids, which were observed in the scanning electron microscope analysis. Investigation of the mechanical properties showed that by using Al powders with commercial purity, the 0.25 wt.% GNS sample possessed the maximum hardness, ultimate shear strength, and uniform normal displacement in comparison with the other samples. The highest mechanical properties were observed in the 0.25 wt.% GNSs composite, resulting from the embedding of exfoliated GNSs between Al powders, excellent mechanical bonding, and grain refinement. In contrast, agglomerated GNSs and the existence of microvoids caused deterioration of the mechanical properties in the 1 wt.% GNSs sample., Competing Interests: The authors declare no conflict of interest.