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We present an updated report highlighting significant developments in the field of xenotransplantation since March 2023. The past six months have witnessed significant strides in the field and the emergence of novel research that is expected to facilitate the journey towards clinical trials. We are reviewing here the most pertinent findings from March 2023 to November 2023. [ABSTRACT FROM AUTHOR]

The 2023 IXA conference, hosted in San Diego, CA, brimmed with excitement against the backdrop of recent innovations in both the pre‐clinical and clinical realms with several first‐in‐human applications of xenotransplantation. The theme, "Pigs are flying," alluded to the adage that xenotransplantation would only become a clinical reality "when pigs fly," suggesting a day that might never come. The event witnessed significant attendance, with 600 participants—the highest in the history of an IXA‐IPITA joint congress. Among the attendees were members of the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and corporate sponsors deeply engaged in the field. We summarize the latest topics from the congress, ranging from the pros/cons of decedent models of xenotransplantation and genetic engineering of porcine heart valves, solid organs, and cells for clinical translation and their regulatory and ethical landscape. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article on cell therapy for anal sphincter incontinence. The authors have made corrections to the citations and reference numbers, as well as updated the references in Table 1. Table 3 provides information on the characteristics of primary cells proposed for cell therapy of anal sphincter incontinence. The document also discusses the use of cell therapy for anal sphincter injury, including various studies and clinical trials. It highlights the practical considerations and challenges associated with cell therapy, as well as the need for further research in this area. Additionally, the document is part of a collection of articles exploring regenerative therapies for anal sphincter injury and fecal incontinence, providing valuable insights for researchers and healthcare professionals. [Extracted from the article]

Background: Small bowel obstruction (SBO) is a common hospital admission diagnosis. Identification of patients who will require a surgical resection because of a nonviable small bowel remains a challenge. Through a prospective cohort study, the authors aimed to validate risk factors and scores for intestinal resection, and to develop a practical clinical score designed to guide surgical versus conservative management. Patients and Methods: All patients admitted for an acute SBO between 2004 and 2016 in the center were included. Patients were divided in three categories depending on the management: conservative, surgical with bowel resection, and surgical without bowel resection. The outcome variable was small bowel necrosis. Logistic regression models were used to identify the best predictors. Results: Seven hundred and thirteen patients were included in this study, 492 in the development cohort and 221 in the validation cohort. Sixty-seven percent had surgery, of which 21% had small bowel resection. Thirty-three percent were treated conservatively. Eight variables were identified with a strong association with small bowel resection: age 70 years of age and above, first episode of SBO, no bowel movement for greater than or equal to 3 days, abdominal guarding, C-reactive protein greater than or equal to 50, and three abdominal computer tomography scanner signs: small bowel transition point, lack of small bowel contrast enhancement, and the presence of greater than 500 ml of intra-abdominal fluid. Sensitivity and specificity of this score were 65 and 88%, respectively, and the area under the curve was 0.84 (95% CI: 0.80-0.89). Conclusion: The authors developed and validated a practical clinical severity score designed to tailor management of patients presenting with an SBO. [ABSTRACT FROM AUTHOR]

Introduction: In pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLADR3 or HLA-DR4 matches. Methods: We retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878). Results: HLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DRmatches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p<0.01). At five-year post-transplantation, 78% of group B was insulin-independent compared to 24% (group A) and 35% (group C). Insulinindependence correlated with significantly better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe hypoglycemic events. Matching HLAA-B-DR (≥3) independently of HLA- DR3 or HLA-DR4 matching did not improve graft survival. Conclusion: This study suggests that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a significant predictor for long-term islet survival. [ABSTRACT FROM AUTHOR]

The progress of medical therapies, which rely on the transplantation of microencapsulated living cells, depends on the quality of the encapsulating material. Such material has to be biocompatible, and the microencapsulation process must be simple and not harm the cells. Alginate-poly(ethylene glycol) hybrid microspheres (alg-PEG-M) were produced by combining ionotropic gelation of sodium alginate (Na-alg) using calcium ions with covalent crosslinking of vinyl sulfone-terminated multi-arm poly(ethylene glycol) (PEG-VS). In a one-step microsphere formation process, fast ionotropic gelation yields spherical calcium alginate gel beads, which serve as a matrix for simultaneously but slowly occurring covalent cross-linking of the PEG-VS molecules. The feasibility of cell microencapsulation was studied using primary human foreskin fibroblasts (EDX cells) as a model. The use of cell culture media as polymer solvent, gelation bath, and storage medium did not negatively affect the alg-PEG-M properties. Microencapsulated EDX cells maintained their viability and proliferated. This study demonstrates the feasibility of primary cell microencapsulation within the novel microsphere type alg-PEG-M, serves as reference for future therapy development, and confirms the suitability of EDX cells as control model. [ABSTRACT FROM AUTHOR]

Background: Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis. Methods: We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4). Results: Human HSCs treated with IL-1β had increased IL-1β, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1β had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model. Conclusions: We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Increasing occurrence of atypical femoral fractures associated with bisphosphonate use," by Meier et al that was published in the "Archives of Internal Medicine."

Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in "omics' methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score's relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis on 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR respectively (P<0.05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in Grade 3 ACR, 18 were also differentially expressed in Grade 2 ACR. The rejection signal was attributable to activated leukocytes' infiltration. Significantly higher tCRM scores were found in grade 3 ACR (p = 0.007) and grade 2 ACR (p = 0.004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

This updated report highlights significant developments in the field of xenotransplantation since December 2023. Over the past 6 months, there has been a notable increase in discussions regarding the feasibility of clinical trials, with particular emphasis on their progression and associated ethical considerations. This review presents the most pertinent findings from December 2023 to June 2024., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Transplanting organs from cytomegalovirus-seropositive donors into cytomegalovirus-seronegative recipients is an accepted practice. However, outcomes following transplantation of organs from donors with active cytomegalovirus disease are unknown. We present a case involving a patient aged 61 years with end-stage renal disease, seropositive for cytomegalovirus, who underwent dual kidney transplant from a donor with high-grade cytomegalovirus viraemia. The donor was on immunosuppressive therapy for systemic lupus erythematosus and interstitial lung disease and had been admitted with respiratory failure. The donor had high-grade cytomegalovirus viraemia with probable cytomegalovirus pneumonitis (cytomegalovirus viral load >100 000 international units [IU]/mL in plasma and 319 000 IU/mL in bronchoalveolar lavage). Renal biopsy at organ procurement showed the absence of cytomegalovirus inclusions. Following transplantation, the recipient had delayed graft function, with renal recovery after 1 week. The patient received basiliximab induction and standard tacrolimus-based maintenance immunosuppression. He received ganciclovir and valganciclovir treatment for 1 month, followed by valganciclovir prophylaxis (or viral load monitoring, when prophylaxis had to be paused) for 2 additional months to prevent donor-derived cytomegalovirus infection. Transient cytomegalovirus viraemia (peaking at 4480 IU/mL) developed at 4 months and resolved with 1 month of valganciclovir treatment. The patient is doing well 1 year after transplantation, with adequate kidney function. This case highlights the successful and safe transplantation of kidneys from a donor with cytomegalovirus disease into a cytomegalovirus-seropositive recipient. Further research is needed to confirm our findings and define post-transplantation management., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)