Allogeneic Hematopoietic Cell Transplantation in Elderly Patients in a Latin American Country: Analysis of 11 Years of Data from the Brazilian Registry SBTMO/CIBMTR.

This study analyzed recent changes in the utilization of allogeneic HCT for treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative diseases (MPD) and the survival of HCT recipients ≥60 years of age in Brazil. This retrospective registry study included patients who received a first allogeneic HCT from any donor between 2012 and 2023. Of the 6657 patients, 444 (7%) were 60 years of age or older who received grafts from HLA-matched related (42%) or unrelated (20%) donors or HLA-haploidentical donors (32%).

Newborn Screening for Hurler Syndrome Facilitates Early Transplant and Good Outcomes.

Background: Hematopoietic cell transplantation (HCT) is the standard of care treatment for children with Hurler syndrome (HS). This study describes the impact of newborn screening (NBS) on HCT outcomes for these patients.

Methods: Retrospective study of HS patients diagnosed through NBS and referred to Duke from 2017 to 2023.

Imperfect wound healing sets the stage for chronic diseases.

Although the age of the genome gave us much insight about how our organs fail with disease, it also suggested that diseases do not arise from mutations alone; rather, they develop as we age. In this Review, we examine how wound healing might act to ignite disease. Wound healing works well when we are younger, repairing damage from accidents, environmental assaults, and battles with pathogens.

Angiotensin II Type-1 Receptor Antibody in Solid Organ Transplantation - Is It Time to Test?

Angiotensin II type-1 receptor antibody (AT1R-Ab) has been mooted as a potential effector of both acute and chronic antibody mediated rejection (AMR). A growing body of literature on the topic is now coming under scrutiny in the context of the evolving Banff AMR diagnostic classification system and refinement of recommendations for histocompatibility testing by the Sensitization in Transplantation Assessment of Risk (STAR) workgroup. This mini-review discusses the latest understanding of pathophysiological mechanisms, clinical evidence for the pathogenicity of AT1R-Ab, and methods of laboratory testing.

Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring.

Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process.

Challenges in Snakebite Management in India: Insights from a Physician Survey with Special Focus on Kerala and treatment of bites by Hump-nosed Pit Vipers (Hypnale spp.).

Background: India has a high incidence of snakebite-related mortality, making effective snakebite management crucial. This study aimed to explore current practices, challenges, and opportunities for improvement in snakebite management across India.

Methods: A cross-sectional survey was conducted among physicians in India covering aspects such as scope of practice, snake identification, first aid measures, institutional management, and specific management practices for hump-nosed pit viper () bites.

Liver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency.

Lysosomal acid lipase deficiency (LAL-D) is caused by mutations in the LIPA gene, which encodes the lysosomal enzyme that hydrolyzes triglycerides and cholesteryl esters to free fatty acids and free cholesterol. The objective of this study was to develop a curative single-treatment therapy for LAL-D using adeno-associated virus (AAV). Treatment at both early (1-2 days) and late (8-week) timepoints with rscAAVrh74.

Deep learning for rapid analysis of cell divisions in vivo during epithelial morphogenesis and repair.

Cell division is fundamental to all healthy tissue growth, as well as being rate-limiting in the tissue repair response to wounding and during cancer progression. However, the role that cell divisions play in tissue growth is a collective one, requiring the integration of many individual cell division events. It is particularly difficult to accurately detect and quantify multiple features of large numbers of cell divisions (including their spatio-temporal synchronicity and orientation) over extended periods of time.

Novel combined echocardiographic score comprising prognostically validated measures of left ventricular size and function to predict long-term survival following myocardial infarction: A proposal to improve risk stratification.

Background: While left ventricular ejection fraction (LVEF) is the primary variable utilized for prognosis following myocardial infarction (MI), it is relatively indiscriminate for survival in patients with mildly reduced (> 40%) or preserved LVEF (> 50%). Improving risk stratification in patients with mildly reduced or preserved LVEF remains an unmet need, and could be achieved by using a combination approach using prognostically validated measures of left-ventricular (LV) size, geometry, and function.

Aims: The aim of this study was to compare the prognostic utility of a Combined Echo-Score for predicting all-cause (ACM) and cardiac mortality (CM) following MI to LVEF alone, including the sub-groups with LVEF > 40% and LVEF > 50%.

Thorny and Tufted Retinal Ganglion Cells Express the Transcription Factor Forkhead Proteins Foxp1 and Foxp2 in Marmoset (Callithrix jacchus).

The transcription factor forkhead/winged-helix domain proteins Foxp1 and Foxp2 have previously been studied in mouse retina, where they are expressed in retinal ganglion cells named F-mini and F-midi. Here we show that both transcription factors are expressed by small subpopulations (on average less than 10%) of retinal ganglion cells in the retina of the marmoset monkey (Callithrix jacchus). The morphology of Foxp1- and Foxp2-expressing cells was revealed by intracellular DiI injections of immunofluorescent cells.

Case Report: Aplastic anemia related to a novel variant.

A 20-year-old male patient with a history of celiac disease came to medical attention after developing profound fatigue and pancytopenia. Evaluation demonstrated pan-hypogammaglobulinemia. There was no history of significant clinical infections.

Reprogramming macrophages with R848-loaded artificial protocells to modulate skin and skeletal wound healing.

After tissue injury, inflammatory cells are rapidly recruited to the wound where they clear microbes and other debris, and coordinate the behaviour of other cell lineages at the repair site in both positive and negative ways. In this study, we take advantage of the translucency and genetic tractability of zebrafish to evaluate the feasibility of reprogramming innate immune cells in vivo with cargo-loaded protocells and investigate how this alters the inflammatory response in the context of skin and skeletal repair. Using live imaging, we show that protocells loaded with R848 cargo (which targets TLR7 and TLR8 signalling), are engulfed by macrophages resulting in their switching to a pro-inflammatory phenotype and altering their regulation of angiogenesis, collagen deposition and re-epithelialization during skin wound healing, as well as dampening osteoblast and osteoclast recruitment and bone mineralization during fracture repair.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance.