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Haematologica Jan 2024Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician... (Observational Study)
Observational Study
Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician assessment in routine practice. Patient-reported treatment response is central to the experience of chronic GvHD manifestations as well as treatment benefit and toxicity, but how they correlate with clinician- or NIH-responses has not been well-studied. We aimed to characterize 6-month patientreported response, determine associated chronic GvHD baseline organ features and changes, and evaluate which patientreported quality of life and chronic GvHD symptom burden measures correlated with patient-reported response. From two nationally representative Chronic GVHD Consortium prospective observational studies, 382 subjects were included in this analysis. Patient and clinician responses were categorized as improved (completely gone, very much better, moderately better, a little better) versus not improved (about the same, a little worse, moderately worse, very much worse). At six months, 270 (71%) patients perceived chronic GvHD improvement, while 112 (29%) perceived no improvement. Patient-reported response had limited correlation with either clinician-reported (kappa 0.37) or NIH chronic GvHD response criteria (kappa 0.18). Notably, patient-reported response at six months was significantly associated with subsequent failure-free survival. In multivariate analysis, NIH responses in eye, mouth, and lung had significant association with 6-month patient-reported response, as well as a change in Short Form 36 general health and role physical domains and Lee Symptom Score skin and eye changes. Based on these findings, patient-reported responses should be considered as an important complementary endpoint in chronic GvHD clinical trials and drug development.
Topics: Humans; Bronchiolitis Obliterans Syndrome; Quality of Life; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Chronic Disease; Patient Reported Outcome Measures
PubMed: 37226713
DOI: 10.3324/haematol.2023.282734 -
Brazilian Journal of Veterinary Medicine 2023Manipulation of skin biogeography has been the subject of study by the present authors for a very long while. Previous description and report identified the benefical...
Manipulation of skin biogeography has been the subject of study by the present authors for a very long while. Previous description and report identified the benefical application of skin microbiota transplantation (SMT) by the same researcher group, whom described unenriched skin microbiota transplantation at clinical veterinary practice for the first time among dogs. This study to our knowledge again for the first time reported herein aimed to investigate Un-smt application for treatment of feline atopic skin syndrome (FASS). This novel treatment intervention was performed similarly to previous description and methodology by use of Nivea Refining Clear-Up Strips (Ni-RcUs) either in autologue or heterologue route. Clinical biomarker for detecting the efficacy of Un-smt via Ni-RcUs evolved epidermal corneometric analytes (i.e. epidermal hydration and pH), relevant clinical scores The Feline Dermatitis Extent and Severity Index (FeDESI) and Visual Analogue Scale (VAS pruritus) and clinical observations performed weekly, at least. Both FeDESI and VAS pruritus scores were changed in relationship with smt. Pre-treament day 0 FeDESI scores (median ± SE) (72.5 ± 9.34), were significantly (p=0.001) higher than scores on day 10 (13.5 ± 2.55) switching the severity of the disease in all cases. Besides day 0 VAS pruritus scores were 6.0 ± 0.49 (median ± SE) (prior to treatment), whereas owner VAS pruritus score was decreased to 2.0 ± 0.34 (median ± SE) significantly (p=0.001). There were no side effects attributable to treatment applications. All cases were monitored for 6 months after completion of treatment in which no recurrence was observed. As a preliminary conclusion with selected number of cats with FASS, Un-smt with Ni-RcUs should be novel strategy for manuplating skin microbiome with treatment success.
PubMed: 38093985
DOI: 10.29374/2527-2179.bjvm002823 -
Hepatology Communications Oct 2023Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse.
METHODS
A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series.
RESULTS
Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45-180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21-42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493-2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659-3.303; p = 0.3).
CONCLUSIONS
This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.
Topics: Humans; Liver Transplantation; Living Donors; Graft vs Host Disease; Immunosuppressive Agents; Risk Factors
PubMed: 37755878
DOI: 10.1097/HC9.0000000000000260 -
Frontiers in Immunology 2023Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection...
Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating CD4T-bet T cells, CD8T-bet T cells, and CD4FOXP3 regulatory T cells were reduced. Single cell RNA sequencing revealed a unique expression profile in immune cells in the skin of baricitinib plus CsA treated mice, including decreased inflammatory neutrophils and increased CCR2 macrophages. In a fully major histocompatibility mismatched mismatched heart allograft model, baricitinib plus CsA prevented graft rejection for the entire 28-day treatment period compared with 9 days in controls. Our findings establish that the combination of baricitinib and CsA prevents rejection in allogeneic skin and heart graft models and supports the study of JAK inhibitors in human solid organ transplantation.
Topics: Humans; Animals; Mice; Cyclosporine; Graft Rejection; Heart Transplantation; Sulfonamides
PubMed: 37744381
DOI: 10.3389/fimmu.2023.1264496 -
Frontiers in Molecular Biosciences 2024Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding.... (Review)
Review
Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.
PubMed: 38690295
DOI: 10.3389/fmolb.2024.1362338 -
Biomolecules Apr 2024The skin is the outer layer of the human body, and it is crucial in defending against injuries and damage. The regenerative capacity of aging and damaged skin caused by... (Review)
Review
The skin is the outer layer of the human body, and it is crucial in defending against injuries and damage. The regenerative capacity of aging and damaged skin caused by exposure to external stimuli is significantly impaired. Currently, the rise in average life expectancy and the modern population's aesthetic standards have sparked a desire for stem-cell-based therapies that can address skin health conditions. In recent years, mesenchymal stem cells (MSCs) as therapeutic agents have provided a promising and effective alternative for managing skin regeneration and rejuvenation, attributing to their healing capacities that can be applied to damaged and aged skin. However, it has been established that the therapeutic effects of MSC may be primarily mediated by paracrine mechanisms, particularly the release of exosomes (Exos). Exosomes are nanoscale extracellular vesicles (EVs) that have lipid bilayer and membrane structures and can be naturally released by different types of cells. They influence the physiological and pathological processes of recipient cells by transferring a variety of bioactive molecules, including lipids, proteins, and nucleic acids such as messenger RNAs (mRNAs) and microRNAs (miRNAs) between cells, thus playing an important role in intercellular communication and activating signaling pathways in target cells. Among them, miRNAs, a type of endogenous regulatory non-coding RNA, are often incorporated into exosomes as important signaling molecules regulating protein biosynthesis. Emerging evidence suggests that exosomal miRNAs from MSC play a key role in skin regeneration and rejuvenation by targeting multiple genes and regulating various biological processes, such as participating in inflammatory responses, cell migration, proliferation, and apoptosis. In this review, we summarize the recent studies and observations on how MSC-derived exosomal miRNAs contribute to the regeneration and rejuvenation of skin tissue, with particular attention to the applications of bioengineering methods for manipulating the miRNA content of exosome cargo to improve their therapeutic potential. This review can provide new clues for the diagnosis and treatment of skin damage and aging, as well as assist investigators in exploring innovative therapeutic strategies for treating a multitude of skin problems with the aim of delaying skin aging, promoting skin regeneration, and maintaining healthy skin.
Topics: Humans; Exosomes; Mesenchymal Stem Cells; MicroRNAs; Skin; Animals; Regeneration; Mesenchymal Stem Cell Transplantation
PubMed: 38672475
DOI: 10.3390/biom14040459 -
Tzu Chi Medical Journal 2024Hematopoietic stem cell transplantation (HSCT) can cure malignant and nonmalignant hematological disorders. From 1983 to 2022, Taiwan performed more than 10,000 HSCT... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) can cure malignant and nonmalignant hematological disorders. From 1983 to 2022, Taiwan performed more than 10,000 HSCT transplants. The Taiwan Blood and Marrow Transplantation Registry collects clinical information to gather everyone's experience and promote the advances of HSCT in Taiwan to gather everyone's experience and promote advances of HSCT in Taiwan. Compared with matched sibling donors, transplants from matched unrelated donors exhibited a trend of superior survival. In Taiwan, transplant donors showed remarkable growth from unrelated (24.8%) and haploidentical (10.5%) donors. The number of older patients (17.4%; aged ≥61 years) who underwent transplantation has increased markedly. This review summarizes several significant developments in HSCT treatment in Taiwan. First, the use of Anti-thymocyte globulin (ATG) and intravenous busulfan regimens were important risk factors for predicting hepatic sinusoidal obstruction syndrome. Second, a new, machine learning-based risk prediction scoring system for posttransplantation lymphoproliferative disorder has identified five risk factors: aplastic anemia, partially mismatched related donors, fludarabine use, ATG use, and acute skin graft-versus-host disease. Third, although the incidence of idiopathic pneumonia syndrome was low (1.1%), its mortality rate was high (58.1%). Fourth, difficult-to-treat mantle cell and T-cell lymphomas treated with autologous HSCT during earlier remission had higher survival rates. Fifth, treatment of incurable multiple myeloma with autologous HSCT showed a median progression-free survival and overall survival of 46.5 and 70.4 months, respectively. Sixth, different haploidentical transplantation strategies were compared. Seventh, caution should be taken in administering allogeneic HSCT treatment in older patients with myeloid leukemia with a Charlson Comorbidity Index ≥3 because of a higher risk of nonrelapse mortality.
PubMed: 38645784
DOI: 10.4103/tcmj.tcmj_276_23 -
ACS Applied Materials & Interfaces Aug 2023Morbid dermal templates, microangiopathy, and abnormal inflammation are the three most critical reasons for the scarred healing and the high recurrence rate of diabetic...
Morbid dermal templates, microangiopathy, and abnormal inflammation are the three most critical reasons for the scarred healing and the high recurrence rate of diabetic wounds. In this present study, a combination of a methacrylated decellularized extracellular matrix (ECMMA, aka EM)-based hydrogel system loaded with copper-epigallocatechin gallate (Cu-EGCG) capsules is proposed to fabricate bio-printed dermal scaffolds for diabetic wound treatment. Copper ions act as a bioactive element for promoting angiogenesis, and EGCG can inhibit inflammation on the wound site. In addition to the above activities, EM/Cu-EGCG (E/C) dermal scaffolds can also provide optimized templates and nutrient exchange space for guiding the orderly deposition and remodeling of ECM. In vitro experiments have shown that the E/C hydrogel can promote angiogenesis and inhibit the polarization of macrophages to the M1 pro-inflammatory phenotype. In the full-thickness skin defect model of diabetic rats, the E/C dermal scaffold combined with split-thickness skin graft transplantation can alleviate pathological scarring via promoting angiogenesis and driving macrophage polarization to the anti-inflammatory M2 phenotype. These may be attributed to the scaffold-actuated expression of angiogenesis-related genes in the HIF-1α/vascular endothelial growth factor pathway and decreased expression of inflammation-related genes in the TNF-α/NF-κB/MMP9 pathway. The results of this study show that the E/C dermal scaffold could serve as a promising artificial dermal analogue for solving the problems of delayed wound healing and reulceration of diabetic wounds.
Topics: Rats; Animals; Cicatrix; Copper; Diabetes Mellitus, Experimental; Vascular Endothelial Growth Factor A; Inflammation; Hydrogels; Printing, Three-Dimensional
PubMed: 37535406
DOI: 10.1021/acsami.3c04733 -
Seminars in Nephrology Jan 2024Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis.... (Review)
Review
Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.
Topics: Humans; Kidney Transplantation; Neoplasms; Skin Neoplasms; Sarcoma, Kaposi; Lymphoproliferative Disorders; Kidney Failure, Chronic; Immunosuppression Therapy; Immunosuppressive Agents; Lung Neoplasms; Anus Neoplasms; Prostatic Neoplasms; Colorectal Neoplasms; Risk Factors; Transplant Recipients
PubMed: 38538455
DOI: 10.1016/j.semnephrol.2024.151494 -
JCI Insight Dec 2023Hair loss is a debilitating condition associated with the depletion of dermal papilla cells (DPCs), which can be replenished by dermal sheath cells (DSCs). Hence,...
Hair loss is a debilitating condition associated with the depletion of dermal papilla cells (DPCs), which can be replenished by dermal sheath cells (DSCs). Hence, strategies aimed at increasing the populations of DPCs and DSCs hold promise for the treatment of hair loss. In this study, we demonstrated in mice that introduced exogenous DPCs and DSCs (hair follicle mesenchymal stem cells) could effectively migrate and integrate into the dermal papilla and dermal sheath niches, leading to enhanced hair growth and prolonged anagen phases. However, the homing rates of DPCs and DSCs were influenced by various factors, including recipient mouse depilation, cell passage number, cell dose, and immune rejection. Through in vitro and in vivo experiments, we also discovered that the CXCL13/CXCR5 pathway mediated the homing of DPCs and DSCs into hair follicle niches. This study underscores the potential of cell-based therapies for hair loss by targeted delivery of DPCs and DSCs to their respective niches and sheds light on the intriguing concept that isolated mesenchymal stem cells can home back to their original niche microenvironment.
Topics: Mice; Animals; Hair Follicle; Cells, Cultured; Alopecia; Cell- and Tissue-Based Therapy; Mesenchymal Stem Cells
PubMed: 37917167
DOI: 10.1172/jci.insight.173549