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International Wound Journal Jul 2024Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive...
Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive burns. The aim of this study was to investigate whether the use of JACE® contributes to survival rate in extensive burns. In this study, 119 cases were selected from 3990 cases in Tokyo Burn Unit Association registry data from 2009 to 2023, excluding cases with less than 40% total body surface area, cases of deaths within 4 weeks and cases with unknown length of hospital stay. In total, 25 patients treated with JACE® were selected and matched with another 25 patients who did not receive JACE® using propensity score matching. The results showed that patients treated with JACE® had a significantly higher survival rate than did those who were not treated with JACE® at all time points between 6 and 9 weeks post-injury. In addition, there was no significant difference in length of hospital stay between the groups. These results suggest that the use of JACE® in patients with extensive burns contributes to patient survival and does not prolong hospital stay.
Topics: Humans; Burns; Male; Female; Registries; Propensity Score; Middle Aged; Adult; Skin Transplantation; Aged; Tokyo; Survival Rate; Young Adult; Length of Stay; Autografts; Retrospective Studies; Transplantation, Autologous; Adolescent; Treatment Outcome
PubMed: 38923296
DOI: 10.1111/iwj.14952 -
Antibodies (Basel, Switzerland) Jun 2024The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we...
The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5 skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5 leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5 BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy.
PubMed: 38920972
DOI: 10.3390/antib13020048 -
Annals of Vascular Diseases Jun 2024Lymphedema is caused by dysfunction of the lymphatic system. It is divided into primary edema with no apparent cause and secondary edema with an exogenous cause. The... (Review)
Review
Lymphedema is caused by dysfunction of the lymphatic system. It is divided into primary edema with no apparent cause and secondary edema with an exogenous cause. The main symptoms are edema and heaviness, skin changes such as skin hardening, lymphocysts, lymphorrhoea, papillomas, and recurrent cellulitis. They are often irreversible and progressive, thus greatly reducing quality of life of the patients. Diagnosis is made by image examinations that can evaluate lymphatic flow and functions such as lymphoscintigraphy and indocyanine green fluorescence lymphangiography. Linear pattern and dermal backflow are the main findings. Conservative treatment consists of four components: compression therapy with elastic garments, exercise therapy, manual lymphatic drainage, and skin care, which is called complex physical therapy (CPT). Although CPT has become the gold standard of treatment, with evidence of efficacy reported in terms of volume reduction, maintenance, and prevention of cellulitis, it is a symptomatic treatment and does not improve impaired lymphatic flow. On the other hand, surgical treatment, such as lymphaticovenous anastomosis and vascularized lymph node transplantation, can create new lymphatic flow and improve lymphatic dysfunctions. Although these techniques are expected to be effective in volume reduction, cellulitis prevention, and improving quality of life, there is a need for more studies with a higher level of evidence in the future. In Japan, lymphedema is treated with a combination of conservative and surgical therapies, but lymphedema is intractable and few cases are completely cured. Therefore, how to improve the outcome of treatment is an important issue to be addressed in the future. (This is a translation of Jpn J Vasc Surg 2023; 32: 141-146.).
PubMed: 38919315
DOI: 10.3400/avd.ra.24-00011 -
European Journal of Dermatology : EJD Jun 2024Seborrheic Dermatitis of the scalp (SSD) is a chronic and relapsing inflammatory skin condition. Current SSD treatments mainly consist of topical applications of... (Review)
Review
Seborrheic Dermatitis of the scalp (SSD) is a chronic and relapsing inflammatory skin condition. Current SSD treatments mainly consist of topical applications of anti-fungals and anti-inflammatory agents. to review information about SSD and to provide dermatologists with practical recommendations for managing adult SSD. Material and methods: Between September and December 2023, an international group of experts in dermatology and hair and scalp disorders met to discuss published data about SD, SSD, dandruff, and management options. A total of 131 manuscripts available from PubMed were analysed, discussed and used for the present consensus. Each author was asked to complete a table listing currently used treatments to treat SSD according to the literature and to their own experience. The authors confirmed their use and regimen and commented on local treatment exceptions. They then agreed on prescription practices and proposed a general treatment approach. Currently, approved therapies to manage moderate and severe forms of SSD do not exist and there is a need for adapted and approved medications that treat efficiently and safely the disease. We propose a treatment algorithm that allows for the treatment of all severity grades of SSD. This algorithm may be completed with local treatment specifications. Despite the lack of approved therapies to manage moderate forms of SSD, a treatment algorithm is proposed and may help prescribers to manage SSD more efficiently.
Topics: Dermatitis, Seborrheic; Humans; Scalp Dermatoses; Adult; Consensus; Algorithms; Antifungal Agents; Dermatologic Agents; Anti-Inflammatory Agents; Severity of Illness Index
PubMed: 38919137
DOI: 10.1684/ejd.2024.4703 -
Asian Pacific Journal of Cancer... Jun 2024Recent studies have highlighted the potential of fetal hepatic stem cells in regenerative treatments for liver diseases. This study aimed to evaluate the short-term...
BACKGROUND AND OBJECTIVES
Recent studies have highlighted the potential of fetal hepatic stem cells in regenerative treatments for liver diseases. This study aimed to evaluate the short-term effects of fetal stem cell transplantation in patients with liver cirrhosis resulting from chronic hepatitis C.
MATERIALS AND METHODS
Thirty patients with liver cirrhosis of all Child-Turcotte-Pugh classes due to chronic hepatitis C, aged 18 to 65 years, were selected for this study. A single intravenous dose of 1 ml containing 6*106 fetal hepatic stem cells, diluted in 20.0 ml of 0.9% sodium chloride solution, was administered. The efficacy of the treatment was assessed by measuring levels of ALT, AST, total and direct bilirubin, gamma-glutamyltranspeptidase, alkaline phosphatase, total protein, and albumin before and after cell therapy.
RESULTS
Post-treatment, a significant reduction was noted in the Child-Pugh score from 8 [6-9] to 7 [6-8] (p<0.001) and the MELD index from 11 [7-15] to 10 [7-14] (p=0.004). Skin itching decreased from 36.7% to 10%. Complaints of weakness increased significantly from 3.3% to 23.3% after 30 days of therapy (p=0.014), and the incidence of reduced appetite increased from 20% to 46.7% (p=0.021). No statistical differences were observed in the frequency of nosebleeds (86.7% initially vs. 90% at day 30, p=0.655) or drowsiness (63.3% initially vs. 76.7% at day 30, p=0.157). Significant reductions were noted in ALT levels by 35% and total bilirubin by 44%. The lack of significant changes in indicators of hepatic-cell insufficiency, particularly the protein-forming function as reflected in total protein and albumin levels, is likely due to the extent of liver tissue damage and thus a delayed recovery.
CONCLUSION
The findings of this study affirm the clinical efficacy and promise of fetal hepatic stem cell therapy as part of a comprehensive treatment regimen for patients with liver cirrhosis.
Topics: Humans; Liver Cirrhosis; Middle Aged; Male; Female; Adult; Adolescent; Hepatitis C, Chronic; Young Adult; Aged; Hepacivirus; Stem Cell Transplantation; Follow-Up Studies; Prognosis
PubMed: 38918672
DOI: 10.31557/APJCP.2024.25.6.2099 -
BioRxiv : the Preprint Server For... Jun 2024Costimulation blockade (CoB)-based immunotherapy is a promising alternative to immunosuppression for transplant recipients; however, the current limited understanding of...
Costimulation blockade (CoB)-based immunotherapy is a promising alternative to immunosuppression for transplant recipients; however, the current limited understanding of the factors that impact its efficacy restrains its clinical applicability. In this context, pro- and anti-inflammatory cytokines are being recognized as having an impact on T cell activation beyond effector differentiation. This study aims at elucidating the impact of direct IL-10 signaling in T cells on CoB outcomes. We used a full-mismatch skin transplantation model where recipients had a T cell-restricted expression of a dominant negative IL-10 receptor (10R-DN), alongside anti-CD154 as CoB therapy. Unlike wild-type recipients, 10R-DN mice failed to benefit from CoB. This accelerated graft rejection correlated with increased accumulation of T cells producing TNF-α, IFN-γ, and IL-17. In vitro experiments indicated that while lack of IL-10 signaling did not change the ability of anti-CD154 to modulate alloreactive T cell proliferation, the absence of this pathway heightened T1 effector cell differentiation. Furthermore, deficiency of IL-10 signaling in T cells impaired Treg induction, a hallmark of anti-CD154 therapy. Overall, these findings unveil an important and novel role of IL-10 signaling in T cells that defines the success of CoB therapies and identifies a target pathway for obtaining robust immunoregulation.
PubMed: 38915537
DOI: 10.1101/2024.06.12.598652 -
Nature Communications Jun 2024Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish...
Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.
Topics: Animals; Bionics; Rats; Muscle, Skeletal; Feedback, Sensory; Proprioception; Ganglia, Spinal; Mechanoreceptors; Muscle Spindles; Male; Female; Touch; Skin
PubMed: 38914540
DOI: 10.1038/s41467-024-49580-8 -
Tissue Engineering and Regenerative... Jun 2024Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another....
BACKGROUND
Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging.
METHODS
In this study, we isolated and characterized adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of male Sprague Dawley rats. We assessed the in vitro differentiation of Ad-MSCs into epidermal progenitor cells (EPCs) using ascorbic acid and hydrocoritsone. Additionally, we induced skin aging in female Sprague Dawley rats via daily intradermal injection of D-galactose over a period of 8 weeks. Then we evaluated the therapeutic potential of intradermal transplantation of Ad-MSCs and conditioned media (CM) derived from differentiated EPCs in the D-galactose-induced aging rats. Morphological assessments, antioxidant assays, and histopathological examinations were performed to investigate the effects of the treatments.
RESULTS
Our findings revealed the significant capability of Ad-MSCs to differentiate into EPCs. Notably, compared to the group that received CM treatment, the Ad-MSCs-treated group exhibited a marked improvement in morphological appearance, antioxidant levels and histological features.
CONCLUSIONS
These results underscore the effectiveness of Ad-MSCs in restoring skin aging as a potential therapy for skin aging.
PubMed: 38913224
DOI: 10.1007/s13770-024-00643-3 -
Cureus Jun 2024Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem paraneoplastic disorder due to an underlying plasma cell...
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem paraneoplastic disorder due to an underlying plasma cell neoplasm, and its occurrence among HIV patients is extremely rare. The diagnosis of POEMS syndrome can be challenging in this context, particularly if its disabling polyneuropathy is misdiagnosed as neuropathy related to HIV. Herein, we report the case of a female patient with treated HIV who later developed POEMS syndrome. After a misdiagnosis of chronic inflammatory demyelinating polyneuropathy related to HIV and unsuccessful corticosteroids and cyclophosphamide therapies, the correct diagnosis of POEMS syndrome was made. The patient achieved significant hematological and neurological improvement after six cycles of lenalidomide. Autologous stem cell transplantation was then scheduled to prevent eventual relapses.
PubMed: 38912072
DOI: 10.7759/cureus.62820 -
Familial Cancer Jun 2024Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with...
Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with FA have an elevated risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. Hematopoietic cell transplantation (HCT) is the most effective treatment for FA related bone marrow failure but can increase the risk of cancer development. Information on benign tumors and NMSC is lacking in patients with FA. Our objective was to characterize patients with FA enrolled in the National Cancer Institute IBMFS Study who have experienced non-melanoma skin cancers (NMSC) and/or benign tumors (BT). A total of 200 patients diagnosed with FA were enrolled in the Institutional Review Board approved study "Etiologic Investigation of Cancer Susceptibility in IBMFS: A Natural History Study" (NCT00027274). Through medical records review, we identified 30 patients with at least one NMSC, either squamous or basal cell carcinoma, or benign tumor. The remaining 170 patients comprised the control group. Out of 200 patients, 12 had NMSC, 25 had benign tumors, with an age range of 11-64 and 0-56 years, respectively. The median age at HCT was 30.5 years for NMSC patients, 9 years for benign tumor patients, and 9.1 years for controls. The most common genotype observed was FANCA, followed by FANCC and FANCI. Benign tumors spanned diverse anatomical locations. Early onset NMSC in patients with FA compared to the general population emphasizes the need for consistent monitoring in patients with FA, while the diverse anatomical locations of benign tumors underscore the importance of comprehensive surveillance for timely interventions in managing symptomatology and heightened cancer risk.
PubMed: 38907138
DOI: 10.1007/s10689-024-00410-2