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Transplant International : Official... 2024The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be...
The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved for 24 h with either SNMP ( = 3) or SCS ( = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.
Topics: Animals; Organ Preservation; Perfusion; Swine; Vascularized Composite Allotransplantation; Graft Survival; Hindlimb; Composite Tissue Allografts; Models, Animal; Transplantation, Homologous; Allografts
PubMed: 38813393
DOI: 10.3389/ti.2024.12338 -
Clinical Kidney Journal May 2024hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a...
BACKGROUND
hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression.
METHODS
Single-center retrospective analysis of adult kidney transplant recipients between 1 January 2010 and 31 December 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg.
RESULTS
Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the 3 years following transplantation was associated with an increased risk of skin cancer ( = 0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26-5.15, = 0.007). There was a higher rate of basal cell carcinoma with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06-6.43, = 0.037) and (HR 3.03, 95%CI 1.22-7.55, = 0.017, respectively). However, no significant association was observed between HCTZ exposure and squamous cell carcinoma.
CONCLUSIONS
These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased ultraviolet exposure area.
PubMed: 38812910
DOI: 10.1093/ckj/sfae126 -
Frontiers in Allergy 2024The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously... (Review)
Review
The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.
PubMed: 38812719
DOI: 10.3389/falgy.2024.1404735 -
Journal of Pharmaceutical Analysis May 2024The "gut-skin" axis has been proved and is considered as a novel therapy for the prevention of skin aging. The antioxidant efficacy of oligomannonic acid (MAOS) make it...
The "gut-skin" axis has been proved and is considered as a novel therapy for the prevention of skin aging. The antioxidant efficacy of oligomannonic acid (MAOS) make it an intriguing target for use to improve skin aging. The present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in mice. The data indicated the skin aging phenotypes, oxidative stress, skin mitochondrial dysfunction, and intestinal dysbiosis (especially the butyrate and HIF-1α levels decreased) in aging mice. Similarly, fecal microbiota transplantation (FMT) from aging mice rebuild the aging-like phenotypes. Further, we demonstrated MAOS-mediated colonic butyrate-HIF-1α axis homeostasis promoted the entry of butyrate into the skin, upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1α/mitophagy loop in skin of mice. Overall, our study offered a better insights of the effectiveness of alginate oligosaccharides (AOS), promised to become a personalized targeted therapeutic agents, on gut-skin axis disorder inducing skin aging.
PubMed: 38807706
DOI: 10.1016/j.jpha.2023.12.001 -
Heliyon May 2024Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent...
BACKGROUND
Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC.
MATERIALS AND METHODS
We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs.
RESULTS
Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included and . We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the gene.
CONCLUSION
The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.
PubMed: 38803922
DOI: 10.1016/j.heliyon.2024.e31194 -
Cureus Apr 2024Basal cell carcinoma is a skin cancer with a more benign clinical course, compared to other skin cancers. However, when left neglected, it can cause serious morbidity...
Basal cell carcinoma is a skin cancer with a more benign clinical course, compared to other skin cancers. However, when left neglected, it can cause serious morbidity and mortality. A basal cell carcinoma larger than 5 cm is defined as giant. Common causes of these carcinomas are negligence, immunosuppression, low socioeconomic status, physical or mental dysfunction, light exposure, exposure to radiation, existence of a previous lesion, recurrence after treatment, and aggressive histologic pattern. In some cases, giant basal cell carcinoma has been described to infiltrate multiple intracranial structures and to be associated with distant metastasis. Herein, we present a case of a giant basal cell carcinoma on the temporary scalp of a renal transplant recipient with depression.
PubMed: 38800195
DOI: 10.7759/cureus.58956 -
Frontiers in Immunology 2024Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA)....
Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11bCD11c), mature (CD11bCD11cMHCII) and active (CD11bCD11cCD40) DCs and cDC2 subset (CD11bCD11c MHCII) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4IL-17) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.
Topics: Animals; Dendritic Cells; Skin Transplantation; Mice; Hindlimb; Graft Rejection; Mice, Inbred C57BL; Mice, Inbred BALB C; Composite Tissue Allografts; Vascularized Composite Allotransplantation; CD8-Positive T-Lymphocytes; Male; Tissue Donors; Skin
PubMed: 38799435
DOI: 10.3389/fimmu.2024.1395945 -
Frontiers in Immunology 2024Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by high immunogenicity which makes it particularly suitable for immune checkpoint inhibitors...
BACKGROUND
Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by high immunogenicity which makes it particularly suitable for immune checkpoint inhibitors (ICIs) treatment.
CASE PRESENTATION
We report the case of a 53-year-old man with metastatic DM successfully treated with the combination of anti-CTLA-4 and anti-PD-1 antibodies, who developed serious immune-related adverse events (irAEs). The primary tumor was characterized by absent PD-L1 expression and no-brisk lymphocytes infiltration. NGS showed absence of BRAF mutation, a high tumor mutational burden, and an UV-induced DNA damage signature. Metastatic lesions regressed rapidly after few cycles of ICIs until complete response, however the patient developed serious irAEs including hypothyroidism, adrenal deficiency, and acute interstitial nephritis which led to the definitive suspension of treatment. Currently, the patient has normal renal functionality and no disease relapse after 26 months from starting immunotherapy, and after 9 months from its definitive suspension.
CONCLUSION
Efficacy and toxicity are two sides of the same coin of high sensitivity to ICIs in DM. For this reason, these patients should be closely monitored during ICIs therapy to promptly identify serious side effects and to correctly manage them.
Topics: Humans; Male; Melanoma; Middle Aged; Immune Checkpoint Inhibitors; Immunotherapy; Skin Neoplasms; CTLA-4 Antigen; Treatment Outcome; Programmed Cell Death 1 Receptor
PubMed: 38799429
DOI: 10.3389/fimmu.2024.1369531 -
Journal of Medical Case Reports May 2024All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous... (Review)
Review
A rare incidence of severe dermatological toxicities triggered by concomitant administration of all-trans retinoic acid and triazole antifungal in patients with acute promyelocytic leukemia: a case series and review of the literature.
BACKGROUND
All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous xerosis, rash, and pruritus are well reported, ATRA associated severe dermatological toxicities are extremely rare. ATRA is primary metabolized by cytochrome P450 (CYP450) enzyme system, and triazole antifungals are notorious for their strong inhibitory effect on CYP450.
CASE PRESENTATION
Three Asian APL patients experienced rare ATRA-induced severe dermatological toxicities: exfoliative dermatitis (ED) in cases 1 and 2, and necrotic scrotal ulceration in case 3. Both case 1 (33-year-old female), and case 2 (28-year-old male) landed in emergency department with dehydration, generalized skin erythema and xerosis during their induction chemotherapy. Both of these patients also developed invasive aspergillosis and required concomitant triazole antifungals during their chemotherapy. For ED, intravenous fluids and broad-spectrum antibiotics were started along with application of local emollients to prevent transdermal water loss. Although their general condition improved but skin exfoliation continued with complete desquamation of palms and soles. Dermatology was consulted, and clinical diagnosis of ED was established. Discontinuation of ATRA resulted in complete resolution of ED. Case 3 (15-year-old boy) reported two blackish mildly tender scrotal lesions during induction chemotherapy. He also had mucocutaneous candidiasis at presentation and was kept on triazole antifungal. Local bacterial & fungal cultures, and serological testing for herpes simplex virus were reported negative. Despite adequate local care and optimal antibiotic support, his lesions persisted, and improved only after temporary discontinuation of ATRA. After a thorough literature review and considering the temporal association of cutaneous toxicities with triazole antifungals, we speculate that the concomitant use of triazole antifungals inhibited the hepatic metabolism of ATRA, resulting in higher serum ATRA concentration, and markedly accentuated cutaneous toxicities in our patients.
CONCLUSION
By highlighting this crucial pharmacokinetic interaction, we want to caution the fellow oncologists to be mindful of the inhibitory effect of triazole antifungals on CYP450. We propose using a non-myelosuppressive combination of ATRA and arsenic trioxide for management of APL hence, obliterating the need of prophylactic antifungals. However, in the event of invasive fungal infection (IFI), we suggest using alternative class of antifungals.
Topics: Humans; Leukemia, Promyelocytic, Acute; Male; Antifungal Agents; Female; Tretinoin; Adult; Triazoles; Antineoplastic Agents; Aspergillosis; Drug Eruptions
PubMed: 38797854
DOI: 10.1186/s13256-024-04577-1 -
Biomedical Journal May 2024After transplantation of allogeneic tissues and organs, recognition by recipient T cells of donor MHC molecules initiates the pro-inflammatory adaptive immune response...
After transplantation of allogeneic tissues and organs, recognition by recipient T cells of donor MHC molecules initiates the pro-inflammatory adaptive immune response leading to allograft rejection. T cell allorecognition has long been known to be mediated via two distinct pathways: the direct pathway in which T cells recognize intact allogeneic MHC molecules displayed on donor cells and the indirect pathway whereby T cells recognize donor MHC peptides processed and presented by recipient antigen-presenting cells (APCs). It is believed that direct allorecognition is the driving force behind early acute allograft rejection while indirect allorecognition is involved in chronic allograft rejection, a progressive condition characterized by graft vasculopathy and tissue fibrosis. Recently, we and others have reported that after transplantation of allogeneic skin and organs, donor MHC molecules are transferred from donor cells to the host's APCs via trogocytosis or extracellular vesicles. Recipient APCs having captured donor MHC molecules can either present them to T cells in the intact form on their surface (semi-direct pathway) or the form of peptides bound to self-MHC molecules (indirect pathway). The present article provides an overview of recent studies evaluating the role of intercellular exchange of MHC molecules in T cell alloimmunity and its contribution to allograft rejection and tolerance.
PubMed: 38797478
DOI: 10.1016/j.bj.2024.100749