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1.
Mater Today Bio ; 27: 101123, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38988817

ABSTRACT

Ten-eleven translocation (TET) proteins orchestrate deoxyribonucleic acid (DNA) methylation-demethylation dynamics by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and are frequently inactivated in various cancers. Due to the significance of 5hmC as an epigenetic biomarker for cancer diagnosis, pathogenesis, and treatment, its rapid and precise quantification is essential. Here, we report a highly sensitive electrochemical method for quantifying genomic 5hmC using graphene sheets that were electrochemically exfoliated and functionalized with biotin and gold nanoparticles (Bt-AuNPs) through a single-step electrical method. The attachment of Bt-AuNPs to graphene enhances the specificity of 5hmC-containing DNA and augments the oxidation of 5hmC to 5-formylcytosine in DNA. When coupled to a gold electrode, the Bt-AuNP-graphene-based sensor exhibits exceptional sensitivity and specificity for detecting 5hmC, with a detection limit of 63.2 fM. Furthermore, our sensor exhibits a remarkable capacity to measure 5hmC levels across a range of biological samples, including preclinical mouse tissues with varying 5hmC levels due to either TET gene disruption or oncogenic transformation, as well as human prostate cancer cell lines. Therefore, our sensing strategy has substantial potential for cancer diagnostics and prognosis.

2.
Transplant Proc ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39079788

ABSTRACT

BACKGROUND: Simultaneous pancreas and kidney transplant (SPK) is the most common type of pancreas transplant performed worldwide. In contrast, there are a few drawbacks to pancreas after kidney transplant (PAK), such as the requirement for an additional operation, the immunologic risk, etc. SPK is the best option, but because of a lack of deceased donors and a lengthy waiting period, it is not always possible to use it. METHODS: From 2015 to 2022, we performed 23 SPKs and 21 PAKs at the Pusan National University Yangsan Hospital in Korea. We compared the findings of PAK and SPK conducted within the same time period. RESULTS: The waiting time for pancreatic graft was significantly shorter in the PAK than SPK group (345 days vs 1350 days, P ≤ .001). Throughout the monitoring period, just 1 pancreatic graft was lost in patients who underwent PAK, and the 7-year graft survival was 95%, with no statistically significant difference compared to SPK (90.3%, P = .600). Moreover, the graft survival of SPK or PAK was superior to that of pancreatic transplant alone (63.7%, P = .016). Only 1 pancreatic graft loss was a case of mortality with a functioning graft. No additional kidney transplant loss was observed in PAK recipients. There was no variation in creatinine levels between the pretransplant and posttransplant periods. There were 2 incidents of pancreatic graft and kidney graft rejection, respectively, but the grafts entirely recovered following rejection treatment. CONCLUSION: According to our experiences, PAK could be another best choice for individuals with diabetic end-stage renal disease, especially in cases where deceased donors were severely deficient but living donor kidney transplants were actively performed in countries like Korea.

3.
Int J Integr Care ; 24(2): 20, 2024.
Article in English | MEDLINE | ID: mdl-38828123

ABSTRACT

Introduction: Since 2019, the Korean government has implemented a pilot project for integrated care to encourage healthy aging of older adults. This study investigated the changes in hospitalization rates among older adults who participated in the integrated care pilot project. Methods: Administrative survey data collected from 13 local governments and the National Health Insurance Database were used in present study. The participants comprised 17,801 older adults who participated in the pilot project between August 01, 2019 and April 30, 2022 and 68,145 matched controls. A propensity score matching method was employed to select the control group, and this study employed difference-in-differences (DID) approach to examine variations in the hospitalization rate. Results: The DID analysis revealed that the odds ratio for rates of hospitalization among older adults who participated in the pilot project was 0.88 (95% confidence interval [CI] 0.84, 0.91) in comparison to control group. In specifically, as compared to the control group, the odds ratio for hospitalization rates among the pilot project's discharged patients was 0.17 (95% CI 0.15, 0.20). Although not statistically significant, the odds ratio of older adults who utilized LTCI services was 0.93 (95% CI 0.83, 1.05), and the odds ratio of older adults who applied for LTCI but were rejected or were intensive social care was 1.09 (95% CI 0.95, 1.26) compared to the comparison group. Discussion: The findings imply that the discharged patient group had greater medical demands than the other types, and it can be claimed that this is the group that may anticipate greater efficacy while using health services. In addition, the integrated care services provided by the pilot project have the effect of reducing unnecessary hospitalization such as social hospitalization. Conclusion: Participants in the integrated care pilot project showed a lower hospitalization rate than the older adults who did not participate in the project but had similar characteristics. In particular, the admission rate of discharged patients showed a sharp decline.

4.
Medicine (Baltimore) ; 103(26): e38694, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941432

ABSTRACT

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.


Subject(s)
Exploratory Behavior , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Schizophrenia , Humans , Schizophrenia/genetics , Male , Female , Republic of Korea/epidemiology , Pilot Projects , Adult , Middle Aged , Genetic Predisposition to Disease , Young Adult
5.
Exp Mol Med ; 56(7): 1479-1487, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38945955

ABSTRACT

The development of chemoresistance is a major challenge in the treatment of several types of cancers in clinical settings. Stemness and chemoresistance are the chief causes of poor clinical outcomes. In this context, we hypothesized that understanding the signaling pathways responsible for chemoresistance in cancers is crucial for the development of novel targeted therapies to overcome drug resistance. Among the aberrantly activated pathways, the PI3K-Akt/Wnt/ß-catenin signaling pathway is clinically implicated in malignancies such as colorectal cancer (CRC) and glioblastoma multiforme (GBM). Aberrant dysregulation of phospholipase D (PLD) has been implicated in several malignancies, and oncogenic activation of this pathway facilitates tumor proliferation, stemness, and chemoresistance. Crosstalk involving the PLD and Wnt/ß-catenin pathways promotes the progression of CRC and GBM and reduces the sensitivity of cancer cells to standard therapies. Notably, both pathways are tightly regulated and connected at multiple levels by upstream and downstream effectors. Thus, gaining deeper insights into the interactions between these pathways would help researchers discover unique therapeutic targets for the management of drug-resistant cancers. Here, we review the molecular mechanisms by which PLD signaling stimulates stemness and chemoresistance in CRC and GBM. Thus, the current review aims to address the importance of PLD as a central player coordinating cross-talk between the PI3K/Akt and Wnt/ß-catenin pathways and proposes the possibility of targeting these pathways to improve cancer therapy and overcome drug resistance.


Subject(s)
Drug Resistance, Neoplasm , Neoplastic Stem Cells , Phosphatidylinositol 3-Kinases , Phospholipase D , Proto-Oncogene Proteins c-akt , Wnt Signaling Pathway , Humans , Phospholipase D/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Animals , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Molecular Targeted Therapy
6.
Foods ; 13(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38790867

ABSTRACT

Yeast, crucial in beer production, holds great potential owing to its ability to transform into a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of the BSY residue (641.90 µg/mg) was higher than that of SC (553.52 µg/mg) and SB (591.56 µg/mg). The yields of alkali-extracted water-soluble polysaccharides were 33.62%, 40.76%, and 42.97% for BSY, SC, and SB, respectively, with BSY comprising a comparable proportion of water-soluble saccharides made with SC and SB, including 49.31% mannan and 20.18% ß-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential to act as an effective functional food material.

7.
Microorganisms ; 12(5)2024 May 10.
Article in English | MEDLINE | ID: mdl-38792793

ABSTRACT

The VITEK MS PRIME (bioMérieux, Marcy-l'Étoile, France), a newly developed matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside the VITEK PICKME pen (PICKME), offers easy sample preparation for bacteria and yeasts. The VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against MicroIDSys Elite (ASTA) results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO databases on 289 filamentous fungi against molecular sequencing. The concordance rates for species-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, and about 83.4-85.3% between the VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes' identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus versicolor, Exophiala xenobiotica, and Nannizzia gypsea, failed to be identified. The VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For filamentous fungi, combined use of the RUO database can be beneficial, especially for basidiomycetes.

8.
Sci Rep ; 14(1): 7979, 2024 04 05.
Article in English | MEDLINE | ID: mdl-38575634

ABSTRACT

In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0-1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1-11-year-old group. Conversely, the 12-19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.


Subject(s)
Dermatitis, Atopic , Adult , Adolescent , Humans , Aged , Infant, Newborn , Infant , Child, Preschool , Child , Young Adult , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/therapy , Dermatitis, Atopic/diagnosis , Prevalence , Cohort Studies , Retrospective Studies , Adrenal Cortex Hormones/therapeutic use , Republic of Korea/epidemiology , Severity of Illness Index , Treatment Outcome
10.
Australas J Dermatol ; 65(3): e13-e20, 2024 May.
Article in English | MEDLINE | ID: mdl-38288519

ABSTRACT

BACKGROUND/OBJECTIVES: Nail psoriasis, a subtype of psoriasis, can cause significant pain, disability, and reduced quality of life. Despite the established efficacy of anti-IL17 secukinumab in improving skin psoriasis, there is a lack of clinical trials focusing on nail psoriasis as primary endpoint. This study aims to investigate the efficacy of secukinumab in treating nail psoriasis in patients with moderate to severe psoriasis. METHODS: We prospectively recruited patients newly diagnosed with moderate to severe psoriasis in single centre from January 2021 to January 2022 who were treated with secukinumab. RESULTS: A total of 16 patients consisting of 9 males and 7 females were included. Their mean age was 38.88 ± 10.29 years. They had an average initial Nail Psoriasis Severity Index (NAPSI) score of 45.06 ± 20.39 and an average NAPSI score at 12 weeks of 8.94 ± 13.50, showing a significant (p < 0.05) decrease of NAPSI score after 12 weeks of secukinumab treatment. After 24 weeks of treatment, NAPSI score was decreased to 5.12 ± 8.52. CONCLUSION: Secukinumab rapidly improved nail psoriasis after 12 weeks of treatment, with further enhancement at 24 weeks, suggesting its potential as a potent therapeutic option for nail psoriasis.


Subject(s)
Antibodies, Monoclonal, Humanized , Nail Diseases , Psoriasis , Severity of Illness Index , Humans , Psoriasis/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Adult , Nail Diseases/drug therapy , Middle Aged , Follow-Up Studies , Prospective Studies , Treatment Outcome , Dermatologic Agents/therapeutic use
11.
Dermatology ; 240(2): 262-270, 2024.
Article in English | MEDLINE | ID: mdl-38228126

ABSTRACT

INTRODUCTION: As research on the role of the Th17/IL-23 pathway gains importance, the relationship between atopic dermatitis (AD) and psoriasis is becoming elucidated. OBJECTIVE: The objective of this study wasto evaluate whether AD and its severity affect the risk for psoriasis. METHODS: This retrospective population-based study used the database from the 2009 National Health Insurance Services-Health Screening Cohort in Korea. A total of 3,957,922 adult subjects were included and observed until 2018. The primary outcome was newly diagnosed psoriasis. RESULTS: After adjusting for possible confounding factors, the moderate-to-severe AD group had the highest hazard ratio (HR) for psoriasis (HR = 2.50; 95% confidence interval (CI), 2.40-2.61), followed by the mild AD group (HR = 2.31; 95% CI: 2.19-2.44) compared with the non-AD group during a median 8.11 ± 1.19 years of follow-up. LIMITATIONS: It is difficult to define AD, which is not standardized, using a claims database and exclude patients who were misdiagnosed with AD. CONCLUSION: Patients with severe AD showed an increased risk for psoriasis compared to controls, and the risk for psoriasis was increased according to AD severity. This suggests that psoriasis and AD could share inflammatory, immune, and genetic features.


Subject(s)
Dermatitis, Atopic , Psoriasis , Adult , Humans , Dermatitis, Atopic/diagnosis , Retrospective Studies , Psoriasis/diagnosis , Th17 Cells , Risk Factors
13.
J Cosmet Dermatol ; 23(1): 215-226, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37381171

ABSTRACT

BACKGROUND: The excessive production and accumulation of melanin in the epidermal skin layer can result in skin hyperpigmentation and darkening. Current technologies for regulating melanin are based on inhibiting melanin biosynthesis. They have low effectiveness and safety issues. AIMS: This study aimed to evaluate the potential role of Pediococcus acidilactici PMC48 as a probiotic strain in medicines and cosmetics for skin treatment. MATERIALS AND METHODS: Meanwhile, our research team has reported that P. acidilactici PMC48 strain isolated from sesame leaf kimchi can directly decompose the already synthesized melanin. It can also inhibit melanin biosynthesis. In the present study, we investigated the skin-whitening effect of this strain by arranging an 8-week clinical trial with 22 participants. PMC48 was applied to each participant's artificially UV-induced tanned skin in the clinical trial. Its whitening effect was investigated based on visual evaluation, skin brightness, and melanin index. RESULTS: PMC48 showed a significant effect on the artificially induced pigmented skin. The color intensity of the tanned skin was decreased by 47.647%, and skin brightness was increased by 8.098% after the treatment period. PMC48 also significantly decreased the melanin index by 11.818%, indicating its tyrosinase inhibition capacity. Also, PMC48 improved skin moisture content level by 20.943%. Additionally, 16S rRNA-based amplicon sequencing analysis showed a distinct increase in Lactobacillaceae in the skin by up to 11.2% at the family level without affecting other skin microbiota. Furthermore, it showed no toxicity in in vitro or in vivo analyses. DISCUSSION: These results indicate that P. acidilactici PMC48 is a promising probiotic strain that can be used to develop medicines and cosmetic products to solve skin-related problems. CONCLUSIONS: These results demonstrate that P. acidilactici PMC48 can be a potential probiotic for the cosmetic industry against different skin disorders.


Subject(s)
Cosmetics , Hyperpigmentation , Pediococcus acidilactici , Humans , Pediococcus acidilactici/genetics , Melanins , RNA, Ribosomal, 16S , Skin , Hyperpigmentation/drug therapy , Cosmetics/pharmacology
14.
J Korean Med Sci ; 38(49): e377, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38111280

ABSTRACT

BACKGROUND: Hormone replacement therapy (HRT) is used to relieve menopause symptoms, but has been reported to be associated with coronary heart disease and cancers in women. However, a link between HRT and psoriasis has yet to be established. The aim of this study was to determine the association between HRT and the risk of psoriasis. METHODS: We executed a nationwide population-based study. A total of 1,130,741 post-menopause women were enrolled in the national health care insurance database based on the enrollment criteria. The study population was classified into four groups based on the duration of the HRT, and the risk of psoriasis was analyzed. RESULTS: The incidence rates of psoriasis per 1,000 person-years were 3.36 and 4.09 in the no history of HRT and ≥ 5 years of HRT, respectively. After adjustment for age, smoking, alcohol intake, regular exercise, body mass index, diabetes mellitus, hypertension, and dyslipidemia, the most prolonged duration of the HRT group (≥ 5 years) exhibited significantly increased risk of developing psoriasis (hazard ratio, 1.22; 95% confidence interval, 1.16-1.29). CONCLUSION: We propose that HRT in post-menopausal women is associated with an increased likelihood of psoriasis development.


Subject(s)
Hormone Replacement Therapy , Menopause , Humans , Female , Child, Preschool , Cohort Studies , Hormone Replacement Therapy/adverse effects , Postmenopause , Smoking
16.
Int J Mol Sci ; 24(17)2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37686119

ABSTRACT

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.


Subject(s)
Biological Products , Psoriasis , Humans , Quality of Life , Psoriasis/drug therapy , Combined Modality Therapy , Skin
17.
Lab Med ; 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37706544

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the prognostic impact of variables, including thrombocytopenia and the amount of platelet transfusion, for predicting survival in venoarterial extracorporeal membrane oxygenation (ECMO) recipients. Additionally, we aimed to identify the predictors of increased transfusion requirement during venoarterial ECMO support. METHODS: All patients who received venoarterial ECMO between December 2008 and March 2020 were retrospectively analyzed. Univariate and multivariate Cox regressions were used to evaluate in-hospital mortality according to variables including thrombocytopenia and daily average of platelet concentrate transfusion. Stepwise multiple linear regression analysis was used to identify independent predictors for transfusion requirements. RESULTS: Analysis of 218 patients demonstrated severe thrombocytopenia as an independent predictor of in-hospital mortality (hazard ratio = 2.840, 95% CI: 1.593-5.063, P < .001), along with age, pre-ECMO cardiac arrest, and pH. In contrast, the amount of platelet transfusion was not associated with in-hospital mortality. Multiple variables, including the type of indication for ECMO were associated with transfusion requirements. CONCLUSION: Our findings identified severe thrombocytopenia as an independent prognostic factor of in-hospital mortality. However, daily average platelet transfusion was not associated with survival outcomes. Additionally, our study identified predictive variables of increased transfusion requirements.

18.
J Clin Lab Anal ; 37(15-16): e24961, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37694947

ABSTRACT

BACKGROUND: Endothelial cells are vital in the transplant immune system as semiprofessional antigen-presenting cells. Few studies have investigated the importance of anti-endothelin subtype A receptor (ETAR) antibodies in kidney transplantation. Here, we aimed to analyze the association between anti-angiotensin II type I receptor (AT1R) and anti-ETAR antibodies and the association between the presence of anti-endothelial antibodies and the risk of allograft rejection in kidney transplantation. METHODS: In total, 252 patients who underwent kidney transplantation were enrolled in this study. Antibodies for human leukocyte antigens (HLAs) and non-HLAs were analyzed immediately before transplantation. Patients were categorized based on the occurrence of antibody-mediated rejection (AMR) or T-cell-mediated rejection (TCMR) by 2017 Banff classification. All p-values were two-tailed, and statistical significance was set at p < 0.05. RESULTS: Patients with anti-AT1R antibodies had a 3.49-fold higher risk of TCMR than those without anti-AT1R antibodies. Patients with anti-ETAR antibodies had a 5.84-fold higher risk of AMR than those without anti-ETAR antibodies. The hazard ratio of AMR in patients with both HLA DSAs and anti-ETAR antibodies, relative to patients without anti-ETAR antibodies and HLA DSAs, was 32.85 (95% CI = 1.82-592.91). CONCLUSION: Our findings indicated that anti-ETAR antibodies are associated with AMR, and patients with both anti-ETAR antibodies and de novo HLA DSAs were at a high risk of AMR.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Endothelial Cells , Transplantation, Homologous , Antibodies , HLA Antigens , Graft Rejection , Allografts
19.
Transpl Immunol ; 80: 101901, 2023 10.
Article in English | MEDLINE | ID: mdl-37442212

ABSTRACT

INTRODUCTION: Autoantibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been previously associated with de novo donor-specific antibody (DSA) formation in lung transplantation. However, data regarding the clinical significance of AT1R-Ab in long-term graft function after lung transplantation are lacking. METHODS: Seventy-one patients who underwent lung transplantation between July 2016 and January 2020 were enrolled in this study. We examined the relationship between pre-transplant AT1R-Ab levels and graft function, clinical outcomes, and human leukocyte antigen (HLA) DSA levels during the first 3 years post-transplantation. RESULTS: Seventeen (23.9%) patients were AT1R-Ab-positive, and 54 (76.1%) were AT1R-Ab-negative. The median antibody value of the AT1R-Ab-positive group was 18 [18-22.5] U/mL, while that of the AT1R-Ab-negative group was 5.1 [3.5-8.0] U/mL (p < 0.001). There was no significant difference in the median acute cellular rejection (ACR) scores between the two groups (median [interquartile range] 1 [0.8-3] vs. 0.7 [0-1]; p = 0.145). However, there was a significant difference in the distribution of the ACR scores between the two groups (p = 0.015). Most (41.2%) patients in the pre-transplant AT1R-positive group scored above 1. The incidence of de novo DSA was also higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (52.9% vs. 20.4%, p = 0.009). The incidence of chronic lung allograft dysfunction (CLAD) within 3 years was significantly higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (58.3% vs. 11.8%; p < 0.001). In the multivariate Cox regression analysis, AT1R-Ab positivity (hazard ratio, 9.46; 95% confidence interval, 2.89-30.94; p < 0.001) was significantly associated with early CLAD. Furthermore, Kaplan-Meier analysis showed that AT1R-Ab-positive patients had a shorter survival time (χ2 = 39.62, p < 0.001). CONCLUSION: High AT1R-Ab levels in the pre-transplant serum of lung recipients were associated with the development of de novo HLA-DSA, ACR, early CLAD, and short survival.


Subject(s)
Receptor, Angiotensin, Type 1 , Transplant Recipients , Humans , Autoantibodies , Transplantation, Homologous , HLA Antigens , Graft Survival , Lung , Graft Rejection , Retrospective Studies
20.
Ann Lab Med ; 43(5): 470-476, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37080748

ABSTRACT

Background: The currently recommended pre-transfusion testing techniques for patients with autoantibodies are complex, time-consuming, and labor-intensive. Therefore, although the red blood cell (RBC) selection method using crossmatched RBC agglutination reaction grades (i.e., the "least incompatible" transfusion) is discouraged, many institutions still use it. We aimed to evaluate the effectiveness of this method combined with Rh subgroup phenotyping. Methods: We retrospectively investigated RBC transfusions from January 2019 to December 2021 in patients presenting as auto-control-positive via antibody identification (auto-control (+) group), where Rh subgroup phenotype-matched RBCs were selected based on the agglutination reaction grades of crossmatched units. For each study patient, an auto-control-negative patient was matched based on age, sex, department, and pre-transfusion Hb levels (auto-control (-) group). The mean Hb change per unit, transfusion-associated symptom/sign reports, and agglutination reaction grades upon crossmatching were analyzed. Results: In the auto-control (+) group, the Hb change per unit among different agglutination reaction grades of transfused RBCs and among different relative grades of transfused RBCs and crossmatching auto-controls was not significantly different (P=0.392 and P= 0.132, respectively). No significant difference was observed in Hb changes and transfusion-associated symptom/sign occurrence between the auto-control (+) and auto-control (-) groups (P=0.121 and P=0.822, respectively). In addition, no definite evidence of hemolysis in the auto-control (+) group was observed in the medical record review. Conclusions: Together with Rh subgroup phenotyping, selecting the RBC unit with the lowest agglutination reaction grade upon crossmatching does not adversely affect transfusion efficiency.


Subject(s)
Autoantibodies , Transfusion Reaction , Humans , Retrospective Studies , Tertiary Care Centers , Blood Grouping and Crossmatching , Agglutination
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