Mycophenolate mofetil (MMF) is usually prescribed with a reduced fixed dose in Asian kidney transplant recipients (KTRs). However, the clinical efficacy and safety of the fixed dose have not yet been investigated via therapeutic drug monitoring. We evaluated whether reduced fixed-dose MMF is an optimal dosing strategy to achieve the therapeutic target of mycophenolic acid (MPA) exposure in Korean KTRs. Methods: This open-label, prospective study enrolled 50 de novo KTRs prescribed with tacrolimus, corticosteroid, and fixed-dose MMF (1.0–1.5 g/day). The trough level (C0) and area under the curve (AUC0–12 hr) of MPA were measured at 1 and 24 weeks after kidney transplantation (KT). The relationship of body weight (BW)-adjusted MMF dose with MPA C0 and MPA AUC0–12 hr was assessed using linear regression analysis. Results: The initial fixed dose of MMF of 1.44 ± 0.16 g/day was adjusted in 24 patients (48.0%) and then reduced to a mean dose of 1.19 ± 0.31 g/day at 24 weeks after KT. Most patients (≥84.0%) attained the minimum required MPA C0 of 1.0 μg/mL and MPA AUC0–12 hr of 30 μg × hr/mL at 1 and 24 weeks. The BW-adjusted MMF dose demonstrated significant positive correlations with MPA C0 and MPA AUC0– 12 hr at 1 and 24 weeks after KT. Moreover, 14 patients (28.0%) reported MPA-related adverse events that were predictable based on MPA AUC0–12 hr (cutoff level, 46.4 μg × hr/mL). Conclusion: The current reduced fixed-dose MMF strategy can help achieve the therapeutic target of MPA exposure in tacrolimus- treated Korean KTRs during the early posttransplant period.

The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

Cytoreductive nephrectomy (CN) has long been the standard of care for patients with metastatic renal cell carcinoma (mRCC) since 2 clinical trials revealed its role during the cytokines era. With discovery of novel and effective drugs, such as vascular endothelial growth factor-targeted therapies, the role of CN started to be challenged. The 2 recent prospective randomized trials Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) and Immediate Surgery or Surgery After Sunitinib in Treating Patients with Metastatic Kidney Cancer trial (SURTIME) have changed the therapy paradigm for patients with mRCC. The CARMENA trial was performed to reveal whether CN is required in the targeted therapy, whereas SURTIME evaluated whether initial sunitinib can aid in the selection of patients who are most likely to benefit from subsequent CN or identify patients with innate resistance to targeted therapy. These trials suggest that CN does not provide a survival benefit for patients with poor‑risk disease. Especially, current evolutions in systemic therapies have demonstrated improved oncological outcomes from immunotherapy (IO) such as immune checkpoint inhibitor, particularly in its combination or combination with tyrosine kinase inhibitor. Accordingly, the role of CN continues to be questioned. Taken together, these findings reinforce the concept that the ultimate impact of CN on oncologic outcomes of mRCC patients in the era of IO still needs further investigation to represent a key for unmet clinical need.

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5Especific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry.Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

Cis-AB and B(A) alleles encode an ABO enzyme with dual A and B glycosyltransferase activity. Although globally rare, the cis-AB phenotype is found relatively often in Korean, Japanese, and Chinese populations. Cases of the B(A) allele have been reported mostly in the Chinese population. Forward typing performed in a Cambodian woman with an ABO discrepancy demonstrated a strong reaction with anti-A and anti-B reagents, while there was no reaction with lectin anti-A 1. The anti-A 1 antibody was detected in reverse typing. Through ABO gene sequence analyses of exons 6 and 7, one of the alleles was identified as ABO*B.01. In contrast, the other allele harboring a c.803G＞C substitution was either ABO*cisAB.05 or ABO*BA.06 allele. The ABO*cisAB.05 and ABO*BA.06 alleles remain indistinguishable despite routine serological testing and ABO genotyping. To the best of the author’s knowledge, this is the first case report of these variants discovered in a Cambodian individual residing in Korea.

Cis-AB and B(A) alleles encode an ABO enzyme with dual A and B glycosyltransferase activity. Although globally rare, the cis-AB phenotype is found relatively often in Korean, Japanese, and Chinese populations. Cases of the B(A) allele have been reported mostly in the Chinese population. Forward typing performed in a Cambodian woman with an ABO discrepancy demonstrated a strong reaction with anti-A and anti-B reagents, while there was no reaction with lectin anti-A 1. The anti-A 1 antibody was detected in reverse typing. Through ABO gene sequence analyses of exons 6 and 7, one of the alleles was identified as ABO*B.01. In contrast, the other allele harboring a c.803G＞C substitution was either ABO*cisAB.05 or ABO*BA.06 allele. The ABO*cisAB.05 and ABO*BA.06 alleles remain indistinguishable despite routine serological testing and ABO genotyping. To the best of the author’s knowledge, this is the first case report of these variants discovered in a Cambodian individual residing in Korea.

Weak D type 102 allele (RHD*01W.102) carrying a missense variant (c.73A＞T, p.Ile25Phe) in exon 1 of the RHD has not been reported in Koreans to date. This is the first report of the weak D type 102 allele in the Korean population. The proposita, a 35-year-old woman, showed a serological weak D phenotype in routine RhD typing. Sequencing of all 10 RHD exons and zygosity testing targeting the hybrid Rhesus box revealed this proposita to harbor the weak D type 102 allele, as well as an RHD deletion (RHD*01W.102/RHD*01N.01). Family studies showed that the weak D type 102 allele was also present in her father and older brother (both assumed to be RHD*01W.102/RHD*01) but not in her mother and oldest brother (both assumed to be RHD*01/RHD*01N.01). In silico analysis of the replacement of isoleucine by phenylalanine at position 25 was done with PolyPhen-2, SIFT, and PROVEAN. While PolyPhen-2 predicted the variant as benign, SIFT and PROVEAN predicted it as damaging and deleterious, respectively, suggesting RHD c.73A>T (I25F) as the cause of serologic weak D phenotype. This patient should be treated as D-negative, when transfusion is needed.

Antibodies to high-incidence red blood cell antigens should be considered if panagglutination reactions are noted in all panel cells, and negative reactions to autologous red blood cells are detected on antibody screening and identification tests. In Korea, most of those antibodies are identified through international reference laboratories. To prevent a hemolytic transfusion reaction, antigen-negative red cells should be provided for those patients who have antibodies to red cell antigens. However, this is nearly impossible when the antibody has specificity to high-incidence red cell antigen. In those cases, transfusion of autologous blood, cryopreserved rare blood and the least incompatible blood components can be considered. In the case of surgery, acute normovolemic hemodilution or intraoperative blood salvage can also be considered. For the patients who have antibodies to high-incidence red cell antigens, it should be discussed to set up a national reference laboratory to quickly identify antibody specificities, and to consider establishing rare blood donor registry and frozen rare blood storage/supply system. This article reviews characteristics of antibodies to high-incidence antigens found in Koreans and also the transfusion experiences of those patients based on literature.
Antibodies ; Antibody Specificity ; Blood Donors ; Erythrocytes ; Hemodilution ; Humans ; Isoantibodies ; Korea ; Mass Screening ; Operative Blood Salvage ; Sensitivity and Specificity ; Transfusion Reaction

BACKGROUND: Infection, one of the complications associated with procedures, can cause fatal outcomes for patients. Although the local anesthetic agent we use is less susceptible to infection due to its antibacterial action, we performed this study to check the change in the antibacterial effect of lidocaine in various clinical conditions. METHODS: After exposing lidocaine to five contaminated environments, we checked on whether the bacteria could be cultured in blood agar plate (BAP) media. In each contaminated environment, lidocaine was exposed for 4 h (n = 9) and 8 h (n = 9), and the results were compared. Lidocaine was swabbed with chlorhexidine (group A), brought into contact with saliva (group B), skin (group C), an operating room floor and an outpatient room floor (group D), operating room air for 24 h (group A-a), and outpatient room air for 24 h (group A-b). After exposure, the culture was initiated. RESULTS: In 2 of 9 BAP media where lidocaine was exposed to saliva (group B) for 8 h, growth of a colony was observed. In gram staining, it was found to be Streptococcus viridans. No bacteria were found in any other groups. CONCLUSIONS: Though lidocaine has strong antibacterial activity, it has been found that long-term exposure to a contaminated environment reduces its antibacterial activity and that drug contamination can be heavily affected not only by environmental but also human effects. Therefore, the use of aseptic drugs is necessary, and stopping the reuse of the drug is a way to prevent complications, including infection.
Agar ; Bacteria ; Chlorhexidine ; Drug Contamination ; Fatal Outcome ; Humans ; Lidocaine ; Operating Rooms ; Outpatients ; Saliva ; Skin ; Viridans Streptococci