Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Backgruound: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.

Association between heat and hospital admissions in people with disabilities in South Korea: a nationwide, case-crossover study.

Background: Despite extensive findings on the hazardous impacts of environmental heat exposure, little is known about the effect on people with disabilities. This study aimed to estimate the association between environmental heat exposure and emergency department admissions for people with disabilities compared with people without disabilities.

Methods: In this nationwide, case-crossover study, we linked data on emergency department admissions (cases) for any cause in the warm season in South Korea from the Korean National Health Insurance Service (NHIS)-National Sample Cohort database (a nationally representative database of 1 million systematically sampled beneficiaries covering all ages) from Jan 1, 2002, to Dec 31, 2019, and short-term daily mean temperature exposure (measured via Google Earth Engine at a 9 km spatial grid, aggregated to district).

Biological response of nonhuman primates to controlled levels of acute blood loss.

Introduction: The global shortage of human blood for medical use has prompted the development of alternative blood sources. Nonhuman primates (NHPs) are commonly used owing to their physiological similarities to humans. The objective of the current study was to establish a controlled-blood-loss model in NHPs to explore their clinical and biological responses.

A Comparison Between ; and ; Pig Kidneys Transplanted in Nonhuman Primates.

Because there is a shortage of donor kidneys, researchers are exploring the possibility of using genetically modified pig kidneys for transplantation. Approaches involving knockout of carbohydrate genes or knockin of protective proteins have been attempted to determine the best gene modifications. In this study, we utilized ; and ; pigs for transplantation in nonhuman primates (NHPs).

Initial investigation on the feasibility of porcine red blood cells from genetically modified pigs as an alternative to human red blood cells for transfusion.

The decline in blood donation rates and the ongoing shortage of blood products pose significant challenges to medical societies. One potential solution is to use porcine red blood cells (pRBCs) from genetically modified pigs as an alternative to human red blood cells (hRBCs). However, adverse immunological reactions remain a significant obstacle to their use.

Comparative transcriptome analysis between long- and short-term survival after pig-to-monkey cardiac xenotransplantation reveals differential heart failure development.

Cardiac xenotransplantation is the potential treatment for end-stage heart failure, but the allogenic organ supply needs to catch up to clinical demand. Therefore, genetically-modified porcine heart xenotransplantation could be a potential alternative. So far, pig-to-monkey heart xenografts have been studied using multi-transgenic pigs, indicating various survival periods.

Recent trends in perioperative blood transfusion during elective kidney transplantation.

Background: Accurately predicting the demand for blood transfusions is crucial for blood banks. Given the potential for emergency situations, it is imperative that blood banks maintain a sufficient inventory of blood products. In this study, we examined the use of perioperative transfusions in patients undergoing elective kidney transplants.

Impact of the COVID-19 Pandemic on the Usage of Blood for Transfusions: A 2-Year Experience from a Tertiary Center in Korea.

The coronavirus disease (COVID-19) outbreak affected the utilization and management of blood products in hospitals. Blood shortages occurred owing to social distancing policies and reduction in blood donors. However, only a few studies examined whether these changes affected blood usage and transfusion patterns.

Clinical Applicability of Automated Hematology Analyzer Research Parameters for Disease Diagnosis: a Reference Interval Study.

Background: We established reference intervals for research parameters of complete blood cell count and examined their usefulness for diagnosing certain diseases.

Methods: Reference intervals for 26 basic and 38 research parameters were established for 3,457 and 1,325 men and 2,742 and 830 women aged 20 - 59 and ≥ 60 years, respectively. Research parameter values for patients with iron deficiency anemia (IDA), appendicitis, sepsis, and myelodysplastic syndromes (MDS) were compared against gender- and age-matched reference values.

Treatment strategies for Lennox-Gastaut syndrome: outcomes of multimodal treatment approaches.

Background: Multimodal treatment approaches are often considered for patients with Lennox-Gastaut syndrome (LGS). Creating an algorithm that can guide healthcare providers in selecting treatment options for patients with LGS remains a challenge. Herein, we assessed the long-term seizure-free and neurodevelopmental outcomes of stepwise multimodal treatment in patients with LGS.

Effect of Factor H on Complement Alternative Pathway Activation in Human Serum Remains on Porcine Cells Lacking -Glycolylneuraminic Acid.

Background: Triple knockout (TKO) donor pigs lacking alpha-1,3-galactose (Gal), -glycolylneuraminic acid (Neu5Gc), and Sd(a) expressions were developed to improve the clinical success of xenotransplantation. Neu5Gc, a sialic acid expressed on cell surfaces, recruits factor H to protect cells from attack by the complement system. Lack of Neu5Gc expression may cause unwanted complement activation, abrogating the potential benefit of gene-modified donor pigs.

Early Interferon-Gamma Response in Nonhuman Primate Recipients of Solid-Organ Xenotransplantation.

Background: To understand changes in biological responses in nonhuman primate (NHP) recipients of xenotransplantation (XTP), we retrospectively investigated chronological changes in cytokine profiles of NHP recipients after solid-organ XTP.

Methods: Plasma samples were collected from 7 NHP recipients of pig heart or kidney XTP with α-1,3-galactosyltransferase gene knockout (GTKO) under anti-CD154-based immune suppression at the following time points: immediately before; 2 hours, 3 days, and 7 days after XTP; and weekly thereafter until the graft failed. The plasma levels of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, IL-12p70, IL-8, IL-10, IL-15, tumor necrosis factor, interferon gamma (IFN-γ), D-dimer, C3a, and histone-complexed DNA fragments.

Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing.

Introduction: We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time.

Methods: Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets.

Results: Clonal IGH and IGK rearrangements were observed in 74.

A comparison of the analysis of 3 types of body fluids using the XN-350 hematology analyzer versus light microscopy assessment.

We evaluated the capacity of the XN-350 instrument to analyze 3 different types of body fluid samples under "body fluid mode."The performance of XN-350 was evaluated in terms of precision, carryover, limit of blank, limit of detection, limit of quantification, and linearity. Cell enumeration and differential data produced by the XN-350 were compared to manual chamber counting results in 63 cerebrospinal fluid (CSF), 51 ascitic fluid, and 51 pleural fluid (PF) samples.

Immunoglobulin M and Immunoglobulin G Subclass Distribution of Anti-galactose-Alpha-1,3-Galactose and Anti-N-Glycolylneuraminic Acid Antibodies in Healthy Korean Adults.

Background: Human preformed antibodies (Abs), anti-galactose-alpha-1,3-galactose (Gal) and anti-N-glycolylneuraminic acid (Neu5Gc), can react with porcine antigens of wild-type pigs. To provide basic population data of the Abs for potential application in clinical xenotransplantation, we developed enzyme-linked immunosorbent assay methods and investigated the serum titers of anti-Gal and anti-Neu5Gc Abs, including immunoglobulin (Ig) M and IgG along with its subclasses, in humans.

Methods: Anti-Gal and anti-Neu5Gc Abs serum titers were measured in 380 healthy Korean adults using the in-house enzyme-linked immunosorbent assays.

Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms.

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation).

Long-term porcine islet graft survival in diabetic non-human primates treated with clinically available immunosuppressants.

Background: Although pancreatic islet transplantation is becoming an effective therapeutic option for patients with type 1 diabetes (T1D) who suffer from a substantially impaired awareness of hypoglycemia, its application is limited due to the lack of donors. Thus, pig-to-human islet xenotransplantation has been regarded as a promising alternative due to the unlimited number of "donor organs." Long-term xenogeneic islet graft survival in pig-to-non-human primate (NHP) models has mainly been achieved by administering the anti-CD154 mAb-based immunosuppressant regimen.

Establishment of sex-specific reference intervals for automated haematology analyser-delivered research parameters in healthy Korean adults: a retrospective database review.

Objectives: Automated haematology analysers measure various parameters of relevance to clinical research along with routine complete blood count (CBC)-related components. We aimed to establish ethnicity-specific and sex-specific reference intervals for 26 research-specific parameters as well as 18 routinely reported components using a large cohort of healthy Korean adults. The necessity of requiring separate sex-specific reference intervals for each parameter was also examined.

Tolerability of Alternative Dosing Schedules for Sunitinib: A Systematic Review and Meta-Analysis.

Purpose: The standard schedule for sunitinib treatment is 4 weeks on and 2 weeks off (4/2) in first-line treatment for metastatic renal cell carcinoma (mRCC). Schedule modifications, including 2 weeks on and 1 week off (2/1), appear to reduce the total number of treatment-related adverse events (TRAEs) without compromising efficacy. Even though TRAEs can qualitatively differ from each other, it is not clear as to what effects a 2/1 schedule has on individual TRAEs.

Immature platelet fraction: A useful marker for identifying the cause of thrombocytopenia and predicting platelet recovery.

Introduction: The assessment of bone marrow thrombopoietic activity in patients with thrombocytopenia is necessary to achieve an accurate diagnosis and administer effective treatment. We evaluated the discriminatory power of the immature platelet fraction (IPF) in differentiating hyperdestructive/consumptive thrombocytopenia from hypoproductive thrombocytopenia and its potential use as a predictive marker for platelet recovery.

Methods: In this observational study, platelet indices, including IPF, were measured in 105 healthy individuals, 27 patients with hyperdestructive/consumptive thrombocytopenia (all with immune thrombocytopenic purpura [ITP]), and 35 patients with hypoproductive thrombocytopenia (5 with aplastic anemia and 30 with cancer who were undergoing chemotherapy) using a Sysmex XN-3000 hematology analyzer.

Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study.

Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects.

Plasma vs. serum in circulating tumor DNA measurement: characterization by DNA fragment sizing and digital droplet polymerase chain reaction.

Background Choosing the specimen type is the first step of the pre-analytical process. Previous reports suggested plasma as the optimal specimen for circulating tumor DNA (ctDNA) analysis. However, head-to-head comparisons between plasma and serum using platforms with high analytical sensitivity, such as droplet digital polymerase chain reaction (ddPCR), are limited, and several recent studies have supported the clinical utility of serum-derived ctDNA.