Perioperative glucose monitoring with continuous glucose monitors identifies risk factors for post-transplant diabetes mellitus in kidney transplant recipients.

Post-transplantation diabetes mellitus (PTDM) negatively affects graft and patient survival after kidney transplantation (KT). This prospective study used continuous glucose monitoring (CGM) to evaluate perioperative blood glucose dynamics, identify PTDM risk factors, and compare predictive accuracy with capillary blood glucose monitoring (CBGM) in 60 non-diabetic living-donor KT recipients. Patients underwent 2-week pre- and postoperative CGM, including routine CBGM during their in-hospital stays. PTDM-related risk factors and glucose profiles were analyzed with postoperative CGM and CBG. PTDM developed in 14 (23.3%) patients and was associated with older age, male sex, higher baseline HbA1c, high-density lipoprotein cholesterol, and 3-month cumulative tacrolimus exposure levels. Male sex and postoperative time above the range (TAR) of 180 mg/dL by CGM were PTDM-related risk factors in the multivariate analysis. For predictive power, the CGM model with postoperative glucose profiles exhibited higher accuracy compared with the CBGM model (areas under the curves of 0.916, and 0.865, respectively). Therefore, we found that male patients with a higher postoperative TAR of 180 mg/dL have an increased risk of PTDM. Postoperative CGM provides detailed glucose dynamics and demonstrates superior predictive potential for PTDM than CBGM.

The role of artificial intelligence measured preoperative kidney volume in predicting kidney function loss in elderly kidney donors: A multicenter cohort study.

BACKGROUND: The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors. MATERIALS METHODS: A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model. RESULTS: A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76 mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001). CONCLUSION: This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.

The Impact of Simulator Training of Vascular Anastomosis and Video Assessment for Surgical Residents.

BACKGROUND: The rapid increase of minimally invasive surgery and the shortened training period for surgical residents has resulted in limited opportunities to acquire proficiency in open surgical techniques, such as vascular anastomosis. However, vascular anastomosis remains an essential skill in every surgery for bleeding control. This study aimed to validate the effectiveness of surgical education model for vascular anastomosis and assess the impact on the comprehension, skill, and confidence of surgical residents in performing vascular anastomosis. METHODS: A total of 21 surgical residents with first to third years of experience at Seoul National University Hospital participated in a 4-week vascular anastomosis training program. The program included an educational lecture and the performance of an end-to-side anastomosis on a procedural model, with evaluations being conducted using the Objective Structured Assessment of Technical Skills (OSATS) and the End-Product Rating Score (EPRS) in pretraining and posttraining surveys. RESULTS: Significant improvement was observed in the OSATS score (from 9.22 ± 2.4 in week 1 to 12.87 ± 3.1 in week 4; P < 0.001) and the EPRS score (from 12.47 ± 4.1 in week 1 to 17.57 ± 2.2 in week 4; P < 0.001). Additionally, the surgical performance time significantly decreased from 20.99 ± 4.6 min to 16.33 ± 4.2 min (P = 0.019) CONCLUSIONS: Simulator training of in vitro vascular anastomosis, when accompanied by expert-led instruction, can effectively enhance the surgical proficiency, confidence, and overall surgical outcomes of residents, as inferred from the observed improvements in OSATS and EPRS scores. The results suggest that integration of this training model into surgical curricula could be a promising strategy for enhancing vascular surgical training.

Effects of Ulmus macrocarpa Extract and Catechin 7-O-ß-D-apiofuranoside on Muscle Loss and Muscle Atrophy in C2C12 Murine Skeletal Muscle Cells.

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-ß-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-ß-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.

Comprehensive analysis of nationwide anticancer drug-related complications in Korea: incidence, types, and cancer-specific considerations in contemporary oncology.

Background: The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking. Objectives: This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea. Design: Retrospective cohort study. Methods: We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects. Result: We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6-12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash. Conclusion: This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement.

Cysteine as an Innovative Biomarker for Kidney Injury.

BACKGROUND: Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. METHODS: We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. RESULTS: This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. CONCLUSIONS: If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.

A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients.

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.

The Impact of Ulmus macrocarpa Extracts on a Model of Sarcopenia-Induced C57BL/6 Mice.

Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.

Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study.

BACKGROUND: The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation. MATERIALS AND METHODS: We conducted a retrospective cohort study involving 11,868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting. RESULTS: Tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were: 0.69 (95% CI 0.55-0.85, P<0.001) for 5.0-5.9 ng/mL; 0.81 (95% CI 0.67-0.98, P=0.033) for 6.0-6.9 ng/mL; and 0.73 (95% CI 0.60-0.89, P=0.002) for 7.0-7.9 ng/mL (compared to levels ≥8.0 ng/mL). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53-0.87, P=0.002) for 5.0-5.9 ng/mL and 0.65 (95% CI 0.50-0.85, P=0.001) for 6.0-6.9 ng/mL. These optimal ranges showed reduced rates of severe infection (6 y), malignancy (6 y), and mortality (1 y). CONCLUSION: This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2-12 and 12-72 months following kidney transplantation.

Olaris Global Panel (OGP): A Highly Accurate and Reproducible Triple Quadrupole Mass Spectrometry-Based Metabolomics Method for Clinical Biomarker Discovery.

Mass spectrometry (MS)-based clinical metabolomics is very promising for the discovery of new biomarkers and diagnostics. However, poor data accuracy and reproducibility limit its true potential, especially when performing data analysis across multiple sample sets. While high-resolution mass spectrometry has gained considerable popularity for discovery metabolomics, triple quadrupole (QqQ) instruments offer several benefits for the measurement of known metabolites in clinical samples. These benefits include high sensitivity and a wide dynamic range. Here, we present the Olaris Global Panel (OGP), a HILIC LC-QqQ MS method for the comprehensive analysis of ~250 metabolites from all major metabolic pathways in clinical samples. For the development of this method, multiple HILIC columns and mobile phase conditions were compared, the robustness of the leading LC method assessed, and MS acquisition settings optimized for optimal data quality. Next, the effect of U-13C metabolite yeast extract spike-ins was assessed based on data accuracy and precision. The use of these U-13C-metabolites as internal standards improved the goodness of fit to a linear calibration curve from r2 < 0.75 for raw data to >0.90 for most metabolites across the entire clinical concentration range of urine samples. Median within-batch CVs for all metabolite ratios to internal standards were consistently lower than 7% and less than 10% across batches that were acquired over a six-month period. Finally, the robustness of the OGP method, and its ability to identify biomarkers, was confirmed using a large sample set.

Medication-related incidents in acute care hospitals among different age groups: An analysis of national patient safety report data.

PURPOSE: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups. METHODS: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed. RESULTS: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively. CONCLUSIONS: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group.

The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection.

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.

A 20-Year Analysis of Ruptured Abdominal Aortic Aneurysm Outcomes and Associated Factors in Korea.

BACKGROUND: Unlike western countries, which have reported distinct decreases in incidence of ruptured abdominal aortic aneurysm (rAAA) over the last few decades, epidemiologic studies in Korea have not shown significant changes in incidence or mortality of rAAA. The purpose of this study was to analyze the changes in rAAA treatment outcomes and various associated risk factors over the past 2 decades. METHODS: A 20-year retrospective multicenter review for rAAA cases from the period of January 2000 to December 2020 was undertaken. Preoperative, intraoperative and postoperative clinical data were extracted for patients diagnosed with rAAA. For analysis, outcomes from the early era, defined as patients treated between January 1, 2000, and December 31, 2010, were compared with outcomes from the late era, defined as patients treated between January 1, 2011, and December 31, 2020. RESULTS: The total in-hospital mortality was 34.1% in the early era compared to 44.8% in the late era. Patients in the late era were older than those in the early era (75.2 ± 10.3 years vs. 70.3 ± 8.9 years; P = 0.009). Treatment with rAAA endovascular aneurysm repair increased from 2.3% in early to 13.8% in late era (P = 0.031). In the early era, more patients were operated by experienced surgeons than the late era (78.1% vs. 45.9%; P = 0.002). The emergency room to operating room time did not show improvement over the 20 years. CONCLUSIONS: The results indicate that mortality rate of rAAA in Korea has not changed over the last 2 decades. The study suggests the need for national preventive strategies, improved systemic coordination, and potential centralization of vascular services to enhance survival rates for rAAA.

Prediction of acute rejection in renal allografts using shear-wave dispersion slope.

OBJECTIVES: To evaluate the role of shear-wave dispersion slope for predicting renal allograft dysfunction. METHODS: We retrospectively reviewed 128 kidney transplant recipients (median age, 55 years [interquartile range, 43-62 years]; male, 68) who underwent biopsy for allograft evaluation from November 2022 to February 2023. Cortex and renal sinus fat stiffness and shear-wave dispersion slope were obtained at shear-wave elastography (SWE). Cortex-to-sinus stiffness ratio (SR) and dispersion slope ratio (DSR)-related clinical and pathologic factors were evaluated using multivariable linear regression analysis. We conducted univariate and multivariate analyses for multiparametric ultrasound (US) parameters for identifying acute rejection and calculated the area under the receiver operating curve (AUC) values. RESULTS: Of 128 patients, 31 (24.2%) demonstrated acute rejection. The SR value did not differ between patient groups (1.21 vs. 1.20, p = 0.47). Patients with acute rejection demonstrated a higher DSR than those without rejection (1.4 vs. 1.21, p < 0.01). Interstitial fibrosis and tubular atrophy grade (IFTA; coefficient, 0.11/grade; p = 0.04) and renal transplant and biopsy interval (coefficient, 0.00007/day; p = 0.03) were SR determinant factors, whereas only IFTA grade (coefficient, 0.10/grade; p = 0.01) for DSR. Multivariate analysis revealed mean resistive index (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.14, p = 0.01) and DSR value (OR 16.0, 95% CI 3.0-85.8, p = 0.001) as independent factors for predicting acute rejection. An AUC of 0.74 for detecting acute rejection was achieved by combining the resistive index and DSR value. CONCLUSION: Shear-wave dispersion slope obtained at SWE may help identify renal allograft dysfunction. CLINICAL RELEVANCE STATEMENT: Acute rejection in renal allografts is a major cause of allograft failure, but noninvasive diagnosis is a challenge. Shear-wave dispersion slope can identify acute rejection non-invasively. KEY POINTS: • The interstitial fibrosis and tubular atrophy grade was a determinant factor for stiffness ratio and shear-wave dispersion slope ratio between cortex and renal sinus fat. • Shear-wave dispersion slope ratio between cortex and renal sinus fat could identify acute rejection in renal allografts. • A shear-wave dispersion slope has a potential to reduce unnecessary renal biopsy for evaluating renal allografts.

T cell posttransplant lymphoproliferative disorder after kidney transplantation progressing to acute liver failure: a case report.

Posttransplant lymphoproliferative disorder (PTLD) is a rare and serious complication of kidney transplantation (KT), with 85% of cases being of B cell lineage. We present a case of T cell PTLD (T-PTLD) that rapidly progressed to liver failure, septic shock, and death despite various therapeutic interventions. A 50-year-old woman underwent ABO- and human leukocyte antigen-compatible preemptive living donor KT for diabetic endstage kidney disease under basiliximab induction therapy. During routine monitoring, 2 months after KT, her Epstein-Barr (EB) viral load was found to be elevated to 318,443 copies/mL. Despite a reduction in maintenance immunosuppressants and preemptive rituximab treatment, the EB viremia continued to increase. Eight months after KT, abdominopelvic computed tomography revealed multifocal splenic lesions and nonspecific lymph node enlargement. Concurrently, the patient's liver function tests began to deteriorate without evidence of viral hepatitis infection. A liver biopsy confirmed the diagnosis of EB virus-associated T-PTLD with CD3 and CD56 expression. Only 2 months after the PTLD diagnosis, the patient developed acute and severe liver failure. She died 12 days after being hospitalized, despite the administration of rescue cytotoxic chemotherapy. This case exemplifies the challenges of managing refractory EB virus-associated T-PTLD after KT, for which no specific treatment options are currently available. Further research into preventative and therapeutic methods for T-PTLD is warranted.

Association of high intra-patient variability in tacrolimus exposure with calcineurin inhibitor nephrotoxicity in kidney transplantation.

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05-0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2-355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity.

Anterior quadratus lumborum block for analgesia after living-donor renal transplantation: a double-blinded randomized controlled trial.

INTRODUCTION: Limited non-opioid analgesic options are available for managing postoperative pain after renal transplantation. We aimed to investigate whether the unilateral anterior quadratus lumborum (QL) block would reduce postoperative opioid consumption after living-donor renal transplantation in the context of multimodal analgesia. METHODS: Eighty-eight adult patients undergoing living-donor renal transplantation were randomly allocated to receive the unilateral anterior QL block (30 mL of ropivacaine 0.375%) or sham block (normal saline) on the operated side before emergence from anesthesia. All patients received standard multimodal analgesia, including the scheduled administration of acetaminophen and fentanyl via intravenous patient-controlled analgesia. The primary outcome was the total opioid consumption during the first 24 hours after transplantation. The secondary outcomes included pain scores, time to first opioid administration, cutaneous distribution of sensory blockade, motor weakness, nausea/vomiting, quality of recovery scores, time to first ambulation, and length of hospital stay. RESULTS: The total opioid consumption in the first 24 hours after transplantation did not differ significantly between the intervention and control groups (median (IQR), 160.5 (78-249.8) vs 187.5 (93-309) oral morphine milligram equivalent; median difference (95% CI), -27 (-78 to 24), p=0.29). No differences were observed in the secondary outcomes. CONCLUSIONS: The anterior QL block did not reduce opioid consumption in patients receiving multimodal analgesia after living-donor renal transplantation. Our findings do not support the routine administration of the anterior QL block in this surgical population. TRIAL REGISTRATION NUMBER: NCT04908761.

Application of microphysiologic system to assess neutrophil extracellular trap in xenotransplantation.

Transplantation of organs, cells, or tissues from one species to another, known as xenotransplantation, has the potential to alleviate organ donor shortages and enhance the success of organ transplantation. However, the possibility of immunological rejection by the recipient is one of the biggest difficulties associated with xenotransplantation. The creation of neutrophil extracellular traps (NETs), also known as NETosis, is hypothesized as a mechanism of rejection. Innovations in microfluidics and co-culturing techniques have provided access to several classes of microengineered model systems in experimental models, connecting animal research and traditional in vitro methods such as organoids, microphysiological systems, and organs-on-chip. To achieve this goal, we established a perfusable 3D Xeno vessel chip using a porcine aortic endothelial cell line and examined how NETs grow when isolated human and primate neutrophils were used. Neutrophils from both humans and monkeys displayed the usual NETosis phases, including nuclear decondensation, enlargement, and rounding of DNA, occupying the entire cytoplasm, and discharge of fragmented DNA after cell membrane rupture. Using confocal fluorescence imaging of DNA and citrullinated histone colocalization and DNA histone complex formation in supernatants from xeno vessel chips, we confirmed NETs generation by human and monkey neutrophils when cocultured in a xeno-vessel chip.

Validation of I71.3 code for ruptured abdominal aortic aneurysm in Korea: misplaced diagnosis in claims data.

Purpose: Studies in western countries have shown a decline in the incidence of ruptured abdominal aortic aneurysm (rAAA) with advancements in endovascular repair and screening. However, according to health insurance data in Korea based on rAAA code (I71.3), overall rAAA has been increasing. This study aimed to validate the I71.3 code for rAAA and attempt to define the true incidence of rAAA in Korea. Methods: A 20-year multicenter retrospective review of rAAA was undertaken from the period of January 1, 2000 to December 31, 2020. All patients were diagnosed with the rAAA code I71.3 in each of the 4 hospitals. The CT images and surgical records of these patients were reviewed to differentiate true rAAA and misdiagnosis. Further data on true rAAA patient outcomes including mortality and treatment success were also collected. Results: A total of 305 rAAA (I71.3) codes were identified in the 4 centers. However, medical record review showed true rAAA in only 131 (43.0%). The remaining 174 cases (57.0%) were misdiagnosed. Impending ruptures were the most common misdiagnoses (37.9%). The total in-hospital mortality including deaths before treatment was 38.9% (n = 51), while mortality of treated patients was 24.4% (n = 15). Conclusion: The analysis of I71.3 code for rAAA showed that only 43.0% were true rAAA and the remaining 57.0% were misdiagnosed. This indicates that the I71.3 code is overestimated in National Health Insurance-based data and that the true incidence of rAAA could be much lower.

The Clinical Course and Prognosis of Patients With Nontuberculous Mycobacterial Pulmonary Disease After Solid Organ Transplantation.

BACKGROUND: Due to impaired cell-mediated immunity, solid organ transplantation (SOT) recipients are at increased risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD). However, the clinical course of NTM-PD in SOT patients and the impact of SOT on the prognosis of NTM-PD remain unclear. METHODS: We analyzed patients who developed NTM-PD after receiving SOT between January 2001 and December 2020, at a tertiary referral hospital in South Korea. Baseline characteristics, clinical course, and prognosis were evaluated. Propensity score-matched analysis was performed to assess the impact of SOT on long-term survival in patients with NTM-PD. RESULTS: Among 4,685 SOT recipients over 20 years, 12 patients (median age, 64 years; interquartile range [IQR], 59-67 years; men, 66.7%) developed NTM-PD. Seven (58.3%) and five (41.7%) patients underwent kidney and liver transplantation, respectively, before the diagnosis of NTM-PD. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.7 cases per 100,000 person-years among liver transplant recipients. The median time between transplantation and the diagnosis of NTM-PD was 3.3 (IQR, 1.5-10.8) years. The most common mycobacterial species was Mycobacterium avium (50.0%). Antibiotic treatment was initiated in five (41.7%) patients, and two patients (40.0%) achieved microbiological cure. Two patients died during a median follow-up of 4.2 (IQR, 2.3-8.8) years and NTM-PD was assumed to be the cause of death in one patient. When matched to patients without a history of SOT, patients with a history of SOT did not show worse survival (P value for log-rank test = 0.62). CONCLUSION: The clinical course of NTM-PD in SOT recipients was comparable to that of patients without SOT, and SOT did not increase the risk of all-cause mortality in patients with NTM-PD.