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.

Development of in-vitro pulsatile flow generator for evaluating the performance of hemodialysis catheters.

Hemodialysis (HD) using an HD catheter is performed widely on renal failure patients. The catheter was evaluated using the recirculation ratio in pre-clinical status, which is a crucial index indicating its performance. However, pre-clinical in-vivo experiments have limitations: high cost, and ethical issues. Hence, computational and in-vitro methods have been developed as alternatives. However, computational methods require fluid dynamic knowledge, whereas in-vitro experiments are complicated and expensive. In this study, we developed a pulsatile flow generator to mimic blood flow achieving cost effectiveness and user convenience. The device used iterative learning control, achieving blood flow in the superior and inferior vena cava within a 3.3% error. Furthermore, the recirculation ratios were measured based on two insertion directions and two different external pipe materials to evaluate the catheter regarding patients' posture and blood vessel stiffness. The results provide a better understanding of cardiovascular device performance without complicated and costly pre-clinical tests.

Analysis of tip malposition and correction of peripherally inserted central catheters under ultrasound-guidance: 5-year outcomes from a single center.

BACKGROUND: Peripherally inserted central catheter (PICC) has become a common procedure. Although ultrasound (US)-guidance has improved success rates, a small percentage of malposition is inevitable. The purpose of our study is to evaluate malposition rates of US-guided bedside PICC catheter insertion, and the clinical factors associated with malposition. METHODS: This is a retrospective cohort study evaluating 5981 patients who had undergone ultrasound-guided bedside PICC placement from January 2017 to December 2021 at a single tertiary center. Final tip location was confirmed on chest radiograph. RESULTS: Patients were categorized into optimal, suboptimal, and malposition groups according to final tip location. 4866 cases (81.7%) showed optimal tip position, 790 (13.3%) were suboptimal, and 299 (5.0%) were malpositioned. Logistic regression analysis identified six variables associated with tip malposition; height (odds ratio (OR) 1.044; 95% confidence interval (CI), 1.028-1.061; p < 0.001), body mass index (BMI) (OR 1.051; 95% CI, 1.017-1.087; p = 0.003), prior failure at accessing peripheral intravenous (IV) access (OR 1.718; 95% CI, 1.215-2.428; p = 0.002), side of the arm (OR 3.467; 95% CI, 2.457-4.891; p < 0.001), length of the catheter (OR 0.763; 95% CI, 0.734-0.794; p < 0.001), and number of previous central catheter insertions (OR 1.069; 95% CI, 1.004-1.140; p = 0.038). Malpositioned catheters were corrected by either bedside repositioning, bedside reinsertion, fluoroscopic reinsertion, switching to jugular catheters or catheter removal. No patient related factors were significantly associated with malposition or success of reposition. CONCLUSION: US-guidance can help reduce catheter malposition during bedside PICC insertion. Patients with risk factors such as multiple previous central vein insertions, failed peripheral line insertions, left arm insertion, or high BMI should undergo thorough sonographic evaluation of the arm vessels to prevent malposition.

Anatomical feasibility of fenestrated stent graft to treat complex abdominal aortic aneurysms from a Korean single institute database.

Purpose: This study aims to investigate the feasibility of Zenith Fenestrated AAA Endovascular Graft (Z-FEN, Cook Medical) from a single Korean institution database by evaluating the vascular anatomy of Korean abdominal aortic aneurysm (AAA) patients with hostile aortic neck. Methods: This is a retrospective study on patients with AAA who underwent endovascular aortic repair (EVAR) and open surgery repair between January 2012 and December 2021 (n = 211). The anatomic characteristics of the aortic neck were evaluated using 3-dimensional reconstructed computed tomographic scans. For the juxtarenal AAA patients (n = 39), feasibility of fenestrated stent graft was evaluated under the protocol of fenestrated EVAR. For those who were not suitable for the application of Z-FEN, the reasons for unsuitability were analyzed. Results: Among 211 AAA patients, 108 patients (51.2%) had complex aortic neck, and 39 (18.5%) had insufficient aortic neck length (<15 mm) for conventional EVAR. Of the 39 patients with juxtarenal AAAs, 13 (33.3%) were determined feasible for Z-FEN. Twenty-six patients (66.7%) were noncandidate for Z-FEN due to severe neck angulation, short aortic neck length, inadequate iliac artery anatomy, large aortic neck diameter, and severe calcification and thrombosis. Proximal aortic neck length of the non-feasible group was significantly shorter than that of the feasible group (P = 0.002). Conclusion: Z-FEN was applicable to 33.3% of the juxtarenal AAA patients. As recent studies confirm, the effectiveness and safety of fenestrated EVAR, Z-FEN can be an option for AAA patients with short aortic neck.

Contrast enhanced duplex ultrasound for early postoperative follow-up after endovascular aneurysm repair: Relation to patient's initial risk of complications.

OBJECTIVES: Current guidelines recommend initial postoperative follow-up with computed tomography angiography (CTA) after endovascular aneurysm repair (EVAR). However, CTA has risks associated with ionizing radiations and nephrotoxic contrast agents. We investigated possibilities to replace the initial postoperative CTA with contrast enhanced duplex ultrasound (CE-DUS) in selected patients. METHODS: Out of the 273 consecutive patients who underwent EVAR, 173 were excluded and the 100 patients who underwent CTA and CE-DUS imaging concurrently (≤1 month interval between CTA and CE-DUS imaging) within 60 days after EVAR were analyzed. Patients who underwent EVAR outside the manufacturer's instructions for use or who had endoleaks discovered on intraoperative angiography were classified as the high-risk group, otherwise, they were classified as the low-risk group. Measurements of diagnostic values of CE-DUS ​​related to the detection of complications were calculated using CTA as the gold standard. McNemar's test was performed to compare these values and Pearson correlation coefficient was derived to compare CE-DUS measurements of sac diameters with CTA. RESULTS: In the low-risk group, no difference was observed between CE-DUS and CTA in the detection of EVAR-related complications (sensitivity = 0.95, specificity = 0.93). In the high-risk group, CE-DUS was not as accurate as CTA for the detection of overall EVAR-related complications (sensitivity = 0.57, specificity = 0.86, p = 0.04) and for the detection of complications other than endoleaks (p = 0.02). Regarding sac diameter measurement, there was good agreement between CE-DUS and CTA (r = 0.92, p < 0.001). CONCLUSIONS: First postoperative CE-DUS was reliable for the evaluation of EVAR-related complications compared to CTA in selected patients. Individualized EVAR follow-up strategy using CE-DUS based on the initial risk of EVAR-related complications should be considered.

Preliminary outcomes of the LifeStream balloon-expandable stentgraft in Zenith Iliac branch device to preserve pelvic circulation: A Korean multicenter study.

BACKGROUND: To evaluate early outcomes of aortoiliac or isolated iliac artery aneurysm repair using the Zenith® Bifurcated Iliac Side (ZBIS) stent graft combined with the LifeStream™ Balloon Expandable Vascular Covered Stent as a bridging stentgraft. METHODS: Between August 2018 and February 2020, 38 patients (37 male, mean age 72.7 years) received 46 LifeStream stents in conjunction with 38 ZBIS stent grafts to bridge hypogastric arteries for aneurysm repair in six university hospitals in Korea. The primary outcomes were technical success rate and procedure-related complications. Secondary outcomes were bridging stent graft patency and re-intervention. RESULTS: All procedures were performed as elective standard endovascular aortic aneurysm repair (EVAR) and unilateral iliac branch device (IBD). Mean follow-up was 13.1 months, and patient overall survival rate was 96.7%. Technical success rate was 76.3% (n = 29). Causes of failure included seven total endoleaks; six type Ic and one type IIIc from the IBD junction, one unintentional IIA coverage, and one failure to deploy the IIA stent graft. Procedure-related complications occurred in two patients: one LifeStream migration and one ZBIS stent graft migration. Overall patency rates for the LifeStream and ZBIS stents were 97.4% and 97.2%, respectively. CONCLUSION: This multicenter preliminary experience with the LifeStream™ Balloon Expandable Vascular Covered Stent in IBD demonstrated good patency; however, an unexpectedly high rate of type Ic endoleaks was observed. Combined use of the LifeStream stent with the ZBIS stent graft is safe and feasible to preserve pelvic circulation with good patency and a low rate of device-related reintervention.

Efficacy of blood flow measurement using intraoperative color flow Doppler ultrasound as a predictor of autologous arteriovenous fistula maturation.

INTRODUCTION: Hemodialysis vascular access parameters of intraoperative Color flow Doppler ultrasound remain controversial. This study aimed to evaluate the optimal cut-off value and efficacy of intraoperative arteriovenous fistula parameters identified by Color flow Doppler ultrasound for arteriovenous fistula maturation success. METHODS: This retrospective study consisted of a review of the medical records of 137 consecutive patients who underwent their first autologous arteriovenous fistula formation under local anesthesia for end-stage renal disease from April 9, 2020 to March 19, 2021. RESULTS: The receiver operating characteristic curve analysis revealed that the optimal cut-off for intraoperative cephalic vein flow volume for brachiocephalic arteriovenous fistula maturation at the 4-week follow-up was 349.53 ml/min (area under the curve, 0.792; p, 0.036; Youden index, 0.514). CONCLUSION: Intraoperative color Doppler ultrasound outflow cephalic vein flow volume is a useful factor in predicting arteriovenous fistula maturation. Intraoperative Color flow Doppler ultrasound should be performed.

TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patients.

BACKGROUND: Transcutaneous oxygen pressure (TcPO2) is a noninvasive, nonradiological test to measure local oxygen released from capillaries through the skin. Since it reflects the metabolic state of the lower limb, it can predict wound healing in patients with critical limb threatening ischemia (CLTI). The purpose of this study was to determine the effectiveness of TcPO2 test in evaluating wound healing potential of patients with CLTI. METHODS: This was a retrospective, single-center, nonrandomized, and observational study. A prospectively registered database of patients who visited Vascular Surgery Department of St. Mary's Hospital for CLTI and underwent TcPO2 tests from October 1, 2015 to July 1, 2021 was reviewed. Patients were divided into 2 groups: (1) those who had amputation only; and (2) those who underwent revascularization procedures. Patients whose wound healing status could not be determined were excluded. The clinical characteristics of patients, patient characteristics related to lower TcPO2 value, treatment success rate, and time for the wound to be healed were analyzed. RESULTS: A total of 84 patients were included in this study. There was no difference in background patient characteristics between the 2 groups despite better survival within 12 months and shorter healing time in the revascularization group. A total of 76 patients survived 12 months after surgery, and 63 patients were healed. Higher HbA1c, higher serum creatinine, history of stroke, and history of coronary artery disease were related to lower TcPO2 value on multiple linear regression. The cutoff value of TcPO2 was determined to be 40 mm Hg for predicting wound healing. This value was similar to those of previous studies. In addition, there was a negative correlation between TcPO2 and wound healing time. Correlations among the anklebrachial index (ABI), toe-brachial index (TBI), and TcPO2 were not determined because ABI and TBI for some patients could not be obtained due to wound condition. CONCLUSIONS: The TcPO2 value can predict the wound healing process of ischemic lower extremity injury.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Characteristics and Effect of Rivaroxaban on Venous Thromboembolism in Korean Patients Compared to Western Population: A Subgroup Analysis from XALIA(-LEA) Study.

Purpose: This study aimed to compare the characteristics of venous thromboembolic disease (VTE) in Korean to Caucasian population. Materials and Methods: XALIA-LEA and XALIA were phase IV non-interventional prospective studies with identical designs that investigated the effect of rivaroxaban versus standard anticoagulation for VTE. Koreans accounted for the largest proportion of the overall enrolled population of XALIA-LEA. However, in the XALIA study, most patients were Caucasian. Therefore, Korean data from XALIA-LEA and Caucasian data from XALIA were used in this study. This study compared the clinical characteristics and primary outcomes of the XALIA program, including major bleeding, recurrent VTE, and all-cause mortality. Results: The Korean population was older, was less obese, and had more active cancer at baseline than the Caucasian population. Provoked VTE was more common in the Korean population. Interestingly, Koreans showed less accompanying thrombophilia than Caucasians, and factor V Leiden mutations were not detected. Korean analyses comparing the effects of rivaroxaban and standard anticoagulation with primary outcomes showed a lower incidence of major bleeding, recurrent VTE, and all-cause mortality with rivaroxaban. Similar results were obtained in the propensity score matching analysis. Conclusion: Characteristic differences were found between Korean and Caucasian VTE patients. Despite these ethnic differences, the effectiveness and safety of rivaroxaban therapy in these patients were consistent.

Structural analysis of carboxyspermidine dehydrogenase from Helicobacter pylori.

Spermidine is a cationic polyamine that plays key roles in diverse biological processes, including biofilm formation and cell viability in bacteria. In some human gastrointestinal bacteria, such as Helicobacter pylori and Campylobacter jejuni, spermidine is biosynthesized using carboxyspermidine dehydrogenase (CASDH) and carboxyspermidine decarboxylase through an alternative pathway rather than the classical pathway found in most bacteria and eukaryotes. CASDH condenses putrescine and aspartate ß-semialdehyde into carboxyspermidine in an NADPH-dependent manner. Because structural information on CASDH is not available, the exact enzymatic mechanism of CASDH has not been elucidated. To reveal the structural features of CASDH required for cofactor and substrate recruitment, we determined the crystal structures of the H. pylori CASDH protein alone and in complex with NADP. CASDH consists of three domains (D1, D2, and D3) and assembles into a homodimer exclusively using the D3 domain. The CASDH structure harbors a dent between the D1 and D3 domains. The NADP cofactor is inserted into the interdomain dent and induces structural rearrangements in CASDH, including dent closure and local structural changes in the D1 and D3 domains. A comparative analysis suggests that the substrate of CASDH binds in a cavity near the nicotinamide moiety of NADPH for the condensation reaction.

Structural basis of flagellar motility regulation by the MogR repressor and the GmaR antirepressor in Listeria monocytogenes.

The pathogenic Listeria monocytogenes bacterium produces the flagellum as a locomotive organelle at or below 30°C outside the host, but it halts flagellar expression at 37°C inside the human host to evade the flagellum-induced immune response. Listeria monocytogenes GmaR is a thermosensor protein that coordinates flagellar expression by binding the master transcriptional repressor of flagellar genes (MogR) in a temperature-responsive manner. To understand the regulatory mechanism whereby GmaR exerts the antirepression activity on flagellar expression, we performed structural and mutational analyses of the GmaR-MogR system. At or below 30°C, GmaR exists as a functional monomer and forms a circularly enclosed multidomain structure via an interdomain interaction. GmaR in this conformation recognizes MogR using the C-terminal antirepressor domain in a unique dual binding mode and mediates the antirepressor function through direct competition and spatial restraint mechanisms. Surprisingly, at 37°C, GmaR rapidly forms autologous aggregates that are deficient in MogR neutralization capabilities.

Successful ABO-incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch-positive donor-specific class I HLA antibodies following COVID-19 vaccination.

The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.

Application of venous thromboembolism prophylaxis program in patients with colorectal cancer using the enhanced recovery after surgery protocol.

INTRODUCTION: The incidence of postoperative symptomatic venous thromboembolism (VTE) in western colorectal cancer is 1.1-2.5%. Anticoagulation and mechanical devices are recommended for moderate-to high-risk patients. Hospital stay and immobilization, as risk factors for VTE, are reduced by enhanced recovery after surgery (ERAS). This study aimed to evaluate short- and long-term outcomes for a VTE prophylaxis program after minimally invasive colorectal cancer surgery with ERAS protocol. In addition, predicting factors associated with VTE were investigated. MATERIALS AND METHODS: We included 1043 patients diagnosed with colorectal cancer who required surgical treatment between January 2017 and December 2019 at a single institution. The patients enrolled followed the VTE prophylaxis program. RESULTS: Five (0.5%) patients developed symptomatic VTE, and the median follow-up period was 21 months. The Caprini score for all VTE patients was ≤8 points; thus, only mechanical prophylaxis was applied. The incidence rate of postoperative symptomatic VTE was only 0.5%. There was no association between variables considered as associated with VTE onset, such as age, perioperative complication, and length of postoperative day. TNM staging (OR 2.44, 95% CI 1.4-4.16, p = 0.001) and the Caprini score (OR 1.75, 95% CI 1.1-2.8, p = 0.001) were associated with VTE onset. CONCLUSION: Although pharmacological prophylaxis was only performed for Caprini scores ≥9, the VTE incidence rate of patients with colorectal cancer undergoing VTE prophylaxis program was 0.6%; 0.7% is the incidence criterion of the moderate group recommended for pharmacological prophylaxis. Continuous follow-up is required for patients with advanced-stage colorectal cancer with high-risk Caprini scores.

Bean Extract-Based Gargle for Efficient Diagnosis of Active COVID-19 Infection Using Rapid Antigen Tests.

The antigen-based rapid diagnostic test (Ag-RDT) using saliva specimens is fast, noninvasive, and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing. We evaluated a novel Beanguard gargle (BG)-based virus collection method that can be applied to Ag-RDT as an alternative to the current RT-PCR with an NPS for early diagnosis of COVID-19. This clinical trial comprised 102 COVID-19-positive patients hospitalized after a governmental screening process and 100 healthy individuals. Paired NPS and BG-based saliva specimens from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs, whose diagnostic performance for detecting SARS-CoV-2 was compared. BG-Ag-RDTs showed high sensitivity (97.8%) and specificity (100%) in 45 patients within 6 days of illness and detected all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic active COVID-19 cases, both BG-Ag-RDTs and BG-RT-PCR showed sensitivities and specificities of 100%. Sensitivities of BG-Ag-RDT and BG-RT-PCR toward salivary viral detection were highly concordant, with no discrimination between symptomatic (97.0%), asymptomatic (100%), or SARS-CoV-2 variant (100%) cases. The intermolecular interactions between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from the bean extract (BE), were observed in terms of physicochemical properties. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis. Using BG-based saliva specimens remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables noninvasive, rapid, and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management. IMPORTANCE An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness. The method represents an attractive alternative to nasopharyngeal swabs for the early diagnosis of symptomatic and asymptomatic COVID-19 cases. The evidence suggests that the method could have a potential for mass screening and monitoring of COVID-19 cases.

Kidney Transplantation From Deceased Donors With Bloodstream Infection: A Multicenter Retrospective Study.

BACKGROUND: The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). METHODS: A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. RESULTS: Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. CONCLUSION: Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.