Developing national level high alert medication lists for acute care setting in Korea

Background@#High-alert medications (HAMs) are medications that bear a heightened risk of causing significant patient harm if used in error. To facilitate safe use of HAMs, identifying specific HAM lists for clinical setting is necessary. We aimed to develop the national level HAM list for acute care setting. @*Methods@#We used three-step process. First, we compiled the pre-existing lists referring HAMs. Second, we analyzed medication related incidents reported from national patient safety incident report data and adverse events indicating medication errors from the Korea Adverse Event Reporting System (KAERS).We also surveyed the assistant staffs to support patient safety tasks and pharmacist in charge of medication safety in acute care hospital. From findings from analysis and survey results we created additional candidate list of HAMs. Third, we derived the final list for HAMs in acute care settings through expert panel surveys. @*Results@#From pre-existing HAM list, preliminary list consisting of 42 medication class/ingredients was derived. Eight assistant staff to support patient safety tasks and 39 pharmacists in charge of medication safety responded to the survey. Additional 44 medication were listed from national patient safety incident report data, KAERS data and common medications involved in prescribing errors and dispensing errors from survey data. A list of mandatory and optional HAMs consisting of 10 and 6 medication classes, respectively, was developed by consensus of the expert group. @*Conclusion@#We developed national level HAM list for Korean acute care setting from pre-existing lists, analyzing medication error data, survey and expert panel consensus.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia

The authors regret that there were errors in (Text/Table 1). This notice corrects on page 4 and page 5.

Klotho as a potential predictor of deceased donor kidney transplantation outcomes

Purpose@#Klotho is an antiaging factor mainly produced by renal tubular cells. Klotho is reportedly decreased in an animal model of acute kidney injury and patients with chronic kidney disease. However, information on Klotho expression after kidney transplantation is limited. We analyzed the correlation between donor Klotho expression and clinical outcomes of kidney transplantation. @*Methods@#Sixty patients who underwent deceased donor kidney transplantation between March 2015 and October 2017 were enrolled. Serum and tissue Klotho expression levels were measured by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Graft function was assessed by estimated glomerular filtration rate (eGFR). @*Results@#Patients were divided into 2 groups according to donor Klotho expression in renal tissues. A greater improvement in eGFR was observed at 1 week after transplantation in patients receiving kidneys with higher Klotho expression (47.5 ± 21.9 mL/min/1.73 m2 vs. 63.9 ± 28.2 mL/min/1.73 m2, P = 0.030). Patients were also classified into 2 groups according to donor serum Klotho level. There was a tendency for a higher eGFR at 12 months after transplantation in patients receiving kidneys from donors with a higher Klotho level (51.0 ± 18.0 mL/min/1.73 m2 vs. 61.2 ± 16.5 mL/min/1.73 m2, P = 0.059). When subgrouped into patients with or without biopsy-proven acute rejection, 12-month eGFR remained higher in patients receiving kidneys from donors with higher serum Klotho. @*Conclusion@#Our data demonstrated that donor tissue expression of Klotho correlated with early recovery of eGFR after kidney transplantation. Donor serum Klotho level tended to be associated with posttransplant 12-month eGFR. Donor Klotho expression might be a new predictor for deceased donor kidney transplantation outcome.

Risk of Graft Failure in Kidney Recipients with Cured Post-Transplant Cancer

Background@#Post-transplant cancer (PTC) is a critical complication after kidney transplantation. However, whether successfully cured PTC affects the long-term graft outcome remains unclear. @*Methods@#We retrospectively reviewed 1,629 kidney transplant recipients from 1995 to 2017 after excluding patients with post-transplant hematologic or advanced non-curable cancers and who underwent allograft nephrectomy because of cancer. Cured PTCs were defined as cancers treated with curative methods and/or adjuvant therapy without recurrence during ≥ 2 years. Propensity score matching was performed to match cured PTC patients with cancer-naïve patients (i.e., non-PTC group). @*Results@#During the median period of 7 years (maximum, 23 years), 70 patients (4.3%) had cured PTCs. The PTC group showed significantly higher risks of death-censored graft failure (adjusted hazard ratio [HR], 2.56 [1.05–6.23]), class II donor-specific antibodies (adjusted HRs, 3.37 [1.30–8.71]), estimated glomerular filtration rate 1 g (adjusted HR, 3.61 [1.92–6.79]) compared to non-PTC group. However, the risk of mortality was not different between the PTC and non-PTC groups. According to the cancer type, only urogenital cancer had a significant association with graft failure (adjusted HR, 4.26 [1.19–15.22]) and the gastrointestinal cancer showed elevated risk of T cell mediated rejection compared to non-PTC (adjusted HR, 20.44 [6.02–69.39]). @*Conclusion@#Appropriate monitoring of graft function is necessary in patients with cured PTCs.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia

The authors regret that there were errors in (Text/Table 1). This notice corrects on page 4 and page 5.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia

Klotho as a potential predictor of deceased donor kidney transplantation outcomes

Purpose@#Klotho is an antiaging factor mainly produced by renal tubular cells. Klotho is reportedly decreased in an animal model of acute kidney injury and patients with chronic kidney disease. However, information on Klotho expression after kidney transplantation is limited. We analyzed the correlation between donor Klotho expression and clinical outcomes of kidney transplantation. @*Methods@#Sixty patients who underwent deceased donor kidney transplantation between March 2015 and October 2017 were enrolled. Serum and tissue Klotho expression levels were measured by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Graft function was assessed by estimated glomerular filtration rate (eGFR). @*Results@#Patients were divided into 2 groups according to donor Klotho expression in renal tissues. A greater improvement in eGFR was observed at 1 week after transplantation in patients receiving kidneys with higher Klotho expression (47.5 ± 21.9 mL/min/1.73 m2 vs. 63.9 ± 28.2 mL/min/1.73 m2, P = 0.030). Patients were also classified into 2 groups according to donor serum Klotho level. There was a tendency for a higher eGFR at 12 months after transplantation in patients receiving kidneys from donors with a higher Klotho level (51.0 ± 18.0 mL/min/1.73 m2 vs. 61.2 ± 16.5 mL/min/1.73 m2, P = 0.059). When subgrouped into patients with or without biopsy-proven acute rejection, 12-month eGFR remained higher in patients receiving kidneys from donors with higher serum Klotho. @*Conclusion@#Our data demonstrated that donor tissue expression of Klotho correlated with early recovery of eGFR after kidney transplantation. Donor serum Klotho level tended to be associated with posttransplant 12-month eGFR. Donor Klotho expression might be a new predictor for deceased donor kidney transplantation outcome.

Nationwide Epidemiologic Study of Abdominal Aortic Aneurysms in Korea: A Cross-Sectional Study Using National Health Insurance Review and Assessment Service Data

PURPOSE: The prevalence and treatment patterns of abdominal aortic aneurysm (AAA) vary according to ethnicity and region. This study analyzed nationwide data on the epidemiology, practice patterns, and mortality rates of AAA in Korea.MATERIALS AND METHODS: Data from patients treated for AAA from 2012 to 2016 were extracted from the Korean Health Insurance Review and Assessment (HIRA) database.RESULTS: A total of 30,766 patients in Korea had treatment codes for AAA and 2,618 patients were treated for ruptured AAA. Of the 6,356 patients treated surgically, 1,849 and 4,507 underwent open surgical aneurysmal repairs (OSAR) or endovascular aneurysmal repairs (EVAR), respectively. The number of surgical treatments performed annually for AAA increased from 1,129 cases in 2012 to 1,501 cases in 2016. The number of EVAR cases increased from 753 to 1,109 during these five years, while the number of OSAR cases remained similar, at 376 and 392, respectively. The 30-day mortality rates after EVAR and OSAR were 4.2% and 10.6%, respectively. The mortality rates were significantly higher in patients with hypertension, dyslipidemia, chronic renal disease, diabetes mellitus, and congestive heart failure. There were significant differences in the prevalence, proportion of EVAR, and mortality rates according to the regional area.CONCLUSION: The prevalence of AAA and the proportion of EVAR in Korea increased in the past 5 years, while the rupture rate and the proportion of OSAR remained similar. To minimize mortality and regional discrepancies, nationwide registry and treatment standardization are needed.

Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4–47.8) months and 8.2 (range, 2.8–98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.

Proposal of a Selective Prophylaxis Strategy Based on Risk Factors to Prevent Early and Late Pneumocystis jirovecii Pneumonia after Renal Transplantation / 대한이식학회지

BACKGROUND: Currently, trimethoprim-sulfamethoxazole is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, but it is associated with frequent adverse effects. This study evaluated the efficacy and safety of the current protocol and proposes an individualized risk-based prophylaxis protocol. METHODS: The PJP incidence and risk factors during the first 6 months (early PJP) and afterwards (late PJP) was assessed in renal transplant recipients with (prophylaxis group) and without (no-prophylaxis group) 6-month PJP prophylaxis. RESULTS: In 578 patients, there were 39 cases of PJP during a median follow-up of 51 months. Renal adverse events were encountered frequently during trimethoprim-sulfamethoxazole prophylaxis, leading to premature discontinuation. Patients without the prophylaxis had a significantly higher incidence of early PJP (n=27, 6.6%) compared to patients with the prophylaxis (n=0). The incidence of late PJP was 2.2%, without between-group differences. The factors associated with early PJP were preoperative desensitization and acute rejection within 1 month, whereas late PJP was associated with age, deceased donor transplant, and acute rejection requiring antithymocyte globulin treatment. CONCLUSIONS: Based on the simulation results of several risk-based scenarios, the authors recommend universal prophylaxis up to 6 months post-transplant and extended selective prophylaxis in patients aged ≥57 years and those with a transplant from deceased donors.

Outcomes after Arterial or Venous Reconstructions in Limb Salvage Surgery for Extremity Soft Tissue Sarcoma

BACKGROUND: Limb salvage surgery with vascular reconstruction is currently considered as the standard treatment for extremity soft tissue sarcoma (STS), showing equivalent oncologic outcome compared with amputation. In this retrospective study, the surgical and functional outcomes after arterial or venous reconstruction in limb salvage surgery for STS were analyzed. METHODS: Consecutive patients who underwent vascular resection and reconstruction as part of limb salvage surgery for extremity STS from July 2009 to June 2015 were included in this study. Incidence of surgical complication, graft patency, and patients' functional outcome were reviewed. RESULTS: During the study period, 14 arteries and 13 veins were reconstructed in 17 patients (artery only in 4, vein only in 3, artery and vein in 10). Autologous great saphenous vein (GSV) was the most commonly used vascular conduit in both arterial and venous reconstruction (78.6% and 77.0%). The patency of synthetic graft was significantly lower than that of the autologous vein conduit (log rank test, P = 0.001). Among 15 patients with tumors in lower extremity, 13 were ambulatory after limb salvage surgery. During median follow up of 23.3 months (interquartile range 39.9 months), 2 patients (11.7%) needed amputation of the initially salvaged limb due to local recurrence. CONCLUSION: Limb salvage surgery of soft tissue tumor combined with vascular reconstruction showed favorable functional outcome with good local control. Autologous vein conduit is preferred over synthetic graft both in arterial and venous reconstruction.

Kidney Transplantation in Patients with Atypical Hemolytic Uremic Syndrome due to Complement Factor H Deficiency: Impact of Liver Transplantation

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that is often associated with genetic defects. Mutations of complement factor H (CFH) are the most common genetic defects that cause aHUS and often result in end-stage renal disease. Since CFH is mainly produced in the liver, liver transplantation (LT) has been performed in patients with defective CFH. METHODS: The clinical courses of four kidney allograft recipients who lost their native kidney functions due to aHUS associated with a CFH mutation were reviewed. RESULTS: Subject A underwent kidney transplantation (KT) twice, aHUS recurred and the allograft kidney failed within a few years. Subject B received a KT and soon experienced a recurrence of aHUS coinciding with infection. Her allograft kidney function has worsened, and she remains on plasma infusion therapy. Subject C underwent LT followed by KT. She is doing well without plasma infusion therapy after combined LT-KT for 3 years. Subject D received KT following LT and is now recurrence-free from aHUS. CONCLUSION: In patients with aHUS associated with a CFH mutation, KT without LT was complicated with a recurrence of aHUS, which might lead to allograft loss. Conversely, LT was successful in preventing the recurrence of aHUS and thus might be another option for a recurrence-free life for aHUS patients associated with CFH mutation.

Endovascular Treatment of a Saccular Aneurysm in the Celiomesenteric Trunk: A Case Report and Review of Literature

To present a world-first case of a successful endovascular treatment of a celiomesenteric trunk (CMT) aneurysm. A 45-year-old man had an asymptomatic saccular aneurysm in a rare anomaly of CMT. Endovascular multiple micro-coil embolization of the common hepatic artery, splenic artery and the aneurysm was done, followed by a stent-graft deployment in the superior mesenteric artery covering the orifice to the aneurysm. Postoperative course was uneventful. Only 21 cases have been previously reported in the literature, and all were treated by open surgeries. Endovascular therapy can be safely done in selected cases of a CMT aneurysm with sufficient collaterals to the liver and spleen.

Posttransplantation lymphoproliferative disorder after pediatric solid organ transplantation: experiences of 20 years in a single center / 소아과

PURPOSE: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. METHODS: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. RESULTS: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. CONCLUSION: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.

Late Type 3b Endoleak Mimicking Type 2 Endoleak after Endovascular Aortic Aneurysm Repair

Endovascular abdominal aortic aneurysm (AAA) repair has been widely used for the treatment of AAA as a safe and efficient method, but endoleaks causing persistent expansion of aneurysm sac may cause aneurysmal rupture and death. Type 3 endoleak is rare but a predominant cause of late rupture. Type 3b endoleak can be misdiagnosed as type 2 endoleak, which is more frequent. Here we report two cases of type 3b endoleak mimicking type 2 endoleak, which were successfully treated by open surgery of partial explantation of the stent-graft and endoaneurysmal interposition graft replacement.

Symptomatic Growth of a Thrombosed Persistent Sciatic Artery Aneurysm after Bypass and Distal Exclusion

A 71-year-old woman presented with an enlarging mass in the right buttock, with pain and tingling sensation in sitting position. Five years ago, she was diagnosed with acute limb ischemia due to acute thrombosis of right persistent sciatic artery (PSA), and she underwent successful thromboembolectomy and femoro-tibioperoneal trunk bypass. Computed tomography angiography revealed a huge PSA aneurysm (PSAA). During the previous bypass, the distal popliteal artery was ligated just above the distal anastomosis to exclude the PSAA, whose proximal end was already thrombosed. However, PSAA has grown to cause compression symptoms, and the mechanism of aneurysm growth can be ascribed to type 1a or type 2 endoleak. In order to relieve the compression symptoms, aneurysm excision was performed without any injury to the sciatic nerve. A postoperative tingling sensation due to sciatic-nerve stimulation in the supine position resolved spontaneously one month after surgery.

Validation of the Korean version of the walking impairment questionnaire in patients with peripheral arterial disease

PURPOSE: Intermittent claudication is the most common early symptom of peripheral arterial occlusive disease. Walking impairment questionnaire (WIQ) is a short, inexpensive, easy-to-complete questionnaire to assess intermittent claudication and can provide data of usual walking. The purpose of this study is to validate the new Korean version of WIQ. METHODS: Total 51 patients with claudication were enrolled. While 4 patients were dropped out, 47 patients with claudication into were divided groups based on the treatment received: surgery (n = 33) and medication (n = 14). The surgery group was subdivided into the bypass (n = 13) and intervention (n = 20) groups. WIQ score, ankle-brachial index (ABI), and treadmill test scores were assessed initially and after 12 weeks. RESULTS: The WIQ scores were significantly correlated with ABI and pain-free walking distance (PFWD) and maximum walking distance (MWD) in all groups (except for MWD in the intervention group). Speed and stair-climb scores (2 WIQ domains) were well correlated with ABI, PFWD, and MWD. Distance scores were mostly correlated with ABI, PFWD, and MWD in all groups except ABI in the bypass and intervention groups and MWD in the bypass group. Reproducibility was observed in all groups (intraclass correlation coefficient > 0.8). CONCLUSION: The Korean version of the WIQ is valid and reproducible, and can be effectively used to assess Korean patients with intermittent claudication.

The Need for New Donor Stratification to Predict Graft Survival in Deceased Donor Kidney Transplantation

PURPOSE: The aim of this study was to determine whether stratification of deceased donors by the United Network for Organ Sharing (UNOS) criteria negatively impacts graft survival. MATERIALS AND METHODS: We retrospectively reviewed deceased donor and recipient pretransplant variables of kidney transplantations that occurred between February 1995 and December 2009. We compared clinical outcomes between standard criteria donors (SCDs) and expanded criteria donors (ECDs). RESULTS: The deceased donors consisted of 369 patients. A total of 494 transplant recipients were enrolled in this study. Mean age was 41.7±11.4 year (range 18–69) and 273 patients (55.4%) were male. Mean duration of follow-up was 8.8±4.9 years. The recipients from ECD kidneys were 63 patients (12.8%). The overall mean cold ischemia time was 5.7±3.2 hours. Estimated glomerular filtration rate at 1, 2, and 3 years after transplantation were significantly lower in ECD transplants (1 year, 62.2±17.6 vs. 51.0±16.4, p0.05), although patient survival was lower in ECDs than SCDs (Log rank test, p=0.011). CONCLUSION: Our data demonstrate that stratification by the UNOS criteria does not predict graft survival. In order to expand the donor pool, new criteria for standard/expanded donors need to be modified by regional differences.

Femoral Endovenectomy with Iliac Stenting for Chronic Iliofemoral Venous Occlusion

A 62-year-old man with progressive swelling on his left thigh and leg was referred to the Division of Vascular Surgery. Anticoagulation therapy did not prevent or improve the symptoms of chronic deep vein thrombosis (DVT) from his left external iliac vein to posterior tibial vein. He had no trauma history nor any accidents. He underwent femoral endovenectomy, thrombectomy and stent insertion in left iliac vein. The patient had additional balloon angioplasty for stenosis in left common femoral vein. He had an uneventful postoperative recovery without complication. Leg swelling has been improving and follow-up continues under anticoagulation. We report a case of femoral endovenectomy with iliac stenting, which may be an efficacious treatment for chronic DVT.

Chronological Change of the Sac after Endovascular Aneurysm Repair

PURPOSE: The purpose of this study was to evaluate the potential risk factors of type II endoleak and sac growth after endovascular aneurysm repair (EVAR) and the outcomes of secondary interventions. MATERIALS AND METHODS: Ninety seven patients underwent elective EVAR for infrarenal abdominal aortic aneurysms in two tertiary centers between April 2005 and July 2013. Clinical and imaging parameters were compared among sac growth (>5 mm) and non-growth groups. Risk factors associated with sac growth and persistent type II endoleak were analyzed. The outcomes of reinterventions for persistent type II endoleak were determined. RESULTS: Sac growth was observed in 20 cases (20.6%) and endoleak was found in 90% of them compared to 28.6% (22/77) in the non-growth group (P<0.001). The majority of endoleaks were type II (36/40) and 80.5% were persistent. Sac diameter, neck diameter and number of patent accessory arteries were also statistically significant for sac growth. On multivariate analysis, grade of calcification at the neck, grade of mural thrombus at the inferior mesenteric artery and number of patent accessory arteries were risk factors of persistent type II endoleak. Twenty six reinterventions were done for 16 patients with persistent type II endoleak, with a technical success rate of 88.5%, yet 55.5% showed sac growth regardless of technical success. There were no ruptures during the follow-up period. CONCLUSION: Sac growth after EVAR was mostly associated with persistent type II endoleak. Secondary interventions using transarterial embolization is partially effective in achieving clinical success.