Validation of prediction model for successful discontinuation of continuous renal replacement therapy: a multicenter cohort study

Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71–0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73–0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Mortality of elderly patients with acute kidney injury undergoing continuous renal replacement therapy: is age a risk factor?

Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. Methods: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65–74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. Results: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99–1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30–0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18–10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02–2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36–0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28- day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. Conclusion: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Effects of an Herbal Medicinal Product Composed of Three Herbal Materials on Lipopolysaccharide-induced Depression-like Behaviors in Mice

An herbal medicinal product consisting of three kinds of herbal materials, Prunella vulgaris L. (Lamiaceae), Clematis chinensis Osbeck (Ranunculaceae) and Trichosanthes kirilowii Max. (Cucurbitaceae) has been prescribed in the clinic for treating rheumatoid arthritis in Korea. In the present study, we investigated the antidepressive effect of this herbal complex extract (HCE) on lipopolysaccharide (LPS)-induced depression-like behavior. The effects of HCE on LPSinduced depressive-like behaviors were evaluated using a forced swimming test (FST) and splash test. In addition, we also evaluated locomotor activity and anxiety-like behaviors using the open field test and elevated plus-maze (EPM) test.Inflammatory cytokines were evaluated in the cortical regions. HCE attenuated anxiety-like behavior in the EPM test and depressive- and anhedonia-like behaviors induced by LPS in the FST and splash test. In addition, LPS-induced increases in the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK-3β) and expression levels of proinflammatory factors in the cortex were normalized by HCE. Moreover, decreases in the level of BDNF in the cortex were attenuated by HCE. These results suggest that HCE attenuates inflammation-induced depression-like behaviors through its normalization of Akt-GSK-3β signaling and proinflammatory factors and its upregulation of BDNF in the cortex and that HCE has therapeutic potential for depressive disorders in inflammatory states.

Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients

Background@#The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. @*Methods@#We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary’s Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. @*Results@#The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79–51.56) than in LDKT (OR: 3.76, 95% CI: 0.99–14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. @*Conclusions@#Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients

Background/Aims@#To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). @*Methods@#We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller ( 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). @*Results@#BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). @*Conclusions@#BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Positive culture rate and antimicrobial susceptibilities of Mycoplasma hominis and Ureaplasma urealyticum

OBJECTIVE: To assess positive culture rate and antimicrobial susceptibilities of Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in symptomatic general population and pregnant women admitted with preterm labor and premature rupture of membranes. METHODS: We retrospectively reviewed medical records of patients who have undergone culture test and antimicrobial susceptibilities at our center from January 2017 to April 2018. Patients with positive culture for MH, UU, or both were included in this study. RESULTS: There were 200 patients who were eligible for enrollment. Of these patients, 34 (17%) were pregnant women and 166 (83%) were non-pregnant women. Of these 200 patients, positive culture results were as follows: MH only, n=10 (5%); UU only, n=58 (29%); and both MH and UU, n=36 (18%). Susceptibilities of MH only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 100%, 10%, 40%, and 0%, respectively. Susceptibilities of UU only to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 94.8%, 87.9%, 5.2%, and 81%, respectively. Susceptibilities of both MH and UU to doxycycline, erythromycin, ciprofloxacin, and azithromycin were 97.2%, 5.6%, 11.1%, and 11.1%, respectively. CONCLUSION: UU only was the leading causative pathogen for genitourinary infection in our study. MH only accounted for about one sixth of UU only infections. Doxycycline was still the best antibiotics as most patients with MH only, UU only, or both MH and UU positive culture showed susceptibility. For ciprofloxacin, less than 12% of those with UU only and both MH and UU culture positive results showed susceptibility.

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients

BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. METHODS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. RESULTS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (−) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017–24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R. CONCLUSIONS: Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.

Update of aristolochic acid nephropathy in Korea

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

A Case of Granular Cell Tumor of the Clitoris in a Postmenopausal Woman

Granular cell tumor (GCT) is a rare soft tissue tumor that derived from Schwann cells. Most are benign, less than 2% are malignant and, in the malignant cases, the prognosis of survival is poor. Most of these tumors are less than 3 cm in size, and they are more common in black women. The disease usually occurs in the 40s to the 60s and occurs after menopause, but there are few cases reported in adolescence. A 45-year-old woman visited the outpatient clinic with a solid mass that developed 2 years ago and present to date on the left side of the clitoris. After complete resection, pathologic examination proved to be a granular cell. The patient has been living without recurrence for one year. We report the first case of the GCT of the clitoris in postmenopausal woman in Korea with a brief review of the literature.

Fetal Axillary Cystic Lymphangioma Detected by Prenatal Ultrasonography

Fetal cystic lymphangioma, commonly called hygroma, is formed by multiple cysts ranging from few millimeters to several centimeters in size. Fetal cystic lymphangioma is a rare developmental congenital anomaly of the lymphatic system. Most are found in the neck and axilla, rarely in the retroperitoneum, abdominal viscera, limbs, bones, and cervico-mediastinal area. The prenatal diagnosis of cystic hygroma by ultrasound guidance is commonly localized in the nuchal region. We report a case of rare fetal axillary hygroma that was diagnosed at 27 weeks of gestation and delivered at 37 weeks of gestation.

Minimal change nephrotic syndrome showing complete remission after resection of a neurofibroma in a type I neurofibromatosis patient

No abstract available.

Eosinophils in Colorectal Neoplasms Associated with Expression of CCL11 and CCL24

BACKGROUND: A decrease in the number of tissue eosinophils is known to reflect the malignancy potential of neoplastic lesions and even prognosis. Increased levels of the chemokines CCL11 and CCL24 in serum and tissue are also known to have diagnostic value as serum tumor markers or prognostic factors. The aim of this study was to evaluate the correlation between the degree of tissue eosinophilia and the expression of these chemokines in the glandular and stromal cells of colorectal neoplastic lesions ranging from benign to malignant tumors. METHODS: We counted the number of infiltrating eosinophils in neoplastic lesion tissue and we evaluated the expression of CCL11 and CCL24 in glandular cells and stromal cells by immunohistochemical staining. RESULTS: The results showed that the number of eosinophils decreased significantly and the expression of CCL11 and CCL24 in glandular cells decreased with tumor progression, whereas the stromal expression of CCL11 and CCL24 appeared to increase. CONCLUSIONS: The discrepancy in CCL11 and CCL24 expression between glandular cells and stromal cells might shed light on how colorectal cancer evades the immune system, which would enable further development of immunotherapies that target these chemokines. Further research on eosinophil biology and the expression pattern of chemokines in tumor cells is needed.

Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis

BACKGROUND: Uremic pruritus is a common, but unpleasant, complication of end-stage renal disease. The uremic burden may differ between hemodialysis (HD) and peritoneal dialysis (PD) patients. This difference may also change the clinical characteristics of uremic pruritus between the 2 modalities. In this study, we investigated the uremic pruritus between patients on HD and PD. METHODS: A total of 425 HD and 223 PD patients from the Clinical Research Center registry in Korea were included. Patients were assessed for pruritus intensity, scratching activity, pruritus distribution, and frequency of pruritus-related sleep disturbance using the visual analog scale and questionnaire. RESULTS: The prevalence of uremic pruritus was higher in PD patients than that in HD patients (62.6% vs. 48.3%, P = 0.001). In the multivariable logistic analysis, PD treatment was significantly associated with the prevalence of uremic pruritus (odds ratio, 1.76; 95% confidence interval, 1.20-2.57, P = 0.004) after adjustment for clinical variables. The visual analog scale score, representing a subjective intensity of itchiness, was significantly higher in PD patients (PD 2.11 ± 2.32 vs. HD 1.65 ± 2.28, P = 0.013) compared with HD patients. The intensity of uremic pruritus was independently related with serum albumin levels (β = -0.143, P = 0.006) in HD patients and total weekly Kt/V (β = -0.176, P = 0.028) in PD patients. CONCLUSION: Our data demonstrate the difference in prevalence, intensity, and risk factors of uremic pruritus between HD and PD patients. These findings suggest that careful consideration for uremic pruritus might be needed in end-stage renal disease patients according to the dialysis modality.

The Natural Course of Biopsy-Proven Isolated Microscopic Hematuria: a Single Center Experience of 350 Patients

The increasing interest in healthcare and health screening events is revealing additional cases of asymptomatic isolated microscopic hematuria (IMH). However, a consensus of the evaluation and explanation of the IMH prognosis is controversial among physicians. Here, we present the natural course of IMH together with the pathological diagnosis and features to provide supportive data when approaching patients with IMH. We retrospectively evaluated 350 patients with IMH who underwent a renal biopsy between 2002 and 2011, and the pathological diagnosis and chronic histopathological features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) were reviewed. Deterioration of renal function was examined during follow up. The patients with IMH were evaluated for a mean of 86 months. IgA nephropathy was the most common diagnosis in 164 patients (46.9%). Chronic histopathological changes were observed in 166 (47.4%) but was not correlated with proteinuria or a decline in renal function. Ten patients developed proteinuria, and all of them had IgA nephropathy. Three patients progressed to chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m2 but none progressed to end stage renal disease. In conclusion, IMH had a generally benign course during 7-years of observation, although IgA nephropathy should be monitored if it progresses to proteinuria. Future prospective randomized studies may help conclude the long-term prognosis and lead to a consensus for managing IMH.

Portal Vein Thrombosis with Sepsis Caused by Inflammation at Colonic Stent Insertion Site / 대한소화기학회지

Portal vein thrombosis is an uncommon but an important cause of portal hypertension. The most common etiological factors of portal vein thrombosis are liver cirrhosis and malignancy. Albeit rare, portal vein thrombosis can also occur in the presence of local infection and inflammation such as pancreatitis or cholecystitis. A 52-year-old male was admitted because of general weakness and poor oral intake. He had an operation for colon cancer 18 months ago. However, colonic stent had to be inserted afterwards because stricture developed at anastomosis site. Computed tomography taken at admission revealed portal vein thrombosis and inflammation at colonic stent insertion site. Blood culture was positive for Escherichia coli. After antibiotic therapy, portal vein thrombosis resolved. Herein, we report a case of portal vein thrombosis with sepsis caused by inflammation at colonic stent insertion site which was successfully treated with antibiotics.

Emphysematous pyelonephritis initially presenting as a spontaneous subcapsular hematoma in a diabetic patient

Emphysematous pyelonephritis (EPN) is a life-threatening infection characterized by the formation of gas. Complications of EPN include septic shock, acute renal failure, and disseminated intravascular coagulation. Spontaneous subcapsular hematoma (SCH) has also been reported as a rare complication of EPN, although there have been no reports to date of this occurring prior to the presentation of EPN. We report a case of EPN that initially presented as spontaneous SCH. The patient was admitted for left flank pain, and initial computed tomography revealed SCH without any air shadows. Laboratory findings and clinical symptoms suggested the presence of urinary tract infection and the patient was started on antibiotics. Fever developed 24 hours after admission. On follow-up computed tomography 7 days later, EPN was newly observed, and a percutaneous drain was inserted. Blood, urine, and drainage fluid cultures all revealed growth of extended-spectrum beta-lactamase-negative Escherichia coli.

Case of Acute Methemoglobinemia Caused by Nitrobenzene Ingestion / 대한내과학회지

Nitrobenzene is a poisonous agent, not commonly encountered in clinical practice, which belongs to the aniline dyes. Ingestion of nitrobenzene may cause methemoglobinemia, a condition in which the iron in hemoglobin is oxidized from the ferrous state to the ferric state, resulting in the inability to transport oxygen. A 41-year-old man presented with the clinical features of methemoglobinemia after drinking nitrobenzene. The patient was treated conservatively with intravenous methylene blue. We report a case of acute methemoglobinemia due to ingestion of nitrobenzene.

A Case of Pulmonary MALT Lymphoma Arising from Lymphocytic Interstitial Pneumonitis / 결핵및호흡기질환

Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare disease. This disorder is considered to be a model of antigen-driven lymphoma, which is driven either by autoantigens or by chronic inflammatory conditions. Low-grade B-cell MALT lymphoma may develop from a nonneoplastic pulmonary lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP). A recent estimate predicts that less than 5% of LIP patients acquire malignant, low-grade, B-cell lymphoma. In Korea, there has been no previous report of malignant low-grade, B-cell lymphoma, acquired from LIP. Here, we present the case of a patient with LIP that developed into pulmonary MALT lymphoma, six years after diagnosis.

A Case of Asymptomatic, Localized, and Idiopathic Diffuse Alveolar Damage / 결핵및호흡기질환

Diffuse alveolar damage (DAD) is a histological change in lung tissue, and is generally caused by an acute lung injury, which is characterized by bilateral and widespread damages. Localized DAD occurs very rarely. The causes for DAD are numerous, but the chief cause is acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia, in cases of idiopathic manifestation. The 82-year-old patient, in this case study, showed a DAD lesion in only 1 lobe. The patient was otherwise healthy, with no previous symptoms of DAD. He was admitted to our medical center owing to localized infiltration, observed on his chest radiograph. Laboratory studies showed no signs of infections. DAD was confirmed by a surgical lung biopsy. The patient received corticosteroid treatment and had gradually improved. We report the case of a patient with localized, idiopathic DAD that cannot be classified as acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia.

A Case of Mycobacterium kansasii Lymphadenitis in HIV-infected Patient / 감염과화학요법

Nontuberculous mycobacteria (NTM) are widely present in the environment, although they rarely cause infection in humans. However, infection by NTM has been increasingly recognized worldwide in the context of the human immunodeficiency virus (HIV) epidemic and therapeutic immunosuppression. Mycobacterium kansasii is a slow-growing photochromogenic mycobacterium, which mainly causes pulmonary infection in patients with predisposing lung diseases, and, occasionally, disseminated infection with poor outcomes in immunocompromised patients. We report on the first case of lymphadenitis caused by infection with M.kansasii in an HIV-infected patient in Korea. The patient showed significant improvement after receiving antituberculous therapy (isoniazid, rifabutin) in combination with surgical drainage and highly active antiretroviral therapy (abacavir, lamivudine, and lopinavir/ritonavir).