Desmoplastic Small Round Cell Tumor: Imaging Pattern of Disease at Presentation.

OBJECTIVE: The purpose of this study is to evaluate the clinical, pathologic, and multimodality cross-sectional imaging features of a cohort of 94 patients with desmoplastic small round cell tumor (DSRCT). MATERIALS AND METHODS: This retrospective study of 94 patients with pathologically verified DSRCT was conducted at a tertiary cancer center between 2001 and 2013. Epidemiologic, clinical, pathologic, and imaging findings were recorded. Tumor size, location, and shape and the distribution pattern of metastases at presentation were analyzed. RESULTS: DSRCT most often occurred in young patients (median age, 21.5 years; range, 5-53 years), showing a marked predominance in male patients (86 male patients vs eight female patients). Eighty nine-patients (95%) were white (defined in this study as white or Hispanic), four were African American, and one was of Asian descent. Most patients had symptoms, with abdominal pain noted as the most common symptom. At initial presentation, 85 patients (90%) had multifocal disease, nodular disease, diffuse omental and peritoneal disease, or a combination of these conditions. Thirty-eight patients (40%) had diaphragmatic involvement. Thirty-two patients (34%) had liver metastases, and 49 patients (52%) had retroperitoneal involvement in the form of implants, tumoral extension, or nodal involvement. With regard to thoracic findings, 33 patients (35%) had nodal disease, 17 (18%) had pleural effusions, and only two (2%) had lung metastases at presentation. Twelve patients (13%) had calcified lesions. CONCLUSION: DSRCT is a rare, multifocal peritoneal malignancy with frequently disseminated abdominal disease at presentation. In the abdomen, disease most commonly involves the omentum and peritoneum, followed by the retroperitoneum. The liver is the most common solid visceral metastatic site. A substantial number of patients have diaphragmatic involvement. In the thorax, nodal and pleural involvement is more common than lung involvement.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric ovarian tumors: a novel treatment approach.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used in adults with ovarian carcinoma proving overall survival benefit in randomized trials, but measured in months. Diffuse peritoneal disease from pediatric type ovarian tumors is rare. We applied CRS and HIPEC to pediatric girls with diffuse peritoneal disease as part of a clinical trial. METHODS: In all patients complete cytoreduction was followed by HIPEC using 100 mg/m2 of cisplatin for 90 min in a closed technique. All received neoadjuvant chemotherapy. Patients with disease outside of the abdominal cavity were excluded. RESULTS: Of 101 pediatric CRS and HIPEC operations, 8 had ovarian primary tumors and multifocal peritoneal disease. There were three yolk sac tumors (germ cell, mixed teratoma), one Sertoli­Leydig, one PNET of the ovary, one choriocarcinoma, one juvenile granulosa cell tumor and one adenocarcinoma. Age ranged 4­18 years. Three of the 8 (37 %) recurred and died. The remaining 63 % are disease free 2­6 years post HIPEC. Overall survival and relapse-free survival in this cohort was 64 and 62 %, respectively [CI 0.64 (0.34, 1); 0.62 (0.37, 1)]. CONCLUSIONS: This is the first report of CRS and HIPEC in pediatric ovarian tumors. HIPEC may be effective in pediatric-type ovarian tumors. More study is needed in a larger cohort.

Recurrent osteosarcoma with a single pulmonary metastasis: a multi-institutional review.

BACKGROUND: Late relapse and solitary lesion are positive prognostic factors in recurrent osteosarcoma. METHODS: We reviewed the records of 39 patients treated at three major centres for recurrent osteosarcoma with a single pulmonary metastasis more than 1 year after diagnosis. We analysed their outcomes with respect to clinical factors and treatment with chemotherapy. RESULTS: Median age at diagnosis was 14.6 years. Relapse occurred at a median of 2.5 years (range, 1.2-8.2 years) after initial diagnosis. At relapse, all patients were treated by metastasectomy; 12 (31%) patients also received chemotherapy. There was no difference in time to recurrence or nodule size between the patients who received or did not receive chemotherapy at relapse. Sixteen patients had no subsequent recurrence, 13 of whom survive without evidence of disease. The 5-year and 10-year estimates of post-relapse event-free survival (PREFS) were 33.0±7.5% and 33.0±9.6%, respectively, and of post-relapse survival (PRS) 56.8±8.6% and 53.0±11.0%, respectively. There was a trend for nodules <1.5 cm to correlate positively with PREFS (P=0.070) but not PRS (P=0.49). Chemotherapy at first relapse was not associated with PREFS or PRS. CONCLUSION: Approximately half of the patients with recurrent osteosarcoma presenting as a single pulmonary metastasis more than 1 year after diagnosis were long-term survivors. Metastasectomy was the primary treatment; chemotherapy did not add benefit.

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy.

OBJECTIVE: To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. METHODS: A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS. RESULTS: 312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19-85); 86% women had advanced stage (III-IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR=0.98, 95% CI 0.97-1.00, p=0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index=0.737). CONCLUSION: Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed.

Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.

PURPOSE: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. METHODS: Patients received mifamurtide 2 mg/m(2) intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. RESULTS: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a log-linear manner 2-6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m(2) mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills + fever or headache + fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N = 40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) CONCLUSIONS: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Association between pre-donation serum uric acid concentration and change in renal function after living kidney donation in women.

BACKGROUND: Reduction in renal mass after unilateral nephrectomy causes functional and structural changes in the remaining kidney. AIM: We aimed to investigate the association between pre-donation serum uric acid (SUA) concentration and the change in renal function after living kidney donation. METHODS: This retrospective study included 413 living kidney donors from a single centre. We collected medical history and laboratory findings at baseline and 6 months after donation. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. Main outcomes were the percentage change in eGFR from before to 6 months after donation and the percentage of patients whose eGFR decreased by >25% after donation compared with the pre-donation baseline value. RESULTS: Mean age was 40 ± 11 years, and eGFR was 106 ± 14 mL/min/1.73 m(2). In women, the SUA concentration was linearly associated with the change in eGFR after donation independently of baseline eGFR (standardised coefficient - 0.16, P = 0.04). Multiple logistic analysis showed that a 59.5 µmol/L increase in baseline SUA concentration was associated with a 1.7-fold higher risk of a > 25% decrease in eGFR after donor nephrectomy (95% confidence interval, 1.2-2.5; P = 0.007) in women. In contrast, SUA concentration was not an independent risk factor of decrease in eGFR after donor nephrectomy in men. CONCLUSIONS: Pre-donation SUA concentration is associated independently with the change in renal function after donor nephrectomy in women but not in men.

Pharmacokinetics of a new once-daily controlled-release sarpogrelate hydrochloride compared with immediate-release formulation and the effect of food.

WHAT IS KNOWN AND OBJECTIVE: Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A antagonist that inhibits platelet aggregation and vasoconstriction. The aim of this study was to compare the pharmacokinetics of a sarpogrelate controlled-release formulation (CR) with those of the immediate-release formulation (IR). The effect of food on the pharmacokinetics of CR sarpogrelate was also evaluated. METHODS: A randomized, open-label, 3-period, 3-treatment crossover study was conducted in 50 healthy male subjects. Subjects were allocated into one of six sequence groups. In one period, a 100-mg IR formulation was administered three times at 6-h intervals, and in the other two periods, a 300-mg CR formulation was administered once to fasting and once to fed subjects. Each period was separated by a 7-day washout period. Serial blood samples were collected up to 24 h after the first drug administration in each period. The plasma concentrations of sarpogrelate were analysed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental methods. RESULTS AND DISCUSSION: After the administration of the IR formulation, the plasma concentration reached a peak at 0·48 h and the drug was eliminated with a half-life (t1/2 ) of 0·7 h. After administration of the CR formulation, the plasma concentration reached a peak at 0·5 h and the drug was eliminated with a t1/2 of 3·23 h. The geometric mean ratios (CR/IR) for sarpogrelate area under the plasma concentration-time curve (AUC) and the maximum plasma drug concentration (Cmax) were 1·2040 (90% confidence interval (CI): 1·0992-1·3188) and 0·9462 (90% CI: 0·8504-1·0529). When CR was administered to fed subjects, the time to peak concentration was prolonged to 3·97 h and t1/2 was shortened to 1·45 h. The geometric mean ratios (fasting/fed) for sarpogrelate AUC and Cmax were 0·8573 (90% CI: 0·7687-0·9561) and 0·6452 (90% CI: 0·5671-0·7341). WHAT IS NEW AND CONCLUSION: After the administration of CR and IR formulations of the same daily dose of sarpogrelate hydrochloride, the overall systemic exposure was slightly higher for the CR than for the IR formulation, whereas peak concentration was comparable between the two formulations. Food reduced the bioavailability of sarpogrelate CR.

Urinary angiotensinogen levels reflect the severity of renal histopathology in patients with chronic kidney disease.

BACKGROUND/AIMS: Recent studies have suggested that urinary angiotensinogen (AGT) reflects the activity of the intrarenal renin angiotensin system (RAS), which is involved in tissue injury in patients with chronic kidney disease. In this study, we investigated whether urinary AGT directly reflected the severity of histopathology in such patients. METHODS: AGT was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) on urine and plasma samples obtained from 58 patients on the day of renal biopsy. We measured the urinary transforming growth factor (TGF)-beta1, a representative cytokine of fibrogenic property, and analyzed the correlation among urinary TGF-beta1, urinary AGT, and the severity of renal injury. Mesangial proliferation, glomerulosclerosis, tubular atrophy and interstitial fibrosis were scored for the biopsied tissues. RESULTS: Urinary AGT levels correlated positively with proteinuria, urinary TGF-beta1 levels and diastolic blood pressure, but negatively with the estimated glomerular filtration rate (GFR). Urinary AGT concentrations were increased in patients with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. CONCLUSION: Urinary AGT levels correlated with the deterioration of renal function in patients with chronic kidney disease and reflected the histological severity of renal injury.

Combination treatment with corticosteroid, cyclosporine A, and mycophenolate in refractory nephrotic syndrome.

BACKGROUND/AIMS: Refractory nephrotic syndrome (NS) is problematic because the optimal therapy for this disease is unclear and because persistent NS progresses eventually to end-stage renal disease. We report our experience using a combination of corticosteroid, cyclosporine A (CsA), and mycophenolate mofetil (MMF) to treat 10 refractory NS patients. METHODS: Ten refractory NS patients, who showed resistance to corticosteroid and CsA, were treated with triple immunosuppressive therapy. Cyclophosphamide and MMF had been used previously in 6 patients, but had failed to induce remission. RESULTS: Triple immunosuppressive therapy was discontinued after 4 months in 1 patient because of progressive azotemia. Partial remission was achieved in 9 of the 10 patients after 10 months, and remission was maintained during the treatment (urine protein to creatinine ratio, mg/mg, baseline vs. 12th month; 5.7 ± 1.8 vs. 1.4 ± 0.7). Renal function was preserved in these 9 patients (estimated GFR, ml/min/1.73 m2, baseline vs. 12th month; 71.4 ± 29.1 vs. 68.9 ± 31.5). Of the 7 patients who discontinued triple immunosuppressive therapy, remission and renal function were maintained in 4 patients. CONCLUSION: Triple immunosuppressive therapy significantly reduced proteinuria and preserved renal function in refractory NS patients, indicating a promising role of this therapy for refractory NS.

Purple urine bag syndrome: case report and literature review.

Purple urine bag syndrome (PUBS) is a medical syndrome in which there is purple discoloration of the urine of catheterized patients as well as discoloration of the collecting bag and the associated tubing. This rare condition, which mostly affects women, is generally associated with catheter-associated urinary tract infection, chronic constipation and alkaline urine. PUBS may be caused by sequential chemical reactions involving tryptophan from food in the gastrointestinal tract. The clinical course of PUBS is generally benign, and intensive treatment is not usually needed. We present 3 cases of this unusual and interesting phenomenon and a literature review.

Gynecologic oncology patients are ready for telemedicine in routine care: Results from a pre-COVID survey.

OBJECTIVES: To assess telemedicine readiness of gynecologic oncology patients, particularly those at risk for care access disparities (increased distance to care, rural populations.). METHODS: Patients at all disease/treatment stages completed an anonymous survey during in-person outpatient appointments at an academic comprehensive cancer center from 1/6/2020 to 2/28/2020, conducted prior to the COVID-19 pandemic, before the introduction of telemedicine in this practice. RESULTS: Of 180 patients approached, 170 completed the survey (94.4%). Mean age was 59.6 years; 73.4% identified as White, 23.7% Black, and 2.9% other race. Ovarian cancer was most common (41.2%), followed by endometrial (27.1%), cervical (20.6%), and vaginal/vulvar (7.1%). Most patients traveled > 50 miles for appointments (63.8%); they were more likely from rural counties with significantly higher travel costs/visit ($60.77 vs $37.98, p = 0.026.) The majority expressed interest in using telemedicine (75.7%) or a smartphone app (87.5%) in their care. The majority of patients with difficulty attending appointments (88.9 vs 70.2%, p = 0.02) or from rural counties (88.7% vs 69.6%, p = 0.03) were interested in telemedicine; those with both characteristics reported 100% interest. The majority in both urban and rural counties had home internet access, and reported similarly high rates of daily use (79% vs 75%). Race and age were not associated with differences in internet access or use or telemedicine interest. CONCLUSIONS: Telemedicine is attractive to the majority of patients and may offer financial/logistical advantages. Patients have high internet use rates and comfort with using technology for healthcare. Telemedicine should be incorporated into standard practice beyond the COVID-19 pandemic to reduce healthcare access disparities.

A fully validated HPLC method for the simultaneous determination of acitretin and etretinate in plasma and its application to a pharmacokinetic study in healthy Korean subjects.

OBJECTIVE: Acitretin is used for the treatment of psoriasis. The purpose of this study was to validate an HPLC method for the determination of acitretin and etretinate and to investigate the pharmacokinetic characteristics of acitretin in healthy Korean subjects. MATERIALS AND METHODS: Plasma samples or calibrators were mixed with acetonitrile and retinyl acetate (internal standard). Butanol: acetonitrile (1:1 v/v) and K2HPO4 were added later. After vortexing, 30 microl of the supernatant was injected directly into the analytical column of an HPLC system. The samples were separated by C18 reversed phase HPLC and UV detection was performed at 350 nm. Various assay performances were evaluated. RESULTS: The linearity of acitretin and etretinate was adequate up to 500 ng/ml (R2 = 0.9937 for acitretin and R2 = 0.9923 for etretinate). The accuracy was 89.5 - 113.5% and the precision was satisfactory (within-run CV, 4.4 - 15.8%; between-run CV, 3.3 - 17.4%). The LLOQ was 2 ng/ml and the stability and specificity were satisfactory. However, after storage at room temperature for 24 h under light exposure, the concentrations of acitretin and etretinate decreased by 26.0 - 66.5%. Extraction recovery was 75.1 - 91.5%. Nine healthy Korean subjects were evaluated to study the pharmacokinetics of acitretin. A single oral dose of 30 mg acitretin (Neotigason, Roche Pharmaceuticals) was given to all volunteers. The mean +/- SD pharmacokinetics of acitretin in Koreans were as follows: Cmax 148.7 +/- 93.0 ng/ml, tmax 3.2 +/- 1.3 h, t1/2 81.2 +/- 26.5 h, and AUClast 2641.9 +/- 1274.8 ng h/ml. CONCLUSION: A simple HPLC method for the simultaneous determination of acitretin and etretinate was validated, and the pharmacokinetic characteristics of acitretin in the Korean population were investigated.

Clinical Impact of a Protocolized Kidney Donor Follow-up System.

BACKGROUND: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated. METHODS: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria. RESULTS: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period. CONCLUSION: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors.

Cluster intradermal DNA vaccination rapidly induces E7-specific CD8+ T-cell immune responses leading to therapeutic antitumor effects.

Intradermal administration of DNA vaccines via a gene gun represents a feasible strategy to deliver DNA directly into the professional antigen-presenting cells (APCs) in the skin. This helps to facilitate the enhancement of DNA vaccine potency via strategies that modify the properties of APCs. We have previously demonstrated that DNA vaccines encoding human papillomavirus type 16 (HPV-16) E7 antigen linked to calreticulin (CRT) are capable of enhancing the E7-specific CD+ T-cell immune responses and antitumor effects against E7-expressing tumors. It has also been shown that cluster (short-interval) DNA vaccination regimen generates potent immune responses in a minimal time frame. Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8+ T-cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death. We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8+ T cells, resulting in significant therapeutic antitumor effects in vaccinated mice. We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8+ T-cell immune responses in the systemic circulation as well as in the tumors. In addition, this vaccination regimen also led to significantly lower levels of CD4+Foxp3+ T-regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor-infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death. Thus, our study has significant potential for future clinical translation.

Congenital acantholytic dyskeratotic epidermal naevus following Blaschko's lines versus segmental Darier's disease.

A Japanese newborn male with an unremarkable family history presented at birth with verrucous papules on the left side of the trunk and limbs, distributed along Blaschko's lines. Histological examination showed mild acantholytic dyskeratosis, consistent with Darier's disease; however, search for mutations of the SERCA gene, performed on DNA extracted from cells from involved and uninvolved skin and peripheral blood proved negative. The absence of detectable SERCA mutations did not allow confirmation of the diagnosis of (segmental) Darier's disease, and a tentative diagnosis of congenital acantholytic dyskeratotic epidermal nevus was considered. The relationship between the two conditions is briefly discussed.

The incidence and clinical outcome of YMDD mutants in hepatitis B surface antigen-positive renal allograft recipients after prolonged lamivudine therapy.

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV), prolonged therapy may induce the development of LAM-resistant strains, YMDD mutants. Although YMDD mutants have impaired replication that leads to a benign clinical course compared with wild-type virus, some immunosuppressive agents may enhance replication of YMDD mutants, causing a severe hepatitis flare. We retrospectively investigated the incidence and clinical outcomes of YMDD mutants in renal allograft recipients on immunosuppressive treatment. Clinical records of 25 renal allograft recipients, who underwent renal transplantation between December 1997 and February 2006 were hepatitis B surface antigen positive at the time of transplantation, were reviewed. All patients received LAM treatment after renal transplantation. Over 9 to 98 months of follow-up, 16 patients (64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%) showed persistent or increased levels of HBV DNA. Seven were identified as having developed YMDD mutants. Although genotypic analysis was not performed, YMDD mutants were strongly suspected in another two patients, who developed severe hepatic dysfunction combined with high levels of HBV viremia at close to 2 years of LAM therapy. One patient recovered after hepatic transplantation and another patient died of hepatic failure. In conclusion, the incidence of YMDD mutants was similar to that of nonimmunosuppressed individuals; however, the presence of these mutants made it more likely for severe liver disease to develop in renal transplant recipients. Therefore, close monitoring for the development of YMDD mutants should be performed during LAM treatment, especially in this group of patients.

Predictive Factors of Renal Adaptation After Nephrectomy in Kidney Donors.

BACKGROUND: Despite compensatory hyperfiltration in remaining nephrons following donor nephrectomy, some donors show impaired renal adaptation and low estimated glomerular filtration rate (eGFR). We investigated the factors predicting early renal adaptation after nephrectomy and identified kidney donors at risk of inadequate renal adaptation. METHODS: A total of 265 living kidney donors from 2010 to 2013 were retrospectively analyzed. Renal function was serially followed for 6 months after the operation. Regression analyses were performed to identify the independent predictors of low eGFR (eGFR <60 mL/min/1.73 m2) and impaired renal adaptation (%Modification of Diet in Renal Disease [MDRD] <66% of baseline eGFR). RESULTS: A total of 148 donors belonged to the low eGFR group, and changes in eGFR (ΔeGFR) at postoperative (PO) 1 day and 1 month were identified as independent predictors of low eGFR. Impaired renal adaptation was related to age, ΔeGFR PO 2-3 days, and ΔeGFR PO 1 month. Early renal adaptation was associated with age, male gender, and residual kidney computerized tomography angiography (CTA) volume. The best sensitivity and specificity were obtained with a cutoff value of ΔeGFR 31 at PO 1 day and 1 month for predicting low eGFR and with a value of ΔeGFR 27 at PO 2-3 days and 1 month for predicting impaired renal adaptation. CONCLUSIONS: Our study showed that the degree of early renal adaptation determines subsequent renal function in kidney donors. Closer monitoring and management may be required in old or male donors with small residual CTA kidney volume as well as donors with persistent ΔeGFR >27 within 1 month of nephrectomy.

Short-Term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation With Uniform Protocol: Significance of Baseline Anti-ABO Titer.

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin.

D-arabinose dehydrogenase and its gene from Saccharomyces cerevisiae.

D-Arabinose dehydrogenase was purified 843-fold from the cytosolic fraction of Saccharomyces cerevisiae with a recovery of 9%. The purified enzyme gave two bands with a molecular mass of 40 and 39 kDa on SDS-PAGE. The native enzyme had a molecular mass of 74 kDa as estimated by Sephacryl S-200 chromatography. Therefore, this enzyme was considered to be a heterodimer. The purified enzyme exhibited maximum activity at pH 10.0 and around 30 degrees C. The enzyme catalysed the oxidation of D-arabinose, L-xylose, L-fucose and L-galactose in the presence of NADP+. The apparent Km values at pH 10.0 with 50 microM NADP+ for D-arabinose, L-xylose, L-fucose, and L-galactose were 161, 24, 98 and 180 mM, respectively. The pH profile of Vmax and kcat/Km showed one ionisable groups around pH 8.3. D-Erythroascorbic acid was formed in vitro from D-arabinose by D-arabinose dehydrogenase and D-arabinono-1,4-lactone oxidase. The N-terminal amino acid sequence of the heavy subunit was Ser-Thr-Glu-Asn-Ile-Val-Glu-Asn-Met-Leu-His-Pro-Lys-Thr-. The N-terminus of the light subunit was blocked. The obtained peptide sequence was identical to the translational product of an unknown open reading frame, YBR149W, in chromosome II of S. cerevisiae. When compared with the translational product of this open reading frame, the peptide sequence was identical to the amino acid sequences of residues 7 to 20. The first six amino acids of this open reading frame were lost in protein sequence, which may be modified post-translationally. The heavy subunit was composed of 344 amino acid residues and its deduced amino acid sequence contained the motifs I, II, and III of aldo-keto reductase and also leucine zipper motif. This enzyme is the first heterodimeric protein of aldo-keto reductase family. In the deletion mutant of this gene, D-arabinose dehydrogenase activity and D-erythroascorbic acid were not detected.