The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.

Role of surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer.

Ovarian cancer is one of the deadliest gynaecological malignancies and tends to be diagnosed at an advanced stage. Similar to many malignancies, surgery plays a critical role in many aspects of ovarian cancer management. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the induction of hyperthermia and delivery of intraperitoneal chemotherapy directly into the peritoneal cavity. Combined with cytoreductive surgery, HIPEC is an emerging treatment modality for ovarian cancer. Ovarian cancer survival outcomes can be improved by treatment with surgery and HIPEC in selected patients. Thus, this study aimed to review the current role of surgery and HIPEC in epithelial ovarian cancer. Evidence from the monumental and recent literature will be introduced.

EVALUATION OF INTERNAL EXPOSURE TO RADIOACTIVE AEROSOL GENERATED FROM PLASMA MELTING SYSTEM USING THE BIDAS CODE.

The radioactive aerosol generated by the Nuclear Power Plant (NPP) decommissioning process can be inhaled by workers and deposited inside the human body, resulting in internal exposure. Because internal exposure, unlike external exposure, is difficult to measure directly, it is all the more necessary to assess the dose workers receive as a result of internal exposure. Precise assessment of the internal exposure necessitates actual measurements in the work environment such as the workers' respiration rate, kind of nuclide and amount of captured nuclide. However, in the event of difficulties in securing these measurements, the internal exposure dose can be estimated based upon the recommended values by the ICRP (International Commission on Radiological Protection) such as the intake fraction and particle size. In this study, 5 µm was selected as the particle size as recommended by the ICRP, and both heavy and light respiratory rates were used in the calculation. With respect to the nuclides contained in the radioactive aerosol and their concentrations, the data captured for the aerosol in the melting facility on the Kozloduy NPP premises in Bulgaria were applied to estimate workers' internal exposure. As a result, each worker was found not to have received more than 20 mSv/yr, which is the maximum annual permissible dose for workers.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Seven-year Follow-up of Resin Infiltration Treatment on Noncavitated Proximal Caries.

The purpose of this case report is to present success and failure outcomes of seven-year follow-up of resin infiltration treatment (RIT) used for the proximal caries of maxillary premolars. Although resin infiltration can be a good option for micro-invasive treatment, long-term follow-up data are not sufficient, and the outcome of this technique can be affected by factors such as technique sensitivity of procedure, patient's caries risk, and depth of caries progression. Therefore, careful case selection, application, and follow-up are needed.

Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) can lead to life-threatening outcomes with rapid spread of the carbapenemase gene in solid organ transplantation (SOT) recipients because of limitations of available antibiotics. We examined the characteristics and importance of CPE acquisition in SOT recipients with large numbers of CPE isolates. METHODS: Between November 2015 and October 2016, 584 CPE isolates were found in 37 recipients and verified by carbapenemase gene multiplex polymerase chain reaction (PCR). One hundred recipients with at least 2 negative results in carbapenemase PCR for stool surveillance and no CPE isolates in clinical samples were retrospectively included. RESULTS: Most CPE isolates were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (546, 93.5%). The most frequent transplantation organ was lung (43.3%), and the most common sample with CPE isolates other than stool was respiratory tract (22.6%). The median time between SOT and first CPE acquisition was 7 days. All-cause mortality was significantly higher in recipients with CPE than in those without CPE (24.3% vs 10.0%; P = .03). In multivariate regression analysis, stool colonization of vancomycin-resistant Enterococci and/or Clostridium difficile during 30 days before SOT (odds ratio [OR], 3.28; 95% CI, 1.24-8.68; P = .02), lung transplantation (OR, 4.50; 95% CI, 1.19-17.03; P = .03), and intensive care unit stay ≥2 weeks (OR, 6.21; 95% CI, 1.72-22.45; P = .005) were associated with acquisition of CPE. CONCLUSIONS: Early posttransplantation CPE acquisition may affect the clinical outcome of SOT recipients. Careful screening for CPE during the early posttransplantation period would be meaningful in recipients with risk factors.

Impact of Korea Network for Organ Sharing Expanded Donor Criteria on Delayed Graft Fuction in Kidney Transplantation: A Single-Center Experience.

BACKGROUND: The shortage of donor organs has been a major challenge in transplantation. In an effort to reduce the donor shortage, kidney transplantation (KT) using expanded criteria donors (ECD) was encouraged. In Korea, transplantation centers used the Korea Network for Organ Sharing (KONOS) ECD criteria, which is different from the United Network for Organ Sharing (UNOS) criteria. The aim of this study is to evaluate the predictive power of KONOS criteria on delayed graft function (DGF) in comparison to UNOS criteria. METHODS: A total of 376 recipients who underwent deceased donor kidney transplantation between January 2005 and December 2014 at Severance Hospital were retrospectively reviewed. Of these, 130 cases satisfied KONOS ECD, while the others followed KONOS standard criteria donor (SCD). RESULTS: Donor age and history of hypertension was significantly higher with KONOS ECD than with KONOS SCD. In KONOS subgroup analysis, donor characteristics were different than with UNOS criteria. The incidence of DGF was higher in the KONOS ECD group than in the KONOS SCD group. However, UNOS ECD showed a high incidence of DGF compared to UNOS SCD with the same KONOS criteria. UNOS ECD was an independent risk factor for DGF in multivariate analysis. However, KONOS ECD was not a risk factor for DGF. Although glomerular filtration rate was inferior in the KONOS ECD group compared to the KONOS SCD group, the UNOS SCD group within the KONOS ECD group showed similar graft function compared to the KONOS SCD group. CONCLUSION: KONOS criteria have a lower predictive power for DGF than UNOS criteria.

Clinical Significance of Macrophage Polarization in Antibody-Mediated Rejection of Renal Allograft.

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.

Impact of Cigarette Smoking on Living Kidney Donors.

BACKGROUND: Smoking is known to result in a decline in renal allograft function and survival of recipients; however, the effect of smoking on living kidney donors remains unknown. In this study we evaluated the impact of cigarette smoking on renal function of kidney donors. METHODS: Among 1056 donors who underwent nephrectomy, 612 completed the 6-month follow-up protocol and were enrolled in the study. The association of smoking status, including pack-years smoking history, and postoperative renal function was evaluated. RESULTS: Among donors, 68.1% had never smoked, 8% were former smokers, and 23.9% were current smokers. Donors who never smoked were older than former and current smokers (42.3 ± 11.8, 41.9 ± 11.1, and 38.3 ± 10.9 years, respectively; P < .001). There was no difference in preoperative renal function between groups; however, postoperative estimated glomerular filtration rate (eGFR) was lower in former and current smokers than in those who never smoked (64.6 ± 13.8, 64.7 ± 12.3, and 67.8 ± 13.1 mL/min/1.73 m2, respectively; P = .023). In former and current smokers, pack-years smoking history was negatively associated with pre- and postoperative eGFR (r = -0.305 and -0.435, P < .001), and correlated with postoperative percent eGFR decline (r = 0.248, P < .001). Smoking history was associated with postoperative development of chronic kidney disease (CKD). Especially in former smokers, a smoking history of more than 12 pack-years was strongly associated with development of CKD (odds ratio = 7.5, P = .003). CONCLUSION: Even if they no longer smoke, donors with a smoking history require close observation due to increased risk of CKD development after kidney donation. A detailed pack-years smoking history should be obtained, and smoking cessation strategies should be implemented in kidney donors.

Carbapenem-resistant Acinetobacter baumannii Bacteremia in Liver Transplant Recipients.

BACKGROUND: Acinetobacter baumannii has become an increasingly important nosocomial pathogen. Carbapenem is the preferred drug of choice for treatment of multidrug-resistant gram-negative bacilli, but carbapenem-resistant A baumannii (CRAB) has now emerged. The aim of this study was to determine the incidence, outcomes, and risk factors for CRAB bacteremia in liver transplant recipients. METHODS: The medical records of 393 subjects who underwent living donor liver transplant at Seoul St. Mary's Hospital from January 2008 to April 2015 were reviewed. RESULTS: A total of 92 (23.4%) bacteremic patients, comprising 156 episodes, were identified. Fourteen patients, totaling 18 episodes, had CRAB bacteremia. The median time of emergence of CRAB bacteremia was 55.5 (range, 2-829) days after transplantation, and 72.2% of episodes (n = 13) occurred within 6 months of transplant. The presumed sources of infection were intra-abdominal (n = 11, 61.1%), biliary tract (n = 3, 16.7%), lung (n = 2, 11.1%), catheter (n = 1, 5.6%), and wound (n = 1, 5.6%). By multivariate analysis, length of post-transplant intensive care unit (ICU) stay (odds ratio [OR], 1.1, 95% confidence interval [CI], 1.11-1.15; P = .04) was associated with CRAB bacteremia. Overall mortality in 14 recipients with CRAB bacteremia was 50% (n = 7), but only 10% (30 of 301) in non-bacteremic patients and 20.5% (16 of 78) in other bacteremic patients excluding CRAB (P < .001). CONCLUSION: In our study, patients with CRAB bacteremia after liver transplant showed an unfavorable outcome and, recently, CRAB has become an increasingly major pathogen at our center. Reducing the length of ICU stay could be a solution for preventing CRAB bacteremia.

Impact of Pretransplant Infections on Clinical Course in Liver Transplant Recipients.

BACKGROUND: Uncontrolled infections are known to be an absolute contraindication for liver transplantation; however, the posttransplant prognosis of recipients treated for pretransplant infection is unclear. The aim of this study was to analyze pretransplant infections among liver transplant recipients and to determine their impact on posttransplant clinical outcomes. METHODS: This study retrospectively analyzed 357 subjects who had undergone living-donor liver transplantation between January 2008 and May 2014. RESULTS: Among 357 recipients, 71 patients (19.8%) had 74 episodes of infectious complications before liver transplantation. These complications consisted of pneumonia (n = 13), spontaneous bacterial peritonitis (n = 12), catheter-related infection (n = 10), urinary tract infection (n = 12), biliary tract infection (n = 6), and skin and soft-tissue infection (n = 3). Twenty-six patients experienced 29 episodes of bacteremia, and the most common pathogens were coagulase-negative staphylococci (n = 8), followed by Klebsiella pneumoniae (n = 7), Staphylococcus aureus (n = 4), and Streptococcus species (n = 3). Twenty-one bacteremic episodes (70%) occurred within 1 month before transplantation (n = 4). Recipients with pretransplant infections had significantly more frequent posttransplant infections (71.8% [51 of 71] vs 47.2% [35 of 286]; P = .0001), posttransplant bacteremia (33.8% [24 of 71] vs 20.3% [58 of 286]; P = .015), and longer posttransplant intensive care unit stays (11.2 ± 10.7 days vs 7.3 ± 4.2 days; P = .0004) than those without pretransplant infections. However, episodes of rejection (P = .36), length of hospitalization (P = .10), 28-day mortality (P = .31), and 1-year mortality (P = .61) after transplantation were not significantly different between the 2 groups. CONCLUSIONS: Pretransplant infection had an impact on posttransplant morbidity, although not on rejection and mortality. Alertness for posttransplant infection and proper management (including effective antimicrobial coverage) would improve patient morbidity.

Usefulness of Multi-Detector Computed Tomography Scanning as a Replacement for Diethylenetriamine Pentaacetic Acid.

BACKGROUND: Diethylenetriamine pentaacetic acid (DTPA) and multi-detector computed tomography (MDCT) can predict postoperative estimated glomerular filtration rate (eGFR) in a live kidney donor. Accordingly, we compared predicted eGFR measured by use of DTPA and MDCT. METHODS: From January 2013 to May 2015, 264 live kidney donors were enrolled. All donors underwent preoperative DTPA and MDCT, and bilateral renal cortex volume was measured by use of MDCT. We estimated DTPA-eGFR [remaining split renal function (%) × preoperative eGFR] and Vol-eGFR [remaining renal volume/total renal volume (%) × preoperative eGFR] and analyzed DTPA-eGFR, Vol-eGFR, and Modification of Diet in Renal Disease (MDRD)-eGFR during week 1 and in months 1, 3, and 6. Additionally, we compared DTPA-eGFR and Vol-eGFR by use of the formula ΔeGFR (maximum eGFR minus minimum eGFR during 6 months). RESULTS: The mean DTPA-eGFR and Vol-eGFR values (mL/min/1.73 m2) were 52.97 ± 10.32 and 51.26 ± 10.26, respectively. Predictions of the dominant side did not agree in 113 of 303 (37.3%) cases. Postoperative MDRD-eGFR exhibited a statistically significant correlation with total renal volume, DTPA-eGFR, and Vol-eGFR (P < .0001). A significant correlation was found between ΔeGFR and total renal volume, DTPA-eGFR, and Vol-eGFR (P < .0001). Receiver operating characteristic curves were generated to predict the possibility of eGFR <60 mL/min/1.73 m2 at 6 months, using DTPA-eGFR and Vol-eGFR, which indicated that DTPA-eGFR (area under the curve = 0.858; P < .0001) and Vol-eGFR (area under the curve = 0.878; P < .0001) could predict chronic kidney disease class III at 6 months. CONCLUSIONS: MDRD-eGFR, Vol-eGFR, and DTPA-eGFR were significantly correlated. Moreover, Vol-eGFR and DTPA-eGFR exhibited high predictive value for chronic kidney disease class III at 6 months, whereas Vol-eGFR was a good predictor of renal function recovery.

Clinical Investigation Into Plasma Neutrophil Gelatinase-Associated Lipocalin and Body Adipose Tissue Associated With Remaining Renal Function in Living Kidney Donor.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) is known to increase in proportion to the degree and period of renal damage. This study aimed to evaluate the clinical relevance of pNGAL and body adipose tissue to remaining renal function in living kidney donors. METHODS: Between July 2013 and February 2015, 75 live kidney donors were enrolled. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and VAT/SAT ratio were measured in preoperative CT scan which performed before surgery. We analyzed the correlation among the variables (VAT, SAT, and VAT/SAT ratio), eGFR and pNGAL. ΔpNGAL-max(=Maximum pNGAL-measures), ΔpNGAL-min(=Minimum pNGAL-measures), ΔeGFR-max(=Maximum eGFR-measures) and ΔeGFR-min(=Minimum eGFR-measures) were also analyzed. RESULTS: The highest value of pNGAL (207.46 ± 76 ng/mL) was observed on postoperative day 7, and the lowest value of eGFR (57.52 ± 11.20 mL/min/1.73 m2) was also measured on postoperative day 7. A significant correlation was found between ΔpNGAL, VAT, and VAT-to-SAT ratio. Moreover, a significant correlation between ΔpNGALmin and ΔeGFRmin was revealed. Also, VAT-to-SAT ratio was correlated with ΔeGFRmin during the all of the follow-up periods, and it was also correlated with ΔpNGALmin until postoperative day 3. CONCLUSION: There was a correlation between the elevation of pNGAL until postoperative day 5 and the decrease of eGFR after living donor nephrectomy. VAT-to-SAT ratio had a significant correlation with both ΔpNGALmin and eGFRmin. Given the metabolism of pNGAL, the increase of pNGAL seemed to be affected as a consequence of body adipose tissue.

Impact of the Ratio of Visceral to Subcutaneous Adipose Tissue in Donor Nephrectomy Patients.

OBJECTIVE: It was reported that a metabolic syndrome affected the remaining renal function after living donor nephrectomy. However, the measurement of waist circumference is unclear because it cannot distinguish between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We investigate the clinical correlation between body adipose tissue and renal function recovery after living donor nephrectomy. METHODS: From July 2013 to February 2015, 75 living kidney donors were enrolled. The VAT and SAT were measured by preoperative computed tomography (CT) scan. Body mass index (BMI), VAT, SAT, and VAT-to-SAT ratio were analyzed according to a postoperative renal function recovery. Receiver operating characteristic (ROC) was performed to predict estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 at postoperative 6 months for BMI, VAT, SAT, and VAT-to-SAT ratio. RESULTS: The lowest value of eGFR (57.52 ± 11.20 mL/min/1.73 m2) was measured at postoperative day 7. There was no statistically significant difference in eGFR between 1 month and 3 months. BMI, VAT, SAT, and VAT-to-SAT ratio showed a statistically significant correlation with each other (Pearson correlation, P < .05). Also, the recovery time of eGFR was correlated with VAT-to-SAT ratio; it was significant at postoperative 1, 3, and 6 months. VAT-to-SAT ratio (0.654, 95% confidence interval 0.525-0.783, P = .024) had higher predictive value in ROC. CONCLUSION: We developed a new variable to predict the value of lower eGFR (less than 60 mL/min/1.73 m2) at a postoperative 6 months in living kidney donor. According to a CT scan, VAT-to-SAT ratio can predict renal function recovery.

Association between 24-hour combined multichannel intraluminal impedance-pH monitoring and symptoms or quality of life in patients with laryngopharyngeal reflux.

OBJECTIVE: To evaluate the association between the parameters of 24-hour multichannel intraluminal impedance (MII)-pH monitoring and the symptoms or quality of life (QoL) in laryngopharyngeal reflux (LPR) patients. DESIGN: Prospective cohort study without controls. SETTING: University teaching hospital. METHODS: Forty-five LPR patients were selected from subjects who underwent 24-hour MII-pH monitoring and were diagnosed with LPR from September 2014 to May 2015. Reflux Symptom Index (RSI), Health-related Quality of Life (HRQoL), Short Form 12 (SF-12) Survey questionnaires were surveyed. Spearman's correlation was used to analyse the association between the symptoms or QoL and 24-hour MII-pH monitoring. RESULTS: Most parameters in 24-hour MII-pH monitoring showed weak or no correlation with RSI, HRQoL and SF-12. Only number of non-acid reflux events that reached the larynx and pharynx (LPR-non-acid) and number of total reflux events that reached the larynx and pharynx (LPR-total) parameters showed strong correlation with heartburn in RSI (R = 0.520, P < 0.001, R = 0.478, P = 0.001, respectively). Multiple regression analysis showed that there was only one significant regression coefficient between LPR-non-acid and voice/hoarseness portion of HRQoL (b = 1.719, P = 0.022). CONCLUSION: Most parameters of 24-hour MII-pH monitoring did not reflect subjective symptoms or QoL in patients with LPR.

Staphylococcus aureus-derived membrane vesicles exacerbate skin inflammation in atopic dermatitis.

BACKGROUND: Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. OBJECTIVE: We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. METHODS: Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD-like skin lesions in a mouse model. RESULTS: The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro-inflammatory cytokine gene expression in vitro. A knock-down of Toll-like receptor 2 or nucleotide-binding oligomerization domain 2 using small interfering RNAs suppressed interleukin-8 gene expression. Topical application of intact S. aureus MVs to AD-like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD-like skin lesions. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.

Outcomes of Kidney Recipients According to Mode of Pretransplantation Renal Replacement Therapy.

The effects of pretransplantation dialysis modality on graft function are key issues in end-stage renal disease patients. The aim of this study was to evaluate post-transplantation outcomes according to pretransplantation renal replacement therapy modality in deceased-donor kidney transplantation. Among 444 deceased-donor kidney transplant recipients in Severance Hospital between April 1993 and Dec 2014, 275 who maintained a unique dialysis modality (hemodialysis [HD; n = 178] or peritoneal dialysis [PD; n = 97]) until transplantation were enrolled. There were no significant differences in sex, age, human leukocyte antigen mismatch, cold ischemic time, or duration of dialysis between groups. There was also no difference in 5-year graft survival between HD and PD groups (87.7% vs. 82.3%, respectively; P = .148). On multivariate Cox regression for risk factors affecting graft survival, renal replacement therapy modality was not found to be a risk factor. However, the rate of delayed graft function was higher in the HD group than in the PD group (32.0% vs. 19.6%, respectively; P = .028). In addition, graft function at 1 week after transplantation in the PD group was superior to that in the HD group. The pretransplantation dialysis modality was found to affect both delayed graft function and early graft function, although not graft survival.

Concurrent Post-Transplantation Diabetes Mellitus in Renal Allograft Recipients With Immunoglobulin A Nephropathy.

BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution. RESULTS: Sixteen patients (14.4%) had PTDM at the time of diagnosis of PTIgAN, which increased to 28 patients (25.2%) at the last follow-up (10.4 years after transplantation). Donor ages were younger in PTIgAN patients with concurrent PTDM. However, other clinical and demographic data were not significantly different between PTIgAN patients with and without PTDM. Histologically, Banff "mm" scores were higher and "M1" of the Oxford classification was more frequent in PTIgAN patients with concurrent PTDM than in patients without PTDM, but the difference did not reach statistical significance. Serum creatinine levels and proteinuria at the time of biopsy and overall graft survival did not vary according to the presence of PTDM both at biopsy and at the last follow-up. CONCLUSIONS: Concurrent PTDM does not significantly influence graft function or outcome for 10 years after transplantation in PTIgAN patients.

Ten-Year Experience With Bowel Transplantation at Seoul St. Mary's Hospital.

A retrospective review of intestinal transplantation (ITx) at Seoul St. Mary's Hospital was made by collecting clinical data over the past 10 years. Fifteen consecutive cases from 2004 were analyzed. Five children and 10 adults (6 months to 69 years of age) were included. Primary diseases in adults included 4 mesenteric vessel thromboses, 2 strangulations, and 1 each of visceral myopathy, malignant gastrointestinal stromal tumor (GIST), mesenteric lymphangiectasis, and injury. Pediatric cases involved 2 Hirschsprung disease, 2 visceral myopathy, and 1 necrotizing enterocolitis. Three of 7 stomas were closed using a serial transverse enteroplasty procedure before transplantation. The ITx were performed using 3 living-donor Itx, 12 deceased-donor ITx, 14 isolated Itx, and 1 modified multivisceral transplantation. Daclizumab, basiliximab, alemtusumab, or basiliximab with rabbit antithymocyte globulin (rATG) was used for the induction; tacrolimus monotherapy was used as the basic maintenance immunosuppressant; and m-TOR inhibitor was used for renal dysfunction patients. Seven cases of acute cellular rejection were treated with rATG. Three cases of antibody-mediated rejection were treated with rituximab alone or with rituximab and bortezomib combination. There were 4 cases of early mortality within 6 months after Itx. Causes of death were declamping shock, cardiac tamponade with acute cellular rejection, dysmotility, and sepsis. Surgical complications consisted of 1 feeding jejunostomy displacement, and a minor leakage at a colo-colostomy site. One-year survival of the patient and graft was 73.33% (Kaplan-Meier survival curve). Although the total number of ITx is small, its social impact has been remarkable in changing the related laws and reimbursement policy in Korea.