Adenoid cystic carcinoma of the retromolar pad region: A case report.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignancies, mostly occurs in the major and minor salivary glands in the oral and maxillofacial region. The development of ACC in the retromolar pad is extremely rare, which limits establishing proper diagnosis and management. PRESENTATION OF CASE: A patient described a 2-month history of finding a mass behind the lower left posterior teeth. Based on the physical examination and radiographic findings, we got an initial impression of a benign mucocele, the nature of which was to be investigated further. Pathological examination of the resected tissue resulted in a diagnosis of ACC. Follow-up visits showed no recurrence during the subsequent 54 months. DISCUSSION: In cases with an uncertain diagnosis based on medical history, clinical features and imaging examinations, it is important to proceed carefully with the possibility of a tumor in mind. CONCLUSION: ACC in the retromolar pad is rare and can be easily misdiagnosed. Clinical, radiographic, and pathological evidence confirm a definitive diagnosis. Long-term follow-up is important for the full analysis of ACC treatment.

Measuring and modelling perceptions of the built environment for epidemiological research using crowd-sourcing and image-based deep learning models.

BACKGROUND: Perceptions of the built environment, such as nature quality, beauty, relaxation, and safety, may be key factors linking the built environment to human health. However, few studies have examined these types of perceptions due to the difficulty in quantifying them objectively in large populations. OBJECTIVE: To measure and predict perceptions of the built environment from street-view images using crowd-sourced methods and deep learning models for application in epidemiologic studies. METHODS: We used the Amazon Mechanical-Turk crowdsourcing platform where participants compared two street-view images and quantified perceptions of nature quality, beauty, relaxation, and safety. We optimized street-view image sampling methods to improve the quality and resulting perception data specific to participants enrolled in the Washington State Twin Registry (WSTR) health study. We used a transfer learning approach to train deep learning models by leveraging existing image perception data from the PlacePulse 2.0 dataset, which includes 1.1 million image comparisons, and refining based on new WSTR perception data. Resulting models were applied to WSTR addresses to estimate exposures and evaluate associations with traditional built environment measures. RESULTS: We collected over 36,000 image comparisons and calculated perception measures for each image. Our final deep learning models explained 77.6% of nature quality, 68.1% of beauty, 72.0% of relaxation, and 64.7% of safety in pairwise image comparisons. Applying transfer learning with the new perception labels specific to the WSTR yielded an average improvement of 3.8% for model performance. Perception measures were weakly to moderately correlated with traditional built environment exposures for WSTR participant addresses; for example, nature quality and NDVI (r = 0.55), neighborhood area deprivation (r = -0.16), and walkability (r = -0.20), respectively. SIGNIFICANCE: We were able to measure and model perceptions of the built environment optimized for a specific health study. Future applications will examine associations between these exposure measures and mental health in the WSTR. IMPACT STATEMENT: Built environments influence health through complex pathways. Perceptions of nature quality, beauty, relaxation and safety may be particularly import for understanding these linkages, but few studies to-date have examined these perceptions objectively for large populations. For quantitative research, an exposure measure must be reproducible, accurate, and precise--here we work to develop such measures for perceptions of the urban environment. We created crowd-sourced and image-based deep learning methods that were able to measure and model these perceptions. Future applications will apply these models to examine associations with mental health in the Washington State Twin Registry.

Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.

BACKGROUND: This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. METHODS: This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. RESULTS: Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR: 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR: 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR: 0.42%, 0.78%, P < 0.001), but lower than in mixed rejection (2.49%, IQR: 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR: 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR: 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR: 2.45 ng/mL, 6.30 ng/mL, P < 0.001), and negative biopsies (3.09 ng/mL, IQR: 1.94 ng/mL, 5.05 ng/mL, P < 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P < 0.001) and peri-tubular capillaritis (r = 0.344, P < 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). CONCLUSIONS: Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.

Predicting Perceptions of the Built Environment using GIS, Satellite and Street View Image Approaches.

BACKGROUND: High quality built environments are important for human health and wellbeing. Numerous studies have characterized built environment physical features and environmental exposures, but few have examined urban perceptions at geographic scales needed for population-based research. The degree to which urban perceptions are associated with different environmental features, and traditional environmental exposures such as air pollution or urban green space, is largely unknown. OBJECTIVE: To determine built environment factors associated with safety, lively and beauty perceptions across 56 cities. METHODS: We examined perceptions collected in the open source Place Pulse 2.0 dataset, which assigned safety, lively and beauty scores to street view images based on crowd-sourced labelling. We derived built environment measures for the locations of these images (110,000 locations across 56 global cities) using GIS and remote sensing datasets as well as street view imagery features (e.g. trees, cars) using deep learning image segmentation. Linear regression models were developed using Lasso penalized variable selection to predict perceptions based on visible (street level images) and GIS/remote sensing built environment variables. RESULTS: Population density, impervious surface area, major roads, traffic air pollution, tree cover and Normalized Difference Vegetation Index (NDVI) showed statistically significant differences between high and low safety, lively, and beauty perception locations. Visible street level features explained approximately 18% of the variation in safety, lively, and beauty perceptions, compared to 3-10% explained by GIS/remote sensing. Large differences in prediction were seen when modelling between city (R2 67-81%) versus within city (R2 11-13%) perceptions. Important predictor variables included visible accessibility features (e.g. streetlights, benches) and roads for safety, visible plants and buildings for lively, and visible green space and NDVI for beauty. CONCLUSION: Substantial within and between city differences in built environment perceptions exist, which visible street level features and GIS/remote sensing variables only partly explain. This offers a new research avenue to expand built environment measurement methods to include perceptions in addition to physical features.

Color Doppler Ultrasound and Hemodynamics for Evaluating Graft Dysfunction in Recurrent Immunoglobulin A Nephropathy.

BACKGROUND The aim of this study was to investigate the diagnostic and prognostic utility of color Doppler ultrasound for graft dysfunction in recurrent immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS We selected a series of 78 biopsies diagnostic of recurrent IgAN following living-donor transplantation from July 2004 to January 2019. Based on Lee's classification, Doppler parameters in different degrees of histopathological injury were retrospectively analyzed. RESULTS The 4-year cumulative graft survival rate after biopsy was 66.3%, and the difference among the Kaplan-Meier curves of Lee's classification (P<0.01) was significant. Doppler parameters showed that echo enhancement, decreasing blood flow distribution, decreasing end-diastolic velocity (EDV) of the main renal artery (MRA), segmental renal atery (SRA) and interlobar renal artery (IRA), and an elevated resistance index (RI) of the arcuate renal artery (ARA) were significantly different among grades I-V of Lee's classification (P<0.05). Logistic multivariate analysis indicated that echo enhancement (HR 13.6, 95% CI 2.7-68.4) and decreasing EDV of the SRA (HR 1.1 for a 1-cm/s, 95% CI 1.0-1.2) were independent predictors of severe injury (IV-V). The ROC curve fitted by echo enhancement and decreasing EDV of the SRA had an area under the curve of 0.87. The cutoff was 17.5 cm/s (decreasing EDV of the SRA) without echo enhancement. The sensitivity and specificity were 72.2% and 91.7%, respectively. CONCLUSIONS Color Doppler ultrasound successfully evaluated the graft dysfunction in recurrent IgAN; a decreasing EDV of the SRA indicated severe histopathological injury and poor prognosis.

Successful single kidney transplantation from pediatric donors less than or equal to 10 kg to adult recipient: a retrospective cohort study.

BACKGROUND: Kidneys from very small pediatric donors (≤10 kg) are underutilized. Compared to en bloc kidney transplantation (EBKT), single kidney transplantation (SKT) can maximize donor resources. However, it remains unknown whether it's appropriate to perform SKTs from donors weighing ≤10 kg. METHODS: A total of 35 adult recipients undergoing kidney transplantation from donors weighing ≤10 kg at our center from December 2014 to December 2019 were included and grouped into SKT group (n=20) and EBKT group (n=15). Transplant outcomes were retrospectively analyzed and compared between 2 groups. RESULTS: The 1-year and 3-year death-censored graft survival in SKT group was 95%, it is not significantly higher than that in EBKT group (80%, log-rank test, P=0.38). Significant improvement in estimated glomerular filtration rate (eGFR) was noted in both groups, despite eGFR at 1 year was lower in the SKT group (P<0.01). Proteinuria was common in both groups but subsided gradually during the follow-up time. Complication rates were similar between 2 groups with no vascular thrombosis in the SKT group. CONCLUSIONS: In conclusion, SKTs from donors weighing ≤10 kg to adult recipients achieves comparable outcomes with EBKTs, which provides evidence to support performing SKTs from donors weighing ≤10 kg in certain donor and recipient scenarios.

Clinical and Pathologic Feature of Patients With Early Versus Late Active Antibody-Mediated Rejection After Kidney Transplantation: A Single-Center Experience.

OBJECTIVE: Active antibody-mediated rejection (aABMR), particularly late aABMR, remains a major challenge for long-term renal allograft survival. This single-center retrospective study aimed to compare clinical features between early vs late aABMR and to identify risk factors for allograft failure among patients with aABMR. METHOD: Forty-one patients diagnosed with aABMR at our hospital were included and were divided into 2 groups: early aABMR (≤6 months; n = 10) vs late aABMR (>6 months; n = 31) based on the time from transplant to diagnosis. Their clinical and pathologic data were compared. This study was performed in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Of 10 patients with early aABMR, none had allograft failure, whereas 8 of 31 patients with late aABMR had developed allograft failure at the time of follow-up (25.8%). At the time of biopsy, patients with early aABMR had higher positive grade in urine occult blood test than patients with late aABMR (P = .01); however, the late aABMR group displayed more intensive interstitial fibrosis and tubular atrophy (P = .03) and more frequent HLA-DQ-type donor-specific antibodies. Interestingly, donor-specific antibody conversion from positive to negative was not associated with C4d grade but was correlated with time from transplant to biopsy. Multivariate Cox regression analysis indicated that high levels of serum creatinine or proteinuria and concomitant T-cell-mediated rejection were independent risk factors for allograft failure in patients with aABMR. CONCLUSION: These data not only confirm that early aABMR has better clinical outcomes than late aABMR but highlight the importance of early diagnostic biopsy and early therapeutic interventions in ABMR, particularly in patients with high levels of serum creatinine or proteinuria in the early posttransplant phase.

Detection of Proximal Tubule Involvement by BK Polyomavirus in Kidney Transplant Recipients With Urinary Sediment Double-Immunostaining.

Background: The extent and depth of BK polyomavirus (BKPyV) infection in renal allograft correlate with prognosis. This study was designed to evaluate the value of urinary sediment double-immunostaining for predicting BKPyV infection in proximal tubular epithelium. Materials and methods: A total of 76 urine sediment cell blocks, as well as the corresponding transplanted kidney tissues with BK polyomavirus associated-nephropathy (BKPyVAN), were evaluated by automatic double-immunostaining with anti-58-kDa Golgi protein (58K, a proximal renal tubular marker) + anti-SV40-T and anti-homogentisate 1, 2-dioxygenase (HGD, a renal tubular marker) + anti-SV40-T. Results: Immunohistochemical staining demonstrated that 58K was expressed in proximal tubular epithelium but not in distal tubular epithelium or transitional epithelium. Of the 76 patients, 28 (36.8%) had urinary 58K(+)/SV40-T(+) cells and HGD(+)/SV40-T(+) cells, 41 (53.9%) had only HGD(+)/SV40-T(+) cells, one (1.3%) had only 58K(+)/SV40-T(+) cells, and six (7.9%) had only 58K(-)/HGD(-)/SV40-T(+) cells. The presence of urinary 58K(+)/SV40-T(+) cells was correlated with BKPyV infection in proximal tubular epithelium (P < 0.001, r = 0.806). The mean extent of SV40-T staining was significantly more extensive in patients with urinary 58K(+)/SV40-T(+) cells than those without urinary 58K(+)/SV40-T(+) cells (21.4 vs. 12.0%, P < 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity of urinary 58K(+)/SV40-T(+) cells for predicting BKPyV infection in proximal tubular epithelium were 89.7% (95% CI: 71.5-97.3%), 91.5% (95% CI: 78.7-97.2%), 86.7% (95% CI: 68.4-95.6%), and 93.5% (95% CI: 81.1-98.3%), respectively. Conclusion: Urinary sediment double-immunostaining with anti-58K and anti-SV40-T is valuable for predicting the extent and depth of BKPyV infection in renal allograft.

Urine Donor-Derived Cell-Free DNA Helps Discriminate BK Polyomavirus-Associated Nephropathy in Kidney Transplant Recipients With BK Polyomavirus Infection.

Background: Studies have shown that plasma donor-derived cell-free DNA (dd-cfDNA) can predict renal allograft antibody-mediated rejection. This study was performed to evaluate the value of urine dd-cfDNA concentration and dd-cfDNA fraction (%) for discriminating BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients with urinary BK polyomavirus (BKPyV) infection. Methods: In this retrospective single-center observational study, we enrolled kidney transplant recipients who were diagnosed with urine BKPyV infection between August 2018 and May 2019 at the First Affiliated Hospital of Sun Yat-sen University. Urine dd-cfDNA was measured by using a novel target region capture sequencing methodology. The pathological diagnosis of BKPyVAN was confirmed by anti-SV40-T immunohistochemical staining and classified using the American Society for Transplantation schema. Receiver operating characteristic curve analysis was used to investigate the relations of urine dd-cfDNA and dd-cfDNA% to intrarenal allograft BKPyV infection states. Results: In total, 93 patients were enrolled, including 40 cases of proven BKPyVAN, seven cases of probable BKPyVAN, 23 cases of possible BKPyVAN, and 23 cases of resolving BKPyVAN. Urine dd-cfDNA level in proven BKPyVAN (22.09 ± 21.27 ng/ml) was comparable to that in probable BKPyVAN (15.64 ± 6.73 ng/ml, P = 0.434) but was significantly higher than that in possible BKPyVAN (5.60 ± 3.53 ng/ml) and resolving BKPyVAN (5.30 ± 3.34 ng/ml) (both Ps < 0.05). Urine dd-cfDNA% of proven BKPyVAN (0.71 ± 0.21) was lower than that of probable BKPyVAN (0.91 ± 0.04, P < 0.001), but was significantly higher than that of possible BKPyVAN (0.56 ± 0.30) and resolving BKPyVAN (0.46 ± 0.28) (both Ps < 0.05). For distinguishing biopsy-proven BKPyVAN from biopsy-excluded BKPyVAN, the discrimination capacity of urine dd-cfDNA (AUC: 0.842, 95% CI: 0.735, 0.918) was superior to that of plasma BKPyV DNA load (AUC: 0.660, 95% CI: 0.537, 0.769) with 0.181 (95% CI: 0.043, 0.319) difference between areas under ROC curves (P = 0.010). Conclusion: The elevated urine dd-cfDNA level may help discriminate BKPyVAN in kidney transplant recipients with BKPyV viruria.

Pathological characteristics of BK polyomavirus-associated nephropathy with glomerular involvement.

BACKGROUND: This study aimed to investigate the pathological characteristics of BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) with glomerular involvement in kidney transplant recipients. METHODS: Forty-four patients with glomerular BKPyV infection were retrospectively included for analysis. Immunohistochemical (IHC) staining was performed on paraffin sections using monoclonal mouse anti-SV40 large T antigen antibody. RESULTS: In BKPyV-infected glomeruli, the glomerular parietal epithelial cells (GPECs) were swollen, hyperchromatic, and enlarged, with an increased nuclear to cytoplasm (N/C) ratio and smudgy basophilic intra-nuclear viral inclusions. IHC staining revealed the distribution of BKPyV involvement in GPECs, podocytes, and shedding cells within Bowman's space. Notably, BKPyV affected GPEC proliferation and caused crescent formation (7 biopsies, 15.9%). Three biopsies exhibited fibrous crescents and the absence of viral inclusions. The other 4 biopsies exhibited cellular and fibro-cellular crescents, with viral cytopathic changes and positive IHC staining in the proliferative GPECs. Electron microscopy showed viral particles in both GPECs and podocytes. BKPyV-infected GPECs were degenerative, with mitochondrial swelling, endoplasmic reticulum expansion, and multi-layered membranous structure formation. Twelve (27.3%) patients received repeat biopsies within 1.6 to 39.5 months (median: 13.5 months), but none revealed persistent glomerular BKPyV infection. CONCLUSIONS: Distinct glomerular changes in BKPyVAN biopsies should raise the possibility of glomerular involvement.

Graft failure of IgA nephropathy in renal allografts following living donor transplantation: predictive factor analysis of 102 biopsies.

BACKGROUND: To investigate predictive factors related to graft failure of IgA nephropathy(IgAN) in renal allografts following living donor transplantation. METHODS: We identified a series of 102 biopsies diagnosed as IgAN in renal allografts following living donor transplantation from July 2004 to January 2017 at our center, and assess the predict value of the Lee's classification and the 2009 Oxford classification in IgAN in renal allografts, clinical, ultrasonic and pathological characteristics at biopsy and the outcomes were retrospectively analyzed. RESULTS: The 5-year graft cumulative survival rate after transplantation was 91.4%. The 4-year graft cumulative survival rate after biopsy diagnosis of IgAN in renal allografts was 59.6%. The mean time ± SD to disease was 4.7 ± 3.5 years. The color doppler ultrasound and blood flow imagine showed the echo enhancement, the reduced blood flow distribution, the reduced peak systolic velocity of main renal artery, and the increased resistance index of arcuate renal artery were valuable in evaluating the graft dysfunction. The Cox multivariate analysis revealed that the 24-h urinary protein level (HR 1.6 for 1-g increase, 95%CI 1.2-2.0), estimated glomerular filtration rate (eGFR) (HR 1.0 for 1-mL/min/1.73 m^2 decline, 95%CI 1.0-1.1), and mesangial C1q deposition (HR 3.0, 95%CI 1.2-7.4) at biopsy were independent predictive factors of graft failure of IgAN in renal allografts. CONCLUSIONS: IgAN in renal allografts occurred frequently within 5 years after transplantation. The risk of graft failure should be taken seriously in patients who exhibit heavy proteinuria and/or a declined eGFR as the initial symptoms; a high lesion grade (grade IV-V of Lee's classification) and/or mesangial C1q deposition may also indicated a poor outcome.

Induction therapy with thymoglobulin or interleukin-2 receptor antagonist for Chinese recipients of living donor renal transplantation: a retrospective study.

BACKGROUND: Recipients of living donor renal transplantation are typically considered to have a relatively lower immunological risk. This retrospective study aimed to compare the therapeutic efficacy and safety between rabbit antithymocyte globulin (rATG) or interleukin-2 receptor antagonist (IL2-RA) induction therapies in Chinese population. METHODS: A total of 188 patients receiving living donor renal transplantation between February 2004 and December 2013 were included and divided into the rATG group and based on their induction therapy. The primary outcome was clinically-suspected rejection. The incidences of de novo donor-specific antigen (dn-DSA), graft survival, and infection were also compared between groups. A multivariate Cox regression analysis was performed to investigate the influential factors associated with clinically-suspected acute rejection and graft survival. RESULTS: The rATG group had a higher panel reactive antibody (PRA) score and more complete HLA mismatches than the IL2-RA group (both P < 0.001). The incidences of clinically-suspected acute rejection (9.8% vs. 8.8%; P = 0.832) and dn-DSA formation (4.9% vs. 5.4%, P = 0.44) were not significantly different between groups. Kaplan-Meier curve analysis demonstrated that the graft survivals of two groups were comparable (P = 0.857). After adjusting for patients' age, sex, PRA, HLA mismatch confounders, and the use of corticoids, the multivariate Cox regression analysis showed that methods of induction therapy were not associated with clinically-suspected acute rejection and graft survival (both P > 0.05). The incidences of complications (infections, pneumonia, liver injury and myelosuppression) were all comparable between groups (all P > 0.05). CONCLUSIONS: These results suggested that rATG could be a safe and efficient immunosuppressant when used in a Chinese recipient population with a higher immunological risk in living donor renal transplantation.

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center.

BACKGROUND: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. METHODS: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. RESULTS: After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ±â€Š9.2 vs. 32.8 ±â€Š20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ±â€Š9.8 vs. 33.5 ±â€Š20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ±â€Š14.3 vs. 26.5 ±â€Š12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042). CONCLUSION: Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.

A Cost-effectiveness Analysis of Rabbit Antithymocyte Globulin Versus Antithymocyte Globulin-fresenius as Induction Therapy for Patients With Kidney Transplantation From Donation After Cardiac Death in China.

PURPOSE: Induction immunosuppression therapy is used to support optimal outcomes in kidney transplantation. This study was to assess the cost-effectiveness of rabbit antithymocyte globulin (r-ATG) versus ATG-Fresenius (ATG-F) in kidney transplantation in the Chinese setting from the perspective of the health care payer. METHODS: A 2-part survival model was developed, consisting of a short-term part and a long-term part. The short-term part analyzed the first year, using the decision tree, and consisted of the functioning transplant, acute rejection (AR), delayed graft function (DGF), dialysis, and death health states. The long-term part analyzed 2 to 5 years, using Markov model, and consisted of the functioning transplant, chronic dysfunction, recurring primary disease, dialysis, and death health states, with capture of the association between DGF and graft loss. Costs, including drug acquisition and other direct medical costs, were derived from China IQVIA database (formerly known as IMS) hospitaldatabase, chart review, and physician interviews. Clinical outcomes and utility were retrieved from published literature. The model calculated quality-adjusted life-years (QALYs) and total costs per patient. Costs and QALYs were discounted at an annual rate of 3.5%. Univariate sensitivity analysis and probability sensitivity analysis (PSA) were conducted to assess the impact of uncertainty of the variables on the results. FINDINGS: Patients who received r-ATG had more clinical effectiveness than patients who received ATG-F mainly because of less AR, DGF, and dialysis. The incremental QALY was 0.01 over a 1-year time horizon and 0.0496 over a 5-year time horizon. R-ATG and ATG-F drug costs were ¥10,783 and ¥8409, respectively. However, the total treatment costs of the r-ATG arm were lower than the ATG-F arm because of lower costs related to DGF, AR, dialysis, and adverse events. In total, r-ATG saved ¥5423 over the 1-year and ¥7042 over the 5-year time horizon. R-ATG was dominant with lower total direct medical costs and higher QALYs compared with ATG-F. Both univariate sensitivity analysis and PSA found the robustness of the model results. PSA results indicated that r-ATG was cost-effective compared with ATG-F in 86.81% of the simulations, considering <3 times the gross domestic product per capita as the threshold. IMPLICATIONS: From the perspective of the health care payer, r-ATG should be considered as the preferred treatment agent for induction therapy for Chinese patients undergoing kidney transplantation because of its lower overall medical costs and greater QALYs gained compared with ATG-F. The study was limited by lack of long-term efficacy data among the Chinese population and lack of comprehensive real-world higher quality costs data.

Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies.

AIM: The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes. METHODS: We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema. RESULTS: Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively. CONCLUSIONS: A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.

MicroRNA-214-5p/TGF-ß/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis.

Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)­214­5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed. When dexamethasone­induced adipogenic differentiation was performed, miR­214­5p expression was increased compared with the control group, as determined by RT­qPCR. Furthermore, oil red O staining, RT­qPCR and western blot analysis demonstrated that overexpression of miR­214­5p promoted adipogenic differentiation, inhibited alkaline phosphatase (ALP), runt­related transcription factor 2 (Runx2), osteocalcin (OC) and collagen α­1 (I) chain (COL1A1) mRNA expression, and suppressed transforming growth factor (TGF)­ß, phosphorylated (p)­Smad2 and collagen type IV α1 chain (COL4A1) protein expression in BMSCs. Additionally, downregulation of miR­214­5p increased the ALP, Runx2, OC and COL1 mRNA expression and increased TGF­ß, Smad2 and COL4A1 protein expression in BMSCs. Furthermore, a TGF­ß inhibitor was employed to inhibit TGF­ß expression in BMSCs following miR­214­5p downregulation, which led to reduced Smad2, TGF­ß and COL4A1 protein expression, and ALP, Runx2, OC and COL1 mRNA expression was also reduced, compared with the miR­214­5p downregulation only group. It was demonstrated that miR­214­5p may weaken osteogenic differentiation of BMSCs through regulating COL4A1. In conclusion, the results of the present study indicated that miR­214­5p may promote the adipogenic differentiation of BMSCs through regulation of the TGF­ß/Smad2/COL4A1 signaling pathway, and potentially may be used to develop a novel drug for postmenopausal osteoporosis.

The potential of microRNAs as human prostate cancer biomarkers: A meta-analysis of related studies.

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta-analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007-2017. According to the inclusion criteria, 104 records were included for this meta-analysis. The pooled or stratified analyze showed 10 up-regulated miRNAs (miR-18a, miR-34a, miR-106b, miR-141, miR-182, miR-183, miR-200a/b, miR-301a, and miR-375) and 14 down-regulated miRNAs (miR-1, miR-23b/27b, miR-30c, miR-99b, miR-139-5p, miR-152, miR-187, miR-204, miR-205, miR-224, miR-452, miR-505, and let-7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR-32 and low expression of let-7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR-21, miR-30c, miR-129, miR-145, and let-7c) could predict poor RFS of PC, while the evaluation of miR-375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large-scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.

Evaluation of quality of kidneys from donation after circulatory death/expanded criteria donors by parameters of machine perfusion.

AIM: To investigate whether the parameters of machine perfusion could predict the quality of kidneys from donation after circulatory death (DCD) donors and expanded criteria donors (ECD). METHODS: Fifty-eight kidneys from DCD/ECD donors were harvested in our hospital from July 2011 to August 2014. All kidneys were preserved with machine perfusion (Life Port), and parameters of machine perfusion were collected. All kidneys were biopsied before transplantation. The primary endpoints were delayed graft function (DGF), graft loss and patient death. RESULTS: After kidney transplantation, 26 patients (44.8%) had DGF. We chose 1 h RI as a predictive parameter to predict DGF after transplant, and made the ROC curve. The ROC curve showed that 1 h RI = 0.4 was the best cut-off point for predicting DGF after transplant. The sensitivity was 61.54%, and the specificity was 81.25%. Fifty-eight recipients were divided into two groups according to 1 h RI of machine perfusion. 22 cases in high RI group (RI > 0.4) and 36 cases in low RI group (RI ≤0.4). DGF rate was significantly higher in the high RI group (72.7% vs. 27.8%). One year serum creatinine levels were also significantly higher in the high RI group (P < 0.05). Acute rejection rate and 1 year graft and patient survival were comparable. CONCLUSIONS: One hour RI of machine perfusion is associated with DGF and 1 year graft function in DCD/ECD kidney transplantation, and may be a non-invasive tool for evaluating quality of DCD/ECD kidneys.

Comparison of outcomes of kidney transplantation from donation after brain death, donation after circulatory death, and donation after brain death followed by circulatory death donors.

BACKGROUND: There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors. METHODS: We retrospectively reviewed 469 recipients who received deceased kidney transplantation in our hospital from February 2007 to June 2015. The recipients were divided into three groups according to the source of their donor kidneys: DBD, DCD, or DBCD. The primary endpoints were delayed graft function (DGF), graft loss, and patient death. RESULTS: The warm ischemia time was much longer in DCD group compared to DBCD group (18.4 minutes vs 12.9 minutes, P < .001). DGF rate was higher in DCD group than in DBD and DBCD groups (22.5% vs 10.2% and 13.8%, respectively, P = .021). Urinary leakage was much higher in DCD group (P = .049). Kaplan-Meier analysis showed that 1-, 2-, and 3-year patient survivals were all comparable among the three groups. CONCLUSION: DBCD kidney transplantation has lower incidences of DGF and urinary leakage than DCD kidney transplant. However, the overall patient and graft survival were comparable among DBD, DCD, and DBCD kidney transplantation.

Ethylene carbodiimide-fixed donor splenocytes combined with α-1 antitrypsin induce indefinite donor-specific protection to mice cardiac allografts.

Peritransplant infusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs) induces protection of islet and cardiac allografts. However, pro-inflammatory cytokine production during the peritransplantation period may negate the effect of ECDI-SPs. Therefore, we hypothesized that blocking pro-inflammatory cytokine secretion while increasing levels of anti-inflammatory cytokines would enhance the tolerance-induced efficacy of ECDI-SPs. The objective of this study was to determine the effectiveness of using ECDI-SPs combined with a short course of α1-antitrypsin (AAT) for induction of tolerance. Using a mice cardiac transplant model, we demonstrated that ECDI-SPs + AAT effectively induced indefinite mice cardiac allograft protection in a donor-specific fashion. This effect was accompanied by modulation of cytokines through decreasing levels of pro-inflammatory cytokines (including IFN-γ, TNF-α, IL-1ß, IL-6, IL-17, and IL-23) and increasing levels of anti-inflammatory cytokines (including IL-10, IL-13, and TGF-ß), and by inhibition of effector T cells (Teff) and expansion of regulatory T cells (Tregs). Therefore, we concluded that combined ECDI-SPs and AAT appeared to modulate the expression of cytokines and regulate the Teff:Treg balance to create a support milieu for graft protection. Our strategy of combining ECDI-SPs and AAT provides a promising approach for inducing donor-specific transplant tolerance.