Pre-transplant donor HBV DNA+ and male recipient are independent risk factors for treatment failure in HBsAg+ donors to HBsAg- kidney transplant recipients.

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Modulatory effect of aquaporin 5 on estrogen-induced epithelial-mesenchymal transition in prostate epithelial cells.

BACKGROUND: Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate. METHODS: Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-ß1 (TGF-ß1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells. RESULTS: BPH tissues exhibited greater EMT (TGF-ß1: 1.362 ±â€Š0.196 vs. 0.107 ±â€Š0.067, P = 0.003; vimentin: 1.581 ±â€Š0.508 vs. 0.221 ±â€Š0.047, P < 0.001; E-cadherin: 0.197 ±â€Š0.188 vs. 1.344 ±â€Š0.088, P < 0.001), higher AQP5 (1.268 ±â€Š0.136 vs. 0.227 ±â€Š0.055, P < 0.001) and estrogen receptor (ER) α (1.250 ±â€Š0.117 vs. 0.329 ±â€Š0.134, P < 0.001) expression but lower ERß (0.271 ±â€Š0.184 vs. 1.564 ±â€Š0.130, P < 0.001) expression than NP tissues. E2-stimulated cells had higher AQP5 expression (1.298 ±â€Š0.058 vs. 1.085 ±â€Š0.104, P = 0.049), increased cell proliferation (1.510 ±â€Š0.089 vs.1.000 ±â€Š0.038, P < 0.001), and EMT (TGF-ß1 concentration: 0.352 ±â€Š0.021 ng/mL vs. 0.125 ±â€Š0.014 ng/mL, P < 0.001; vimentin: 1.641 ±â€Š0.120 vs. 0.188 ±â€Š0.020, P = 0.002; E-cadherin: 0.075 ±â€Š0.030 vs. 0.843 ±â€Š0.046, P < 0.001) than controls. E2-stimulated cells with AQP5 knockdown exhibited decreased EMT (TGF-ß1 concentration: 0.223 ±â€Š0.041 ng/mL vs. 0.352 ±â€Š0.021 ng/mL, P = 0.016; vimentin: 0.675 ±â€Š0.056 vs. 1.641 ±â€Š0.120, P = 0.001; E-cadherin: 0.159 ±â€Š0.037 vs. 0.075 ±â€Š0.030, P = 0.040) than E2-stimulated cells with non-related small interfering RNA (siRNA). CONCLUSION: Our findings suggest that estrogen induces BPH possibly by promoting AQP5 expression. Hence, AQP5 might be a novel target for modulating EMT in prostate epithelial cells.

Individualized Preconditioning for ABO-Incompatible Living-Donor Kidney Transplantation: An Initial Report of 48 Cases from China.

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

Steroid withdrawal or avoidance is safe in high-risk kidney transplants: A systematic review and meta-analysis.

The present study is aimed to assess the safety and efficacy of steroid withdrawal or avoidance (SWA) in high-risk kidney transplant (HRKT). We performed a systematic review of the literature and pooled analysis of the available data concerning SWA following HRKT. HRKT is associated with patients undergoing repeat kidney transplantation, in African American recipients, or in patients with panel-reactive antibody levels >20%. Seven cohort studies and one randomized controlled trial, involving a total of 22 075 patients, were included. Pooled analysis to estimate the risk ratio (RR) and 95% confidence interval (CI) demonstrated comparable graft loss (RR = 0.91, 95% CI 0.76-1.09) between the SWA and corticosteroid maintenance groups, but with reduced mortality in the SWA group (RR = 0.90, 95% CI 0.84-0.98). A subanalysis suggested that SWA was not associated with increased graft loss in patients undergoing steroid withdrawal within 1 week of transplantation, in African American recipients, or in patients with follow-up >5 years. Additionally, SWA was associated with reduced death in those undergoing withdrawal within 1 week (RR = 0.90, 95% CI 0.84-0.98), in African Americans (RR = 0.90, 95% CI 0.83-0.98), and in those with follow-up extended to >5 years (RR = 0.91, 95% CI 0.84-0.98). SWA was not associated with an increased risk of acute rejection (RR = 0.95, 95% CI 0.75-1.21) or cytomegalovirus infection (RR = 1.86, 95% CI 1-3.47); however, it was associated with a reduced risk of posttransplant diabetes mellitus (RR = 0.60, 95% CI 0.37-0.97). SWA following HRKT is safe in terms of graft survival and rejection, and patients undergoing an SWA regimen had a lower risk of death and posttransplant diabetes mellitus. Future prospective studies are required to confirm these findings.

Effect of renin-angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta-analysis.

Renin-angiotensin system inhibitors, specifically angiotensin II converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), have confirmed renoprotective benefits in patients with proteinuria and hypertension. However, it remains controversial whether these agents are beneficial to kidney recipients. We conducted this meta-analysis to evaluate the effects of ACEI/ARB treatment on patient and allograft survival after kidney transplant. The PubMed, Embase and Cochrane Library databases were searched for eligible articles from before May 2016, and we included 24 articles (9 randomised controlled trials [RCTs] and 15 cohort studies with 54,096 patients), in which patient or graft survival was compared between an ACEI/ARB treatment arm and a control arm. Pooled results showed that ACEI/ARB was associated with decreased risks of patient death (relative risk [RR] = 0.64; 95% confidence interval [CI]:0.49-0.84) and graft loss (RR = 0.59; 95%CI:0.47-0.74). Subgroup analysis of the cohorts revealed significantly reduced patient death (RR = 0.61; 95%CI:0.50-0.74) and graft loss (RR = 0.58; 95%CI:0.46-0.73), but this was not seen in RCTs (patient survival: RR = 0.84, 95%CI:0.39-1.81; graft survival: RR = 0.70, 95%CI:0.17-2.79). Significantly less graft loss was noted among patients with biopsy-proved chronic allograft nephropathy (CAN) (RR = 0.26, 95%CI:0.16-0.44). Furthermore, the benefit of ACEI/ARB on patient survival (RR = 0.62; 95%CI:0.47-0.83) and graft survival (RR = 0.58, 95%CI:0.47-0.71) was limited to those with ≥3years' follow-up. ACEI/ARB decreased proteinuria (P < 0.001) and lowered haemoglobin (P = 0.002), but the haemoglobin change requires no additional treatment (from 119-131 g/L to 107-123 g/L). We therefore concluded that ACEI/ARB treatment may reduce patient death and graft loss, but additional well-designed prospective studies are needed to validate these findings.

Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis.

Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58-1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37-2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29-1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64-1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation.

Circumcision with "no-flip Shang Ring" and "Dorsal Slit" methods for adult males: a single-centered, prospective, clinical study.

This paper was aimed to compare the clinical effectiveness and safety of adult male circumcision using the Shang Ring™ (SR) with the no-flip technique compared with Dorsal Slit (DS) surgical method. A single-centered, prospective study was conducted at the West China Hospital, where patients were circumcised using the no-flip SR (n = 408) or the DS (n = 94) procedure. The adverse events (AEs) and satisfaction were recorded for both groups, and ring-removal time and percentage of delayed removals were recorded for the SR group. Finally, complete follow-up data were collected for 76.1% of patients (SR: n = 306; DS: n = 76). The average ring-removal time for the SR group was 17.62 ± 6.30 days. The operation time (P < 0.001), pain scores during the procedure (P < 0.001) and at 24 h postoperatively (P < 0.001), bleeding (P = 0.001), infection (P = 0.034), and satisfaction with penile appearance (P < 0.001) in the SR group were superior to those in the DS group. After two postoperative weeks, the percentage of patients with edema in the SR group (P = 0.029) was higher but no differences were found at 4 weeks (P = 0.185) between the two groups. In conclusions, the no-flip SR method was found to be superior to the DS method for its short operation time (<5 min), involving less pain, bleeding, infection, and resulting in a satisfactory appearance. However, the time for recovery from edema took longer, and patients may wear device for 2-3 weeks after the procedure.

Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy for nonlocalized prostate cancer: a systematic review and meta-analysis.

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT) alone versus combined with radiation therapy (RT) or chemotherapy for locally advanced and metastatic prostate cancer (PCa). A literature search was performed using OvidSP. Randomized controlled trials (RCTs) that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus docetaxel-estramustine (n = 413) in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall survival (OS) was 1.43 (95% confidence interval 1.20-1.71) when compared ADT plus RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01-1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.

[Learning Curve of Retroperitoneal Laparoscopic Donor Nephrectomy and Risk Analysis of Intraoperative Complications].

OBJECTIVES: To investigate the learning curve of retroperitoneal laparoscopic donor nephrectomy (LDN) and evaluate the risk factors of intraoperative complications with data from a single center. METHODS: We evaluated perioperative data of 527 consecutive kidney donors who received retroperitoneal LDN between April 2009 and April 2014. The patients were divided into two groups according to the learning curve which was determined by the operation time:group 1 (on the learning curve) and group 2 (learning curve completed). RESULTS: The mean operation time was (88.4±38.07) min. The asymptote of the surgeon's learning curve for retroperitoneal LDN was achieved at the 100th case. The operation time and the incidence of intraoperative complications in group 1 were significantly higher than those of group 2. When cases completed, body mass index (BMI) and intraoperative complications were correlated to operative time. The incidence of intraoperative complications was 1.90% and BMI was correlated to the incidence of intraoperative complications. When the learning curve was completed, renal artery numbers and right kidney were found being correlated to operative time. CONCLUSIONS: Retroperitoneal LDN is a safe and effective operation method with a low incidence of complications. Technical proficiency in retroperitoneal LDN could be achieved after 100 surgeries.

Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis.

In this study, we evaluated if male circumcision was associated with lower HIV acquisition for HIV (-) males and HIV (-) females during normal sexual behavior. We performed a systematic literature search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies that compared HIV acquisition for the circumcised and uncircumcised groups. The reference lists of the included and excluded studies were also screened. Fifteen studies (4 RCTs and 11 prospective cohort studies) were included, and the related data were extracted and analyzed in a meta-analysis. Our study revealed strong evidence that male circumcision was associated with reduced HIV acquisition for HIV(-) males during sexual intercourse with females [pooled adjusted risk ratio (RR): 0.30, 95% CI 0.24 0.38, P < 0.00001] and provided a 70% protective effect. In contrast, no difference was detected in HIV acquisition for HIV (-) females between the circumcised and uncircumcised groups (pooled adjusted RR after sensitivity analysis: 0.68, 95%CI 0.40-1.15, P = 0.15). In conclusion, male circumcision could significantly protect males but not females from HIV acquisition at the population level. Male circumcision may serve as an additional approach toward HIV control, in conjunction with other strategies such as HIV counseling and testing, condom promotion, and so on.

Retroperitoneal laparoscopic management method of Castleman's disease in the adrenal gland: two cases report and review of the literature.

PURPOSE: Castleman's disease (CD) is a rare and complex disease of lymphoid tissues typically involving a mediastinal mass. CD in the adrenal area is an even rarer occurrence. In the present study, two extremely rare cases of adrenal Castleman's disease at our hospital are reported, and the relevant literatures were reviewed. Significant findings: A 51-year-old woman had abdominal pain for 1 month. Physical examination revealed a mass in the left abdominal. A computed tomography (CT) scan confirmed the presence of the mass. Additionally, a left suprarenal mass was detected in a 56-year-old male patient during a regular medical checkup. He had no symptoms when he arrived at our hospital. The two patients underwent mass excision via a retroperitoneal laparoscopic approach. Postoperative histopathological examination of both patients' specimens suggested a diagnosis of the hyaline vascular-type of CD. CONCLUSIONS: These two rare cases confirm that CD can occur in the adrenal gland area. In addition, we also demonstrate that retroperitoneoscopic surgical management is effective in the treatment of the disease.

Active targeted therapy for metastatic collecting duct carcinoma of the kidney: a case report and review of the literature.

Collecting duct carcinoma (CDC) is a rare and aggressive renal cell carcinoma (RCC) with extremely poor prognosis, which has been shown to have a poor response to several kinds of systemic therapy. Targeted agents have greatly changed the therapeutic landscape in advanced RCC. Nonetheless, patients with CDC are always excluded from the prospective trials with targeted therapies due to its rarity. We present a case of metastatic CDC that responded favorably to the multiple tyrosine kinase inhibitor, sorafenib, achieving a partial response in both lungs and retroperitoneal lymph nodes metastases. We also reviewed the limited number of reports of metastatic CDC treated with targeted agents and found that 33.33 % (4/12) of patients had favorable clinical activity. These suggest that targeted therapy should be considered for the treatment of metastatic CDC and its prospective evaluation is encouraged.