Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis.

BACKGROUND: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial. OBJECTIVE: To compare the efficacy of different hormonal regimens in this context and to rank them. SEARCH STRATEGY: MEDLINE and Scopus databases were searched through January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order. MAIN RESULTS: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment. CONCLUSION: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required. TWEETABLE ABSTRACT: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery.

Comparison of disease activity between tacrolimus and mycophenolate mofetil in lupus nephritis: a randomized controlled trial.

We conducted a prospective multicenter, opened-label, parallel, randomized, controlled trial to compare tacrolimus (TAC) and mycophenolate mofetil (MMF) for induction and maintenance therapy in lupus nephritis (LN). Adult patients with biopsy-proven LN International Society of Nephrology/Renal Pathology Society classes III-V and active nephritis were to receive prednisolone (0.7-1.0 mg/kg/day for four weeks of run-in period and tapered) and randomly assigned to receive TAC (0.1 mg/kg/day) or MMF (1.5-2 g/day) as induction therapy for six months. All patients who had remission received azathioprine (AZA) 1-2 mg/kg/day as standard treatment in the maintenance phase. The primary outcome was Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) at six and 12 months, and the secondary outcomes included renal SLEDAI, non-renal SLEDAI, modified SLEDAI-2K, immunity SLEDAI, and disease activity remission. Eighty-four patients were randomized. One patient who was randomized to the TAC group withdrew from the study immediately after randomization. Therefore, 42 patients received MMF and 41 patients received TAC. Disease activity remission rate and time to disease activity remission were similar in both groups. Twelve patients (28.57%) in the MMF group and 10 patients (24.39%) in the TAC group achieved disease activity remission. For disease activity scores, both regimens significantly improved SLEDAI-2K during induction and maintenance therapy. Overall, SLEDAI-2K score in the MMF group decreased more compared with the TAC group. In the MMF group, mean SLEDAI-2K decreased from 11.6 ± 4.8 to 6.3 ± 3.9 after induction therapy and to 5.4 ± 4.4 after maintenance therapy. In the TAC group, mean SLEDAI-2K decreased from 9.0 ± 3.7 to 6.3 ± 5.1 after induction therapy and to 7.1 ± 5.4 after maintenance therapy. Renal SLEDAI and modified SLEDAI-2K showed a similar pattern with SLEDAI-2K. In non-renal SLEDAI and immunity SLEDAI, both regimens also resulted in decreased disease activity scores during the first two months. After that the scores were slightly increased. In the MMF group, the scores were still lower than baseline but in the TAC group were not. In conclusion, disease activity remission rate was similar in the MMF and TAC groups. For disease activity score as measured by SLEDAI-2K, TAC was comparable with MMF during induction but MMF was more effective on disease activity of active LN classes III and IV at 12 months, especially in the renal system.

Outcome of Pretransplantation Therapeutic Plasma Exchange in Highly Sensitized Deceased-donor Kidney Transplant Recipients.

BACKGROUND: Sensitization is associated with a high rate of post-transplantation rejection. A desensitization protocol using therapeutic plasma exchange (TPE) was proposed to reduce anti-HLA antibody before transplantation, but there has been limited data regarding the efficacy of pretransplantation TPE in highly sensitized deceased-donor kidney transplantation (DDKT). METHODS: A retrospective cohort study of 142 patients who received DDKT was conducted and divided into two groups: a high-panel-reactive antibody (PRA) >50% group and a low-PRA ≤50% group. The high-PRA group was sub-divided into those who received and did not receive pretransplantation TPE. Donor-specific anti-HLA antibodies (DSA) were also collected pretransplantation in the high-PRA group. RESULTS: The probability of acute rejection was 26, 4, and 9 cases/1000/person month in the high-PRA group with no TPE, the high-PRA group receiving TPE, and the low-PRA group, respectively (P = .0208). In the multivariable logistic regression analysis, the hazard ratio for graft rejection was 2.37 (95% confidence interval: 0.89 to 6.35) and 2.22 (95% confidence interval: 0.54 to 9.13) in the group of high-PRA who received TPE and high-PRA with no TPE, compared with the low-PRA group, respectively (P value not significant). The incidence of antibody-mediated rejection in 6 months in the DSA-positive subgroup was not different between those who received TPE or no TPE. CONCLUSION: Desensitization with TPE is a reasonable alternative for highly sensitized DDKT. Patients who received pretransplantation TPE had a lower incidence of acute rejection compared to the group that did not receive TPE. However, pretransplantation TPE alone was not effective in the prevention of acute rejection in recipients with DSA.

Increased urine transforming growth factor ß1 (TGF-ß1) and serum uric acid are associated with an early decline of glomerular filtration rate in kidney transplant recipients.

BACKGROUND: The renin-angiotensin system (RAS) and transforming growth factor ß1 (TGF-ß1) may play a role in the pathogenesis of fibrosis in kidney allografts. Experimental hyperuricemia shows activation of intrarenal RAS. However, the association between uric acid (UA), RAS, and TGF-ß1 in allograft recipients has not been demonstrated. Therefore we investigated the association between serum UA levels, RAS, and TGF-ß1 in kidney transplant recipients during the 1st year after transplantation. METHODS: Sixty-two transplant recipients were included in the study. Serum UA level, plasma renin activity (PRA), and urine TGF-ß1 concentration were studied at 3, 6, and 12 months after transplantation. Statistical correlation was demonstrated with the use of Spearman rank correlation coefficient. Receiver operating characteristic curve analysis and area under the curve were performed to assess the diagnostic performance to discriminate between estimated glomerular filtration rate (eGFR) <60 and ≥ 60 mL/min/1.73 m(2). RESULTS: For all 62 patients, urine TGF-ß1 and serum UA had a tendency to increase during the 1-year follow-up period, despite no statistically significant change in eGFR. We found that increased urine TGF-ß1 was correlated with rising serum UA levels and a decrease of the eGFR (r = 0.27 [P = .01]; r = -0.38 [P = .0003]). In contrast, there was no significant change in PRA and it was not correlated with eGFR or TGF-ß1 (r = -0.01; P = .93). CONCLUSIONS: Increased urine TGF-ß1 and serum UA level during the 1st year after transplantation correlated with a decline in eGFR. The evaluation of these parameters in the early post-transplantation period may identify patients at risk of allograft dysfunction.

Significance of C1q-fixing donor-specific antibodies after kidney transplantation.

OBJECTIVES: De novo donor-specific HLA antibodies (DSA) are associated with allograft rejection and allograft loss. However, not all DSA are equally detrimental to allograft function. The ability to activate complement may be an important factor differentiating clinically relevant DSA from nonrelevant DSA. The C1q assay detects a subset of HLA antibodies that can fix complement. This study aimed to investigate the correlation between C1q-fixing de novo DSA (dnDSA) and clinical outcomes posttransplant. METHODS: This retrospective study included 193 sera from kidney transplant recipients who underwent posttransplant DSA testing and/or kidney biopsy for clinical causes. Thirty-five of the 193 (18.1%) had immunoglobulin G DSA. Seventeen of the 35 patients were excluded owing to the presence of pretransplant HLA antibodies. We then analyzed C1q DSA at the time of biopsy in 18 recipients who developed dnDSA. The clinical outcomes of patients with C1q-positive DSA and C1q-negative DSA were compared. RESULTS: C1q-positive DSA were detected in 10 of 18 patients (55.6%). The incidences of transplant glomerulopathy were significantly higher among patients with C1q-positive DSA than patients with C1q-negative DSA (80% vs 0%; P = .001). Although patients with C1q-positive DSA experienced more chronic antibody-mediated rejection and graft loss (80% vs 37.5% [P = .145]; 60% vs 25% [P = .188]), the differences were not significant. The receiver operating characteristic curve analysis showed that the C1q assay was an excellent predictor of transplant glomerulopathy with area under the curve of 0.9 (95% CI, 0.769-1.000). CONCLUSION: The presence of C1q-positive dnDSA was associated with an increased risk of transplant glomerulopathy. The C1q assay is potentially a powerful method for identifying patients at risk for transplant glomerulopathy.

Sperm motility and DNA integrity affected by different g-forces in the preparation of sperm in urine specimens.

Retrograde ejaculation, a common type of anejaculation, is attributable to many causes, some of which can be treated with medication and some of which cannot. For infertility treatment, sperm must be collected from the urine of the patients. Our study attempts to ascertain the effects of different g-forces on sperm motility, morphology and DNA integrity in sperm preparation by the Sil-Select™ density gradient method of isolating sperm from urine specimens. Forty-seven semen samples with normal semen analyses according to World Health Organisation (WHO) 1999 criteria were included in this study. Semen samples of 1 ml were mixed with 20 ml alkalinised normal urine and then divided equally into tubes A and B. The two samples were prepared by the Sil-Select™ density gradient centrifugation method at 350 g (tube A) and at 700 g (tube B). Total motile sperm after centrifugation at 700 g was significantly higher than after centrifugation at 350 g [6.7 (0.4-23.0) million versus 3.1 (0.1-13.7) million] (P < 0.001). There was no significant difference between the either the percentage of sperm with normal morphology or with DNA damage between centrifugation at 350 g and 700 g (P > 0.05), although centrifugation at 700 g achieves a higher number of total motile sperm compared with Sil-Select™ sperm preparation at 350 g centrifugation.

Long-term outcome of kidney retransplantation in comparison with first kidney transplantation: a report from the Thai Transplantation Registry.

INTRODUCTION: Kidney retransplantation is a high-risk procedure that is increasingly performed because of previous graft failure. The aim of this study was to determine the long-term outcomes of kidney retransplantations compared with first kidney transplantations under the current era of immunosuppression. METHODS: Since the first retransplantation in Thailand was performed in 1993, this study included all consecutive cases registered in the Thai Transplantation Registry database from January 1993 to December 2011. A total of 3337 kidney transplantations were available for the analysis. Graft loss was defined as a return to dialysis or graft removal. Death with a functioning graft was censored. RESULTS: Of 3337 kidney transplantations during the study period, 113 were second and 3 were third transplantations. Among these 116 retransplantations, the most common identified causes of end-stage renal disease were chronic glomerulonephritis (38.8%), followed by hypertensive nephropathy (13.0%), diabetic nephropathy (6.0%), and lupus nephritis (1.7%). The retransplantation recipients were older (mean age, 46.2 ± 12.8 years) than the first transplantation group (mean age, 42.2 ± 12.8 years). The proportion of living-related kidney transplantations and male sex were similar between first and retransplantation recipients. Fourteen percent of retransplantation recipients showed high immunologic risk as defined by current panel reactive antibodies ≥30% compared with 3% of those in the first transplantation group (P < .001). The percentages of induction therapy with antithymocyte globulin and anti-interleukin-2 antibody in the retransplantation and first transplantation groups were 18.3% versus 4.3% and 60.0% versus 32.6%, respectively. The graft survival rates (95% confidence interval [CI]) at 1, 5, and 10 years were 88.6% (80.7-93.3), 87.3% (79.1-92.5), and 74.4% (53.7-86.9) among retransplantation, versus 95.0% (94.1-95.7), 87.0% (85.5-88.5), and 70.7% (67.4-73.8) among first transplantation groups, respectively (P = .63). Patient survival rates were not different between first and retransplantation groups (P = .42). The leading cause of graft loss in the retransplantation group was chronic allograft nephropathy (22%), whereas infection (57%) was the major cause of death in this group. CONCLUSION: The 10-year patient and graft survival rates of kidney retransplantation were acceptable. The combination of induction therapy with a calcineurin inhibitor and a mycophenolate mofetil/mychophenolic acid-based regimen lead to outcomes comparable to first kidney transplantations among our cohort of 3337 patients.

Comparison of cryopreserved human sperm from solid surface vitrification and standard vapor freezing method: on motility, morphology, vitality and DNA integrity.

Solid surface vitrificaition (SSV) is a cryoperservative method that has been used in the cryopreservation of oocytes, and embryos. Here, we report an application of the SSV in the cryopreservation of human spermatozoa. We compared the SSV with a standard freezing method in terms of sperm motility, morphology, vitality and DNA integrity. Sperm motility was determined by computer assisted semen analysis, morphology and vitality were determined by eosin-methylene blue staining, and DNA integrity was determined by a TUNEL assay. We found that while both cryopreservative methods produced spermatozoa with comparable vitality and motility, the SSV gave slightly, but significantly fewer sperm with DNA damage, and loose tail. We concluded that, a cryopreservation of human spermatozoa by SSV is feasible and provides a quick and practical way to preserve human spermatozoa with a comparable, if not better, quality of the preserved spermatozoa to the standard freezing method.

Different etiologies of graft loss and death in Asian kidney transplant recipients: a report from Thai Transplant Registry.

BACKGROUND: Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade. PATIENTS AND METHODS: The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths. RESULTS: Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%). CONCLUSION: Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations.

Prevalence of chronic kidney disease: a systematic review and meta-analysis.

AIMS: Many studies have estimated the prevalence of chronic kidney disease (CKD) but results have varied due partly to the type of equation used to estimate GFR, type of subjects, and ethnicity. This review aimed to estimate the prevalence of CKD Stage III, accounting for these factors. METHODS: 403 studies were identified from Medline using the PubMed search engine, of which 34 studies were eligible. Data were independently extracted by two reviewers, and heterogeneity was assessed using metaregression. RESULTS: The pooled prevalence was estimated using a random effects model. In the general population, the prevalences of CKD Stage III using MDRD equation were 3.6% (95% CI: 2.5, 4.8), 10.7% (95% CI: 4.5 - 16.9%), and 16.3% (95% CI: 2.1 - 30.5%) for age groups 60 years. The prevalence was about double using the Cockcroft-Gault equations, i.e. 7.5% (95% CI: 6.9 - 8.2%) and 34.9 (95% CI: 25.9 - 44.8%) in age 50 years, respectively. The prevalence was similar in Caucasians and Asians aged. < or = 60, i.e. 9.9 versus 9.3%. The prevalence was also higher in the diabetic population than in the general population, i.e. 18.2% versus 10.6%. CONCLUSIONS: The pooled prevalence of CKD in the general population varied according to age groups. The prevalence is similar in Caucasians and Asians within age 60 years or younger but other age groups need more studies in order to pool. Individual patient meta-analysis would be appropriate to resolve the causes of heterogeneity.

Factors predisposing to peptic ulcer disease in asymptomatic cirrhotic patients.

BACKGROUND: There is a high prevalence of peptic ulcer in cirrhotic patients, but the pathogenesis of peptic ulcer in cirrhosis remains inconclusive. AIM: To investigate factors associated with peptic ulcer and to evaluate peptic ulcer prevalence in asymptomatic cirrhotic patients. METHODS: A total of 130 cirrhotics were recruited into the study for endoscopic screening. Data were collected and biochemical tests were done. Doppler ultrasound was used to assess the portal vein velocity and size. Patients underwent endoscopy for the presence of varices and peptic ulcer. Helicobacter pylori infection was confirmed by urease test, histology and 14C-urea breath test. Statistical analysis was performed. RESULTS: Peptic ulcer was detected in 50 (39%) cases. Between peptic ulcer and non-peptic ulcer groups, there were no significant differences in age, sex, alcoholic drinking, smoking, non-steroidal anti-inflammatory drug use, portal vein velocity and size, except for H. pylori infection (P = 0.006), serum albumin (P = 0.02) and Child-Pugh score (P = 0.03). By multivariate analysis, H. pylori infection (OR: 3.26; 95% CI: 1.49-7.13; P = 0.003), Child-Pugh classes B (OR: 2.48; 95% CI: 1.04-5.91; P = 0.04) and C (OR: 3.26; 95% CI: 1.2-8.81; P = 0.02) were independently associated with peptic ulcer. CONCLUSION: H. pylori infection and advanced cirrhosis are important factors associated with active peptic ulcer.

Nevirapine- versus efavirenz-based highly active antiretroviral therapy regimens in antiretroviral-naïve patients with advanced HIV infection.

OBJECTIVE: To compare virological and immunological responses to nevirapine (NVP)-based and efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens in antiretroviral-naïve patients with advanced HIV infection. METHODS: A retrospective observational cohort study was conducted on antiretroviral-naïve HIV-infected patients whose pretreatment CD4 cell counts were less than 100 cells/microL or whose viral loads were greater than 100,000 HIV-1 RNA copies/mL. RESULTS: Baseline characteristics of patients in the NVP (n=24) and EFV (n=29) groups were not different. The proportion of patients with viral loads >100,000 copies/mL was higher in the EFV group. The probability of virological success estimated by the Kaplan-Meier method showed that 3- and 6-month success rates were 30.8% [95% confidence interval (CI): 16.7-52.2%] and 63.1% (95% CI: 44.7-81.3%) for the NVP group. The corresponding values were 41.2% (95% CI: 25.8-61.0%) and 62.9% (95% CI: 45.7-80.1%) for the EFV-based group. The median success times of the two groups were about 4 and 3 months (P=0.678), respectively, for NVP and EFV. Cox's proportional hazard was used after adjusting for age, previous opportunistic infections (OIs), and viral load at baseline, and showed that patients who received the NVP-based regimen had about 25% [hazard ratio (HR)=0.75, 95% CI: 0.37-1.51] less chance of virological success than patients who received the EFV-based regimen (P=0.415). The median times to CD4 > or =100 cells/microL were 5.6 and 4.4 months for the NVP- and EFV-based regimens, respectively (log-rank test, P=0.144). CONCLUSIONS: NVP- and EFV-based HAART regimens as initial regimens in patients with advanced HIV infection are effective and comparable, in term of virological and immunological responses. However, further large-scale randomized controlled clinical trials in this group of patients with advanced HIV infection are needed.