Association between obesity and sperm quality

There is awareness of likelihood of abnormal spermatozoa in obese men; however, results from previous studies are inconclusive. Advances in computer‐aided sperm analysis (CASA) enable precise evaluation of sperm quality and include assessment of several parameters. We studied a retrospective cohort of 1285 men with CASA data from our infertility clinic during 2016. Obesity (BMI ≥30) was associated with lower (mean ± SE) volume (?0.28 ± 0.12, p‐value = .04), sperm count (48.36 ± 16.51, p‐value = .002), concentration (?15.83 ± 5.40, p‐value = .01), progressive motility (?4.45 ± 1.92, p‐value = .001), total motility (?5.50 ± 2.12, p‐value = .002), average curve velocity (μm/s) (?2.09 ± 0.85, p‐value = .001), average path velocity (μm/s) (?1.59 ± 0.75, p‐value = .006), and higher per cent head defects (0.92 ± 0.81, p‐value = .02), thin heads (1.12 ± 0.39, p‐value = .007) and pyriform heads (1.36 ± 0.65, p‐value = .02). Obese men were also more likely to have (odds ratio, 95% CI) oligospermia (1.67, 1.15–2.41, p‐value = .007) and asthenospermia (1.82, 1.20–2.77, p‐value = .005). This is the first report of abnormal sperm parameters in obese men based on CASA. Clinicians may need to factor in paternal obesity prior to assisted reproduction.     

Systematic review and meta‐analysis of post‐transplant lymphoproliferative disorder in lung transplant recipients

A systematic review of papers in English on post‐transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random‐effects model, and heterogeneity among studies was quantitated using I² values. Fourteen studies published from 2005 to 2015 were included in the meta‐analysis. One hundred and sixty‐four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67‐fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98‐29.70; P = .003). pOR of death for early onset PTLD (<1 year post‐LT) vs late onset (> 1 year post‐LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20‐1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI ?0.48‐0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08‐2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31‐3.52, P = .94). This meta‐analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.     

Relationship between nuclear DNA fragmentation,mitochondrial DNA damage and standard sperm parameters in spermatozoa of fertile and sub‐fertile men before and after freeze‐thawing procedure

The aim of this study was to assess the stability of nuclear and mitochondrial DNA (n‐DNA and mt‐DNA) of spermatozoa under freeze‐thawing and to find out the correlation between them and their association with standard sperm parameters. Forty‐three semen samples were collected from fertile (G.1; n = 29) and sub‐fertile (G.2; n = 14). N‐DNA fragmentation was determined by TUNEL assay and mt‐DNA using caspase 3 staining. Each semen sample was frozen at ?196°C by the programmed freezer. Freeze‐thawing decrease vitality, total motility and membrane integrity from (43.02 ± 22.74%; 31.63 ± 18.15%; 51.5 ± 24.82%) to (22.71 ± 17.3%; 9.21 ± 6.61%; 34.64 ± 19.92% respectively [p < .001]). G.1 native spermatozoa stained positive with TUNEL and caspase 3 were (14.85 ± 17.6% and 5.8 ± 11.59%) and increased after freeze‐thawing to 27.54 ± 19.74% (p = .004) and 7.3 ± 6.13% (p = .01) respectively. In G.2, TUNEL and caspase 3 were (19.84 ± 17.52% and 7.53 ± 8.56%) and increased to (29.48 ± 16.97% [p = .03] and 10.21 ± 11.73%). In conclusion, freeze‐thawing process affects not only semen parameters but also n‐DNA and mt‐DNA. Therefore, n‐DNA and mt‐DNA could be used as sensitive parameters for assessment of the cryodamage of human spermatozoa.     

Efficacy of antioxidant therapy on sperm quality measurements after varicocelectomy: A systematic review and meta‐analysis

Antioxidants were proved to be efficient to improve the quality of spermatozoa after varicocelectomy. We carried out a systematic review and performed a meta‐analysis to evaluate the efficacy of antioxidant therapy in sperm parameters' quality after varicocelectomy during 3 or 6 months' treatment cycle. During research, randomised controlled trials were searched by MEDLINE, EMBASE and the Cochrane Controlled Trials Register, and necessary parameters were compared between two groups after varicocelectomy. Finally, six studies including 576 patients were included in our meta‐analysis. As for sperm parameters, significant improvements of sperm concentration (p < .0001), sperm motility (p = .03), progressive sperm motility (p < .00001) and sperm morphology (p < .00001) were existed in antioxidant group 3 months after varicocelectomy. With regard to the 6 months' outcomes, sperm parameters were improved as well except sperm motility (p = .72) and progressive sperm motility (p = .57). Referring to pregnancy rate, no significant difference was existed between two groups (p = .36), and the FSH level of antioxidant group was lower than placebo group 3 or 6 months after varicocelectomy (3 months, p = .02; 6 months, p = .03). In conclusion, compared with the placebo, the antioxidant therapy after varicocelectomy can improve the quality of sperm parameters and construct a favourable living condition for spermatozoa by reducing FSH level.     

Testosterone replacement therapy improves health‐related quality of life for patients with late‐onset hypogonadism: a meta‐analysis of randomized controlled trials

Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late‐onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta‐analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed‐effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health‐related quality of life in terms of the decrease in the AMS total score [WMD = ?2.96 (?4.21, ?1.71), p < .00001] and the psychological [WMD = ?0.89 (?1.41, ?0.37), p = .0008], somatic [WMD = ?0.89 (?1.41, ?0.37), p = .0008] and sexual [WMD = ?1.29 (?1.75, ?0.83), p < .00001] subscale score.     

Effect of Twice‐Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial

We conducted an open‐label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3–5.9%) in 46 patients in the denosumab group and decreased by ?0.5% (95% CI ?1.8% to 0.9%) in 44 patients in the control group (between‐group difference 5.1% [95% CI 3.1–7.0%], p < 0.0001). Denosumab also increased aBMD at the total hip by 1.9% (95% CI, 0.1–3.7%; p = 0.035) over that in the control group at 12 months. High‐resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C‐terminal telopeptide of type I collagen, procollagen type I N‐terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection.     

Is there any correlation between sperm parameters and chromatin quality with embryo morphokinetics in patients with male infertility?

The main goal was to evaluate the correlation between sperm parameters and chromatin quality with embryo kinetics via time‐lapse monitoring system (TLM). A total of 40 couples involved in the ICSI program as a result of male infertility. For assessment of sperm chromatin and DNA quality, we used aniline blue, toluidine blue, chromomycin A3, acridine orange and terminal transferase‐mediated deoxyuridine triphosphate biotin end labelling assays. All mature oocytes were injected, and the generated zygotes (2PNs) were cultured in TLM. In day 3 after injection, single embryo transfer (SET) was carried out according to the morphology and morphokinetics. The patients were followed up until delivery. There were positive significant correlations between sperm count with CC2 (r = .330, p = .049), T4 (r = .329, p = .038), T6 (r = .342, p = .035) and T7 (r = .374, p = .025). Also, there were positive significant correlations between nonprogressive motility and T2 (r = 0.323, p = .042), T3 (r = .411, p = .013) and T4 (r = .418, p = .007). Regarding the sperm chromatin quality assays, there were negative significant correlations between CMA3 and CC2 (r = ?.272, p = .049) and between acridine orange and T5 (r = ?.221, p = .040). It seems that the abnormal sperm parameters and chromatin alteration affect the normal embryo kinetics in ICSI program.     

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized,double‐blind,placebo‐controlled trial

This study was carried out to determine the effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double‐blind, placebo‐controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (β [difference in the mean of outcomes measures between treatment groups] ?0.56 cm; 95% CI, ?0.92, ?0.20; p = 0.003), width (β ?0.35 cm; 95% CI, ?0.64, ?0.05; p = 0.02) and depth (β ?0.18 cm; 95% CI, ?0.33, ?0.02; p = 0.02). In addition, co‐supplementation led to a significant reduction in fasting plasma glucose (β ?13.41 mg/dL; 95% CI, ?20.96, ?5.86; p = 0.001), insulin (β ?1.45 μIU/ml; 95% CI, ?2.37, ?0.52; p = 0.003), insulin resistance (β ?0.60; 95% CI, ?0.99, ?0.20; p = 0.003) and HbA1c (β ?0.32%; 95% CI, ?0.48, ?0.16; p < 0.003), and a significant elevation in insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (β ?10.08 mg/dL; 95% CI, ?19.70, ?0.46; p = 0.04), LDL‐cholesterol (β ?5.88 mg/dL; 95% CI, ?11.42, ?0.34; p = 0.03), high sensitivity C‐reactive protein (hs‐CRP) (β ?3.42 mg/L; 95% CI, ?4.44, ?2.41; p < 0.001) and malondialdehyde (MDA) (β ?0.30 μmol/L; 95% CI, ?0.45, ?0.15; p < 0.001), and increased HDL‐cholesterol (β 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (β 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co‐supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL‐ and HDL‐cholesterol, hs‐CRP, TAC, and MDA levels.     

Bilateral is superior to unilateral varicocelectomy in infertile men with bilateral varicocele: Systematic review and meta‐analysis

To investigate whether bilateral surgery can bring more benefits to infertile patients with bilateral varicocele than unilateral surgery. A search of PubMed, Web of Science, EMBASE and the Cochrane Library on 13 January 2019 was conducted to identify studies published in English that used varicocelectomy. The protocol of the present meta‐analysis was pre‐published on PROSPERO (registration number CRD42019093894). Primary outcomes were spontaneous pregnancy rates. A total of eleven articles were finally enrolled in, with a total of 1,743 patients. Spontaneous pregnancy rate was higher in patient with bilateral varicocelectomy than unilateral varicocelectomy with an odds ratio (OR) of 1.89 (95% CI 1.52–2.35; I² = 0%; p < .00001). The results indicated bilateral is superior than unilateral varicocelectomy concerning sperm concentration (SMD: 2.88 × 10⁶/ml; 95% CI: 1.06, 4.70; I² = 93%), sperm motility (SMD: 5.08; 95% CI: 2.65, 7.50; I² = 0%), progression of sperm motility (SMD: 6.48; 95% CI: 5.16, 7.81; I² = 0%) and sperm morphology (SMD: 2.38%; 95% CI: 0.72, 4.03; I² = 94%) between bilateral and unilateral varicocelectomy. Bilateral varicocelectomy may be superior to unilateral in regard to spontaneous pregnancy rate and sperm motility for infertile male with bilateral varicocele (both left clinical and right subclinical varicocele and bilateral clinical varicocele).     

Hypoadiponectinemia,elevated iron and high‐sensitivity C‐reactive protein levels and their relation with prostate size in benign prostatic hyperplasia

Elevated iron, high‐sensitivity C‐reactive protein (CRP) and hypoadiponectinemia are known to initiate tumour development. There is paucity of data regarding the above‐mentioned parameters and their relation with prostate size in benign prostatic hyperplasia (BPH). The present study was designed to assess the levels of iron, hs‐CRP and adiponectin levels and their association with prostate size in BPH patients. A total of 37 BPH cases and 36 controls were enrolled in the study. Iron, hs‐CRP and adiponectin were estimated in both the groups. Iron and hs‐CRP were significantly increased and adiponectin was significantly reduced in BPH cases when compared with controls. Iron (r = .397, p = .015), hs‐CRP (r = .341, p = .039) and adiponectin (r = ?.464, p = .004) were significantly associated with prostate size in BPH cases. Multivariate linear regression analysis showed that iron acts as predictor of prostate size in BPH (R² = 0.395, β = 0.526, p = .001). We conclude that iron and hs‐CRP are elevated and adiponectin is reduced in BPH cases and associated with prostate size.     

Association between human papillomavirus infection and sperm quality: A systematic review and a meta-analysis

Human papillomavirus (HPV) has a high incidence rate in both males and females. HPV infection in women has been shown to affect fertility and lead to foetal death and pregnancy loss. However, research on HPV infection in men is limited. The aim of this study was to study the effect of HPV infection in semen on sperm quality and present the findings of previous studies through a meta-analysis. Databases including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, WanFang data and China National Knowledge Infrastructure were searched for relevant studies. A systematic review and meta-analysis were performed, and 17 studies were included for analyses based on a set criterion. Meta-analyses indicated that HPV infection in semen significantly reduced sperm concentration (SMD = −0.12, 95% CI: −0.21 to −0.03, p = .009), sperm motility (SMD = −0.55, 95% CI: −0.780 to −0.33, p = .000), sperm viability (SMD = −0.55, 95% CI: −0.780 to −0.33, p = .000) and sperm morphology (SMD = −0.34, 95% CI: −0.61 to −0.07, p = .015). The high-risk HPV (HrHPV) infection could significantly reduce sperm count (SMD = −0.65, 95% CI: −1.11 to −0.18, p = .007) compared with high-risk HPV (LrHPV) infection. In conclusion, HPV infection in semen significantly reduced sperm quality, and the HrHPV infection could significantly reduce sperm count compared with LrHPV.     

Sperm telomere length in motile sperm selection techniques: A qFISH approach

Several studies have associated telomere shortening with alterations in reproductive function. The objective of the present study was to determine telomere length (TL) in spermatozoa selected by either density‐gradient centrifugation (DGC) or swim‐up. The analysis of TL was performed using quantitative fluorescent in situ hybridisation (qFISH) using PNA probes in combination with a chromatin decompaction protocol in sperm cells. Results of TL were 24.64 ± 5.00 Kb and 24.95 ± 4.60 Kb before and after DGC, respectively, and 19.59 ± 8.02 Kb and 20.22 ± 5.18 Kb before and after swim‐up respectively. Sperm selected by DGC or swim‐up did not show any significant differences in TL as compared to nonselected sperm (p > .05). Negative correlations between TL and sperm motility (r = ?.308; p = .049) and concentration (r = ?.353; p = .028) were found. Furthermore, exposure of sperm to increasing concentrations of hydrogen peroxide during incubation resulted in a reduction in TL. These data indicate that oxidative stress may be one of the main factors involved in the reduction of TL in sperm. Preliminary clinical results from patients included in this study indicate that TL was shorter in spermatozoa from couples who never achieved a pregnancy compared to couples who did achieve at least one natural pregnancy (p < .05); however, the clinical utility of this biomarker still needs to be confirmed in further studies.     

Vitamin E administration does not ameliorate tramadol-associated impairment of testicular function in Wistar rats

Tramadol is widely abused in Nigeria and has been reported to cause fertility decline via testicular oxidative stress. This study investigated the effect of vitamin E, an antioxidant on some reproductive parameters in male Wistar rats administered tramadol. Twenty male Wistar rats (180–200 g) were randomly assigned into four groups (n = 5) thus: Control (0.2 ml vehicle: olive oil), tramadol-treated (20 mg/kg of tramadol), vitamin E-treated (100 mg/kg of vitamin E) and tramadol + vitamin E-treated (received tramadol and vitamin E) groups. Drugs were administered orally and daily for 28 days. Sperm count, Johnsen's score, germinal epithelial height and serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were significantly (p < .05) decreased in tramadol-treated and tramadol + vitamin E compared with control and vitamin E-treated groups. Sperm motility, morphology, viability, seminiferous tubular diameter, Leydig cell count, Sertoli cell count and malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase concentrations were not significantly different among the groups. Histology of testis and epididymis in all groups showed no toxicity but decreased sperm population in tramadol-treated and tramadol + vitamin E-treated groups. Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion. Vitamin E administration could not attenuate this impairment in testicular function.     

Loco‐regional Control After Neo‐adjuvant Chemotherapy and Conservative Treatment for Locally Advanced Breast Cancer Patients

Breast‐conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco‐regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo‐adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty‐four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow‐up of 6.3 years, the loco‐regional control rate was 91% (95% CI: 86–94%). The 10‐year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9–16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9–15.2%]; p = 0.8). Ten‐year overall survival (OS) rates (63% [95% CI: 46–79%] in the BCT group; 60% [95% CI: 47–73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2–5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2–30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1–5.9; p = 0.03) were independent predictors of LRR. Ten‐year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely omitted in selected breast cancer patients (nonstage III tumors or those which do not require adjuvant hormone suppression) which respond to NCT are required.     

Hypertension might be a risk factor for erectile dysfunction: a meta‐analysis

The study aimed to evaluate whether hypertension was a risk factor for erectile dysfunction (ED). Databases including PubMed and Embase were retrieved to identify studies related to hypertension in ED patients. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect size. Subgroup analyses stratified by total number of enrolled subjects and research regions were performed. Sensitivity analysis was performed by removing a single study at one time. Egger's test was used to evaluate the publication bias. Totally, 40 studies including 121,641 subjects were included in the meta‐analysis. As a result, hypertension was closely related to ED (OR = 1.74, 95% CI, 0.63–0.80, p < .01). Subgroup analysis indicated hypertension was the risk factor for ED whatever the participants numbers. When stratified by different regions, hypertension was a risk factor for ED in Africa (OR = 3.35, 95% CI, 1.45–7.77, p < .01), Americas (OR = 1.97, 95% CI, 1.68–2.31, p < 0.01), Asia (OR = 1.46, 95% CI, 1.16–1.84, p < .01) and Europe (OR = 1.83, 95% CI, 1.34–2.49, p < .01), but not in Australia. Hypertension may be a potential risk factor for ED.     

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo‐astheno‐teratozoospermia,with and without varicocele: A double‐blind placebo‐controlled study

Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double‐blind, placebo‐controlled trial investigated the effect of 6 months of supplementation with l ‐carnitine, acetyl‐l ‐carnitine and other micronutrients on sperm quality in 104 subjects with oligo‐ and/or astheno‐ and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow‐up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.     

Alterations of naïve and memory B‐cell subsets are associated with risk of rejection and infection in heart recipients

Rejection and infection are relevant causes of mortality in heart recipients. We evaluated the kinetics of the maturation status of B lymphocytes and its relationship with acute cellular rejection and severe infection in heart recipients. We analyzed B‐cell subsets using 4‐color flow cytometry in a prospective follow‐up study of 46 heart recipients. Lymphocyte subsets were evaluated at specific times before and up to 1 year after transplantation. Higher percentages of pretransplant class‐switched memory B cells (CD19+CD27+IgM‐IgD‐ >14%) were associated with a 74% decrease in the risk of severe infection [Cox regression relative hazard (RH) 0.26, 95% confidence interval (CI), 0.07–0.86; P = 0.027]. Patients with higher percentages of naïve B cells at day 7 after transplantation (CD19+CD27‐IgM+IgD+ >58%) had a 91% decrease in the risk of developing acute cellular rejection (RH 0.09; 95% CI, 0.01–0.80; P = 0.02). Patients with infections showed a strong negative correlation between baseline serum B‐cell–activating factor (BAFF) concentration and absolute counts of memory class‐switched B cells (R =   ?0.81, P = 0.01). The evaluation of the immunophenotypic maturation status of B lymphocytes could prove to be a useful marker for identifying patients at risk of developing rejection or infection after heart transplantation.     

Efficacy and safety of everolimus with reduced tacrolimus in living‐donor liver transplant recipients: 12‐month results of a randomized multicenter study

In a multicenter, open‐label, study, 284 living‐donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non‐inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7% (90% CI ?5.2%, 3.7%); P < .001 for non‐inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non‐inferiority (P < .001 for non‐inferiority), but not superiority and was similar between groups overall (mean ?8.0 vs. ?12.1 mL/min/1.73 m², P = .108), and in patients continuing randomized treatment (?8.0 vs. ?13.3 mL/min/1.73 m², P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC‐treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non‐inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.     

Relationship between human spermatozoa–hyaluronan‐binding assay,conventional semen parameters and fertilisation rates in intracytoplasmic spermatozoa injection

Selecting the best spermatozoa for intracytoplasmic spermatozoa injection (ICSI) has recently been a topic of great interest among embryologists. The study aimed to evaluate the relationship between the spermatozoa‐hyaluronan‐binding assay (HBA), routine semen analysis results and fertilisation rates as recorded during conventional ICSI therapy. Ninety‐one patients undergoing conventional ICSI treatment in the Medfem Fertility Clinic in Johannesburg (South Africa) were included in the study. A total of 797 oocytes were injected of which 457 oocytes fertilised (57.3%, range 0–100%). None of the semen parameters correlated with the fertilisation rates (Table 2). HBA scores, however, revealed a highly significant association (p ≤ 0.0001) with the fertilisation rates. The HBA scores also correlated significantly with the biochemical pregnancy values (Spearman r = 0.24, P = 0.02, 95% CI 0.039–0.43); however, the HBA scores did not correlate with the clinical pregnancy rates (Spearman r = 0.14, P = 0.16, 95% CI ?0.06 to 0.34). No correlation was recorded between HBA and the standard semen parameters. The study showed that HBA is significantly associated with fertilisation in conventional ICSI. The HBA scores were also significantly associated with the fertilisation rates and biochemical pregnancies.     

Value of a flow cytometry cross‐match in the setting of a negative complement‐dependent cytotoxicity cross‐match in heart transplant recipients

Complement‐dependent cytotoxicity cross‐match (CDCXM) is used for evaluation of preformed HLA‐specific antibodies in patients undergoing heart transplantation. Flow cytometry cross‐match (FCXM) is a more sensitive assay and used with increasing frequency. To determine the clinical relevance of a positive FCXM in the context of negative CDCXM in heart transplantation, the United Network for Organ Sharing (UNOS) database was analyzed. Kaplan‐Meier analysis and Cox proportional hazard modeling were used to assess graft survival for three different patient cohorts defined by cross‐match results: T‐cell and B‐cell CDCXM+ (“CDCXM+” cohort), CDCXM? but T‐cell and/or B‐cell FCXM+ (“FCXM+” cohort), and T‐cell/B‐cell CDCXM? and FCXM‐ (“XM?” cohort). During the study period, 2558 patients met inclusion criteria (10.7% CDCXM+, 18.8% FCXM+, 65.5% XM?). CDCXM+ patients had significantly decreased graft survival compared to FCXM+ and XM? cohorts (P = .003 and <.001, respectively). CDCXM? and FCXM+ patients did not have decreased graft survival compared to XM? patients (P = .09). In multivariate analysis, only CDCXM+ was associated with decreased graft survival (HR 1.22, 95% CI 1.01‐1.49). In conclusion, positive FCXM in the context of negative CDCXM does not confer increased risk of graft failure. Further study is needed to understand implications of CDCXM and FCXM testing in heart transplant recipients.