Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index (ET‐DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET‐DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18–25; 3: >25–35; 4: >35), and ET‐DRI. Mean ET‐DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET‐DRI. Accordingly, four ET‐DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET‐DRI categories with labMELD revealed significant differences in long‐term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET‐DRI > 2 and labMELDcategory 3 combined with ET‐DRI > 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs (ET‐DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET‐DRI > 2 should be avoided in patients with a labMELD of >25–35.     

Mindfulness‐based Coping with University Life: A Non‐randomized Wait‐list‐controlled Pilot Evaluation

The aim of this study was to explore the feasibility of implementing a new 8‐week mindfulness‐based programme, ‘Mindfulness‐Based Coping with University Life’ (MBCUL), specifically tailored to the needs and demand of students and to explore its impact in a pilot evaluation. Participants were drawn from the University of Northampton (MBCUL N = 10; control N = 6). A non‐randomized wait‐list‐controlled design was employed. Measures examined anxiety and depression, perceived stress, mindfulness and personally relevant change before and immediately after the programme. The diurnal profile of salivary cortisol and alpha‐amylase level was collected for two consecutive days. No significant intergroup differences were observed on any of the measures at either time point. However, significant change was observed for the MBCUL group in terms of perceived stress (d = 1.06; z = ?2.25, p = 0.03), anxiety (d = 1.04; z = ?2.14, p = 0.03), depression (d = 0.52; z = ?0.69, p = 0.5) and personally relevant change (d = 2.63; z = ?2.68, p = 0.01), along with an increase in mindfulness (d = 1.06; z = ?1.89, p = 0.06). In contrast, no significant change was found in the daily profiles of cortisol and alpha‐amylase. The data from this pilot tentatively suggest that MBCUL appears to be a promising programme that warrants further evaluation using a randomized study with a larger sample size. Copyright © 2011 John Wiley & Sons, Ltd.     

International clones of extended‐spectrum β‐lactamase (CTX‐M)‐producing Escherichia coli in peri‐urban wild animals,Brazil

CTX‐M‐type extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli clones have been increasingly reported worldwide. In this regard, although discussions of transmission routes of these bacteria are in evidence, molecular data are lacking to elucidate the epidemiological impacts of ESBL producers in wild animals. In this study, we have screened 90 wild animals living in a surrounding area of São Paulo, the largest metropolitan city in South America, to monitor the presence of multidrug‐resistant (MDR) Gram‐negative bacteria. Using a genomic approach, we have analysed eight ceftriaxone‐resistant E. coli. Resistome analyses revealed that all E. coli strains carried bla_CTX‐M‐type genes, prevalent in human infections, besides other clinically relevant resistance genes to aminoglycosides, β‐lactams, phenicols, tetracyclines, sulphonamides, trimethoprim, fosfomycin and quinolones. Additionally, E. coli strains belonged to international sequence types (STs) ST38, ST58, ST212, ST744, ST1158 and ST1251, and carried several virulence‐associated genes. Our findings suggest spread and adaptation of international clones of CTX‐M‐producing E. coli beyond urban settings, including wildlife from shared environments.     

Effects of the dopamine D3 receptor agonist 7‐hydroxy‐2‐(di‐N‐propylamino) tetralin in hyperthyroidism‐induced premature ejaculation rat model

Various factors are involved in the aetiology of premature ejaculation (PE). Hyperthyroidism is one of the causes of acquired PE, but the exact mechanism by which it causes the disorder is not yet understood. The aim of this study was to evaluate the role of the dopaminergic system in hyperthyroidism‐induced PE by the intracerebroventricular microinjection of the preferentially active dopamine receptor agonist 7‐hydroxy‐2‐(di‐N‐propylamino) tetralin (7‐OH‐DPAT) in a rat model of this disorder. Wistar rats were randomly divided into hyperthyroid and control groups, and ejaculation was induced by the ICV administration of 7‐OH‐DPAT. To evaluate the emission and expulsion phases of ejaculation, measurements of seminal vesicle pressure (SVP) and electromyographic recordings of the bulbospongiosus muscle were taken. The interval between the 7‐OH‐DPAT administration and the first ejaculation was significantly less in the hyperthyroid group (p < .01) than in the control group, and the maximum amplitude of the SVP values revealed a statistically significant difference between the groups (p < .01). The intervals between contractions of the seminal vesicle and bulbospongiosus muscles were also significantly less in the hyperthyroid group (p = .0187) than in the control group. No other results differed significantly between the groups. This study determined that hyperthyroidism altered only the emission phase of ejaculation.     

Detection of New Delhi Metallo‐beta‐Lactamase and Extended‐Spectrum beta‐Lactamase Genes in Escherichia coli Isolated from Mastitic Milk Samples

In this study, eight Escherichia coli isolates were obtained from milk samples of dairy cattle suffering from clinical/subclinical mastitis. Isolates were characterized for antimicrobial resistance traits and virulence genes. Results revealed that one isolate was harbouring New Delhi metallo‐beta‐lactamase gene (bla_NDM). Cloning and sequencing of the PCR amplicon confirmed the identity of the gene (GenBank accession no. KC769583 ) having 100% homology with bla_NDM‐5 (GenBank accession no. JN104597.1 ), and this isolate was susceptible to colistin, chloramphenicol and tetracycline only. Moreover, another isolate carried extended‐spectrum beta‐lactamase (ESBL) gene – bla_CTX‐M, and all isolates possessed bla_TEM gene. Of the eight isolates, only one isolate was positive for shiga toxin gene (stx2), and none were harbouring stx1 gene. Occurrence of New Delhi metallo‐beta‐lactamase (bla_NDM) in one E. coli isolate and ESBL genes in other isolates poses a potential threat to human health following possible entry and spread through food chain.     

Effects of 4‐chloro‐2,6‐bis‐(2‐hydroxyl‐benzyl)‐phenol on Healing of Skin Wounds and Growth of Bacteria

In this investigation, the effects of synthesized 4‐chloro‐2,6‐bis‐(2‐hydroxyl‐benzyl)‐phenol (CBHBP) on cutaneous wound healing and growth of some of the wound contaminating microorganisms were studied. The antibacterial effects of this compound were then evaluated on Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Klebsiella spp., using solid dilution method. It was demonstrated that CBHBP has a significant antimicrobial activity against S. aureus but it is not effective in the case of other microorganisms studied in this experiment. The effect of local administration of CBHBP on healing of a standard full‐thickness 2 cm skin incision of skeletally mature rats was evaluated. Histological changes together with mechanical properties and dry weight content of the healing tissues at the site of the lesions were assessed in treated and untreated animals. It was observed that the injured area of the treated animals was more organized and showed more fibroblasts and less inflammatory cells. Much better maturation criteria in treated tissues were observed in comparison with those of the untreated ones which contained numerous polymorphonuclear inflammatory cells after 14 days post‐injury. Many infiltrated macrophages and lymphocytes were present even 28 days after injury induction in the haphazardly organized dermis and also in subcutaneous tissues of the untreated animals. The percentage dry weight content of the treated lesions at 14 days post‐injury was remarkably higher than those of the untreated animals. The results of biomechanical tensile testing showed that the ultimate tensile strength and stress of the injured skin of the treated animals were higher than those of the untreated ones. From these results, it could be concluded that CBHBP can be effective on wound healing and may be considered as a treatment regimen after evaluating its mechanism of action as well as testing its contraindications.     

De novo donor‐specific anti‐HLA antibodies mediated rejection in liver‐transplant patients

The incidence and consequences of de novo donor‐specific anti‐HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver‐transplant patients, without preformed anti‐HLA DSAs, were tested for anti‐HLA antibodies, with single‐antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver‐enzyme levels until the last follow‐up, that is, 34 (1.5–77) months. Twenty‐one patients (14%) developed de novo DSAs. Of these, five patients had C1q‐binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody‐mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B‐cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient‐ and graft‐survival rates did not differ between patients with and without DSAs. In conclusion, liver‐transplant patients with liver abnormalities should be screened for DSAs and AMR.     

In vivo six‐degree‐of‐freedom knee‐joint kinematics in overground and treadmill walking following total knee arthroplasty

No data are available to describe six‐degree‐of‐freedom (6‐DOF) knee‐joint kinematics for one complete cycle of overground walking following total knee arthroplasty (TKA). The aims of this study were firstly, to measure 6‐DOF knee‐joint kinematics and condylar motion for overground walking following TKA; and secondly, to determine whether such data differed between overground and treadmill gait when participants walked at the same speed during both tasks. A unique mobile biplane X‐ray imaging system enabled accurate measurement of 6‐DOF TKA knee kinematics during overground walking by simultaneously tracking and imaging the joint. The largest rotations occurred for flexion‐extension and internal‐external rotation whereas the largest translations were associated with joint distraction and anterior‐posterior drawer. Strong associations were found between flexion‐extension and adduction‐abduction (R ² = 0.92), joint distraction (R ² = 1.00), and anterior‐posterior translation (R ² = 0.77), providing evidence of kinematic coupling in the TKA knee. Although the measured kinematic profiles for overground walking were grossly similar to those for treadmill walking, several statistically significant differences were observed between the two conditions with respect to temporo‐spatial parameters, 6‐DOF knee‐joint kinematics, and condylar contact locations and sliding. Thus, caution is advised when making recommendations regarding knee implant performance based on treadmill‐measured knee‐joint kinematic data. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1634–1643, 2017.

     

Polymorphisms of miR‐146a,miR‐149, miR‐196a2, and miR‐499 are associated with osteoporotic vertebral compression fractures in Korean postmenopausal women

Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case–control association study to determine the association between miR‐146a, miR‐149, miR‐196a2, and miR‐499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non‐OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X‐ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre‐miRNA sequences including miR‐146aC>G (rs2910164), miR‐149T>C (rs2292832), miR‐196a2T>C (rs11614913), and miR‐499A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction‐restriction fragment length polymorphism analysis. The TT genotype of miR‐149aT>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22–0.85, p = 0.014), whereas the miR‐146aCG/ miR‐196a2TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057–25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR‐146a, ‐149, ‐196a2, and ‐449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR‐146aG/‐149T/‐196a2C/‐449G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919–638.6, p = 0.001). Our findings suggest that the TT genotype of miR‐149aT>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR‐146aCG/ miR‐196a2TC combined genotype and the miR‐146aG/‐149T/‐196a2C/‐449G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244–253, 2018.     

Different risk factor profiles distinguish early‐onset from late‐onset BKV‐replication

Two of three reactivations of latent BKV‐infection occur within the first 6 months after renal transplantation. However, a clear differentiation between early‐onset and late‐onset BKV‐replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV‐associated nephropathy (BKVN). Sixty‐seven KTRs with early‐onset BKV‐replication (65%) and 36 KTRs with late‐onset BKV‐replication (35%) were identified. A control group of 598 KTRs without BKV‐replication was used for comparison. Lymphocyte‐depleting induction, CMV‐reactivation, and acute rejection increased the risk of early‐onset BKV‐replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late‐onset BKV‐replication (P < 0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft function (P < 0.05). KTRs with late‐onset BK viremia were more likely not to recover to baseline creatinine after BKV‐replication (P = 0.018). Our data suggest different risk factors in the pathogenesis of early‐onset and late‐onset BKV‐reactivation. While a more intensified immunosuppression is associated with early‐onset BKV‐replication, a chronic inflammatory state in presensitized KTRs may contribute to late‐onset BKV‐replication.     

Pharmacogenetics of steroid‐responsive acute graft‐versus‐host disease

Glucocorticoids are central to effective therapy of acute graft‐versus‐host disease (GVHD). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti‐inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co‐chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T‐cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty‐three SNPs in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP70 gene (O.R. 2.8, 95% CI: 1.3‐6.0, P=.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI: 0.1‐1.0, P=.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNPs did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance.     

The Estimation of Second‐Generation HR‐pQCT From First‐Generation HR‐pQCT Using In Vivo Cross‐Calibration

Second‐generation high‐resolution peripheral quantitative computed tomography (HR‐pQCT) provides the highest resolution in vivo to assess bone density and microarchitecture in 3D. Although strong agreement of most outcomes measured with first‐ (XCTI) and second‐ (XCTII) generation HR‐pQCT has been demonstrated, the ability to use the two systems interchangeably is unknown. From in vivo measurements, we determined the limits of estimating XCTII data from XCTI scans conducted in vivo and whether that estimation can be improved by linear cross‐calibration equations. These data are crucial as the research field transitions to the new technology. Our study design established cross‐calibration equations by scanning 62 individuals on both systems on the same day and then tested those cross‐calibrations on the same cohort 6 months later so that estimated (denoted as XCTII*) and “true” XCTII parameters could be compared. We calculated the generalized least‐significant change (GLSC) for those predictions. There was strong agreement between both systems for density (R² > 0.94), macroarchitecture (R² > 0.95), and most microarchitecture outcomes with the exception of trabecular thickness (Tb.Th, R² = 0.51 to 0.67). Linear regression equations largely eliminated the systematic error between XCTII and XCTII* and produced a good estimation of most outcomes, with individual error estimates between 0.2% and 3.4%, with the exception of Tt.BMD. Between‐system GLSC was similar to within‐XCTI LSC (eg, 8.3 to 41.9 mg HA/cm³ for density outcomes). We found that differences between outcomes assessed with XCTI and XCTII can be largely eliminated by cross‐calibration. Tb.Th is poorly estimated because it is measured more accurately by XCTII than XCTI. It may be possible to use cross‐calibration for most outcomes when both scanner generations are used for multicenter and longitudinal studies. © 2017 American Society for Bone and Mineral Research.     

Effects of acetylo‐L‐carnitine in end‐to‐side neurorrhaphy: A pilot study

Purpose: End‐to‐side (ETS) nerve repair allows for target‐muscle reinnervation, with simultaneous preservation of donor‐nerve function. Acetyl‐L‐carnitine (ALCAR) was shown to enhance axonal sprouting in early regeneration following transection and repair of the sciatic nerve in rodents. The purpose of this article was to determine the ability of ALCAR to enhance axonal regeneration in an ETS rodent model. Method: The right musculocutaneous nerve in 16 adult male Sprague‐Dawley rats was transected to induce biceps muscle paralysis. The distal stump was then coapted by ETS neurorrhaphy through a perineurial window to the ipsilateral median nerve. Experimental groups received ALCAR for 1, 2, 3, and 4 weeks whereas controls received placebo. Results: Weekly postoperative behavioral evaluations revealed increased functional return over control but the difference was not significant. Potentials from biceps were recorded from the third postoperative week in the experimental group and from the fourth week in the control group. Histomorphometric evaluations revealed higher musculocutaneous nerve axon counts, higher myelin thickness in the fourth postoperative week, and differences in the appearance and the number of motor‐end‐plates in the biceps in experimental versus control group. Conclusion: Intraperitoneal administration of ALCAR can expedite biceps muscle recovery in an ETS model by increasing the rate of axonal regeneration. Despite the morphological changes, no behavioral changes were noted and further studies are needed to confirm clinical efficacy of ALCAR for potential use in the development of therapeutic protocols. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.     

Pre‐emptive intravenous ganciclovir versus valganciclovir prophylaxis for de novo cytomegalovirus‐seropositive kidney‐transplant recipients

This sequential study evaluated two strategies regarding human cytomegalovirus (HCMV) infection/disease in HCMV‐seropositive de novo kidney‐transplant patients. The first cohort of patients (group 1; n = 132) was monitored sequentially for HCMV DNAemia; if it was positive (a cut‐off at 3 log₁₀copies/ml), the patient was given pre‐emptive IV ganciclovir therapy (10 mg/kg/day for 3 weeks). The second cohort consisted of 150 patients (group 2) who were given valganciclovir (VGC) prophylaxis (900 mg/day) for the first 3 months posttransplantation. During the mean follow‐up of at least 2 years for both cohorts, VGC prophylaxis resulted in a significant decrease in both CMV infection (68.9% vs. 33.3%; P < 0.001) and disease (9.8% vs. 2.68%, P = 0.021). Factors associated with HCMV reactivation in multivariate analysis were (i) no HCMV prophylaxis; (ii) recipient’s age; (iii) being placed on ciclosporine A and mycophenolic acid from the beginning of transplantation (iv) donor HCMV‐seropositivity; and (v) being a male recipient. No cases of ganciclovir resistance were detected in the prophylactic group. HCMV prophylaxis had no impact on 2‐year patient/graft survival or on kidney‐allograft function. We conclude that VGC‐prophylaxis can be reasonably used to treat HCMV‐seropositive kidney‐transplant recipients.     

Osteoblast‐Specific γ‐Glutamyl Carboxylase‐Deficient Mice Display Enhanced Bone Formation With Aberrant Mineralization

Vitamin K is a fat‐soluble vitamin that is necessary for blood coagulation. In addition, it has bone‐protective effects. Vitamin K functions as a cofactor of γ‐glutamyl carboxylase (GGCX), which activates its substrates by carboxylation. These substrates are found throughout the body and examples include hepatic blood coagulation factors. Furthermore, vitamin K functions as a ligand of the nuclear receptor known as steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR). We have previously reported on the bone‐protective role of SXR/PXR signaling by demonstrating that systemic Pxr‐knockout mice displayed osteopenia. Because systemic Ggcx‐knockout mice die shortly after birth from severe hemorrhage, the GGCX‐mediated effect of vitamin K on bone metabolism has been difficult to evaluate. In this work, we utilized Ggcx‐floxed mice to generate osteoblast‐specific GGCX‐deficient (Ggcx^Δobl/Δobl) mice by crossing them with Col1‐Cre mice. The bone mineral density (BMD) of Ggcx^Δobl/Δobl mice was significantly higher than that of control Col1‐Cre (Ggcx^+/+) mice. Histomorphometrical analysis of trabecular bones in the proximal tibia showed increased osteoid volume and a higher rate of bone formation in Ggcx^Δobl/Δobl mice. Histomorphometrical analysis of cortical bones revealed a thicker cortical width and a higher rate of bone formation in Ggcx^Δobl/Δobl mice. Electron microscopic examination revealed disassembly of mineralized nodules and aberrant calcification of collagen fibers in Ggcx^Δobl/Δobl mice. The mechanical properties of bones from Ggcx^Δobl/Δobl mice tended to be stronger than those from control Ggcx^+/+ mice. These results suggest that GGCX in osteoblasts functions to prevent abnormal mineralization in bone formation, although this function may not be a prerequisite for the bone‐protective effect of vitamin K. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.     

Pituitary‐tumour‐transforming‐gene 1 expression in testicular cancer

Genomic instability is a feature of germ cell tumours. The pituitary‐tumour‐transforming‐gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin‐fixed and paraffin‐embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti‐PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1‐positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.     

Meta‐analysis of Duct‐to‐duct versus Roux‐en‐Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis

This meta‐analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct‐to‐duct or Roux‐en‐Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed‐effects and random‐effects models for meta‐analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux–en‐Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct‐to‐duct and Roux‐en‐Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct‐to‐duct reconstruction should be considered when feasible in patients with PSC.     

Cost‐of‐illness of leg ulcers in the community

Leg ulcer management is complex, time‐consuming and of high socio‐economic importance. Data on cost‐of‐illness in leg ulcer care are sparse. The objective of this study was to evaluate the cost‐of‐illness in leg ulcer treatment in the metropolitan area of Hamburg. About 147 institutions involved in wound care participated in a cross‐sectional study. Patients consecutively recruited underwent a standardised interview and clinical examination. Main economic outcomes were direct, indirect and intangible costs from a societal perspective. Five hundred and two patients with a mean age of 71 years and mean wound duration of 9 years were enrolled. Annual total costs summed up to a mean of 9060€ /patient/year (8288€ direct, 772€ indirect costs). Direct costs carried by statutory health insurances amounted to 7680€ , patients themselves paid on average 607€. Leg ulcer is associated with high costs for health insurances, patients and the society. Exploratory predictor analyses suggest that early, interprofessional disease‐management could lower treatment costs.