bluuebunny/crossref_metadata_2025 huggingface dataset:
Penile lengthening with porcine small intestinal submucosa grafting in Peyronie's disease treatment: long‐term surgical outcomes, patients’ satisfaction and dissatisfaction predictors
Authors: Morgado A. , Morgado M. R. , Tomada N.
Published: August 2018

Background

Peyronie's Disease (PD) is an acquired connective tissue disorder that often leads to penile curvature (PC) and sexual dysfunction. Penile lengthening procedures (PLP) with four‐layered porcine small intestinal submucosa graft (Surgisis®ES; Cook) have been widely used in patients with severe PC when erectile function is preserved. However, complications such as erectile dysfunction (ED) may limit treatment satisfaction.

Objectives

Focusing on patients perspective, our study aims to evaluate longterm patient‐reported outcomes, satisfaction, and dissatisfaction predictors after PLP.

Material and Methods

This prospective study included 32 patients affected by PD with severe PC submitted to PLP with Surgisis®ES between 2011 and 2014. All patients were submitted to a standardized protocol with regular clinical evaluation at 3, 6 and 12 months, and yearly thereafter. After the third year follow‐up, IIEF‐5, modified EDITS and an additional non‐validated questionnaire were completed.

Results

Concerning the surgical procedure, the mean tunical defect area (TDA) was 15.9 ± 6.9 cm2. The mean follow‐up time were 49.6 ± 12.7 months and there was a significant increase in stretched penile length (p = 0.01). Postoperative erectile function as assessed by IIEF‐5 was positively correlated with overall treatment satisfaction evaluated through EDITS (p = 0.01). TDA was negatively correlated with postoperative IIEF‐5 (R = ‐0.56, p < 0.001). TDA ≥ 14.375 cm2 can predict ED with 76.9% sensibility and 58.3% specificity. Moreover, TDA ≥ 21.875 cm2 can predict clinically significant ED (IIEF‐5 score ≤17) with 80% sensibility and 95.2% specificity. Patient‐reported longterm complications were 65.6% decreased penile length, 56.5% diminished rigidity and 25% curvature recurrence.

Conclusion

PLP using a Surgisis® ES is a valuable surgical option for the treatment of PD with severe PC. Although it results in high rates of long‐term patient‐reported overall satisfaction, possible outcomes such as postoperative ED must be acknowledged. TDA is a strong predictor for postoperative ED and should be considered in clinical practice to classify patients in low‐ or high‐risk for postoperative ED.
Accuracy of administrative coding data in colorectal cancer resections and short‐term outcomes
Authors: MacCallum Caroline , Da Silva Nigel , Gibbs Peter , Thomson Benjamin N. J. , Skandarajah Anita , Hayes Ian
Published: August 2018

Background

Administrative data are routinely captured for each hospital admission and may serve as an alternative source for populating databases. This study aims to determine the accuracy of administrative data to provide tumour characteristics and short‐term post‐operative outcomes, after a colorectal cancer (CRC) resection, compared with clinical data.

Methods

A retrospective study of all CRC resections at a single hospital from 1 January 2008 to 31 December 2013 was conducted. Local administrative data were coded as per ICD‐10‐AM (International Classification of Diseases, Tenth Revision, Australian Modification) and Australian Classification of Health Interventions. Clinical data for all patients were extracted from the medical charts and compared with administrative data. Code combinations and algorithms were used to improve the accuracy of administrative data.

Results

A total of 436 patients were identified. The accuracy of algorithms combining tumour location and type of operation for right colon, left colon and rectum were 93, 89 and 88%, respectively. The accuracy of histological type was 89%, lymph node status 92% and metastasis status 88%. The accuracy of return to theatre and in‐hospital mortality was 100%.

Conclusion

Administrative data can provide reliable information on tumour details and short‐term post‐operative outcomes. The potential for administrative data to validate data captured in registries and be used independently for audit and research should be further explored.
Pain and fertility outcomes of nerve‐sparing, full‐thickness disk or segmental bowel resection for deep infiltrating endometriosis—A prospective cohort study
Authors: Hudelist Gernot , Aas‐Eng Mee Kristine , Birsan Tudor , Berger Franz , Sevelda Ursula , Kirchner Lisa , Salama Mohamad , Dauser Bernhard
Published: August 2018

Intoduction

Choosing the optimal treatment for bowel endometriosis, ie, conservative vs radical surgery, is under debate. We aimed to evaluate the surgical outcomes of segmental resection and disk resection regarding fertility, pain symptoms, and quality of life score of women with colorectal deep infiltrating endometriosis.

Material and methods

From March 2011 to December 2016, 134 consecutive patients with symptomatic deep infiltrating endometriosis of the rectosigmoid up to 25 cm from the anal verge undergoing segmental resection or disk resection were prospectively evaluated regarding reduction in pain symptoms, fertility outcomes, and complication rates according to Clavien‐Dindo classification.

Results

Of the 134 women included, segmental resection was performed in 102 (76.1%) women and disk resection was performed in 32 (23.9%) women. There was no difference in duration of surgery, complication rates, mean hospital stay, or discrepancy in hemoglobin level comparing the two groups. There was no significant difference regarding reduction of pain symptoms, fertility, and functional outcomes. One hundred and twelve (83.6%) women were followed up long‐term. In both cohorts, there was a significant reported decrease in pain symptoms and increase in quality of life scores. Of all the 61 infertile women, 26 (42.6%) became pregnant spontaneously, and 13 (21.3%) by in vitro fertilization with an overall pregnancy rate of 63.4%. The overall complication rate (Clavien‐Dindo III‐IV) was 8 of 134 (5.9%) without statistically significant difference between the cohorts.

Conclusions

Both conservative surgery with disk resection, and nerve‐ and vessel‐sparing segmental resection reduce pain symptoms with equal morbidity. Fertility is improved with surgery with both techniques.
The spaces in between care: Considerations of connection and disconnection for subjects of care
Authors: Hanrahan Kelsey B.
Published: August 2018

Drawing on work that explores human vulnerability and the incoherence of the subject in the process of subject formation, I build on the ideas of care as relational and connectedness within human geography. I examine how, in the process of becoming subjects of care, subjects encounter incoherence within themselves and between each other. I explore how this incoherence within and between subjects can be thought of as a disconnection, or the space in between subjects, and how the relationship of care can be conceptualised as the navigation of disconnections as those becoming subjects of care work to build connections. In this paper, I examine ethnographic data from northern Ghana, focusing in on the relationships of care that were constructed during one woman's end of life, highlighting the ways in which connections were forged across spaces of disconnect during the receipt and provision of care. Consideration of these spaces in between has the potential to contribute to our understandings of the experiences of the relational construction of care for both the recipients and providers of care. It also has the potential to contribute an understanding of the meaning and process of care that construct highly contingent and varied outcomes – ranging from soothing and supportive to distressing and invasive – for those involved.
Positive excessive drinker prototypes predict greater drinking and alcohol problems
Authors: Dillard Amanda J. , Ferrer Rebecca A. , Bulthuis Katherine R. K. , Klein William M. P.
Published: August 2018

Objectives

According to the prototype willingness model, risky behaviours such as heavy drinking may be influenced by images of others who engage in this behaviour. In this study, we examined whether college students’ prototypes of an individual who frequently drinks “over the limit” were associated with their own alcohol consumption and experience of alcohol‐related problems during their first 2 years in college.

Methods

We assessed students’ (N = 340) prototypes of excessive drinkers and their own alcohol consumption and problems at four time points, across their first 2 years in college. Along with examining the trajectory of prototypes, consumption, and problems, we tested whether prototypes significantly predicted consumption and problems across the 2 years. Additional analyses examined whether the predictive value of prototypes was unique from related variables including perceived descriptive norms, perceived injunctive norms, and peer pressure to drink alcohol.

Results

Primary analyses indicated that more positive prototypes of an excessive drinker were significantly associated with greater alcohol consumption in both year 1 and year 2. More positive prototypes were also significantly associated with experiencing more alcohol‐related problems in year 2. These findings held when controlling for perceived descriptive and injunctive norms, and peer pressure.

Conclusions

Findings further support the importance of drinker prototypes to one's own drinking behaviour. By examining prototypes over time and their relationship to alcohol‐related problems, this study makes a novel contribution to the existing research.

Statement of contribution

What is already known on this subject?

Perceived norms (beliefs about how much others drink and what they approve of) are associated with own drinking.

Individuals construct “risk prototypes,” or images of people who engage in risky behaviours like drinking alcohol.

Positive risk prototypes of drinkers have been associated with own willingness to drink and subsequent drinking.

What does this study add?

This study shows the trajectory of drinker prototypes across the first 2 years of college.

Findings highlight consistent patterns of positive associations between drinker prototypes and own drinking.

More positive drinker prototypes are associated with a greater number of problems with alcohol.
How collective action produces psychological change and how that change endures over time: A case study of an environmental campaign
Authors: Vestergren Sara , Drury John , Chiriac Eva Hammar
Published: August 2018

Previous research on collective action has suggested that both intra‐ and intergroup interactions are important in producing psychological change. In this study, we examine how these two forms of interaction relate to each other over time. We present results from a longitudinal ethnographic study of participation in an environmental campaign, documenting endurance and prevalence of psychological change. Participants, locals (n = 14) and self‐defined activists (n = 14), connected enduring psychological changes, such as changes in consumer behaviour and attitudes to their involvement in the environmental campaign. Thematic analysis of interviews suggested that participants linked the process of change to categorizing themselves in a new environmental‐activist way that influenced their everyday lives beyond the immediate campaign. This recategorization was a result of a conflictual intergroup relationship with the police. The intergroup interaction produced supportive within‐group relationships that facilitated the feasibility and sustainability of new world views that were maintained by staying active in the campaign. The data from the study support and extend previous research on collective action and are the basis of a model, suggesting that intragroup processes condition the effects of intergroup dynamics on sustained psychological change.
From ‘Green Laggard’ to Regional Leader: Explaining the Recent Development of Environmental Policy in Chile
Authors: MADARIAGA ALDO
Published: August 2018

Environmental policy in Chile has developed rapidly in recent years, and the country has become a regional leader in renewable energy, climate change policy, recycling, and nature conservation. This contrasts with the previous neglect of environmental issues in the country and its depiction as a ‘green laggard’ (Orihuela, 2014: 251) within Latin America. In this article the recent development of environmental policy in Chile is reviewed and five factors affecting this development are analysed: international influences, institutional legacies, a window of opportunity opened by environmental movements, policy entrepreneurship, and business power.
Narrating hope and resistance: A critical analysis of sources of agency among Palestinian children living under military violence
Authors: Veronese Guido , Cavazzoni Federica , Antenucci Silvia
Published: August 2018

Background

In light of critical and socioconstructionist theories, the aim of our research was to analyze source of agency, psychological adjustment to trauma as protective factors against political violence in children living in three different refugee camps in Palestine, as well as exploring the risks to which these children are exposed.

Methods

Thematic content analysis was applied to children's written and drawn productions in order to extract the main categories and themes.

Results

Four main domains of agency emerged from the analysis: personal growth, political well‐being, social relationships, and geographical context. For each domain, specific dimensions are discussed.

Conclusions

The results of this preliminary exploration of children's agency suggest that the children's living environment plays a key role in shaping their suffering and reactions to war and ongoing violence. Furthermore, the social nature of the children affected by war‐related suffering forces practitioners and policymakers to question the effectiveness of intervention programs that are predominantly focused on symptoms.
Altered CD4+ T cell immunity in nurses occupationally exposed to viral pathogens
Authors: Elias G , Souquette A , Heynderickx S , De Meester I , Jansens H , Beutels P , Van Damme P , Smits E , Thomas P G , Van Tendeloo V , Ogunjimi B
Published: August 2018

Pathogen exposure, including but not limited to herpesviruses, moulds the shape of the immune system, both at a basal state and in response to immune challenge. However, little is known about the impact of high exposure to other viruses on baseline immune signatures and how the immune system copes with repetitive exposures to maintain a balanced functionality. Here we investigated baseline immune signatures, including detailed T cell phenotyping, antigen-specific CD4+ and CD8+ T cell responses and cytokine profile in paediatric (PED) nurses, who have high occupational exposure to viral pathogens including varicella zoster virus (VZV) and respiratory viruses, and in neonatal intensive care unit (NICU) nurses, as a control group with infrequent occupational exposure. Our results show a lower CD4+ T cell response to two VZV proteins (IE62 and gE) and to tetanus toxoid (TT) in PED nurses who are cytomegalovirus (CMV)-seronegative, compared to CMV-seronegative NICU nurses, and that the decline might be more pronounced the more sustained the exposure. This decline might be due to an attrition of VZV- and TT-specific T cells as a result of the continuous pressure on the CD4+ T cell compartment. Moreover, our data suggest that the distinct T cell phenotypes known to be associated with CMV-seropositivity might be less prominent in PED nurses compared to NICU nurses, implying a plausible attenuating effect of occupational exposure on CMV-associated immunosenescence. Overall, this pilot study reveals an impact of occupational exposure to viral pathogens on CD4+ T cell immunity and supports further investigation in a larger cohort.
Facilitated expansion of Th17 cells in lupus nephritis patients
Authors: Jakiela B , Kosałka J , Plutecka H , Bazan-Socha S , Sanak M , Musiał J
Published: August 2018

The objective of this study was to investigate the mechanisms of T helper type 17 (Th17) expansion in lupus nephritis (LN) patients, and to determine whether or not it is associated with impaired function of regulatory T cells (Treg). Major effector subsets of peripheral blood CD4+ T cells were assessed by flow cytometry in 33 LN patients with different activity of the disease and 19 healthy controls. The percentage of circulating Th17 cells was increased in LN (median = 1·2% of CD4+ compared to 0·6% in the control group, P < 0·01), while Treg cells remained unchanged (12·3 versus 12·1% in controls), resulting in a significantly lower Treg/Th17 ratio. Th17 expansion in the patient group was not related to LN activity, renal histology or blood and urine inflammatory biomarkers, but has been associated with a higher cumulative dose of cyclophosphamide. Treg cells in LN displayed mainly effector memory phenotype and expressed higher levels of transforming growth factor (TGF)-β; however, their suppressant activity in lymphocyte proliferation assay was diminished compared to controls (~fourfold, P < 0·05). Co-culture of Treg and conventional CD4+ T cells resulted in marked suppression of the Th1 subset in both of the groups studied, but also in a potent expansion of Th17 cells, which in LN was twofold higher, as in controls (P < 0·05). In conclusion, our results demonstrate that Th17 expansion in LN is not increased during disease exacerbation, but is related to chronic immunosuppressive therapy. This immune signature is probably linked to the abnormal function of Treg cells, which were less suppressive in LN patients and even facilitated differentiation of Th17 cells.
Precipitating anti-dsDNA peptide repertoires in lupus
Authors: Wang J J , Colella A D , Beroukas D , Chataway T K , Gordon T P
Published: August 2018

Anti-double-stranded (ds)DNA autoantibodies are prototypical serological markers of systemic lupus erythematosus (SLE), but little is known about their immunoglobulin variable (IgV) region composition at the level of the secreted (serum) proteome. Here, we use a novel proteomic workflow based on de novo mass spectrometric sequencing of anti-dsDNA precipitins to analyse IgV subfamily expression and mutational signatures of high-affinity, precipitating anti-dsDNA responses. Serum anti-dsDNA proteomes were oligoclonal with shared (public) expression of immunoglobulin (Ig)G heavy chain variable region (IGHV) and kappa chain variable region (IGKV) subfamilies. IgV peptide maps from eight subjects showed extensive public and random (private) amino acid replacement mutations with prominent arginine substitutions across heavy (H)- and light (L)-chains. Shared sets of L-chain complementarity determining region 3 (CDR3) peptides specified by arginine substitutions were sequenced from the dominantly expressed IGKV3-20 subfamily, with changes in expression levels of a clonal L-chain CDR3 peptide by quantitative multiple reaction monitoring (MRM) paralleling the rise and fall of anti-dsDNA levels by Farr radioimmunoassays (RIA). The heavily mutated IgV peptide signatures of precipitating anti-dsDNA autoantibody proteomes reflect the strong selective forces that shape humoral anti-dsDNA responses in germinal centres. Direct sequencing of agarose gel precipitins using microlitre volumes of stored sera streamlines the antibody sequencing workflow and is generalizable to other precipitating serum antibodies.
Long‐term effect of cataract phacoemulsification on the inflammation control and clinical outcome in uveitis patients,
Authors: Sharief Lazha , Lightman Sue , Baltinas Julijana , Tomkins‐Netzer Oren
Published: August 2018

Importance

Cataract is one of the most common complications associated with uveitis, and is the leading cause of vision loss in these patients.

Background

The study aimed to evaluate the effect of phacoemulsification on the long‐term clinical outcome and inflammation control in uveitis patients.

Design

Longitudinal study.

Participants

Of 1907 eyes with uveitis, 309 eyes underwent phacoemulsification were compared to a control group of 300 phakic eyes with uveitis.

Method

The risk of vision loss and macular oedema in pseudophakic eyes were compared to the phakic group. The rates of corticosteroids administration and uveitis relapse were also measured in pseudophakic eyes and compared to preoperative period.

Main Outcome Measures

Change in uveitis activity post phacoemulsification by measuring rate of uveitis relapse and use of topical and systemic steroids. Also, to measure the risk of vision loss and macular oedema post surgery.

Results

Over a median follow‐up time of 6.7 years or 2249 eye‐years (EY), pseudophakic eyes had a greater risk of vision loss (hazard ratio [HR] 2.4, CI 1.4 to 4.0; P < 0.001) and macular oedema (HR 2.2, CI 1.4 to 3.4, P < 0.001) compared to the phakic uveitis group. Over 5 years post‐surgery, the annual rate of uveitis relapses was less than the same period pre surgery (−1.2, 95% CI −2.0 to −0.2, P = 0.012) with no significant change in the annual rate of using topical and systemic prednisolone >7.5 mg/day.

Conclusions and Relevance

There was no significant increase in uveitis relapse rate post‐phacoemulsification with the use of current prophylactic inflammation control measures.
Ten‐year trends in contact allergy to formaldehyde and formaldehyde‐releasers
Authors: Fasth Ida M. , Ulrich Nina H. , Johansen Jeanne D.
Published: August 2018

Background

Preservatives such as formaldehyde and formaldehyde‐releasers are common causes of contact allergy.

Objectives

To examine trends in contact allergy to formaldehyde and formaldehyde‐releasers in patch tested patients in Denmark over a 10‐year period (2007‐2016), and to investigate relevant sources of formaldehyde among the patients.

Methods

A cross‐sectional registry study on patch test data from patients tested with formaldehyde and formaldehyde‐releasers (N = 8463) was performed. The presence of released formaldehyde in products from formaldehyde‐allergic patients was identified with chemical analyses (chromotropic acid or acetylacetone test).

Results

The prevalence of contact allergy to formaldehyde 1% was 1.5%, and ranged between 0.97% and 2.3%, with a decreasing trend in this 10‐year period. Contact allergy to formaldehyde 2% was found in 2.4%, and no significant trend was observed. Quaternium‐15 was the formaldehyde‐releaser most often positive (0.86%). Patients allergic to formaldehyde often had simultaneous positive patch test reactions to formaldehyde‐releasers (36%). Almost 63% of the patients with formaldehyde allergy used products that released formaldehyde; cosmetics were the most common sources.

Conclusions

Although contact allergy to formaldehyde 1% decreased in this 10‐year time period, contact allergies to formaldehyde and formaldehyde‐releasers overall remain frequent in patients. In most cases, formaldehyde‐allergic patients are exposed to ≥1 products containing formaldehyde. Improved regulation on permitted amounts of free formaldehyde in cosmetics is still warranted, including direct labelling of formaldehyde when it is present in small but relevant amounts.
More Than the Eye Can See: A Computational Model of Color Term Acquisition and Color Discrimination
Authors: Beekhuizen Barend , Stevenson Suzanne
Published: August 2018

We explore the following two cognitive questions regarding crosslinguistic variation in lexical semantic systems: Why are some linguistic categories—that is, the associations between a term and a portion of the semantic space—harder to learn than others? How does learning a language‐specific set of lexical categories affect processing in that semantic domain? Using a computational word‐learner, and the domain of color as a testbed, we investigate these questions by modeling both child acquisition of color terms and adult behavior on a non‐verbal color discrimination task. A further goal is to test an approach to lexical semantic representation based on the principle that the more languages label any two situations with the same word, the more conceptually similar those two situations are. We compare such a crosslinguistically based semantic space to one based on perceptual similarity. Our computational model suggests a mechanistic explanation for the interplay between term frequency and the semantic closeness of learned categories in developmental error patterns for color terms. Our model also indicates how linguistic relativity effects could arise from an acquisition mechanism that yields language‐specific topologies for the same semantic domain. Moreover, we find that the crosslinguistically inspired semantic space supports these results at least as well as—and in some aspects better than—the purely perceptual one, thus confirming our approach as a practical and principled method for lexical semantic representation in cognitive modeling.
Cathepsin B regulates non‐canonical NLRP3 inflammasome pathway by modulating activation of caspase‐11 in Kupffer cells
Authors: Chen Nan , Ou Zhibing , Zhang Wenfeng , Zhu Xiwen , Li Peizhi , Gong Jianping
Published: August 2018

Objectives

The non‐canonical inflammasome pathway was described which engages caspase‐11 to mediate pyroptosis and the subsequent release of IL‐1α, IL‐1β and IL‐18 in TLR4‐independent way. Cathepsin B is capable of activating caspase‐11 under cell‐free conditions which may regulate non‐canonical NLRP3 inflammasome pathway. In this study, we aimed to further investigate cathepsin B as potential activators of proinflammatory caspases which may be released upon proinflammatory stimuli and regulate non‐canonical NLRP3 inflammasome pathway by modulating the activity of caspase‐11.

Methods

Pharmacological and gene‐silencing approaches were used to evaluate the impact of cathepsin B on regulating non‐canonical NLRP3 inflammasome pathway in wild‐type and TLR4–/– Kupffer cells. A sepsis model was also created to investigate the effect of cathepsin B on survival. Meanwhile, cathepsin B activity and the expression level of caspase‐4 were detected in human peripheral blood mononuclear cells (PBMC) which were separated from patients suffered from SIRS or sepsis and healthy volunteers.

Results

LPS stimulation caused cathepsin B activity and caspase‐11 expression increase in TLR4–/– mice. Cathepsin B activity inhibition reduced the activation of caspase‐11 and inflammasome and benefited survival in TLR4–/– mice. Upregulation of cathepsin B activity and caspase‐4 activation was found in PBMC of patients with SIRS or sepsis.

Conclusion

Our results suggest a critical role for cathepsin B as activators of proinflammatory caspases‐11 and the regulatory effect in LPS‐induced caspases‐11‐dependent necrosis.
RNA‐binding protein PUM2 suppresses osteosarcoma progression via partly and competitively binding to STARD13 3′UTR with miRNAs
Authors: Hu Ruixi , Zhu Xiaodong , Chen Chao , Xu Ruijun , Li Yifan , Xu Wei
Published: August 2018

Objectives

This work aims to reveal the roles and related mechanisms of RNA binding protein PUM2 in osteosarcoma progression.

Materials and methods

Transcriptome analysis based on RNA sequencing data, real‐time quantitative PCR (RT‐qPCR), and western blot analysis were used to detect the expression of RBPs and miRNAs in OS and normal adjacent tissues, and the correlation between them in OS tissues. RT‐qPCR, western blot, cell viability, transwell migration, tumour spheres formation and in vivo tumour formation assays were used to examine the effects of RBP PUM2 on OS progression. Additionally, RNA immunoprecipitation (RIP) assay combined with RNA sequencing was performed to determine the binding site of RBP PUM2 on STARD13 3′UTR. Luciferase reporter and RIP assays were used to confirm the binding of miRNAs or PUM2 on STARD13 3′UTR.

Results

PUM2 and STARD13 expression was significantly decreased in OS tissues, and positively correlated. Overexpression of PUM2 or STARD13 3′UTR inhibited OS cells proliferation, migration, and stemness. Mechanistically, PUM2 competitively bound to STARD13 3′UTR with miR‐590‐3p and miR‐9. The inhibition of PUM2 on OS cells progression was attenuated by STARD13 knockdown or related miRNAs overexpression.

Conclusion

PUM2 suppresses OS progression via partly and competitively binding to STARD13 3′UTR with miRNAs.
A case‐control study of the risk factors for developing aspergillosis following cardiac transplant
Authors: Cook Jennifer C. , Cook Abigail , Tran Richard H. , Chang Patricia P. , Rodgers Jo E.
Published: August 2018

Background

Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following cardiac transplantation; however, data regarding the predictors of IA in this patient population are limited.

Methods

We conducted a case‐control study to identify the risk factors for IA in patients who underwent cardiac transplantation at a single center from 1986 to 2008 (Cohort 1) and 2009 to 2015 (Cohort 2). Cases of IA were matched to two controls from the same year of transplantation, and data were collected from the date of cardiac transplantation to the date of documented Aspergillus infection for each case, or for an equivalent number of days for each control. Univariate and multivariate logistic regressions were used to identify independent predictors of IA in Cohort 1. After 2009, targeted antifungal prophylaxis with oral voriconazole was initiated in patients with risk factors for IA. The incidence of IA was compared pre‐ and postintervention.

Results

IA was identified in 23 of 189 (8.0%) patients within Cohort 1. Significant risk factors for IA on multivariate analysis included an increased number of pretransplant hospitalizations (OR 1.81, 95% CI 1.19‐2.76) and posttransplant acute cellular allograft rejection (ACR) (OR 1.99, 95% 1.06‐3.75). Following the implementation of targeted antifungal prophylaxis in 2009, IA was identified in 2 of 107 (2.0%) patients in Cohort 2.

Conclusions

Increased pretransplant hospitalizations and posttransplant ACR episodes represent significant risk factors for IA following cardiac transplant. Targeted antifungal prophylaxis in at‐risk patients reduces the incidence of IA.
A national survey of valganciclovir dosing strategies in pediatric organ transplant recipients
Authors: Shaikh Suhail , Jasiak‐Panek Natalia , Park Jeong M.
Published: August 2018

Purpose

Data remain limited on the most appropriate valganciclovir (VGCV) dosing strategy for cytomegalovirus (CMV) prophylaxis and treatment in pediatric organ transplant recipients. Therefore, the objective of this study was to describe methods used to calculate VGCV dosing among pediatric transplant centers.

Methods

A survey of pharmacists was conducted to assess VGCV dosing strategies for CMV prophylaxis and treatment among pediatric organ transplant centers in the U.S.

Findings

Of 54 centers that perform pediatric organ transplants, 22 (40.7%) centers responded to the survey. Fourteen centers (53.8%) utilize the Food and Drug Administration (FDA) recommended VGCV dosing strategy of 7 × body surface area (BSA) × creatinine clearance (CrCl) for CMV prophylaxis. Other dosing strategies reported included weight based and 520 mg/m2 × BSA per day. Dosing strategies of VGCV for the treatment of CMV also differed across centers, with a majority (43.5%) using 7 × BSA × CrCl twice daily.

Conclusion

Less than two‐thirds of centers utilize the FDA‐approved daily dosing regimen with various methods of CrCl calculation and serum creatinine assay measurements used. More retrospective and prospective studies with clinical outcomes associated with VCGV dosing strategies are warranted to determine the most appropriate prophylaxis and treatment strategies for CMV.
Laparoscopic left lateral section procurement in living liver donors: A single center propensity score‐matched study
Authors: Gautier Sergey , Monakhov Artem , Gallyamov Eduard , Tsirulnikova Olga , Zagaynov Evgeny , Dzhanbekov Timur , Semash Konstantin , Khizroev Khizry , Oleshkevich Denis , Chekletsova Elena
Published: August 2018

Background

Laparoscopic living donor liver procurement for transplantation has increased in popularity over the past decade. The purpose of this study was to compare the laparoscopic and open approaches in living donor left lateral sectionectomy (LLS) and to assess the safety and feasibility of this laparoscopic approach.

Methods

A total of 103 living donor LLSs were performed at our center from May 2016 to December 2017. Of these, 35 were completely laparoscopic procedures, which represented the subject of this study. An additional 68 open living donor LLSs performed during the same period were studied as a comparison group. To overcome selection bias, LLS donors were balanced on a 1:1 ratio (laparoscopic [n = 35]: open [n = 35]) according to covariates with similar values. The PSM was based on the operation date, recipient age, diagnosis, recipient weight, and donor age.

Results

There were significant differences between the laparoscopic and open LLS groups (P < 0.001) in terms of blood loss (96.8 ± 16.5 vs 155.8 ± 17.8 mL) as well as the duration of hospital stay (4 ± 0.4 vs 6.9 ± 0.5 days).

Conclusion

Laparoscopic LLS is a feasible and efficacious in the setting of a developed program with advanced laparoscopic expertise.
Quality of life and treatment goals in psoriasis from the patient perspective: results of an Austrian cross‐sectional survey
Authors: Wolf Peter , Weger Wolfgang , Legat Franz , Painsi Clemens , Saxinger Werner , Müllegger Robert , Sator Paul , Ratzinger Gudrun , Selhofer Sylvia , Richter Leo , Salmhofer Wolfgang , Lange‐Asschenfeldt Bernhard , Trautinger Franz , Mlynek Alexander , Strohal Robert , Augustin Matthias , Quehenberger Franz
Published: August 2018

Background

Patients with psoriasis experience impairment in quality of life. Thus, high‐quality dermatological care is of particular importance.

Patients and methods

We performed a nationwide cross‐sectional survey in Austria (BQSAustria Psoriasis 2014/2015) with a special focus on quality of life and satisfaction with treatment among psoriasis patients predominantly treated at tertiary care centers.

Results

Overall, 70.2 % of 1,184 patients reported impaired quality of life (DLQI 2–5: 29.4 %; 6–10: 19.3 %; 11–15: 11.5 %; 16–20: 5.2 % and > 20: 4.9 %) despite treatment over the preceding four weeks (topical treatment in 88.2 % of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined subjective treatment goals was achieved to a sufficient degree. In particular, 82.2 % of patients continued to have pruritus despite treatment, which was highly significantly associated with a poor general health status over the preceding week (Spearman's rank correlation; p  =  1.1e‐45), the extent of body surface area (p  =  3.2e‐11) and scalp area (p  =  3.2e‐11) affected, as well as pain (p  =  2.3e‐22). Treatment with a biologic was significantly correlated with higher patient satisfaction (Wilcoxon‐Test, p  =  2.0e‐16).

Conclusions

Despite dermatological care, the majority of Austrian psoriasis patients continues to experience impaired quality of life; there is potential for improvement in the achievement of treatment goals.
Nonmelanoma skin cancer – from actinic keratosis to cutaneous squamous cell carcinoma
Authors: Schmitz Lutz , Oster‐Schmidt Claus , Stockfleth Eggert
Published: August 2018

Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life‐threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression. In addition to a broad armamentarium of procedures as well as pharmaceutical treatment options, primary prevention through diligent UV protection likewise plays a crucial role. New clinical, histomorphological, or molecular classifications are needed to be able to reliably stratify patients based on their individual risk. Especially in light of socio‐economic aspects, such a step might prevent over‐ and undertreatment of an ever‐growing patient population and help develop treatment concepts based on individual patient needs.
Novel method of biliary cannulation for patients with Roux‐en‐Y anastomosis using a unique, uneven, double‐lumen cannula (Uneven method)
Authors: Takenaka Mamoru , Yamao Kentaro , Kudo Masatoshi
Published: August 2018

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Hemostasis with hemostatic forceps for bleeding during endoscopic necrosectomy
Authors: Matsumi Akihiro , Matsumoto Kazuyuki , Okada Hiroyuki
Published: August 2018

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Endoscopic mucosal resection for intraductal growing‐type intrahepatic cholangiocarcinoma under direct peroral cholangioscopy
Authors: Jung Jang Han , Park Se Woo , Shin Eun
Published: August 2018

The current standard treatment for intrahepatic cholangiocarcinoma is surgical resection. However, in case the patient does not agree with surgical resection or is not fit for surgery, there are a few alternative treatments. We present a case of an 83‐year‐old male patient with abdominal pain who was diagnosed with polypoid intrahepatic cholangiocarcinoma in the left intrahepatic duct (IHD) with peripheral IHD dilatation. He refused to undergo curative surgery. Alternatively, he underwent endoscopic mucosal resection (EMR) with direct peroral cholangioscopy (POC) using standard upper endoscopy with a transparent cap. At 1‐year follow up, there was no evidence of locoregional recurrence or distant metastasis. We suggest that intraductal EMR could serve as an effective and safe alternative treatment for patients with polypoid intrahepatic cholangiocarcinoma using direct POC.
‘Bioethical Realism’: A Framework for Implementing Universal Research Ethics
Authors: Barugahare John
Published: August 2018

Implementation of existing ethical guidelines for international collaborative medical and health research is still largely controversial in sub‐Saharan Africa for two major reasons: One, they are seen as foreign and allegedly inconsistent with what has been described as an ‘African worldview’, hence, demand for their strict implementations reeks of ‘bioethical imperialism’. Two, they have other discernible inadequacies – lack of sufficient detail, apparent as well as real ambiguities, vagueness and contradictions. Similar charges exist(ed) in other non‐Western societies. Consequently, these guidelines have been correctly judged as an inadequate response to the complex and ever shifting dilemmas met by researchers and research regulators in the field. This paper proposes a framework for effective implementation of existing guidelines without much worry about bioethical imperialism and other inadequacies. This framework is proposed using an analogy of Legal Realism, specifically its key assertions on how, in reality, judicial systems operate using general legal rules to settle specific cases. Legal realists assert that in judicial decision‐making, general legal rules do not totally dictate court decisions in specific cases. This analogy is used to coin a new term, ‘Bioethical Realism.’ The framework suggests that local Research Ethics Committees ought to be construed as analogues of judicial courts with the resulting implications. Consequently, just like legal rules are general rules that do not always dictate court decisions, similarly international bioethical guidelines are general ethical rules that should not always dictate local RECs’ decisions and such decisions (ought to) enjoy considerable immunity from outsiders.
Maternal obesity and risk of cerebral palsy in children: a systematic review and meta‐analysis
Authors: Zhang Jian , Peng Linrui , Chang Qingxian , Xu Ruoting , Zhong Nanbert , Huang Qitao , Zhong Mei , Yu Yanhong
Published: August 2018

Aim

Several studies have examined the links between maternal obesity and the risk of cerebral palsy (CP) in children, with inconsistent results. The aim of our study was to investigate whether maternal obesity is associated with increased risk of CP in offspring by using meta‐analysis.

Method

PubMed and Web of Science were searched until August 2017. Observational studies relevant to the maternal obesity and risk of CP in children were extracted and compiled. Meta‐analyses were performed for different obesity levels and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported.

Results

A total of five cohort studies involving 12 324 cases and 7 919 288 participants were included in our meta‐analysis. The pooled crude and adjusted ORs (95% CIs) were 1.65 (1.38–1.98) and 1.51 (1.24–1.84) respectively. Additionally, the pooled OR (95% CI) for CP in offspring in relation to maternal obesity class I (body mass index [BMI] 30.0–34.9), class II (BMI 35.0–39.9), and class III (BMI≥40.0) compared with normal weight during prepregnancy or pregnancy was 1.31 (1.15–1.50), 1.65 (1.34–2.02), and 2.37 (1.91–2.94) respectively.

Interpretation

This meta‐analysis demonstrated that increasing grades of maternal obesity are associated with a higher risk of CP in offspring.

What this paper adds

Meta‐analysis demonstrates a significant positive association between maternal obesity and the risk of cerebral palsy (CP) in children.

Subgroup analysis indicates that higher grades of maternal obesity are associated with increasing risk of CP.
Efficacy and safety of fixed‐dose combination therapy with gemigliptin (50 mg) and rosuvastatin compared with monotherapy in patients with type 2 diabetes and dyslipidaemia (BALANCE): A multicentre, randomized, double‐blind, controlled, phase 3 trial
Authors: Bae Ji Cheol , Min Kyung Wan , Kim Yong Hyun , Kim Kyoung‐Ah , Hong Eun‐Gyoung , Park Cheol‐Young , Han Song , Cha Bong‐Soo
Published: August 2018

Aim

To evaluate the efficacy and safety of a fixed‐dose combination (FDC) of gemigliptin and rosuvastatin in patients with type 2 diabetes and dyslipidaemia.

Research Design and Methods

A total of 33 hospitals in Korea participated in this randomized, double‐blind trial of diabetic patients with dyslipidaemia. A total of 290 participants were randomly assigned at a 1:1:1 ratio to receive an FDC of gemigliptin (50 mg) and rosuvastatin (20 mg) (GEMI/ROSU FDC group), gemigliptin (50 mg) (GEMI group) or rosuvastatin (20 mg) (ROSU group). Rosuvastatin was up‐titrated from 5 to 20 mg/d throughout the study period. Primary efficacy measures were changes in HbA1c and LDL‐C from baseline to Week 24 between the GEMI/ROSU FDC and ROSU groups and between the GEMI/ROSU FDC and GEMI groups, respectively. Secondary efficacy measures were changes in HbA1c and LDL‐C between the GEMI/ROSU FDC and GEMI groups and between the GEMI/ROSU FDC and ROSU groups, respectively.

Results

After 24 weeks of treatment, a significant reduction in HbA1c from baseline was noted in the GEMI/ROSU FDC group (−0.81% of LS mean; P < 0.0001 vs ROSU group), in addition to a significant reduction in LDL‐C concentration (−51.9% of LS mean percentage changes, P < 0.0001 vs GEMI group). HbA1c was significantly reduced from baseline in both the GEMI/ROSU FDC and GEMI groups, but the reduction in HbA1c was significantly greater in the GEMI group than in the GEMI/ROSU FDC group, despite receiving the same dose of gemigliptin. The decrease in LDL‐C over time was similar between the GEMI/ROSU FDC and ROSU groups. There were no significant differences in adverse events among the groups.

Conclusion

The FDC of gemigliptin and rosuvastatin is safe and is effective in reducing both blood glucose and LDL‐C levels; thus, it could be a good therapeutic choice for type 2 diabetic patients with dyslipidaemia.
Positive reinforcement and c‐Fos expression following abuse‐like thinner inhalation in mice: Behavioural and immunohistochemical assessment
Authors: Malloul Hanaa , Bennis Mohammed , Ba‐M'hamed Saadia
Published: August 2018

Thinners are organic solvents widely used in industrial applications, but they have also been subject to abuse by inhalation for their psychoactive and rewarding properties. In spite of the prevalence of inhalant abuse, the addictive potential and pathways mediating their reinforcing effects are not yet fully understood and thus still subject of further investigations. Here, we assessed in mice the locomotor activity and the ability of paint thinner to reinforce the conditioning in the place preference paradigm following acute (1 day), subchronic (6 weeks) and chronic (12 weeks) exposures to 300 and 600 ppm of thinner vapor. While locomotor activity was unaffected by the different thinner treatments, a positive conditioned place preference to inhaled thinner was found upon subchronic and chronic exposures. To investigate the activated brain structures underlying such behavioural changes, we analyzed the distribution of c‐Fos immunoreactivity, a marker for neuronal activation, following acute and repeated exposures to 600 ppm of thinner. Notably, thinner exposure increased the number of c‐Fos immunoreactive neurons with increasing duration of exposure in the majority of structures examined; including those typically involved in the processing of rewarding or emotionally stimuli (e.g., ventral tegmental area, core and shell of nucleus accumbens, amygdala, bed nucleus of the stria terminalis, and cingulate cortex), and olfactory stimuli (e.g., piriform cortex and olfactory tubercle). Moreover, prolonged, but not acute thinner inhalation significantly increased c‐Fos immunoreactivity in all hippocampal subregions. Taken together, the expanded distribution of thinner‐induced c‐Fos expression may underlie the observed positive reinforcement upon long‐term thinner inhalation.
Post hoc analysis of the Exenatide‐PD trial—Factors that predict response
Authors: Athauda Dilan , Maclagan Kate , Budnik Natalia , Zampedri Luca , Hibbert Steve , Aviles‐Olmos Iciar , Chowdhury Kashfia , Skene Simon S. , Limousin Patricia , Foltynie Thomas
Published: August 2018

Exenatide, a glucagon‐like peptide‐1 agonist and a licensed treatment for Type 2 diabetes significantly reduced deterioration in motor symptoms in patients with Parkinson's disease in a randomized, placebo‐controlled trial. In addition, there were trends favouring the exenatide group in assessments of nonmotor symptoms, cognition, and quality of life. The aim of this exploratory post hoc analysis was to generate new hypotheses regarding (a) whether candidate baseline factors might predict the magnitude of response to exenatide; and (b) whether the beneficial effects of exenatide reported for the overall population are consistent in various subgroups of patients. Univariate and multivariate analyses were conducted to determine possible predictors of motor response to exenatide in this cohort. Potential treatment by subgroup interactions for changes in; motor severity, nonmotor symptoms, cognition, and quality of life after 48‐weeks treatment with exenatide were evaluated among post hoc subgroups defined by age, motor phenotype, disease duration, disease severity, body mass index (BMI), and insulin resistance. In the subgroup analyses, exenatide once‐weekly was associated with broadly improved outcome measures assessing motor severity, nonmotor symptoms, cognition, and quality of life across all subgroups, however, tremor‐dominant phenotype and lower Movement Disorder Society‐Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part‐2 scores predicted greatest motor response to exenatide and there was an indication that patients with older age of onset and disease duration over 10 years responded less well. While patients with a range of demographic and clinical factors can potentially benefit from exenatide once‐weekly, these data support an emphasis towards recruiting patients at earlier disease in future planned clinical trials of gluacagon‐like peptide‐1 (GLP‐1) receptor agonists in Parkinson's disease (PD).