bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafiltration and reinfusion of residual cardiopulmonary bypass pump blood: A prospective non‐randomized controlled study
Authors: Yan Shujie , Zhao Yu , Lou Song
Published: December 2018

The aim of the study was to investigate whether processing residual pump blood with ultrafiltration could increase the increment of hemoglobin after residual pump blood reinfusion and evaluate its influence on plasma‐free hemoglobin (pFHb) level and postoperative renal function. Sixty adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were assigned to 2 groups, based on pump blood processing strategy: ultrafiltration plus reinfusion (n = 30) or reinfusion (control; n = 30). Increment in hemoglobin and pFHb after reinfusion (ΔHgb, ΔpFHb), reinfusion volume, postoperative chest drainage volume (first 24 h), duration of mechanical ventilation, changes in serum creatinine, and prevalence of AKI were compared between the 2 groups. Higher levels of both ΔHgb and ΔpFHb were observed after reinfusion in the ultrafiltration group [ΔHgb 1.8 ± 1.1 g/dL vs. 1.2 ± 0.6 g/dL, P = 0.03, ΔpFHb 100 (0, 200) mg/L vs. 0 (−100, 0) mg/L, P = 0.03]. The reinfusion volume was lower in the ultrafiltration group [550 (325, 615) mL vs. 1000 (900, 1180) mL, P < 0.001]. No differences were found in postoperative chest drainage volume (first 24 h), duration of mechanical ventilation, changes in serum creatinine, and prevalence of AKI. Compared to the unprocessed group, ultrafiltration before reinfusion of residual pump blood improved the hemoglobin level and reduced volume loading. Despite an increase in pFHb, the processing procedure was not related to postoperative kidney injury.
Evaluation of energy dissipation rate as a predictor of mechanical blood damage
Authors: Faghih Mohammad M. , Sharp Michael Keith
Published: December 2018

A long‐standing goal in the field of biofluid mechanics has been to reliably predict hemolysis across the wide range of flows that can occur in prosthetic cardiovascular devices. A scalar representation of the complex three‐dimensional fluid stresses that are exerted on cells is an attractive alternative for the simplicity that it lends to the computations. The appropriateness of the commonly used von‐Mises‐like scalar stress as a universal hemolysis scaling parameter was previously evaluated, finding that erythrocyte membrane tensions calculated for laminar shear and extensional flows and for three cases of turbulent flow were widely divergent for the same value of scalar stress. The same techniques are applied in this study to laminar and turbulent flows that each have the same energy dissipation rate. Results showed that agreement of membrane tension between laminar shear and turbulent shear inside an eddy was improved relative to the common scalar stress cases, but disagreement between laminar shear and laminar extension remained the same and disagreement between laminar shear and other turbulent flows increased. It is therefore concluded that energy dissipation rate alone is also likely not sufficient to universally scale blood damage across the range of different flows that can be encountered clinically.
Human/robotic interaction: vision limits performance in simulated vitreoretinal surgery
Authors: de Smet Marc D. , de Jonge Nicky , Iannetta Danilo , Faridpooya Koorosh , van Oosterhout Eric , Naus Gerrit , Meenink Thijs C.M. , Mura Marco , Beelen Maarten J.
Published: December 2018

Purpose

Compare accuracy and precision in XYZ of stationary and dynamic tasks performed by surgeons with and without the use of a tele‐operated robotic micromanipulator in a simulated vitreoretinal environment. The tasks were performed using a surgical microscope or while observing a video monitor.

Method

Two experienced and two novice surgeons performed tracking and static tasks at a fixed depth with hand‐held instruments on a Preceyes Surgical System R0.4. Visualization was through a standard microscope or a video display. The distances between the instrument tip and the targets (in μm) determined tracking errors in accuracy and precision.

Results

Using a microscope, dynamic or static accuracy and precision in XY (planar) movements were similar among test subjects. In Z (depth) movements, experience lead to more precision in both dynamic and static tasks (dynamic 35 ± 14 versus 60 ± 37 μm; static 27 ± 8 versus 36 ± 10 μm), and more accuracy in dynamic tasks (58 ± 35 versus 109 ± 79 μm). Robotic assistance improved both precision and accuracy in Z (1–3 ± 1 μm) in both groups. Using a video screen in combination with robotic assistance improved all performance measurements and reduced any differences due to experience.

Conclusions

Robotics increases precision and accuracy, with greater benefit observed in less experienced surgeons. However, human control was a limiting factor in the achieved improvement. A major limitation was visualization of the target surface, in particular in depth. To maximize the benefit of robotic assistance, visualization must be optimized.
Predictors of relapse following infliximab de‐escalation in patients with inflammatory bowel disease: the value of a strategy based on therapeutic drug monitoring
Authors: Lucidarme Camille , Petitcollin Antoine , Brochard Charlène , Siproudhis Laurent , Dewitte Marie , Landemaine Amandine , Bellissant Eric , Bouguen Guillaume
Published: December 2018

Background

There are limited data concerning infliximab drug monitoring during de‐escalation of the treatment of inflammatory bowel disease (IBD).

Aim

To define the rate and the predictors of relapse following infliximab de‐escalation in IBD patients in remission.

Methods

All IBD patients at a single referral centre in clinical and biological remission and in whom the dose of infliximab had been de‐escalated were included. Patients in remission with a high trough level of infliximab (>7 mg/L) were considered to be trough level‐based de‐escalation patients. The data were retrieved from a prospective IBD database. Actuarial analysis was performed for statistical purposes.

Results

A total of 146 de‐escalations were performed in 96 patients (Crohn's disease/ulcerative colitis: 68%/32%); 54 (37%) were based on clinical remission only, and 92 (63%) were based on clinical remission associated with a trough level above 7 mg/L. The cumulative probabilities of relapse following infliximab de‐escalation were 16% and 47% at 1 and 2 years, respectively. Ulcerative colitis was associated with an increased risk of relapse (HR = 3.2, P = 0.005). Conversely, combination therapy at infliximab initiation (HR = 0.39, P = 0.0110) and trough level‐based de‐escalation were associated with decreased risk of relapse (HR = 0.45, P = 0.024). Trough levels before and after de‐escalation were well correlated; a decrease by half was observed following a 2‐week interval increase or a half‐dose decrease.

Conclusion

The use of trough levels to assess the feasibility of dose de‐escalation seems to be a prerequisite for decreasing the risk of relapse.
Randomised clinical trial: vonoprazan versus lansoprazole for the initial relief of heartburn in patients with erosive oesophagitis
Authors: Oshima Tadayuki , Arai Eitatsu , Taki Masato , Kondo Takashi , Tomita Toshihiko , Fukui Hirokazu , Watari Jiro , Miwa Hiroto
Published: December 2018

Background

Proton pump inhibitors (PPIs) are widely used to treat gastro‐oesophageal reflux disease (GORD). However, the onset of action is considered slow and PPIs cannot completely block acid secretion at night. A new potassium‐competitive acid blocker (P‐CAB) can rapidly block acid secretion. However, whether this P‐CAB can relieve GORD symptoms quickly and adequately soon after starting treatment is unknown.

Aim

To determine how rapidly vonoprazan and lansoprazole provide heartburn relief.

Methods

Patients (n = 32) with endoscopically confirmed erosive oesophagitis who experienced heartburn at least once a week were randomised in a double‐blind manner to receive either daily vonoprazan (20 mg) or lansoprazole (30 mg) before breakfast for 14 days. Day time and night time heartburn were assessed daily throughout the study using a five‐point Likert scale. The primary endpoint was the first day of complete day and night heartburn relief for at least seven consecutive days. The ethics committees of the participating institutions approved the study protocol.

Results

Heartburn was relieved sooner with vonoprazan than with lansoprazole (P < 0.05, log‐rank test). Heartburn was completely relieved in 31.3% and 12.5% of patients on day 1 with vonoprazan and lansoprazole, respectively. Significantly more patients achieved complete nocturnal heartburn relief with vonoprazan than lansoprazole (P < 0.01). Both regimens were well tolerated.

Conclusions

Complete sustained heartburn relief was achieved sooner with vonoprazan than with lansoprazole during the first week of therapy. (UMIN000018776)
Review article: implementation of a diet low in FODMAPs for patients with irritable bowel syndrome—directions for future research
Authors: Mitchell Hannah , Porter Judi , Gibson Peter R. , Barrett Jacqueline , Garg Mayur
Published: December 2018

Background

Despite the efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) for patients with irritable bowel syndrome, many questions remain unanswered with respect to its clinical implementation.

Aim

To review literature to identify, synthesise, and provide direction for future research in the implementation and evaluation of the low FODMAP diet.

Methods

Bibliographical searches were performed in Ovid Medline, CINAHL, Scopus and PubMed from database commencement until September 2018, with search terms focused on the population (irritable bowel syndrome) and intervention of interest (FODMAP).

Results

Predictors of response to a low FODMAP diet remain under investigation, with preliminary data supporting faecal microbiota or faecal volatile organic compound profiling. Training of clinicians, and standards for the education of patients about the phases of a low FODMAP diet, as well as the role of Apps, require formal evaluation. There are limited data on the longer term efficacy and safety of the low FODMAP diet with respect to sustained symptom control, effect on quality of life and healthcare utilisation, nutritional adequacy, precipitation of disordered eating behaviours, effects on faecal microbiota and metabolomic markers, and subsequent translation to clinical effects.

Conclusions

Many gaps in implementation of the low FODMAP diet in clinical practice, as well as long‐term safety and efficacy, remain for further investigation.
Flaws in design, execution and interpretation limit CLARITY‐BPA’s value for risk assessments of bisphenol A
Authors: vom Saal Frederick S.
Published: December 2018

The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY‐BPA) involved the Food and Drug Administration, the National Toxicology Program and 14 academic investigators funded by the National Institute of Environmental Health Sciences. Two key questions to be answered by CLARITY‐BPA were as follows: (1) Would the academic investigator studies show effects at low doses of bisphenol A (BPA) while the core guideline study conducted by the FDA only showed toxic effects at high doses? (2) Would the academic investigators be able to replicate their numerous prior studies with animals raised and treated in the FDA's toxicology centre? Several flaws in the design and execution of CLARITY‐BPA biased the experiment towards not finding significant results (Type 2 error): (1) use of the oestrogen‐insensitive NCTR CD‐SD rat, (2) use of a stressful daily gavage BPA administration procedure throughout life, (3) lack of inclusion of non‐gavaged negative controls and (4) lack of a comprehensive examination of animals for BPA contamination. In spite of these flaws, in some of the experiments conducted by CLARITY‐BPA academic investigators, and also in the FDA's core study, there were significant low‐dose effects, but these were ignored by the FDA. Thus, immediately after releasing the results from their core portion of CLARITY‐BPA, the FDA issued a statement concluding BPA was “safe,” and they ignored non‐monotonic dose‐response relationships. The FDA should not base its BPA risk assessment only on outdated guideline studies, but instead on the vast (~8000) number of publications documenting the similar health hazards BPA poses to animals and humans.
Pharmacokinetics, pharmacodynamics, tolerability and prediction of clinically effective dose of ACT‐774312: A novel CRTH2 antagonist
Authors: Géhin Martine , Lott Dominik , Farine Hervé , Issac Milena , Strasser Daniel , Sidharta Patricia , Dingemanse Jasper
Published: December 2018

ACT‐774312 is an antagonist of the chemoattractant receptor‐homologous molecule expressed on T helper (Th) 2 cells (CRTH2), in development for the treatment of nasal polyposis or other allergic and type‐2 inflammatory diseases. Placebo, single doses of 1‐1000 mg, or multiple doses of 30‐500 mg either once or twice daily for 4 days of ACT‐774312 were administered orally to healthy subjects. The single‐ and multiple‐dose pharmacokinetics (PK) of ACT‐774312 were dose proportional and characterized by a time to attainment of maximum plasma concentrations between 1 and 3 hours and a terminal elimination half‐life of about 12 hours In the presence of food, tmax was delayed by 1 hour and exposure to ACT‐774312 slightly decreased. Full blockade (>90% of the maximum effect, Emax) of CRTH2 as measured in a whole blood internalization assay was observed after 50 mg ACT‐774312 twice daily and lasted for at least 9 hours The relationship between ACT‐774312 concentration and CRTH2 blockade was described by a Emax model. The estimated twice‐daily dose of ACT‐774312 at which full blockade of CRTH2 is achieved at trough in at least 80% of subjects was estimated at 109 mg. Administration of ACT‐774312 was safe and well tolerated at all doses. For none of the recorded adverse events, a relationship to dose was discerned, and there were no clinically relevant findings on the measured ECG, clinical laboratory and vital signs variables. The observed PK, pharmacodynamics and safety profile warrant further development of ACT‐774312.
Neurotoxic effects of mercury exposure in dental personnel
Authors: Bjørklund Geir , Hilt Bjørn , Dadar Maryam , Lindh Ulf , Aaseth Jan
Published: December 2018

Numerous studies have reported neurobehavioural effects in dental personnel occupationally exposed to chronic low levels of mercury (Hg). Hg exposure from dental work may also induce various chronic conditions such as elevation of amyloid protein expression, deterioration of microtubules and increase or inhibition of transmitter release at motor nerve terminal endings. Therefore, clinical studies of Hg toxicity in dentistry may provide new knowledge about disturbed metal homeostasis in neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis and mood disorders. The purpose of this MiniReview is to evaluate the evidence of possible relevance between Hg exposure in dentistry and idiopathic disturbances in motor functions, cognitive skills and affective reactions, as well as dose‐response relationships.
Effectiveness of a web‐based treatment decision aid for men with lower urinary tract symptoms due to benign prostatic hyperplasia
Authors: van der Wijden Fieke C. , de Angst Isabel B. , Lamers Romy E.D. , Cuypers Maarten , de Vries Marieke , van Melick Harm H.E. , de Beij Jeltje S. , Oerlemans Dennis J.A.J. , van de Beek Kees , Kil Paul J.M.
Published: December 2018

Objectives

To evaluate the effectiveness of a web‐based decision aid (DA), with values clarification exercises compared with usual care, for men with lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH).

Patients and Methods

Between July 2016 and January 2017, all new patients with LUTS/BPH who consulted the urologist were invited to use the DA and participate in this prospective questionnaire study. Patients who consulted the urologist between December 2015 and February 2016 served as controls. The DA was designed to support patients in making a well‐informed treatment decision, corresponding with their personal preferences and values. Well‐informed decision was measured by using a knowledge questionnaire. Value congruent decision was measured by the correspondence between responses on nine value statements and chosen treatment. The primary outcome, decision quality, was defined as the combination of well‐informed decision and value congruent decision. Secondary outcomes were decisional conflict, involvement and received role in shared decision‐making, decisional regret, and treatment choice.

Results

A total of 109 DA‐users and 108 controls were included. DA‐users were younger (68.4 vs 71.5 years; P = 0.003) and their education level was higher (P = 0.047) compared with the controls. Patients who used the DA made a well‐informed and value congruent decision more often than the control group (43% vs 21%; P = 0.028). DA‐users had less decisional conflict (score 33.2 vs 46.6; P = 0.003), experienced a less passive role in decision‐making (22% vs 41%; P = 0.038), and reported less process regret (score 2.4 vs 2.8; P = 0.034). Furthermore, DA‐users who had not used prior medication chose lifestyle advices more often than the control group (43% vs 11%; P = 0.002). Outcomes were adjusted for significantly different baseline characteristics.

Conclusion

The LUTS/BPH DA seems to improve the decision quality by supporting patients in making more well‐informed and value congruent treatment decisions. Therefore, further implementation of this DA into routine care is suggested.
Prion neurotoxicity
Authors: Le Nhat T. T. , Wu Bei , Harris David A.
Published: December 2018

Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrPSc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrPC molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrPC serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science.
Platforms of in vivo genome editing with inducible Cas9 for advanced cancer modeling
Authors: Jo Norihide , Sogabe Yuko , Yamada Yosuke , Ukai Tomoyo , Kagawa Harunobu , Mitsunaga Kanae , Woltjen Knut , Yamada Yasuhiro
Published: December 2018

The emergence of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has dramatically advanced how we manipulate the genome. Regarding in vivo experiments, Cas9‐transgenic animals could provide efficient and complex genome editing. However, this potential has not been fully realized partly due to a lack of convenient platforms and limited examples of successful disease modeling. Here, we devised two doxycycline (Dox)‐inducible Cas9 platforms that efficiently enable conditional genome editing at multiple loci in vitro and in vivo. In these platforms, we took advantage of a site‐specific multi‐segment cloning strategy for rapid and easy integration of multiple single guide (sg)RNAs. We found that a platform containing rtTA at the Rosa26 locus and TRE‐Cas9 together with multiple sgRNAs at the Col1a1 locus showed higher efficiency of inducible insertions and deletions (indels) with minimal leaky editing. Using this platform, we succeeded to model Wilms’ tumor and the progression of intestinal adenomas with multiple mutations including an activating mutation with a large genomic deletion. Collectively, the established platform should make complicated disease modeling in the mouse easily attainable, extending the range of in vivo experiments in various biological fields including cancer research.
Novel approach for successful endoscopic ultrasound‐guided hepaticogastrostomy using a double‐guidewire technique
Authors: Shiomi Hideyuki , Masuda Atsuhiro , Kodama Yuzo
Published: December 2018

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Digital ITEMS Module 03: Nonparametric Item Response Theory
Authors: Wind Stefanie A.
Published: December 2018

In this digital ITEMS module, we introduce the framework of nonparametric item response theory (IRT), in particular Mokken scaling, which can be used to evaluate fundamental measurement properties with less strict assumptions than parametric IRT models. We walk through the key distinction between parametric and nonparametric models, introduce the two key nonparametric models under Mokken scaling – the monotone homogeneity and double monotonicity model – and discuss modern extensions of the basic models. We also describe how researchers and practitioners can use key nonparametric statistics and graphical visualization tools to evaluate the fundamental measurement properties of an assessment from a nonparametric perspective. Finally, we illustrate the key reasoning steps and associated best practices using video‐based worked examples completed with the mokken package in R.
Tree rings provide no evidence of a CO2 fertilization effect in old‐growth subalpine forests of western Canada
Authors: Hararuk Oleksandra , Campbell Elizabeth M. , Antos Joseph A. , Parish Roberta
Published: December 2018

Atmospheric CO2 concentrations are now 1.7 times higher than the preindustrial values. Although photosynthetic rates are hypothesized to increase in response to rising atmospheric CO2 concentrations, results from in situ experiments are inconsistent in supporting a CO2 fertilization effect of tree growth. Tree‐ring data provide a historical record of tree‐level productivity that can be used to evaluate long‐term responses of tree growth. We use tree‐ring data from old‐growth, subalpine forests of western Canada that have not had a stand‐replacing disturbance for hundreds of years to determine if growth has increased over 19th and 20th centuries. Our sample consisted of 5,858 trees belonging to five species distributed over two sites in the coastal zone and two in the continental climate of the interior. We calculated annual increments in tree basal area, adjusted these increments for tree size and age, and tested whether there was a detectable temporal trend in tree growth over the 19th and 20th centuries. We found a similar pattern in 20th century growth trends among all species at all sites. Growth during the 19th century was mostly stable or increasing, with the exception of one of the coastal sites, where tree growth was slightly decreasing; whereas growth during the 20th century consistently decreased. The unexpected decrease in growth during the 20th century indicates that there was no CO2 fertilization effect on photosynthesis. We compared the growth trends from our four sites to the trends simulated by seven Earth System Models, and saw that most of the models did not predict these growth declines. Overall, our results indicate that these old‐growth forests are unlikely to increase their carbon storage capacity in response to rising atmospheric CO2, and thus are unlikely to contribute substantially to offsetting future carbon emissions.
Habitation environment suitability and population density patterns in China: A regionalization approach
Authors: Liu Cuiling , Wang Fahui , Xu Yaping
Published: December 2018

The stunning disparity in population density between the southeast and northwest in China is highlighted by the “Hu Line,” a famous population demarcation line proposed by Huanyong Hu in 1935. This research seeks to uncover the underlying physical environment factors that shape such a contrast. Specifically, we propose a habitation environment suitability index (HESI) model to integrate topographic factors, climatic suitability, and hydrological condition into one comprehensive index, and then use a GIS‐automated regionalization method termed REDCAP (Regionalization with Dynamically Constrained Agglomerative Clustering and Partitioning) to derive two demarcation lines based on the HESI and population density values, respectively. The two lines that divide China into two regions are largely consistent with each other. The result indicates that the population distribution disparity between the southeast and northwest is largely attributable to the difference in physical environments, and the barrier defined by the Hu Line is here to stay. In addition, the research also explores the (in)consistency between population density and HESI distribution patterns in various regions.
Inactivation mechanisms of electron beam irradiation on Listeria innocua through the integrity of cell membrane, genomic DNA and protein structures
Authors: Shi Feifei , Zhao Hongwei , Wang Li , Cui Xiaorui , Guo Weiling , Zhang Weidong , Song Hongbo , Li Shurong
Published: December 2018

As a non‐thermal sterilisation technology, electron beam irradiation (EBI) has attracted great interest for microbial inactivation in food preservation. This study aims to investigate the effects of EBI on membrane permeability, physiological status, morphological structure, genome integrity and protein structures of Listeria innocua irradiated at doses of 0.75, 1.50, 2.25, 3.00, 3.75 and 5.00 kGy. The results showed that EBI noticeably reduced the total microbial counts of L. innocua by more than 7 log CFU mL−1 with 5.00 kGy treatment. The cell membrane permeability increased, resulting in the leakage of intracellular substances and changes in cell physiological status, which was proven by the cell staining and electron microscopy (EM) observations. Moreover, the integrity of genomic DNA and protein secondary structure, but not the protein primary structure were also disrupted. These findings provide the intrinsic mechanisms for the inactivation of L. innocua affected by EBI, which could serve as a theoretical basis for a better application of EBI in food sterilisation.
Risk‐adjusted proposal for >60 months follow up after surgical treatment of organ‐confined renal cell carcinoma according to life expectancy
Authors: Frees Sebastian K , Kamal Mohammed M , Nestler Sebastian , Levien Patrick MF , Bidnur Samir , Brenner Walburgis , Thomas Christian , Jaeger Wolfgang , Thüroff Joachim W , Roos Frederik C
Published: December 2018

Objectives

To determine the long‐term oncological outcome of organ‐confined (<pT3) renal cell carcinoma.

Methods

We identified 889 patients with complete long‐term follow‐up data, who had been surgically treated for renal cell carcinoma (<T3) at our institution between 1976 and 2009. Kaplan–Meier analysis was used to assess the incidence and time interval of recurrence defined as local recurrences or metastases. We further compared patients who had tumor progression before or after 60 months.

Results

After a median follow‐up period of 74.33 months (range 3–329 months), 44 patients (4.9%) had disease recurrence. A total of 38.6% of the recurrences occurred after 60 months; 76.2% of patients had distant metastases and 23.8% of patients had local recurrences. In patients with low‐grade (G1) and low‐stage (pT1a) tumors, there was a trend to develop recurrence or metastases after longer intervals. Patients with lung metastasis and patients with multiple metastatic locations developed these metastases earlier than patients with bone metastasis. The risk of dying of other causes correlated with age, but the time interval to metastases did not.

Conclusions

Current guidelines recommend a follow‐up period of 60 months after surgical treatment of organ‐confined renal cell carcinoma. Our data shows that one‐third of recurrences of <pT3 renal cell carcinoma occur after 60 months. According to our oncological analysis, we suggest an age‐adjusted strategy of follow‐up balancing the risk of tumor recurrence and the life expectancy of the patient.
Complications associated with the approach to metatarsal head resection in diabetic foot osteomyelitis
Authors: Tardáguila‐García Aroa , Sanz‐Corbalán Irene , Molines‐Barroso Raúl J. , Álvaro‐Afonso Francisco J. , García‐Álvarez Yolanda , Lázaro‐Martínez José L.
Published: December 2018

The aim of this study was to evaluate the recovery time and the development of complications in the dorsal and plantar approach to metatarsal head resections (MHR) in patients with diabetic foot ulcers complicated by osteomyelitis. A retrospective study was carried out involving 108 patients who underwent MHRs for the treatment of diabetic foot osteomyelitis. Two cohorts were defined: dorsal approach with incision closed with sutures and plantar approach with ulcer healed using conservative treatment. The main outcomes were the weeks until healing and complications related to the approaches. Fifty‐three patients (49.1%) underwent a plantar approach and 55 (50.9%) a dorsal approach. Both approaches rendered similar healing times. However, the patients undergoing a dorsal approach developed more post‐surgical complications than patients treated through a plantar approach. The dorsal approach intervention was performed on smaller and shallower ulcers; however, more complications developed at follow up using this approach than through a plantar approach for MHR complicated with osteomyelitis.
Applicability assessment of the CASCade Two Dimensional SEDiment (CASC2D‐SED) distributed hydrological model for flood forecasting across four typical medium and small watersheds in China
Authors: Chao Lijun , Zhang Ke , Li Zhijia , Wang Jingfeng , Yao Cheng , Li Qiaoling
Published: December 2018

Hydrological modelling is a critical tool for preventing and mitigating severe flood disasters. This study aims to assess the applicability of a physically based distributed hydrological model, CASCade Two Dimensional SEDiment (CASC2D‐SED), for flood forecasting in four typical medium and small watersheds across three hydroclimatic zones (semi‐arid, semihumid, and humid) in China. CASC2D‐SED model has the best performance in Xianbeigou (semi‐arid), followed by Luanchuan (semihumid), and Shujia (humid), while has the relatively lowest performance in Chengcun (humid). It tends to underestimate a large portion of the discharges in the watersheds, indicating that the Green‐Ampt infiltration‐excess model, the only runoff generation scheme in CASC2D‐SED model, imposes restrictions on hydrological simulation without further accounting for subsurface and groundwater flows. This limitation is particularly obvious in the semihumid and humid regions. Our analysis suggests that combining infiltration‐excess and saturation‐excess runoff generation mechanisms and accounting for subsurface and groundwater flows in CASC2D‐SED will further enhance its capacity for flood forecasting and hydrological simulation for semihumid and humid hydroclimatic zones.
Clinical performance of one‐piece zirconia dental implants: A systematic review
Authors: ArRejaie Aws S. , Al‐Hamdan Rana S. , Basunbul Ghadeer I. , Abduljabbar Tariq , Al‐Aali Khulud A. , Labban Nawaf
Published: December 2018

The aim of the present review was to evaluate the clinical and radiographic performance of one‐piece zirconia implants (O‐PZI). This review followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis) guidelines that addressed the following focused question: What is the overall clinical and radiographic performance of O‐PZI? The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases were searched. Six clinical studies were included. For studies evaluating O‐PZI compared with one‐piece titanium implants, zirconia implants showed higher crestal bone loss (CBL) in both the studies. However, one study demonstrated a high failure rate compared to titanium dental implants, while one study demonstrated comparable survival rates between zirconia and titanium dental implants. For studies evaluating O‐PZI for the restoration of single crown and fixed dental prostheses, O‐PZI showed comparable bone loss and survival rates for single crowns and fixed dental prostheses. Two studies were included that compared O‐PZI with two‐piece zirconia (T‐PZI). One study showed a higher CBL and low survival rate for O‐PZI compared to T‐PZI, whereas the other study demonstrated comparable CBL and survival rates between O‐PZI and T‐PZI. It is still debatable whether O‐PZI demonstrate better clinical performance when compared with titanium implants or two‐piece design.
Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas
Authors: Shimizu Takeshi , Osanai Yasuyuki , Tanaka Kenji F. , Thai Truc Quynh , Abe Manabu , Natsume Rie , Sakimura Kenji , Ikenaka Kazuhiro
Published: December 2018

Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimulation can be transduced into intracellular biochemical signals through mechanosensors, such as integrin, p130Cas, talin and vinculin. However, the molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that morphology of OL was affected by knockdown of the mechanosensors p130Cas or talin1. Stretching of OL precursor cells induced the phosphorylation of p130Cas and talin‐associated assembly of vinculin. Shear stress decreased the number of OL processes, whereas these effects were mechanically suppressed by dominant‐negative (DN) p130Cas, but not by DN‐talin1. To investigate the roles of p130Cas in post‐natal OLs in vivo, we constructed a novel p130Cas knock‐in mouse and found overexpression of p130Cas in vivo affected the number of mature OLs in the cortex. These results indicate that the mechanosensor p130Cas controls both OL morphogenesis and maturation.

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Exploring bowel dysfunction of patients following colorectal surgery: A cohort study
Authors: Tan Shu‐Hwa , Liao Yuan‐Mei , Lee Kwo‐Chen , Ko Yi‐Li , Lin Pi‐Chu
Published: December 2018

Aims and objectives

To examine changes in patients’ bowel function and to compare patients’ outcome among different operation and treatment after rectal resection.

Background

Anal‐preserving surgery is the trend of treatment of colorectal cancer and bowel function after surgery needs to be concerned.

Design

Prospective cohort study.

Methods

A total of 38 patients with convenience sampling were recruited from a teaching hospital. The low anterior resection syndrome (LARS) score was used to assess bowel function disturbances before discharge and at 1 week, 1 month and 3 months after discharge. We followed the STROBE checklist to ensure rigour in our study.

Results

Approximately half of the patients experienced major LARS, including daily stool frequency of more than seven times and stool clustering at least once a week. The LARS scores observed at 1 month after discharge were significantly higher than those observed before discharge. Patients who received intersphincteric resection had higher LARS scores compared with those who received other surgeries. Furthermore, patients who underwent concurrent chemoradiotherapy, operation (OP) and chemotherapy had the highest LARS scores compared with those who underwent only an OP.

Conclusion

The patients experienced varied intestinal dysfunction after surgery based on their treatment plan and surgical method. Nurses should provide individualised health education for these patients.

Relevance to clinical practice

A health education booklet is recommended to educate patients about LARS symptoms and the techniques to adapt in their daily lives after surgery.
Efficacy of Megasphaera elsdenii inoculation in subacute ruminal acidosis in cattle
Authors: Arik Huzur Derya , Gulsen Nurettin , Hayirli Armagan , Alatas Mustafa Selcuk
Published: December 2018

Two consecutive experiments were carried out to determine efficacy of Megasphaera elsdenii inoculation in alleviation of subacute ruminal acidosis (SARA). In the first experiment, SARA was induced by feeding corn‐ and wheat‐based diets (20%, 40%, 60% and 80% of TMR, DM basis) in six ruminally cannulated heifers. Continuous pH was obtained using data loggers embedded in rumen. In corn (80%)‐ and wheat (60%)‐based diets ruminal pH ranged from 5.2 to 5.6 for 7.77 and 5.93 hr. In the second experiment (5 day), M. elsdenii (200 ml; 2.4 x 1010 cfu/ml) was inoculated during the first two days. During the SARA induction period, M. elsdenii and S. bovis in rumen liquor were more abundant in wheat‐based feeding (7.97 and 8.77) than in corn‐based feeding (7.06 and 7.95 per ml, log basis; p < 0.0001 for both). M. elsdenii inoculation increased total volatile fatty acids (VFA) concentration when corn‐based diet was fed, whereas it decreased total VFA concentration when wheat‐based diet was fed (p < 0.004). There was a decrease in the propionic acid proportion (24.04%–19.08%; p < 0.002), whereas no alteration in lactate and ammonia concentrations was observed. M. elsdenii inoculation increased protozoa count (from 5.39 to 5.55 per ml, log basis; p < 0.009) and decreased S. bovis count (from 9.18 to 7.95 per ml, log basis; p < 0.0001). The results suggest that M. elsdenii inoculation may help prevent SARA depending on dietary grain through altering rumen flora as reflected by a decrease in S. bovis count and an increase in protozoa count.
The use of diffusion tractography to characterize a corpus callosum malformation in a dog
Authors: Johnson Philippa J. , Barry Erica F. , Luh Wen‐Ming , Davies Emma
Published: December 2018

Introduction

The pathogenesis of corpus callosum malformations (CCM) is not well defined in the dog because of inherent limitations of structural magnetic resonance imaging (MRI) to evaluate the white matter. We used the advanced neuroimaging technique of tractography to virtually dissect the white matter projections in a dog with a CCM and in a normal control dog.

Methods

A 9‐month‐old male Coonhound that had a previous structural MRI diagnosis of CCM and a normal control dog underwent anesthesia and 3‐Tesla MRI. Diffusion‐tensor imaging and 3D T1‐weighted and 2D T2‐weighted sequences were acquired. Diffusion data were processed before tensor reconstruction and fiber tracking. Virtual dissections were performed to dissect out the major white matter projections in each dog.

Results

In the dog with CCM, the corpus callosum exhibited interhemispheric crossing fibers at the level of the splenium and formed longitudinal callosal fasciculi (Probst bundles). In addition, the fornix was small and the cingula enlarged and exhibited increased dorsal connectivity relative to the normal control.

Conclusions and Clinical Importance

We used tractography to describe a white matter malformation in a dog. The results suggest that, embryologically, formed axons fail to cross midline and instead create Probst bundles.
Liver disease related to alpha1‐antitrypsin deficiency in French children: The DEFI‐ALPHA cohort
Authors: Ruiz Mathias , Lacaille Florence , Berthiller Julien , Joly Philippe , Dumortier Jérôme , Aumar Madeleine , Bridoux‐Henno Laure , Jacquemin Emmanuel , Lamireau Thierry , Broué Pierre , Rivet Christine , Belmalih Abdelouahed , Restier Lioara , Chapuis‐Cellier Colette , Bouchecareilh Marion , Lachaux Alain ,   Groupe Francophone d’Hépatologie Gastroentérologie et Nutrition Pédiatriques
Published: December 2018

Background & Aims

To identify prognostic factors for liver disease in children with alpha‐1 antitrypsin deficiency, irrespective of phenotype, using the DEFI‐ALPHA cohort.

Methods

Retrospective, then prospective from 2010, multicentre study including children known to have alpha‐1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as “severe” (portal hypertension, liver failure, liver transplantation or death); “moderate” (persistent abnormal liver biology without portal hypertension); and “mild/none” (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model.

Results

In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow‐up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty‐eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0‐11.6): diagnosis of alpha‐1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIMlikeZ in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007).

Conclusion

Alpha‐1 antitrypsin‐deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non‐homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.
Anaphylaxis admissions in pediatric intensive care units: Follow‐up and risk of recurrence
Authors: Pouessel Guillaume , Cerbelle Valentine , Lejeune Stephanie , Leteurtre Stephane , Ramdane Nassima , Deschildre Antoine ,   the French Group for Pediatric Intensive Care Emergencies (GFRUP)
Published: December 2018

Background

Data about the risk of anaphylaxis recurrence in children are lacking. We assessed anaphylaxis recurrence and medical follow‐up in a cohort of children previously hospitalized in a French pediatric intensive care unit (PICU) for anaphylaxis.

Methods

We conducted a telephone survey of 166 children (≤18 years) hospitalized from 2003 to 2013.

Results

In all, 106 (64%) completed the survey (boys, 59%; mean age [SD]: 15.3 years [5.5]). The main index triggers were drugs (45%) and foods (37%). The mean duration follow‐up was of 7.7 years (SD: 2.4). Thirty‐eight (36%) children experienced 399 new allergic reactions during a follow‐up period of 282 patient‐years (incidence rate: 1.4/100 patients/y; 95% CI: 0.64‐2.04). Twelve children experienced 19 anaphylaxis reactions including five requiring PICU admission (anaphylaxis recurrence rate: 0.20/100 patients/y; 95% CI non‐calculable). Food was the trigger for 79% of recurrent reactions and drugs for 8%. The food trigger was previously known in 83%, the same as the index trigger in 69%. Overall, 1.5% of the recurrent reactions were treated with adrenaline injection and 8% an emergency hospital admission. Patients with recurrence had more likely a history of food allergy (P < 10−4), asthma (P < 0.005), atopic dermatitis (P < 0.05) than those without. 31% of the 50 children with food allergy did not see an allergist, 23% had no adrenaline auto‐injector, and 26% lacked a school individual healthcare plan.

Conclusions

Following a PICU admission for anaphylaxis, recurrence is high in children with food allergy compared with drug allergy. Allergic comorbidities increase the risk. Medical follow‐up has to be improved for these at‐risk children.
Etiology of out‐of‐hospital cardiac arrest in psychiatric patients: Chart review
Authors: Ishida Takuto , Miyazaki Kazuki , Yukawa Takahiro , Yamagishi Toshinobu , Sugiyama Kazuhiro , Tanabe Takahiro , Hamabe Yuichi , Mimura Masaru , Suzuki Takefumi , Uchida Hiroyuki
Published: December 2018

Aim

Although sudden cardiac deaths are more common in psychiatric patients than the general population, data on their causes are very limited. The aim of this study was to investigate initial rhythms and causes of out‐of‐hospital cardiac arrest (OHCA) in patients with psychiatric disorders.

Methods

We conducted a systematic chart review of patients resuscitated after OHCA and hospitalized in the Tertiary Emergency Medical Center of Tokyo Metropolitan Bokutoh Hospital in Japan between January 2010 and December 2017. The initial rhythms and causes of OHCA were compared between psychiatric patients and non‐psychiatric patients. Parameters of interest were compared using chi‐squared test, Fisher's exact test, or the Mann–Whitney U‐test, as appropriate.

Results

A total of 49 psychiatric and 600 non‐psychiatric patients were eligible for this study. Fatal but shockable arrhythmias (i.e. ventricular fibrillation and ventricular tachycardia) were less frequently observed as initial rhythms in patients with psychiatric disorders than the others (22.4% vs 49.7%, P < 0.001). Cardiac origin was less common as the cause of OHCA (26.5% vs 58.5%, P < 0.01), while airway obstruction and pulmonary embolism were more frequent in psychiatric versus non‐psychiatric patients (24.5% vs 6.5%, P < 0.01; and 12.2% vs 1.5%, P < 0.01, respectively). The results were similar when psychiatric patients were compared with sex‐ and age‐matched controls selected from the non‐psychiatric patient group.

Conclusion

Although fatal arrhythmias may be less common, non‐cardiac causes such as pulmonary embolism and airway obstruction need to be treated with high clinical suspicion in an event of sudden cardiac arrest in psychiatric patients.
Heritability and familiality of psychopathologic dimensions in Korean families with schizophrenia
Authors: Suh Hwagyu , Lee Byung Dae , Park Je Min , Lee Young Min , Moon Eunsoo , Jeong Hee Jeong , Kim Soo Yeon , Lee Kang Yoon , Chung Young In
Published: December 2018

Aim

Categorical syndromes such as schizophrenia could be a combination of many continuous mental structure phenotypes including several personality development/degeneration dimensions. This study investigated the heritability and familiality of symptom check list (SCL) psychopathologic dimensions in Korean schizophrenia linkage disequilibrium families.

Method

We recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We used the SCL questionnaire to measure psychopathologic dimensions. The heritability of symptomatic dimensions in 543 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Psychopathologic dimensions in the 543 family members were compared with those in 307 healthy unrelated controls to measure familiality on using analysis of variance (ANOVA) analysis.

Results

Five of the nine SCL variables were significantly heritable and were included in the subsequent analyses. The three groups (control, unaffected first‐degree relative, schizophrenia patient) were found to be significantly different with regard to the expected order of average group scores for all heritable dimensions.

Conclusion

Aberrations in several symptomatic dimensions could contribute to the complexity of schizophrenia syndrome as a result of genetic–environment coaction or interaction in spite of some limitations (recruited family, phenotyping).