bluuebunny/crossref_metadata_2025 huggingface dataset:
Rugby Fans in Training New Zealand (RUFIT-NZ): protocol for a randomized controlled trial to assess the effectiveness and cost-effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs in New Zealand
Authors: Maddison Ralph , Hargreaves Elaine Anne , Jiang Yannan , Calder Amanda Jane , Wyke Sally , Gray Cindy M. , Hunt Kate , Lubans David , Eyles Helen , Draper Nick , Heke Ihirangi , Kara Stephen , Sundborn Gerhard , Arandjus Claire , Jenkins Matthew , Marsh Samantha
Published: February 2020

Background

A healthy lifestyle program that appeals to, and supports, obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. In Scotland, Football Fans in Training (FFIT), a weight management and healthy lifestyle program for overweight and obese men aged 35–65 years , delivered by community coaching staff at professional football clubs, has been shown to be beneficial and cost-effective. A pilot program inspired by FFIT but delivered by professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, improved physiological outcomes, and adherence to healthy lifestyle behaviors in overweight and obese men. The objective of this trial is to determine the effectiveness and cost-effectiveness of the Rugby Fans in Training New Zealand (RUFIT-NZ) program.

Methods

A pragmatic, two-arm, multi-center, randomized controlled trial involving 308 overweight and obese men aged 30–65 years, randomized to either an intervention group (n = 154) or a wait-list control group (n = 154). The intervention-group participated in the 12-week RUFIT-NZ program, a gender-sensitized, healthy lifestyle intervention adapted to the environment and cultural diversity of NZ and delivered through professional rugby clubs. Participants in the intervention group undergo physical training sessions, in addition to workshop-based sessions to learn about nutrition, physical activity, sleep, sedentary behavior, and a range of behavior-change strategies for sustaining a healthier lifestyle. The control group receives the program after 52 weeks. The primary outcome is change in body weight from baseline to 52 weeks. Secondary outcomes include change in body weight at 12 weeks; waist circumference, blood pressure, fitness, and lifestyle behaviors at 12 and 52 weeks; and cost-effectiveness. A process evaluation informed by the RE-AIM framework will evaluate potential implementation of RUFIT-NZ as an ongoing program in NZ after the trial.

Discussion

This trial will investigate the effectiveness and cost-effectiveness of the RUFIT-NZ program in overweight and obese NZ men.

Trial registration

Australia New Zealand Clinical Trials Registry, ACTRN12619000069156. Registered on 18 January 2019, according to the World Health Organization Trial Registration Data Set. Universal Trial Number, U1111-1245-0645.
Preventing early childhood caries with silver diamine fluoride: study protocol for a randomised clinical trial
Authors: Gao Sherry Shiqian , Chen Kitty Jieyi , Duangthip Duangporn , Wong May Chun Mei , Lo Edward Chin Man , Chu Chun Hung
Published: February 2020

Background

Silver diamine fluoride (SDF) solution is effective in arresting early childhood caries (ECC). Previous studies have suggested that it might exert a preventive effect in managing ECC. However, no well-designed clinical trials have yet been performed to study the effect of SDF on caries prevention. The objective of this randomised clinical trial is to determine whether 38% SDF solution is superior to 5% sodium fluoride (NaF) varnish in preventing new carious lesions in primary anterior teeth.

Methods/design

This is a phase II, single-centre, randomised, double-blind, active-controlled, parallel-group pragmatic trial. The hypothesis tested is that 38% SDF would be more effective than 5% NaF in preventing new caries development in primary anterior teeth. Approximately 730 3-year-old children who are generally healthy and with parental consent will be recruited from Hong Kong kindergartens. This sample size will be sufficient for appropriate statistical analysis of a superiority trial with 90% power, allowing for a 20% drop-out rate. Stratified randomisation will be adopted for allocating the intervention. The intervention will either be 38% SDF or 5% NaF (as a positive control) therapy on primary upper anterior teeth. A single trained examiner will conduct a dental examination every 6 months until 30 months in kindergarten. Another operator will provide fluoride therapy immediately after each dental examination. The examiner, children and children’s parents will be blinded to the treatment allocation. A questionnaire survey will be conducted to study the children’s oral health-related behaviours and socioeconomic backgrounds. Chi-square tests, t tests, regression analyses and survival analyses will be adopted for data analysis.

Discussion

The effectiveness of 38% SDF in preventing ECC remains uncertain. If the results are as anticipated, care standards using 5% NaF for ECC prevention will be changed. In addition, the results will be widely available and increase the adoption of SDF in other countries to reduce the global burden of ECC.

Trial registration

ClinicalTrials.gov, NCT04075474. Registered on 30 Aug 2019.
Fed-batch enzymatic hydrolysis of alkaline organosolv-pretreated corn stover facilitating high concentrations and yields of fermentable sugars for microbial lipid production
Authors: Gong Zhiwei , Wang Xuemin , Yuan Wei , Wang Yanan , Zhou Wenting , Wang Guanghui , Liu Yi
Published: February 2020

Background

Lignocellulosic biomass has been commonly regarded as a potential feedstock for the production of biofuels and biochemicals. High sugar yields and the complete bioconversion of all the lignocellulosic sugars into valuable products are attractive for the utilization of lignocelluloses. It is essential to pretreat and hydrolyze lignocelluloses at high solids loadings during industrial processes, which is more economical and environmentally friendly as capital cost, energy consumption, and water usage can be reduced. However, oligosaccharides are inevitably released during the high solids loading enzymatic hydrolysis and they are more recalcitrant than monosaccharides for microorganisms.

Results

A fed-batch enzymatic hydrolysis of corn stover pretreated by the sodium hydroxide–methanol solution (SMs) at high solids loading was demonstrated to reach the high concentrations and yields of fermentable sugars. Glucose, xylose, cello-oligosaccharides, and xylo-oligosaccharides achieved 146.7 g/L, 58.7 g/L, 15.6 g/L, and 24.7 g/L, respectively, when the fed-batch hydrolysis was started at 12% (w/v) solids loading, and 7% fresh substrate and a standardized blend of cellulase, β-glucosidase, and hemicellulase were fed consecutively at 3, 6, 24, and 48 h to achieve a final solids loading of 40% (w/v). The total conversion of glucan and xylan reached 89.5% and 88.5%, respectively, when the oligosaccharides were taken into account. Then, a fed-batch culture on the hydrolysates was investigated for lipid production by Cutaneotrichosporon oleaginosum. Biomass, lipid content, and lipid yield were 50.7 g/L, 61.7%, and 0.18 g/g, respectively. The overall consumptions of cello-oligosaccharides and xylo-oligosaccharides reached 74.1% and 68.2%, respectively.

Conclusions

High sugars concentrations and yields were achieved when the enzyme blend was supplemented simultaneously with the substrate at each time point of feeding during the fed-batch enzymatic hydrolysis. Oligosaccharides were co-utilized with monosaccharides during the fed-batch culture of C. oleaginosum. These results provide a promising strategy to hydrolyze alkaline organosolv-pretreated corn stover into fermentable sugars with high concentrations and yields for microbial lipid production.
Cardiac point-of-care ultrasound reveals unexpected, life-threatening findings in two children
Authors: Doniger Stephanie J. , Ng Nicholas
Published: February 2020

Background

The diagnosis of pericardial effusion with cardiac tamponade can at times be elusive in pediatric patients since it is relatively uncommon. Point-of-care ultrasound (POCUS) can readily be performed at the bedside to assess for the presence of a pericardial effusion, tamponade, and can occasionally yield unexpected results.

Case presentation

Two cases where POCUS unexpectedly identified pericardial effusions, with one patient who also had an anterior mediastinal mass.

Conclusions

Though underutilized, cardiac POCUS in children can be immediately life-saving and drastically change the clinical management at the patient’s bedside.
Autologous plasma versus fetal calf serum as a supplement for the culture of neutrophils
Authors: Alipour Razieh , Fatemi Alimohammad , Alsahebfosul Fereshteh , Andalib Alireza , Pourazar Abbasali
Published: February 2020

Objective

Currently, the replacement of fetal calf serum (FCS) by a more suitable alternative is a sought aim in the field of tissue and cell culture research. Autologous plasma (AP) and especially autologous serum (AS) have been shown to be effective substitutes of FCS in culture media for some of the cell types. Nevertheless, there is no comparative data on the most appropriate supplement for cell media in neutrophil studies, it is now unclear whether AP have a relatively equal, superior or inferior performance to FCS in neutrophil cell culture. In the present study, human blood neutrophils were isolated and cultured in FCS- or AP-supplemented medium. After 12, 36 and 60 h of incubation, cell viability, oxidative burst and CD11b expression were determined by flow cytometry.

Results

Compared to the culture of neutrophils in FCS 10% medium, the culture of neutrophils in a medium with AP 10% could prolong their life span without affecting their function. The findings introduce AP as a better supplement for human neutrophil cell culture than FCS and propose a simple and economical procedure for neutrophil isolation and culture.
External validity of Adult Sepsis Event’s simplified eSOFA criteria: a retrospective analysis of patients with confirmed infection in China
Authors:   for the China Critical Care Clinical Trials Group (CCCCTG), Dong Run , Tian Hongcheng , Zhou Jianfang , Weng Li , Hu Xiaoyun , Peng Jinmin , Wang Chunyao , Jiang Wei , Du Xueping , Xi Xiuming , An Youzhong , Duan Meili , Du Bin
Published: February 2020

Background

The US Centers for Disease Control and Prevention (CDC) recently released simplified eSOFA organ dysfunction criteria of Adult Sepsis Event for sepsis surveillance in the US. Our study aimed to compare the prevalence, characteristics, and outcomes of sepsis patients identified by eSOFA criteria versus Sequential Organ Failure Assessment (SOFA) Score (Sepsis-3) and assess the external validity of eSOFA criteria in China.

Methods

We conducted a retrospective cohort study of adult residents of Yuetan Subdistrict, Beijing, China, who were hospitalized from July 1, 2012 to June 30, 2014. Among patients with infection, sepsis was identified if there was a concurrent rise in SOFA score by 2 or more points (Sepsis-3) or the presence of 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, doubling in creatinine, doubling in bilirubin to 2.0 mg/dL or above, 50% or greater decrease in platelet count to less than 100 cells/μL, or lactate equal to or above 2.0 mmol/L. Areas under the receiver operating characteristic curves (AUROCs) for in-hospital mortality were compared between sepsis patients detected by the two criteria, adjusting for baseline characteristics.

Results

Of 1716 hospitalized patients with infection, 935 (54.5%) met Sepsis-3 criteria, 573 (33.4%) met eSOFA criteria, while 475 (27.7%) met both criteria. Demographic and clinical characteristics of sepsis patients meeting Sepsis-3 or eSOFA criteria were similar. In-hospital mortality was higher with eSOFA criteria versus Sepsis-3 (46.6% vs. 32.0%, p < 0.001). eSOFA criteria had high PPV (82.9%), but low sensitivity (50.8%) for the diagnosis of Sepsis-3. Patients meeting both criteria had the highest in-hospital mortality rate (52.8%, all p < 0.001), while patients who only met eSOFA criteria had higher mortality rate than those meeting Sepsis-3 alone (16.3% vs. 10.4%, p = 0.097). The predicted probability for in-hospital mortality was higher with eSOFA criteria versus Sepsis-3 (AUROC 0.830 vs. 0.795, p = 0.001) adjusting for baseline characteristics.

Conclusions

The CDC Adult Sepsis Event’s eSOFA criteria identify a smaller, more severely ill cohort of sepsis patients with similar demographic and clinical characteristics as the more complex Sepsis-3 SOFA score. These results suggest similar performance of eSOFA criteria across diverse populations, with low sensitivity and high specificity for the diagnosis of Sepsis-3.
Fast matrix inversion methods based on Chebyshev and Newton iterations for zero forcing precoding in massive MIMO systems
Authors: Hashima Sherief , Muta Osamu
Published: February 2020

In massive MIMO (mMIMO) systems, large matrix inversion is a challenging problem due to the huge volume of users and antennas. Neumann series (NS) and successive over relaxation (SOR) are two typical methods that solve such a problem in linear precoding. NS expands the inverse of a matrix into a series of matrix vector multiplications, while SOR deals with the same problem as a system of linear equations and iteratively solves it. However, the required complexities for both methods are still high. In this paper, four new joint methods are presented to achieve faster convergence and lower complexity in matrix inversion to determine linear precoding weights for mMIMO systems, where both Chebyshev iteration (ChebI) and Newton iteration (NI) are investigated separately to speed up the convergence of NS and SOR. Firstly, joint Chebyshev and NS method (ChebI-NS) is proposed not only to accelerate the convergence in NS but also to achieve more accurate inversion. Secondly, new SOR-based approximate matrix inversion (SOR-AMI) is proposed to achieve a direct simplified matrix inversion with similar convergence characteristics to the conventional SOR. Finally, two improved SOR-AMI methods, NI-SOR-AMI and ChebI-SOR-AMI, are investigated for further convergence acceleration, where NI and ChebI approaches are combined with the SOR-AMI, respectively. These four proposed inversion methods provide near optimal bit error rate (BER) performance of zero forcing (ZF) case under uncorrelated and correlated mMIMO channel conditions. Simulation results verify that the proposed ChebI-NS has the highest convergence rate compared to the conventional NS with similar complexity. Similarly, ChebI-SOR-AMI and NI-SOR-AMI achieve faster convergence than the conventional SOR method. The order of the proposed methods according to the convergence speed are ChebI-SOR-AMI, NI-SOR-AMI, SOR-AMI, then ChebI-NS, respectively. ChebI-NS has a low convergence because NS has lower convergence than SOR. Although ChebI-SOR-AMI has the fastest convergence rate, NI-SOR-AMI is preferable than ChebI-SOR-AMI due to its lower complexity and close inversion result.
Multiple positive solutions for nonlinear high-order Riemann–Liouville fractional differential equations boundary value problems with p-Laplacian operator
Authors: Zhou Bibo , Zhang Lingling , Addai Emmanuel , Zhang Nan
Published: February 2020

In this paper, we study the existence of multiple positive solutions for boundary value problems of high-order Riemann–Liouville fractional differential equations involving the p-Laplacian operator. Not only new existence conclusions of two positive solutions are obtained by employing functional-type cone expansion-compression fixed point theorem, but also some sufficient conditions for existence of at least three positive solutions are established by applying the Leggett–Williams fixed point theorem. In addition, we demonstrate the effectiveness of the main result by using an example.
Retraction Note: Some new results on the boundary behaviors of harmonic functions with integral boundary conditions
Authors: Xie Xiaozhen , Viouonu Costanza T.
Published: February 2020

The Editors-in-Chief have retracted this article [1] because it significantly overlaps with an article by different authors [2] that was simultaneously under consideration at another journal. The article also showed evidence of authorship manipulation. In addition, the identity of the corresponding author could not be verified: Hasselt University have confirmed that Costanza T Viouonu has not been affiliated with their institution. The authors have not responded to any correspondence about this retraction.
The value of teachable moments in surgical patient care and the supportive role of digital technologies
Authors: Robinson Anna , Slight Robert , Husband Andrew , Slight Sarah
Published: February 2020

Evidence strongly supports improved outcomes following surgery when patients are more physically active, have better dietary intake, or are generally fitter prior to surgery. Having an operation is a major life event for patients, and many are not educated around what they can do as individuals to aid a speedier and more successful recovery following their operation. What if there was a time point before surgery where clinicians could inspire patients to adjust their lifestyles for the better, in order to see fewer complications after surgery? This is where the concept of teachable moments comes into play.

This commentary explores the concept of teachable moments and their value in surgical patient care and discusses the potentially under-utilized opportunities on hand to the surgical multidisciplinary team to remotely support patients using digital health technologies.
Companies profitability under economic instability: evidence from the manufacturing industry in Russia
Authors: Spitsin Vladislav , Ryzhkova Marina , Vukovic Darko , Anokhin Sergey
Published: February 2020

This study analyzes factors affecting the efficiency (profitability) of enterprises in foreign, joint and domestic ownership in countries with unstable economy. The novelty of the study is that for the first time this kind of analysis has been carried out for the manufacturing industry in Russia, whose economy is characterized by the instability (crisis), external sanctions, and the internal trend for import substitution. Using a panel data on 6134 enterprises operating across several industries in Russia over the period of 2012–2016, the article suggests that generally production efficiency and scale efficiency positively affect profitability, whereas the share of borrowed capital, share of fixed assets and rising interest rates exert negative effects. The contribution of external financial factors is minimal, except for foreign and jointly owned firms. Production efficiency has a particularly pronounced effect for the automotive industry, machinery and equipment manufacturing, and in the metal industry. In contrast, in the chemical, electrical and optical manufacturing, and in food processing industries, internal financial factors emerge as a powerful predictor of performance. Firm ownership does not exert a significant effect on the relationship between the variables of interest when the share of borrowed funds is below 50%. When the share of borrowed capital exceeds 50%, internal financial factors emerge as a particularly prominent predictor of profitability.
Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis
Authors: Busch Lindsay M. , Sun Junfeng , Cui Xizhong , Eichacker Peter Q. , Torabi-Parizi Parizad
Published: February 2020

Background

Animal studies reporting immune checkpoint inhibitors (CPIs) improved host defense and survival during bacterial sepsis provided one basis for phase I CPI sepsis trials. We performed a systematic review and meta-analysis examining the benefit of CPI therapy in preclinical studies, and whether variables potentially altering this clinical benefit were investigated. Studies were analyzed that compared survival following bacteria or lipopolysaccharide challenge in animals treated with inhibitors to programmed death-1 (PD-1), PD-ligand1 (PD-L1), cytotoxic T lymphocyte-associated protein-4 (CTLA-4), or B- and T-lymphocyte attenuator (BTLA) versus control.

Results

Nineteen experiments from 11 studies (n = 709) were included. All experiments were in mice, and 10 of the 19 were published from a single research group. Sample size calculations and randomization were not reported in any studies, and blinding procedures were reported in just 1. Across all 19 experiments, CPIs increased the odds ratio for survival (OR, 95% CI) [3.37(1. 55, 7.31)] but with heterogeneity (I2 = 59%, p < 0.01). After stratification by checkpoint molecule targeted, challenge site or type, or concurrent antibacterial treatment, CPIs had consistent effects over most experiments in the 9 that included antibacterial treatment [OR = 2.82 (1.60, 4.98), I2 = 6%, p = 0.39 with versus 4.01 (0.89, 18.05), I2 = 74%, p < 0.01 without]. All 9 antibiotic experiments employed cecal-ligation and puncture (CLP) bacterial challenge while 6 also included a Candida albicans challenge 3–4 days after CLP. In these six experiments (n = 322), CPIs were directed at the fungal challenge when CLP lethality had resolved, and were consistently beneficial [2.91 (2.41, 3.50), I2 = 0%, p = 0.99]. In the three experiments (n = 66) providing antibiotics without fungal challenge, CPIs were administered within 1 day of CLP and had variable and non-significant effects [0.05 (0.00, 1.03); 7.86 (0.28, 217.11); and 8.50 (0.90, 80.03)]. No experiment examined pneumonia.

Conclusions

Preclinical studies showing that CPIs add benefit to antibiotic therapy for the common bacterial infections causing sepsis clinically are needed to support this therapeutic approach. Studies should be reproducible across multiple laboratories and include procedures to reduce the risk of bias.
Developing and validating a nestling photographic aging guide for cavity-nesting birds: an example with the European Bee-eater (Merops apiaster)
Authors: Costa Joana S. , Rocha Afonso D. , Correia Ricardo A. , Alves José A.
Published: February 2020

Background

Accurate estimation of nestlings’ age is essential in avian demography studies as well as in population ecology and conservation. For example, it can be useful for synchronizing nest visits with events of particular interest, such as the age at which young can be safely ringed, or in choosing the best period to attain the most accurate calculation of laying or hatching dates.

Methods

We constructed a photographic guide for aging European Bee-eaters (Merops apiaster) nestlings to 3-day age classes and evaluated the aging method by performing a validation exercise with several observers with no previous experience in aging bee-eater nestlings.

Results

The aging guide for bee-eater nestlings allowed estimating age to within 3 days with an average accuracy of 0.85. We found the optimal period for aging nestlings was between days 13‒18 (with accuracy between 0.94 and 0.99), during which the status of feather development was more easily distinguishable from the preceding and subsequent age classes. During the first 3 days after hatching, nestlings could also be aged with high accuracy (0.93). The small size of the nestling in relation to the eggs and the nestling’s inability to raise its head during these first days allowed for good discrimination from the subsequent age class. Between days 25 and 28, nestlings were correctly aged in only half of assignments (0.55 sensitivity) and nestlings belonging to class 7 (days 7‒9) were the least correctly identified (0.38 sensitivity). However, by visiting the nests at 12 days intervals it is possible to achieve the highest accuracy in age estimation with the smallest disturbance and logistic investment.

Conclusions

This study highlighted how indirect methods and a simple protocol can be established and employed to quickly estimate nestling age in cases where handling nestlings is challenging or impossible, while minimizing disturbance in and around the nest.
Tree diametric-species diversity is affected by human impact in old Scots pine dominated forest in boreal Fennoscandia
Authors: de Quesada Gonzalo , Kuuluvainen Timo
Published: February 2020

Background

Forest structural and compositional variability is of fundamental importance for forest ecosystem functioning and species diversity. The purpose of this research was to examine how human impact has affected the compositional-structural diversity of mature pine-dominated boreal forest in boreal Fennoscandia. For this a new approach was used, based on the classification of tree sizes by the diameter at breast height (dbh) and tree species, resulting in a new variable, the diametric-species, the variation of which describes the compositional-structural diversity of the forest. This variable was used to compare the structural-compositional diversity among three forest classes with different degree of human influence, using rarefaction as the main tool of analysis, complemented by analyses based on common diversity indices.

Results

The results showed that the near-natural forest was the most diverse and the managed forest the least diverse. On the other hand, the diversity of near-natural and selectively logged forests were similar, suggesting that selectively logged forests are equal to the natural forest in their compositional-structural diversity. The analysis solely on tree species showed no significant differences among the forest classes of different human impact. The Shannon diversity index showed no significant difference between the forest classes for the diametric-species and tree species classifications only, but the Simpson index signaled a slight difference between the selectively logged and managed forest classes for the diametric-species classification. Furthermore, the Sorensen index detected a difference among forest classes in the diametric-species classification.

Conclusions

Forest utilization had an adverse impact on forest compositional-structural diversity of mature Scots pine forests. The analysis also shows that the novel approach based on diametric-species classification could be a useful tool for forest diversity analysis and comparison, especially in species-poor forests such as the boreal forest.
Electrochemical biosensors: perspective on functional nanomaterials for on-site analysis
Authors: Cho Il-Hoon , Kim Dong Hyung , Park Sangsoo
Published: February 2020

Background

The electrochemical biosensor is one of the typical sensing devices based on transducing the biochemical events to electrical signals. In this type of sensor, an electrode is a key component that is employed as a solid support for immobilization of biomolecules and electron movement. Thanks to numerous nanomaterials that possess the large surface area, synergic effects are enabled by improving loading capacity and the mass transport of reactants for achieving high performance in terms of analytical sensitivity.

Main body

We categorized the current electrochemical biosensors into two groups, carbon-based (carbon nanotubes and graphene) and non-carbon-based nanomaterials (metallic and silica nanoparticles, nanowire, and indium tin oxide, organic materials). The carbon allotropes can be employed as an electrode and supporting scaffolds due to their large active surface area as well as an effective electron transfer rate. We also discussed the non-carbon nanomaterials that are used as alternative supporting components of the electrode for improving the electrochemical properties of biosensors.

Conclusion

Although several functional nanomaterials have provided the innovative solid substrate for high performances, developing on-site version of biosensor that meets enough sensitivity along with high reproducibility still remains a challenge. In particular, the matrix interference from real samples which seriously affects the biomolecular interaction still remains the most critical issues that need to be solved for practical aspect in the electrochemical biosensor.
Treatment of large, chronic and persistent macular hole with internal limiting membrane transposition and tuck technique
Authors: Fung Nicholas S. K. , Mak Anthony K. H. , Yiu Rachel , Wong Ian Y. H. , Lam Wai Ching
Published: February 2020

Background

Large, chronic full thickness macular holes which failed previous treatments are difficult to manage and even left untreated due to poor prognosis. A retrospective review of consecutive cases with chronic (at least 1 year) full thickness macular holes and internal limiting membrane (ILM) free flap transposition with tuck technique, after previously failed vitrectomy.

Methods

This was a retrospective and interventional study conducted in a single centre by a single surgeon. Patients with full thickness macular hole for at least 1 year and at least one previously failed vitrectomy with ILM peeling were recruited. A 25G vitrectomy with ILM free flap transposition was done without assistance of PFCL, viscoelastic or autologous blood. The free flap was manually tucked into the macular hole free space and gas fluid exchange was performed with 20% SF6 as tamponade. The patients were postured prone for 2 weeks postoperatively. Best corrected visual acuity, macular hole duration, previous surgeries, optical coherence tomography (OCT) appearance, hole size and closure rate were recorded.

Results

8 consecutive patients were included from May 2016 to Feb 2018. Transposition surgery was performed an average of 1481 days (SD 1096) after diagnosis of macular hole and average of 1226 days (SD 1242) after first vitrectomy. Macular hole mean size was 821 μm (SD 361.3), preoperative VA was logMAR 1.038 (SD 0.19), postoperative VA was logMAR 0.69 (SD 0.19) at 3 months. There were 1.13 lines gained and a significant improvement of logMAR 0.33 (p = 0.0084) at 6 months. Hole closure was seen in 7 out of 8 eyes (87.5%). The OCT with failed closure showed ILM flap within a flat hole, however no overlying neurosensory layers was seen. The duration from diagnosis to surgery was 2349 days in this case.

Conclusion

Free flap ILM transposition tuck without the use of additional intraoperative tamponade is an effective technique in treating large chronic macular holes with previously failed primary macular hole surgeries.

Trial registration (IRB of the Hong Kong University and Hospital Authority Hong Kong West Cluster, ref UW19-440), June 17, 2019.
Value of contrast-enhanced multidetector computed tomography in imaging of symptomatic patients after laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy
Authors: Bassiouny Reem Hassan , Chalabi Nivine abdel Moneim
Published: February 2020

Background

To assess the role of contrast-enhanced multidetector computed tomography (MDCT) in the assessment of symptomatic patients following laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy.

Results

We reviewed the studies of 129 cases and found complications in 113 patients: 55 early complications and 48 late complications. All of these complications were diagnosed with intravenous contrast-enhanced MDCT. Statistically significant difference was found between UGIS and MDCT in the diagnosis of many cases.

Conclusion

The rate of complications in bariatric surgery is high and the associated mortality is not negligible. The interpreting radiologists should know the normal postoperative findings and be aware of possible complications.
The use of variational mode decomposition in assisting sedimentary cyclicity analysis: A case study from an Albian carbonate reservoir, Campos Basin, southeast Brazil
Authors: Melani Leandro Hartleben , Honório Bruno César Zanardo , da Costa Correia Ulisses Miguel , Vidal Alexandre Campane
Published: February 2020

The sedimentary cyclicity analysis investigates the cyclic patterns and the different hierarchical orders of cyclicity in the stratigraphic record. The detection of cyclic depositional patterns is a key element of quantitative stratigraphy. It is often based on well-log data, which can be challenging due to the presence of superimposed cycles and nongeologic artifacts. We have developed an approach to assist the detection of sedimentary cyclicity in well-log signals based on a multiscale spectral analysis method. First, we apply variational mode decomposition to decompose the gamma-ray logs into band-limited subsignals, the intrinsic mode functions (IMFs), to investigate different orders of smoothness, signal-to-noise ratio, and the cyclicity embedded in the geologic record. Conventional time-domain analysis is carried out to understand the general trends in the IMFs, which enables us to better identify long-term cycles associated with transgressive-regressive (T-R) sequences. Then, by appropriately selecting a given IMF and extracting the instantaneous frequency (IF) and its mirrored version, we build a cyclicity log that can map expressive behavior change in the time-frequency domain. Because the IF is more sensitive to the signal variations, we could highlight the short-term cycles throughout the formation in detail. The detected short-term cycles are in agreement with the T-R sequence. We apply our method to the Albian carbonate succession of Macaé Group, Campos Basin, Brazil. We understand that our method can be a valuable tool for semiautomated detection of sedimentary cycles, assisting in the characterization of different hierarchical orders of cyclicity.
Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer
Authors: Chera Bhishamjit S. , Kumar Sunil , Shen Colette , Amdur Robert , Dagan Roi , Green Rebecca , Goldman Emily , Weiss Jared , Grilley-Olson Juneko , Patel Shetal , Zanation Adam , Hackman Trevor , Blumberg Jeff , Patel Samip , Thorp Brian , Weissler Mark , Yarbrough Wendell , Sheets Nathan , Mendenhall William , Tan Xianming M. , Gupta Gaorav P.
Published: February 2020

PURPOSE

Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.

METHODS AND MATERIALS

A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.

RESULTS

Forty-five patients were enrolled, and 509 blood samples were analyzed. After a median follow-up time of 19.2 months (range, 14.1-30.6 months), 4 patients (9%) developed disease recurrence. Thirty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 91% to 100%). Eight patients developed a positive ctHPVDNA during post-treatment surveillance, 4 of whom were diagnosed with biopsy-proven recurrence. Four patients had 2 consecutively positive ctHPVDNA blood tests, all 4 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 100% (95% CI, 51% to 100%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 6.6 months (range, 3.3-12.9 months).

CONCLUSION

Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.
RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.
Authors: Cohen Romain , Bennouna Jaafar , Henriques Julie , Tournigand Christophe , De La Fouchardiere Christelle , Tougeron David , Borg Christophe , Mazard Thibault , Chibaudel Benoist , Garcia-Larnicol Marie-Line , Svrcek Magali , Vernerey Dewi , Menu Yves , Andre Thierry
Published: February 2020

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Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.
A phase II study investigating cabozantinib in patients with refractory metastatic colorectal cancer (AGICC 17CRC01).
Authors: Scott Aaron James , Cohen Steven J. , Basu Mallick Atrayee , Dotan Efrat , Gold Philip Jordan , Hochster Howard S. , Subramaniam Somasundaram , Barzi Afsaneh , Blatchford Patrick Jud , Messersmith Wells A.
Published: February 2020

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Background: Therapeutic resistance to antiangiogenics in metastatic colorectal cancer (mCRC) inevitably develops via multiple mechanisms including upregulation of the MET kinase pathway. Cabozantinib, an oral multityrosine kinase inhibitor targeting MET, AXL, and VEGFR, demonstrated significant anti-tumor activity in CRC xenograft and cell line models. Methods: A single-arm, two-stage phase II study was conducted at 7 AGICC centers nationwide. 44 patients (pts) with mCRC who had progressed on or were intolerant of standard of care agents were treated with cabozantinib 60 mg daily in q3 wk cycles. The primary endpoint was 12-wk PFS rate. Based on the control arm of phase III CORRECT study, the Kaplan-Meier 12-wk PFS rate estimate was 13% and served as the null hypothesis. This study was powered at 0.906 to detect the alternative hypothesis of 12-wk PFS rate of 33% with a type I error rate of 0.044. Secondary endpoints were safety, RR, OS, and retrospective analysis of PFS and RR based on RAS, BRAF, and PIK3CA mutation status. Results: 44 pts were enrolled and 34 pts were response-evaluable as having undergone at least the first 6-wk restaging scan. 10 pts discontinued treatment prior to the first 6-wk scan due to clinical disease progression. Median number of cycles was 4 and median follow-up was 2.5 months. As of data-cutoff 8/23/2019, 55 Grade 3/4 AEs were reported with the most common being hypertension, fatigue, diarrhea, pain, HFS, nausea, vomiting, and proteinuria. 32 SAEs occurred in 18 pts. 5 Grade 5 AEs were reported: disease progression (3), disseminated intravascular coagulopathy, and bowel perforation. 15 pts (34%) achieved ≥ 12-wk PFS and 8 patients remain on treatment. Best response was 1 PR and 31 SD with a DCR at 6 wks of 72.7%. Of the pts who achieved ≥ 12-wk PFS, 12 had left-sided primary tumors, 5 had a RAS mutation, 1 had a PIK3CA mutation, and all pts were BRAF WT and MSI stable. Conclusions: Cabozantinib was deemed safe and demonstrates encouraging efficacy in a heavily pretreated mCRC pt population. These results support further investigation of cabozantinib in mCRC. Clinical trial information: NCT03542877.
Phase II study of panitumumab monotherapy in chemotherapy-naïve frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602.
Authors: Ohta Katsuya , Kato Takeshi , Goto Masahiro , Terazawa Tetsuji , Noura Shingo , Satake Hironaga , Kagawa Yoshinori , Kawakami Hisato , Hasegawa Hiroko , Yanagihara Kazuhiro , Shingai Tatsushi , Nakata Ken , Kotaka Masahito , Hiraki Masayuki , Konishi Ken , Nakae Shiro , Sakai Daisuke , Kurokawa Yukinori , Shimokawa Toshio , Satoh Taroh ,   Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)
Published: February 2020

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Background: Single agent of panitumumab (Pmab) is expected to be well tolerated and to improve survival in first-line setting in patients (pts) who are not eligible for intensive chemotherapy, although the efficacy and safety of Pmab for chemotherapy-naïve frail or elderly Japanese pts with wild-type (wt) RAS unresectable colorectal cancer (CRC) have not been yet studied. Methods: We conducted a multi-center phase II study. Pts aged over 76 years, or over 65 who were considered unsuitable for intensive chemotherapy. Pmab 6 mg/kg was administered intravenously every 2 weeks. The primary endpoint was disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and the incidence of grade 3 or 4 toxicities. Sample size was set to 36 with exact p-value of 0.05, a power of 0.90, the null of hypothesis of 45% and alternative hypothesis of 70% based on the Clopper-Pearson method. Results: A total 36 pts were enrolled in February 2017 to August 2018. Two pts were excluded; one was a lack of image examination at baseline, and the other was a lack of measurable lesion. The median age was 81 (67-88), with 29 pts (85%) being aged over 76 years. There were 33 (92%) pts with performance status (PS) 0/1, while two (6%) and one (3%) pts were PS 2/3, respectively. Twenty-eight pts (78%) had left-sided CRC, while eight pts had right-sided CRC. The RR was 50.0% (95%CI, 32.4-67.6) including three cases (8.8%) of complete response, and SD was 26.5%, yielding 76.5% of DCR (p < 0.001, 90% confidence interval [CI], 61.5-87.7). The RR with left sided tumor was 65% (95%CI, 44.3-82.8), while that pts with right-sided tumor was 0% (95%CI, 0.0-36.9)(p = 0.003). The major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 17%), hypomagnesemia (n = 4, 11%), fatigue (n = 3, 8%), paronychia (n = 3, 6%), and hyponatremia (n = 3, 6%). The grade 3 hematologic toxicities was neutropenia (n = 1, 3%). Conclusions: Pmab monotherapy showed the favolable efficacy and feasibility in the frail or elderly pts with RAS wt, unresectable CRC. The survival analysis including OS, PFS and TTF is awaiting. Clinical trial information: UMIN000024528.
Cobimetinib plus vemurafenib (C+V) in patients (Pts) with colorectal cancer (CRC) with BRAF V600E mutations: Results from the TAPUR Study.
Authors: Klute Kelsey , Garrett-Mayer Elizabeth , Halabi Susan , Mangat Pam K. , Nazemzadeh Reza , Yost Kathleen J , Butler Nicole L. , Perla Venu , Schilsky Richard L.
Published: February 2020

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Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with BRAF V600E mutation treated with C+V are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. Recommended dosing was C, 60 mg orally once daily for 21 days, 7 days off and V, 960 mg orally twice daily. Simon two-stage design was used to test the null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Thirty pts enrolled from August 2016 to August 2018; 2 were not evaluable for efficacy. Demographics and outcomes are summarized in Table. All pts had BRAF V600E mutations. Eight PR and 8 SD16+ were observed for DC and OR rates of 57% (90% CI, 43% to 67%) and 29% (95% CI, 13% to 49%), respectively. Twelve pts had at least 1 grade 3 AE or SAE at least possibly related to C+V including elevated liver enzymes, decreased lymphocytes, dyspnea, diarrhea, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper GI hemorrhage, and vomiting. Conclusions: The combination of C+V showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations . Further study is warranted to confirm the efficacy of C+V in this population. Clinical trial information: NCT02693535.

[Table: see text]