Early Disease Control Research Articles

Remote ischemic conditioning for acute respiratory distress syndrome in COVID-19.

Acute respiratory distress syndrome and subsequent respiratory failure remains the leading cause of death (>80%) in patients severely impacted by COVID-19. The lack of clinically effective therapies for COVID-19 calls for the consideration of novel adjunct therapeutic approaches. Though novel antiviral treatments and vaccination hold promise in control and prevention of early disease, it is noteworthy that in severe cases of COVID-19, addressing “run-away” inflammatory cascades are likely more relevant for improvement of clinical outcomes. Viral loads may decrease in severe, end-stage coronavirus cases, but a systemically damaging cytokine storm persists and mediates multiple organ injury. Remote ischemic conditioning (RIC) of the limbs has shown potential in recent years to protect the lungs and other organs against pathological conditions similar to that observed in COVID-19. We review the efficacy of RIC in protecting the lungs against acute injury and current points of consideration. The beneficial effects of RIC on lung injury along with other related cardiovascular complications are discussed, as are the limitations presented by sex and aging. This adjunct therapy is highly feasible, noninvasive, and proven to be safe in clinical conditions. If proven effective in clinical trials for acute respiratory distress syndrome and COVID-19, application in the clinical setting could be immediately implemented to improve outcomes.

A broader aspect of Telehealth and patient's education amid pandemics: A review and an update

The combination of telemedicine, telepharmacy, and teledentistry, etc. comes under telehealth. Telehealth has the ability, capacity, and or functions to alter the manner patients or their caretakers and or assistants are educated about their medical or dental conditions. With the help of the latest computer-generated, cybernetic modes to educate and train patients, healthcare providers can enhance and expand the accessibility, effectiveness, and efficiency of patient care. Patient education involves teaching, training, instructing, and following the proper orders of staff’s health/ medical care staff. Many pandemics such as SARS, MERS, Nipah, Ebola and lately Coronavirus has caused the medical care system to turn all the way around and find a new method to provide healthcare to civilians. Consequently, a few countries battled the COVID-19 by execution of prohibitive measures including health isolate or quarantine, early diagnosis, and infection or disease control measures. Telemedicine has accomplished significantly more consideration during the pandemic since it decreased the danger of pandemics like COVID-19 transmission by limiting face-to-face contact among people.

Platelet activation and hypercoagulability in patients with early primary biliary cholangitis compared with healthy controls.

BackgroundPatients with primary biliary cholangitis (PBC) who have advanced disease are hypercoagulable, with no thrombophilic factors compared to non-cholestatic cirrhotics. We investigated whether hypercoagulability is present in early-stage PBC.MethodsPBC patients with biopsy-documented early disease and healthy controls matched by sex and age were asked to participate in the study. All were evaluated using rotational thromboelastometry (ROTEM), platelet aggregation, and flow cytometry. Four ROTEM parameters were evaluated (clotting time, clotting formation time, α-angle, and maximum clot firmness [MCF]). Platelet aggregation was determined as the maximal change in light transmission after the addition of adenosine diphosphate, collagen and epinephrine. Flow cytometry was used to evaluate the expression of glycoprotein (GP) IIb, GPIIa, and P-selectin on the platelet surface.ResultsWe enrolled 50 individuals in the study (25 PBC patients, 25 controls). Prothrombin time and activated partial thromboplastin time did not differ significantly between PBC patients and controls (P-value not significant). In ROTEM, aaaaaaaa-angle and MCF parameters were abnormally elevated in 9 (36%) PBC patients compared to 3 (12%) healthy controls and the difference was statistically significant (P=0.026). Platelet aggregation in PBC patients was not significantly different from controls. In flow cytometry, GPIIb and P-selectin expression was greater in PBC patients than in the control group and the difference was statistically significant (P=0.005 and P=0.006 respectively).ConclusionIn this study, we used a combination of sophisticated methods to detect evidence of platelet activation and hypercoagulability in patients with early PBC. Our findings may have important clinical implications and merit further investigation.

Impact of COVID‐19 on the provision of paediatric dental care: Analysis of the Australian Child Dental Benefits Schedule

Oral health is essential to maintaining good overall health, and access to dental care is necessary for the early detection, prevention and control of oral diseases. The COVID-19 pandemic has seen a significant disruption in the provision of dental services globally. The aim of this study was to investigate the impact of COVID-19 on dental services provided in Australia through the Child Dental Benefits Schedule. This study was a retrospective analysis of Medicare data on utilization of the Child Dental Benefits Schedule obtained from the Australian Government. Data were analysed for the period February to September 2020, with the number of services provided per month across five categories (diagnostic, preventive, restorative, endodontic and oral surgery) compared with the monthly average for 2019 (95% CI) and the same month for 2019. Total services by month were reported for 2017, 2018 and 2019 to compare the yearly trend with 2020. Differences in services provision by State/Territory were also described. Over the period of March to September, there were 881454 fewer dental services provided in 2020 than 2019, with the largest decline seen in April. There was a greater decline in preventive and diagnostic services, and a smaller decline in endodontic and oral surgery services. A second wave of COVID-19 in Victoria saw 198609 fewer dental services provided in that state from July to September 2020 than 2019. Dental service provision had still not returned to normal levels across Australia by September 2020. The COVID-19 pandemic has had a significant impact on the provision of dental services to children from lower socioeconomic backgrounds who already experience higher levels of dental disease and disadvantage in accessing dental care. Although the restriction of dental services was deemed necessary in order to minimize the risk of transmission of COVID-19 in the dental setting, the impact of these restrictions on oral health will be long lasting. Given the chronic and progressive nature of dental disease, the deferral of necessary dental care is likely to contribute to poorer oral health and long-term problems for many Australians.

Eye movement especially vertical oculomotor impairment as an aid to assess Parkinson's disease.

To detect abnormal eye movements in Parkinson's disease and explore its correlation with clinical characteristics and their value for diagnosis. We recruited forty-nine Parkinson's disease patients, including 35 early Parkinson's disease patients (Hoehn-Yahr: 1 to 2 stage) and 14 advanced Parkinson's disease patients (Hoehn-Yahr: 3 to 5 stage) and 23 healthy controls. Clinical manifestations in Parkinson's disease patients were recorded. Oculomotor performances including fixation, gaze, saccade in horizontal and vertical direction, and smooth pursuit in horizontal and vertical direction were measured by video-oculography. We found that five oculomotor parameters, namely square wave jerk frequency, latency of downward saccade, latency of upward saccade, accuracy of upward saccade, and gain of horizontal smooth pursuit were significantly different in Parkinson's disease patients and controls. When combining all these five parameters, we got the diagnostic sensitivity of 78.3% and specificity of 95.2%. More deficits in upward saccade than in other directions were associated with disease duration and progression of Parkinson's disease. Our primary study suggests that oculomotor examination might serve as an aid in the clinical assessment of Parkinson's disease patients and differentiating between early Parkinson's disease and normal controls.

Rapid vertical flow immunoassay on AuNP plasmonic paper for SERS-based point of need diagnostics

SERS based immunoassays for point-of-care diagnostics are a promising tool to facilitate biomarker detection for early disease diagnosis and disease control. The technique is based on a sandwiched system in which antigen is first captured by a selective plasmonic paper substrate and then labeled by an extrinsic Raman label (ERL), consisting of a 60 nm gold nanoparticle (AuNP) functionalized with a mixed monolayer of detection antibody and 4-nitrobenezenethiol (NBT) as a Raman reporter molecule. Here, we report on the use of AuNP modified filter paper as a novel capture membrane in a vertical flow format. This vertical flow configuration affords reproducible flow of sample and label through the capture substrate to overcome diffusion limited kinetics and significantly reduced assay time. The filter paper was selected due to its affordability and availability, while the embedded AuNPs maximized plasmonic coupling with the ERLs and SERS enhancement. Additionally, the embedded AuNP served as a scaffold to immobilize capture antibody to specifically bind antigen. In this work, a SERS-based rapid vertical flow (SERS-RVF) immunoassay for detection of mouse IgG was developed to establish proof-of-principle. Optimization of assay conditions led to a limit of detection of 3 ng/mL, which is comparable to more traditional formats carried out in multi-well plates, and significantly reduced assay time to less than 2 min. Additionally, IgG was accurately quantified in normal mouse serum to validate the SERS-RVF assay for application to the analysis of biological samples. These results highlight the potential advantages of the SERS-RVF platform for point-of-need testing.

Proteome Analysis of Walnut Bacterial Blight Disease.

The interaction between the plant host, walnut (Juglans regia; Jr), and a deadly pathogen (Xanthomonas arboricola pv. juglandis 417; Xaj) can lead to walnut bacterial blight (WB), which depletes walnut productivity by degrading the nut quality. Here, we dissect this pathosystem using tandem mass tag quantitative proteomics. Walnut hull tissues inoculated with Xaj were compared to mock-inoculated tissues, and 3972 proteins were identified, of which 3296 are from Jr and 676 from Xaj. Proteins with differential abundance include oxidoreductases, proteases, and enzymes involved in energy metabolism and amino acid interconversion pathways. Defense responses and plant hormone biosynthesis were also increased. Xaj proteins detected in infected tissues demonstrate its ability to adapt to the host microenvironment, limiting iron availability, coping with copper toxicity, and maintaining energy and intermediary metabolism. Secreted proteases and extracellular secretion apparatus such as type IV pilus for twitching motility and type III secretion effectors indicate putative factors recognized by the host. Taken together, these results suggest intense degradation processes, oxidative stress, and general arrest of the biosynthetic metabolism in infected nuts. Our results provide insights into molecular mechanisms and highlight potential molecular tools for early detection and disease control strategies.

Integration of Adaptive Technologies with Healthcare for the Early Identification and Control of COVID-19 Pandemic Disease

The impact of the COVID-19 pandemic has spread all over the world and it has affected voluminously everyday lives of billions. Social consequences and virus spread that needs to be addressed to take proper action to resolve the challenges faced during this pandemic period. The pandemic needs proper surveillance, monitoring, diagnosis, and identification of infected patients. Most researchers continue to give ways to detect and control the pandemic diseases of this type. Pandemic has made researchers from all areas and virologists consider cross-disciplinary approaches to combat with COVID-19. It needs to be immediate decisions to deal with uncertain conditions. During such a pandemic, the incorporation of healthcare technologies would bring about many solutions with high benefits. Reliable, sustainable, and accessible approaches can be the emphasis of the new digital healthcare approach. In this direction, IoT based smart solutions are introduced and analyzed. The emergencies spanning the globe demand a smart healthcare solution to manage people's lives at every stage. The first pandemic break-out in any part of the world needs early detection of disease and infected individuals to take reasonable measures forward to contain the spread. Web and Mobile based IoT system integrated with healthcare to support the solution that needs to be solved by the emergency posed during this pandemic. To locate COVID-19 cases and reduce the effects of the pandemic, IoT-enabled cognitive solutions are provided. It also addresses new ubiquitous technologies such as AI, Machine Learning, and Big Data Analytics with new innovative methods to integrate the solutions, including wearable devices, RFID, GPS, mobile apps, etc. Concerning the COVID-19 pandemic, the benefits and operational difficulties faced in digitizing these healthcare-cognitive IoT approaches are analyzed. The study would also address internal and external concerns such as practicality, cost, time to measure and execute, and coverage for implementation of this solution. These solutions may include human-machine interaction with the right decision-making capabilities. The paper also focuses on the ethical issues raised in introducing modern interoperable and predictive Healthcare IoT solutions.

Integration of Adaptive Technologies with Healthcare for the Early Identification and Control of COVID-19 Pandemic Disease

The impact of the COVID-19 pandemic has spread all over the world and it has affected voluminously everyday lives of billions. Social consequences and virus spread that needs to be addressed to take proper action to resolve the challenges faced during this pandemic period. The pandemic needs proper surveillance, monitoring, diagnosis, and identification of infected patients. Most researchers continue to give ways to detect and control the pandemic diseases of this type. Pandemic has made researchers from all areas and virologists consider cross-disciplinary approaches to combat with COVID-19. It needs to be immediate decisions to deal with uncertain conditions. During such a pandemic, the incorporation of healthcare technologies would bring about many solutions with high benefits. Reliable, sustainable, and accessible approaches can be the emphasis of the new digital healthcare approach. In this direction, IoT based smart solutions are introduced and analyzed. The emergencies spanning the globe demand a smart healthcare solution to manage people's lives at every stage. The first pandemic break-out in any part of the world needs early detection of disease and infected individuals to take reasonable measures forward to contain the spread. Web and Mobile based IoT system integrated with healthcare to support the solution that needs to be solved by the emergency posed during this pandemic. To locate COVID-19 cases and reduce the effects of the pandemic, IoT-enabled cognitive solutions are provided. It also addresses new ubiquitous technologies such as AI, Machine Learning, and Big Data Analytics with new innovative methods to integrate the solutions, including wearable devices, RFID, GPS, mobile apps, etc. Concerning the COVID-19 pandemic, the benefits and operational difficulties faced in digitizing these healthcare-cognitive IoT approaches are analyzed. The study would also address internal and external concerns such as practicality, cost, time to measure and execute, and coverage for implementation of this solution. These solutions may include human-machine interaction with the right decision-making capabilities. The paper also focuses on the ethical issues raised in introducing modern interoperable and predictive Healthcare IoT solutions.

S0664 Disease Control and Changes in Individual Treatment Outcomes From Week 14 to Week 52 With Vedolizumab or Adalimumab in Ulcerative Colitis: A VARSITY Trial Post Hoc Analysis

INTRODUCTION: In VARSITY, vedolizumab (VDZ), an anti-α4β7 integrin antibody, achieved superior clinical, endoscopic and histologic outcomes vs adalimumab (ADA), an anti-tumor necrosis factor (TNF) agent, in patients with moderate-to-severe ulcerative colitis (UC) (1). In recent years, the therapeutic goal for UC has evolved from symptom relief to disease control across multiple outcomes. METHODS: This VARSITY post hoc analysis evaluated the trajectory of UC key endpoints and disease control with intravenous VDZ vs subcutaneous ADA between early (Week [W]14) and late (W52) time points. Evolution in disease control over time was assessed based on the proportion of patients who maintained, improved or lost treatment benefit from W14 to W52 for the efficacy endpoints clinical remission, endoscopic and histologic improvement (defined in Figure 1). Data were analyzed within treatment arms in the full analysis population and by prior anti-TNF use (anti-TNF naïve or experienced). Observed data were reported without imputation. RESULTS: The study included 769 patients with UC (386 ADA, 383 VDZ). Most patients (56.0% ADA vs 60.8% VDZ) were male, were not using a corticosteroid at baseline (63.7% vs 63.9%) and were anti-TNF naïve (79.0% vs 79.2%). Median UC duration was 4.5 (ADA) and 4.8 (VDZ) years. At W14 and W52, clinical remission, endoscopic and histologic improvement, and disease control were all achieved more frequently with VDZ vs ADA (Table 1). More patients maintained each efficacy outcome and disease control from W14 to W52 with VDZ vs ADA, in both anti-TNF subgroups (Figure 1). In both arms, more anti-TNF naïve than anti-TNF experienced patients maintained efficacy (Figure 1). The numbers of patients who gained efficacy at W52 were more comparable between anti-TNF naïve and experienced. At W52, the overall rate of disease control was higher with VDZ (47.3% anti-TNF naïve vs 39.0% anti-TNF experienced) than ADA (32.7% vs 24.2%) (Table 1). Further analyses of early predictors of late disease control will be presented. CONCLUSION: VDZ treatment maintains greater early disease control than ADA in moderate-to-severe UC from W14 to W52, especially in anti-TNF naïve patients. These data suggest that VDZ is superior to ADA during both induction treatment evaluated at W14 and maintenance treatment evaluated at W52. Most of the observed treatment differences in anti-TNF naïve patients at W52 were established with early response to treatment between W0 and W14.Table 1.: Clinical Efficacy Outcomes and Disease Control at Weeks 14 and 52 by Anti-TNF Status With Adalimumab and Vedolizumab Treatment in Patients With UCFigure 1.: Changes in Clinical Efficacy Outcomes and Disease Control From Week 14 to Week 52 by Anti-TNF Status (Naïve/Experienced) With Adalimumab (N=305/N=81) and Vedolizumab (N=304/N=79) Treatment in Patients With UC.

Bio-Efficacy of 'SUDOTM' (Pseudomonas fluorescens) as a Bio-Control Agent against Early Blight (Alternaria solani) Disease of Tomato

Tomato (Lycopersicon esculentum Mill) is the most popular vegetable crop grown in India as well as in the world which is attacked by several diseases. Among the various diseases, early blight caused by Alternaria solani has become the constraint resulting in huge yield losses. Continuous usage of chemical methods leads to environment, soil and water pollution. However, biological control of diseases is long lasting, inexpensive, eco-friendly and harmless to target organisms. A field bio-efficacy study was conducted for evacuation of SUDO (Pseudomonas fluorescens) for control of tomato early blight disease. The results compiled suggest that the two sprays with 'SUDO' @ 2.0 ml/L followed or preceded by chemical fungicides was found effective in the management of early blight disease of tomato. Minimum PDI of 9.88 was recorded in T-1 treatment (chemical), followed by combination of treatments of chemicals + SUDO with 11.88 to 28.34 PDI which are significantly lower than control treatment (42.40 PDI). Even SUDO @ 2.0 ml/L alone recorded significantly more plant height (17.42%), and fruit yield (58.10%) with reducing early blight disease by 33.16% over control treatment. Similarly spraying of SUDO did not show any phyto-toxic effect on tomato plants.

Are large scale, urban, comprehensive CHW programs effective? The South African experience

Abstract Background South Africa is an upper middle-income country, but has one of the widest GINI co-efficients in the world. It faces a heavy burden of disease and poor health outcomes remain a challenge for millions of South Africans. Slow economic growth, rapid urbanization and high unemployment could de-rail the efforts to improve access to health care and health outcomes amongst the most vulnerable in the country. Within this context, the introduction of large scale, comprehensive community health worker (CHW) programs, in urban areas are seen to be game changers. However, there is inadequate global evidence on whether such programs work. Methods This is a multi-method, quasi-experimental intervention study measuring the effectiveness of a CHW program in the Ekurhuleni health district; set in an urban province of South Africa, where CHWs support approximately one million people. Health indicator performance was compared in clinics with good coverage of CHWs and those with low or no CHW support. Poor and vulnerable households with CHW support were compared to those with no CHW support. Results Over a nine-year period since implementation, clinics with CHW programs improved better than clinics without; on identified pregnancy, child health, infectious disease and non-communicable disease indicators. Odds ratios showed that households with good CHW coverage had better social support, health-seeking behavior, morbidity and mortality than households without. p-values were statistically significant (<0.05) for social support, chronic disease diagnosis and chronic disease control outputs. Conclusions This CHW program has shown its worth as it has been effective in improving early screening, referrals, diagnosis and disease control across a number of health conditions in an urban setting. Key messages Large-scale comprehensive CHW programs are a good investment towards achieving universal health coverage for all by improving access and care to the poor and vulnerable. Community Health Worker services in households are effective and should be a legitimate level of health care delivery in developing countries.

Multiparametric prostate MRI-based intensity-modulated radiation therapy guided by prostatic calcifications.

The optimal technique to administer image-guided radiation therapy for prostate cancer remains poorly defined. This study assessed outcomes after multiparametric prostate MRI-based planning was delivered with image-guided radiation therapy using prostatic calculi observed on cone beam CT (CBCT). Between January 2015 and December 2017, 94 consecutive patients were treated with CBCT-based image-guided radiation therapy (IGRT) without fiducial markers. MRI was routinely incorporated for target delineation and intraprostatic tumor nodules were boosted to allow reduced doses to normal appearing prostate. The primary endpoint was the prevalence of prostatic calcifications while toxicity and biochemical control were secondary endpoints. Median follow-up was 39.7 months with 82% NCCN intermediate to very high risk. Intraprostatic calculi were noted in 68% of patients. The 3-year biochemical control, late grade ≥2 rectal toxicity and late grade ≥2 urinary toxicity rates were 96%, 3 and 7%, respectively. Biochemical control and toxicity were not significantly impacted by the presence of prostatic calculi. Prostatic calcifications can serve as natural fiducial markers to allow for non-invasive IGRT for prostate cancer with promising early disease control and toxicity outcomes. Prostate calcification-guided IGRT is technically feasible.

The role of large-scale testing platform in the prevention and control of the COVID-19 pandemic: an empirical study based on a novel numerical model

Objective: China adopted an unprecedented province-scale quarantine since January 23rd 2020, after the novel coronavirus (COVID-19) broke out in Wuhan in December 2019. Responding to the challenge of limited testing capacity, large-scale (>20 000 tests per day) standardized and fully-automated laboratory (Huo-Yan) was built as an ad-hoc measure. There is so far no empirical data or mathematical model to reveal the impact of the testing capacity improvement since quarantine. Methods: Based on the suspected case data released by the Health Commission of Hubei Province and the daily testing data of Huo-Yan Laboratory, the impact of detection capabilities on the realization of "clearing" and "clearing the day" of supected cases was simulated by establishing a novel non-linear and competitive compartments differential model. Results: Without the establishment of Huo-Yan, the suspected cases would increase by 47% to 33 700, the corresponding cost of quarantine would be doubled, the turning point of the increment of suspected cases and the achievement of "daily settlement" (all newly discovered suspected cases are diagnosed according to the nucleic acid testing result) would be delayed for a whole week and 11 days. If the Huo-Yan Laboratory could ran at its full capacity, the number of suspected cases could start to decrease at least a week earlier, the peak of suspected cases would be reduced by at least 44%, and the quarantine cost could be reduced by more than 72%. Ideally, if a daily testing capacity of 10 500 tests was achieved immediately after the Hubei lockdown, "daily settlement" for all suspected cases could be achieved. Conclusions: Large-scale, standardized clinical testing platform, with nucleic acid testing, high-throughput sequencing, and immunoprotein assessment capabilities, need to be implemented simultaneously in order to maximize the effect of quarantine and minimize the duration and cost of the quarantine. Such infrastructure, for both common times and emergencies, is of great significance for the early prevention and control of infectious diseases.

Development toxicity and cardiotoxicity in zebrafish from exposure to iprodione

Iprodione is a highly effective broad-spectrum fungicide commonly used for early disease control in fruit trees and vegetables. Pesticides often flow into watercourses due to rainfall, causing toxicity in non-target organisms, eventually entering the food chain. However, little information is available in the current literature about the toxicity of iprodione to cardiac development. The present study aimed to investigate the effect of iprodione on early embryonic development and its cardiotoxicity in aquatic animals, using zebrafish as a model. At 6–72 h post-fertilization (hpf), zebrafish were exposed to concentrations of 15 mg/L, 20 mg/L, and 25 mg/L (72 h-LC50 = 21.15 mg/L). We found that exposure to iprodione resulted in yolk edema, increased mortality, and shortened body length in zebrafish embryos. In addition, iprodione was also found to induce edema in the pericardium of zebrafish, decrease heart rate, and cause the failure of cardiac cyclization. Exposure to iprodione significantly increased the accumulation of ROS and altered the activity of antioxidant enzymes (MDA, CAT) in zebrafish embryos. Moreover, iprodione induced changes in the transcription levels of heart developmental-related genes and apoptosis-related genes. In addition, Astaxanthin (antioxidant) can partially rescue the toxic phenotype caused by iprodione. Apoptosis-related genes and heart developmental-related genes were rescued after astaxanazin treatment. The results suggest that iprodione induces developmental and cardiac toxicity in zebrafish embryos, which provides new evidence of the toxicity of iprodione to organisms in aquatic ecosystems and assessing human health risks.

Endometrioma surgery and possibilities of early disease control

Aim: The purpose of this study is to investigate the efficacy of surgical management in ovarian endometrioma for early disease control and long-term fertility preservation in adolescents and women of very young age. A history of cyclic pains in adolescents is highly associated with endometriosis. Sonography enables the diagnosis of small endometriomas 1-2 cm in diameter. Although it is obvious that the risk of damage to normal ovarian tissue is diminished when operating and removing a 2 cm endometrioma, it is not approved since there are currently no tools available to identify at-risk patients. Additionally, performing laparoscopic surgery with 5 mm instruments in patients with small endometriomas will likely cause more harm than benefit. Methods: A literature review was performed using key words for endometrioma surgery, in vitro fertilization (IVF), implantation rate, pregnancy rate and adolescents. The pros and cons of surgical removal prior to assisted reproductive therapy (ART), outcomes of endometrioma surgical treatment before IVF, and current recommendations for endometrioma removal were investigated. Results: The total patient population from articles supporting removal of endometrioma before assisted reproductive therapy and evidence against were 30,741 and 9983 respectively. However, the only study reporting a statistically significant result found an 8.2% implantation rate for the surgical removal group vs . 12% in the direct-to-IVF group, and 14.9% pregnancy rate in the surgical removal group vs . 24.9% in the direct-to-IVF group. Damage to ovarian reserve and function due to surgery is exacerbated by large cyst size, stripping of the pseudocapsule and older age. Larger endometrioma, ablation of the endometrioma base and younger age are associated with higher recurrence rate. Conclusion: The patient’s age, in addition to the size and type of endometrioma, can direct and indicate the timing of surgical management. Bilateral endometriomas and those larger than 7 cm are associated with more damage to ovarian reserve due to disease and surgery, as compared with unilateral lesions and those smaller than 7 cm. High-risk adolescents and very young women seeking fertility treatment can thus benefit from an early diagnosis of endometrioma. Treatment by trans vaginal hydro-laparoscopy of selected cases can probably be suggested for the treatment of small endometriomas, since 5fr instruments are used following microsurgery principles. Therefore, an early diagnosis of endometrioma, especially in young patients, must be encouraged, improved and standardized, through stepwise clinical reasoning and diagnostic testing.

Antifungal Effects of Volatiles Produced by Bacillus subtilis Against Alternaria solani in Potato.

Antifungal activities of plant-beneficial Bacillus have been widely studied in recent years. Numerous studies have studied the antifungal mechanisms of soluble non-volatile bioactive compounds such as lipopeptides and proteins produced by Bacillus against soil-borne diseases. However, the antagonistic mechanisms of volatile organic compounds (VOCs) from Bacillus against airborne phytopathogens are still largely unknown, and the function of Alternaria solani pathogenic genes has not been well identified. Here, we first isolated a Bacillus strain with strong antifungal activity and finally identified it as B. subtilis ZD01. Then, the antagonistic mechanisms of VOCs produced by strain ZD01, against A. solani, an airborne fungal pathogen that can cause early blight diseases of potato, were studied. We showed that VOCs produced by strain ZD01 can reduce the colony size and mycelial penetration and can cause serious morphological changes of A. solani. Scanning electron microscope (SEM) observation showed that VOCs released by ZD01 could cause more flaccid and gapped hyphae of A. solani. Also, we found that VOCs produced by ZD01 can inhibit the conidia germination and reduce the lesion areas and number of A. solani in vivo significantly. Meanwhile, based on gas chromatography/mass spectrometry (GC/MS) analysis, 29 volatile compounds produced by strain ZD01 were identified. Out of 29 identified VOCs, 9 VOCs showed complete growth inhibition activities against A. solani. Moreover, we identified two virulence-associated genes (slt2 and sod) in A. solani. slt2 is a key gene that regulates the mycelial growth, penetration, sporulation, and virulence in vivo in A. solani. In addition, sod plays a significant role in the SOD synthetic pathway in A. solani. Results from qRT-PCR showed that the transcriptional expression of these two genes was down-regulated after being treated by VOCs produced by ZD01. These results are useful for a better understanding of the biocontrol mechanism of Bacillus and offer a potential method for potato early blight disease control.

THU0093 EARLY REMISSION IS ASSOCIATED WITH LOWER FATIGUE LEVELS ON THE LONG TERM IN PATIENTS WITH RECENT ONSET RHEUMATOID ARTHRITIS

Background:Fatigue is mentioned as a symptom with high impact in many patients with Rheumatoid Arthritis (RA) and this symptom remains difficult to be managed by both the patient and the physician.Objectives:To investigate if rapid suppression of disease activity in early RA could impact fatigue complaints in the long run.Methods:For this study, we included patients from the 2-year pragmatic investigator-initiated Care in Early Rheumatoid Arthritis (CareRA) trial. Most patients were treated intensively, with different combinations of csDMARDs and glucocorticoid remission induction schemes, except one group without classic markers of poor prognosis that was treated with MTX weekly in monotherapy. Patients were followed up at least every 3 months, with more mandatory visits in the first 6 months of treatment. Clinical parameters including DAS28 components were registered at every visit. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-reported instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to no motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Only patients with a filled-out MFI at baseline and available DAS28CRP at week 16 were included in this study.Patients were divided in 2 groups based on their response, defined as achieving or not achieving DAS28CRP remission (<2.6) at week 16. These patients were classified as early responders and controls respectively. The 2 groups were compared by Mann-Whitney-U test. A generalized estimating equation (GEE) compared the 2 groups over the course of the 2-year trial per each of the 5 domains of the MFI, adjusting for baseline DAS28CRP and baseline MFI domain score.Results:Of the 379 patients recruited in the CareRA trial, 343 (90.5%) had a MFI score available at baseline and a DAS28CRP available at week 16 with 236 (68.8%) patients achieving remission, and 107 (31.2%) patients not achieving remission at week 16. After 2 years of treatment, the proportion of patients in DAS28CRP remission was still higher in the early responders versus controls (82.3% versus 63.5%, p=0.001). Every MFI domain after 2 years of treatment showed lower scores for early responders including general fatigue (p=0.017), physical fatigue (p=0.011), reduced activity (p=0.040) and mental fatigue (p=0.042) except reduced motivation (p=0.062) (see figure 1). GEE analysis demonstrated that all MFI domains differed over 2 years between patients in remission or not at week 16, including general fatigue (p<0.001), physical fatigue (p<0.001), reduced activity (p<0.001), mental fatigue (p=0.037) and also reduced motivation (p=0.005).Figure 1.MFI domain scores at baseline and at week 104 per groupConclusion:Patients reaching remission after 16 weeks of treatment achieve lower fatigue levels over 2 years compared to patients not reaching this early remission. This study underlines the importance of early disease control. Successful early intensive treatment improves in the long run not only clinical outcomes but also an important patient preferred outcome such as fatigue.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA).

4504 Background: Clinical outcomes after curative treatment of resectable PDA remain suboptimal. To assess the potential of early control of systemic disease with multiagent peri-op CTx, we conducted a prospective trial in the National Clinical Trials Network. Methods: S1505 was a randomized phase II trial of peri-op CTx (12 weeks pre-, 12 weeks post-op) with either mFOLFIRINOX (Arm 1) or Gem/nabP (Arm 2). Eligibility required confirmed tissue diagnosis of PDA, ECOG PS 0 or 1, and resectable disease per Intergroup criteria. Primary outcome was 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients (pts), accrual up to 150 pts was planned to account for cases deemed ineligible at central radiology review. We previously presented data on eligibility (ASCO 2019 abstr 4137). Here we present the final efficacy and toxicity results for the eligible pts. Results: From 2015 to 2018, 147 pts were enrolled; there were 102 eligible pts; 55 in Arm 1; 47 in Arm 2. For Arms 1 and 2 respectively: median age, 66 (44-76) and 64 (46-76) years; males, 36 (65%) and 24 (51%); and ECOG PS 0, 34 (62%) and 31 (66%) pts. Treatment details are shown in Table. For Arm 1 and Arm 2, respectively: Two-year OS was 41.6% and 48.8%; median OS was 22.4 months and 23.6 months. Neither arm’s 2-year OS estimate was statistically significantly higher than the a priori threshold of 40% (p=0.42 in Arm 1 and p=0.12 in Arm 2). Median disease-free survival (DFS) after resection was 10.9 months in Arm 1 and 14.2 months in Arm 2 (p=0.87). Conclusions: We have demonstrated: 1) two-year OS of 41.6% (median 22.4 months) with mFOLFIRINOX and 48.8% (median 23.6 months) with Gem/nabP for all eligible pts starting treatment for resectable PDA; 2) post-resection DFS of 10.9 months and 14.2 months, respectively; 3) adequate safety and high resectability rates with peri-op CTx; 4) little evidence that either regimen improves OS compared with the historical standard. Clinical trial information: NCT02562716 . [Table: see text]

M5. A MULTIMODAL STUDY ON THE INFLUENCE OF LEFT-BEHIND CHILDREN’S VISUAL PERCEPTION PROCESSING

BackgroundLeft-behind children（LBC has experienced parent-child separation, which is a special parent-child separation and social isolation model. Adverse events in early development may have important effects on the development of the nervous system, including the influence on sensory and perceptual cognitive processing, thus increasing the susceptibility to mental illness. Meanwhile, there are various neurological and brain root causes behind left-behind children’s learning difficulties, non-socialization and other psychological behavior problems. In addition, left-behind may have sensory, perceptual and cognitive processing abnormalities. This study tries to elaborate and extract the eye movement characteristics of left-behind children, lay a foundation for the discussion of the mechanism of abnormal visual processing, and provide a scientific basis for follow-up of left-behind children and the early identification, prevention and control of mental diseases.MethodsThe standards for grouping left-behind children are as follows: the children who are separated from both parents 6 months after birth and spend less than 2 months with their parents each month, and the non-left-behind children with matched gender, age and education years, exclusion criteria is: neurological diseases, family history of mental illness, broken family (single parent, bereavement), high myopia (greater than 1000 degrees), eye and eyelash cannot be identified by infrared light. EyeControl portable eye movement tester (built-in infrared, speed: 100Hz, error <0.5°) developed by Qingtech and its software processing system were used. The subjects’ eye movements and various analysis indexes in various tasks were collected. The eye movement indexes of smooth pursuit eye movement, fixation stability and free browsing were collected, so as to investigate the effects of left-behind on static attention retention, visual tracking and face recognition in social scenes.ResultsAmong the 175 children, the smooth tracking mean deviation of LBC is significantly increased (P=0.017). The mean deviation of the O and S-curve tracking of the LBC is significantly increased (P=0.018; P=0.034), and the OS curve mean deviation and hyperactivity correlated (r=-0.273, P=0.011). In terms of the time that peak deviation takes (F=4.329, P=0.014), there is significant interaction between the age groups and the left-behind groups. In the social scenes, the first fixation time of face (P=0.039), the number of eye entry count (P=0.020), and the eye fixation time (P=0.003) of LBC are all significantly reduced, and the number of mouth entry count (P=0.007) and the number of fixation (P=0.023) of LBC are all significantly increased. Under the circumstance of low facial processing, there is a significant difference between LBC and NLBC (P=0.009), and that difference is not significant under the circumstance of high facial processing, and there is a significant difference between low facial processing LBC and high facial processing NLBC (P=0.007).DiscussionLeft-behind children have obstacles in dynamic visual information processing, insufficient inhibition and control, and poor cognitive flexibility, which may be related to hyperactivity. The attention retention in visual tracking decreased with the increase of age. Left-behind children have difficulties in face recognition in social scenes. In the case of low facial processing, left-behind children aggravated the defects of speech comprehension, while in the case of high facial processing, left-behind children had no significant influence on speech comprehension. Therefore, we should intervene the left-behind children in the early days, and this study provides a scientific basis for the formulation of social policies.