Clinical Features Distinguishing Diabetic Retinopathy Severity Using Artificial Intelligence

BACKGROUND AND HYPOTHESIS: 1 in 29 American diabetics suffer from diabetic retinopathy (DR), the weakening of blood vessels in the retina. DR goes undetected in nearly 50% of diabetics, allowing DR to steal the vision of many Americans. We hypothesize that increasing the rate and ease of diagnosing DR by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients. PROJECT METHODS: This retrospective cohort study was conducted under approval from the Institutional Review Board of Indiana University School of Medicine. Images were deidentified and no consent was taken due to the nature of this retrospective study. We categorized 676 patient files based upon HbA1c, severity of non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Retinal images were annotated to identify common features of DR: microaneurysms, hemorrhages, cotton wool spots, exudates, and neovascularization. The VGG Image Annotator application used for annotations allowed us to save structure coordinates into a separate database for future training of the artificial intelligence system. RESULTS: 228 (33.7%) of patients were diagnosed with diabetes, and 143 (62.7%) of those were diagnosed with DR. Two-sample t tests found significant differences between the HbA1c values of all diabetics compared to diabetics without retinopathy (p<0.007) and between all severities of DR versus diabetics without retinopathy (p<0.002). 283 eyes were diagnosed with a form of DR in this study: 37 mild NPDR, 42 moderate NPDR, 56 severe NPDR, and 148 PDR eyes. POTENTIAL IMPACT: With the dataset of coordinates and HbA1c values from this experiment, we aim to train an artificial intelligence system to diagnose DR through retinal imaging. The goal of this system is to be conveniently used in primary medical clinics to increase the detection rate of DR to preserve the ocular health of millions of future Americans.National Institutes of Health: T35 EY 031282 Clinical and Translational Sciences Institute: UL1TR00252

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Growth, productivity and phytochemicals of Coriander in responses to foliar application of Acacia saligna fruit extract as a biostimulant under field conditions

Abstract The application of natural extracts to vegetable plants can increase production, optimize nutrient and water uptake, and mitigate the effects of stress on vegetable plants by enhancing primary and secondary metabolism. In this study, Acacia saligna (Labill.) H.L.Wendl. fruit aqueous extract (FAE) was applied as a foliar application to assess and demonstrate its effects on growth, productivity, and phytochemicals of coriander (Coriandrum sativum L.) plants. A. saligna FAE (2%, 4%, and 6%), each combined with 50% of the recommended dose of N fertilizer was applied to coriander plants over the course of two successive seasons in the field. These treatments were compared with the control treatment, which used a 100% recommended dose of N. The four tested treatments were set up in a randomized complete block design with three replicates for a total of 12 experimental plots. Each replicate (experimental plot) was 3 m2 (2 × 1.5 m2) in size and included 300 seeds/m2. The phytochemicals were examined using chromatographic and spectrophotometric methods, where the essential oils (EOs) extracted from leaves were analyzed by Gas chromatography–mass spectrometry (GC–MS), while the phenolic and flavonoid compounds were analyzed by High Performance Liquid Chromatography (HPLC). With the application of A. saligna FAE (4%) + 50% N fertilizer, the levels of total solid content, total carbohydrates, total protein, total phenols, and total antioxidant activity, as well as chlorophyll a, chlorophyll b, chlorophyll a + b, and carotenoids, were increased at harvest. The treatment A. saligna FAE at 6% + 50% N fertilizer did not observe significant improvement in the growth parameters of coriander plants because of the anticipated allelopathic effects. By GC–MS analysis, the major compounds in the EO from control treatment were 2-octyn-1-ol (23.93%), and 2-butyl-1-octanol (8.80%), in treated plants with 2% of A. saligna FAE + 50% N fertilizer were (E)-2-decen-1-ol (32.00%), and 1-methoxymethoxy-oct-2-yne (13.71%), in treated plants with 4% A. saligna FAE + 50% N fertilizer were E-2-undecen-1-ol (32.70%), and 3,5,5-trimethyl-1-hexene (8.91%), and in the treated plants with A. saligna FAE (6%) + 50% N fertilizer were phytol (80.44%), and (Z)6,(Z)9-pentadecadien-1-ol (13.75%). The flavonoid components 7-hydroxyflavone, naringin, rutin, quercetin, kaempferol, luteolin, apigenin, and catechin were presented with variable concentrations according to the treatments utilized as identified by HPLC analysis from the methanol extracts of the treated plants with the combination treatments of A. saligna FAE (2, 4, and 6%) and N fertilization (50% from the recommended dose) and control coriander plants (100% N recommended dose). The combination of 50% N fertilizer treatment and the biostimulant A. saligna FAE (4%) seems to improve coriander plant growth while simultaneously lowering N fertilizer consumption. Future research will be needed to further study the effectiveness of several concentrations of A. saligna FAE in various conditions and/or species

Toxoplasma and Toxocara seropositivity in juvenile idiopathic arthritis and its relation to disease activity and type of therapies

Juvenile idiopathic arthritis (JIA) is the most frequently encountered autoimmune rheumatic disease in children. To our knowledge, this is the first study aimed to estimate the frequency of Toxoplasma gondii (T. gondii) and Toxocara seropositivity in JIA and assess its relation to the disease activity, IL-10 levels, and type of the received therapies. This study was conducted on 43 JIA patients and 50 cases as a control group. All participants were evaluated by disease activity score (JADAS-27), and the presence of specific IgG and IgM antibodies against T. gondii and IgG against Toxocara species using an enzyme-linked immunosorbent assay. IL-10 serum levels were measured using an ELISA kit. The results show that JIA patients have significantly higher seropositivity for anti-T. gondii IgG compared to control subjects (p = 0.02) and a non-significant difference for Toxocara seropositivity (p = 0.41). All participants were negative for IgM anti-Toxoplasma gondii. Demographic parameters did not significantly affect these seroprevalence frequencies (p > 0.05). IL-10 was significantly higher among JIA patients compared to controls (p = 0.007) and seropositive anti-T. gondii JIA exhibited significantly higher IL-10 levels compared to seronegative ones (p = 0.03). Seropositive anti-T. gondii IgG JIA patients had a significantly higher disease activity score (JADAS-27) than seronegative anti-T. gondii IgG cases (p = 0.02). There was a significant positive correlation between anti-T. gondii IgG and JADAS-27 score (p = 0.009). A significant association was detected between T. gondii infection and DMARDs including the biological therapies (p < 0.05). Overall, this study supports a possible association between T. gondii infection and JIA, IL-10, disease activity score, and DMARDs therapies. It is possible that IL-10 plays a role in the development of JIA and contributes to persistent asymptomatic infection with T. gondii in JIA patients. As a result, a recommendation for screening tests for T. gondii infection among JIA patients is crucial before and during commencing DMARDs therapies and closely monitoring early signs of infection

FAM72D in plasma cell myeloma: a friend or enemy

Abstract Background Plasma cell neoplasm is characterized by complex genetic and prognostic heterogeneity. FAM72D, a gene located on chromosome 1, and the association between its expression and tumor progression and prognosis remain elusive. Methods The present study aims to assess FAM72D mRNA expression in 60 PCM patients and correlate its expression level with clinical and laboratory markers involved in diagnosing and prognosis of PCM using real-time PCR. Results Unpaired t-test revealed a significantly higher FAM72D expression level in the patients than in the control group with a median of 0.890 vs. /0.030, respectively, and p value = 0.000. The highest median level was denoted in newly diagnosed or relapsed patients (1.905, p value = 0.000). A significant positive correlation was found between FAM72D expression level and each of BMPCs count, M band, and β2 microglobulin (p = 0.000, p = 0.002, p = 0.024, respectively), and negative correlations with both serum albumin and hemoglobin level (p = 0.000, p = 0.035, respectively). The risk of relapse was 18.3-fold when the FAM72D level was greater than 1.547. Conclusion The higher FAM72D expression level in newly diagnosed and relapsed myeloma patients and its positive correlation with BMPCs confirm the stimulating effect of FAM72D on myeloma cell proliferation and its poor prognosis

Natural Plant Extracts and Microbial Antagonists to Control Fungal Pathogens and Improve the Productivity of Zucchini (Cucurbita pepo L.) In Vitro and in Greenhouse

Background: Natural plant extracts and microbial antagonists have the potential for use in increasing the fungal resistance and productivity of horticulture plants. Methods: The purpose of this study was to evaluate the ability of both natural plant extracts and microbial antagonists as a biotical control of some fungal pathogens, i.e., Fusarium ssp., Exserohilum ssp. and Nigrospora ssp., along with improving the growth and productivity performance of zucchini under greenhouse conditions. Eucalyptus camaldulensis leaf extract (LE), Citrus sinensis LE, Ficus benghalensis fruit extract (FE), and two microbial antagonists Pseudomonas fluorescens (accession no. MW647093) and Trichoderma viride (accession no. MW647090) were tested under in vitro and in vivo conditions. Through morphological characteristics and the internal transcribed spacer (ITS) region, Fusarium solani (accession no. MW947256), F. oxysporum (accession no. MW947254), Exserohilum rostratum (accession no. MW947255), and Nigrospora&nbsp;lacticolonia (accession no. MW947253) were identified. HPLC analysis was used for the identification of phenolic compounds (PCs) and flavonoid compounds (FCs) in the extracts. Results: The highest inhibition percentage of fungal growth (IPFG) against F. oxysporum was obtained with P. fluorescens, T. viride, and E. camaldulensis LE (4000 mg/L); F. solani with P. fluorescens, T. viride, and C. sinensis LE (4000 mg/L); Exserohilum rostratum with P. fluorescens, Ficus benghalensis FE (4000 mg/L) and E. camaldulensis LE (4000 mg/L), and N. lacticolonia with P. fluorescens. Using HPLC analysis, the abundant PCs in E. camaldulensis LE were pyrogallol, and caffeic acid, those in C. sinensis LE were syringic acid and ferulic acid, and those in F. benghalensis FE were gallic acid and syringic acid. In addition, the abundant FCs in E. camaldulensis LE were kaempferol, and naringin, those in C. sinensis LE were hesperidin and quercetin, and those in F. benghalensis FE were kaempferol and quercetin. Under greenhouse experiments, T. viride and E. camaldulensis LE (4000 mg/L) followed by P. fluorescens + T. viride treatments gave the best results of zucchini plants in terms of leaf area, fruits number per plant, yield per plant, and total yield (marketable and non-marketable). Conclusions: Plant extracts and bioagents can be used to control some zucchini fungal pathogens and increase the productivity performance of zucchini plants