Patient characteristics that can predict response to omalizumab an (Anti-IgE Antibody) for achieving better control of asthmatic patients

AbstractBackgroundOmalizumab is a monoclonal anti-immunoglobulin E (IgE) antibody indicated for the treatment of inadequately controlled severe persistent asthma despite optimal controller therapy. It is an expensive medication so there is a need to identify those patients most likely to benefit.Aim of the studyTo investigate characteristics associated with response to omalizumab in difficult asthma.Patients and methodsThe study enrolled 42 patients (15 female, 27 male) with age range (20y–52y) with severe asthma that was inadequately controlled despite step 4 treatment as described in (GINA) guidelines. Omalizumab was given as add-on therapy to concomitant asthma treatment and administered subcutaneously every 2 or 4 weeks according to patients’ pretreatment bodyweight and baseline IgE levels, for at least 16 weeks. Those who showed better asthma control were analyzed to investigate whether pre-treatment patient baseline clinical characteristics could be reliably identified and to be predictive of a superior response to omalizumab.Results{(12/42 (28.6%)} of enrolled patients showed better asthma control. Using univariate and multivariate regression analysis, many variables showed significant effect on response to omalizumab including; age, duration of asthma, history of allergic rhinitis, history of allergic dermatitis, bronchial reversibility, no of positive results to common allergen in immediate skin-prick test, sputum eosinophilia and baseline total (IgE).ConclusionOmalizumab is an expensive medication so it is recommended to target its use to patients most likely to benefit rather than recommend widespread use. Further studies are needed to confirm these dat

MyI-Net: Fully Automatic Detection and Quantification of Myocardial Infarction from Cardiovascular MRI Images

A "heart attack" or myocardial infarction (MI), occurs when an artery supplying blood to the heart is abruptly occluded. The "gold standard" method for imaging MI is Cardiovascular Magnetic Resonance Imaging (MRI), with intravenously administered gadolinium-based contrast (late gadolinium enhancement). However, no "gold standard" fully automated method for the quantification of MI exists. In this work, we propose an end-to-end fully automatic system (MyI-Net) for the detection and quantification of MI in MRI images. This has the potential to reduce the uncertainty due to the technical variability across labs and inherent problems of the data and labels. Our system consists of four processing stages designed to maintain the flow of information across scales. First, features from raw MRI images are generated using feature extractors built on ResNet and MoblieNet architectures. This is followed by the Atrous Spatial Pyramid Pooling (ASPP) to produce spatial information at different scales to preserve more image context. High-level features from ASPP and initial low-level features are concatenated at the third stage and then passed to the fourth stage where spatial information is recovered via up-sampling to produce final image segmentation output into: i) background, ii) heart muscle, iii) blood and iv) scar areas. New models were compared with state-of-art models and manual quantification. Our models showed favorable performance in global segmentation and scar tissue detection relative to state-of-the-art work, including a four-fold better performance in matching scar pixels to contours produced by clinicians

USE OF NATURAL ZEOLITES AS A DETOXIFIER OF HEAVY METALS IN WATER AND THE FLESH OF REARED EUROPEAN SEABASS Dicentrarchus labrax

Provedeno je istraživanje kojim su se ispitivali učinci prirodnih zeolita kao pročišćivača vode na učinkovitost uklanjanja teških metala iz podzemne slane vode koja se koristi za uzgoj mlađi Dicentrarchus labrax. Ispitano je pet koncentracija zeolita: 0 (Z0), 2,5 ‰ (Z2,5), 5‰ (Z5), 7,5 ‰ (Z7,5) i 10 ‰ (Z10). Mlađ s početnom tjelesnom masom od 1,53 ± 0,018 g su nasađene u 15 akvarija s gustoćom 10 jedinki/akvarij. Ribe su se hranile komercijalnom hranom (42% proteina i 12,34% lipida) dva puta dnevno (09:30 i 14:00), u udjelu od 5% tjelesne mase ribe, tijekom 42 dana. Evaluirani su rast, iskorištavanje hrane, preživljavanje i učinkovitost uklanjanja teških metala. Indeksi rasta i iskorištenja hrane postupno su se poboljšavali s povećanjem koncentracije zeolita, pri čemu su najznačajnije vrijednosti (P≤0,05) otkrivene sa skupinom Z10. Stopa preživljavanja značajno se smanjila u skupini Z10 pri usporedbi s kontrolom (Z0). Značajno povećanje koncentracije zeolita (P≤0,05) poboljšalo je učinkovitost uklanjanja teških metala iz uzgojne vode sa adsorpcijskom selektivnošću Pb˃Cd˃Fe˃Cu˃Zn. Nadalje, otkriveno je povećanje brzine detoksikacije teških metala u mesu ribe s povećanjem razine zeolita uz selektivnost uklanjanja Fe˃Cu˃Zn˃Pb˃Cd. Zaključno, može se reći da se prirodni zeoliti mogu učinkovito koristiti za smanjenje teških metala u onečišćenim vodama, a posljedično i u mesu ribe, uz poboljšanje performansi rasta ribe.A study was conducted to investigate the effects of natural zeolites as a water clarifier on the heavy metal removal efficiency from the underground saltwater used for rearing Dicentrarchus labrax fry. Five concentrations of zeolites were tested: 0 (Z0), 2.5‰ (Z2.5), 5‰ (Z5), 7.5‰ (Z7.5) and 10‰ (Z10). Fry with an initial body weight of 1.53±0.018 g/fish were stocked in 15 aquaria at a density of 10 fry/aquarium. The fish were fed a commercial diet (42% protein and 12.34% lipid) twice daily (09:30 and 14:00) at 5% of their body weight per day for 42 days. Growth, feed utilization, survival and heavy metal removal efficiency were evaluated. The growth performance and feed utilization indices gradually improved with increasing zeolite concentration, with the most significant (P≤0.05) values detected at Z10. The survival rate decreased significantly at Z10 compared with the control (Z0). Increasing the zeolite concentration significantly (P≤0.05) improved the removal efficiency of heavy metals in the rearing water with adsorption selectivity of Pb˃Cd˃Fe˃Cu˃Zn. Furthermore, an increase in the detoxification rate of heavy metals in fish flesh with increasing zeolite level was detected with the removal selectivity of Fe˃Cu˃Zn˃Pb˃Cd. In conclusion, it can be stated that natural zeolites can be used effectively to reduce heavy metals in polluted waters and subsequently in fish flesh in addition to improving fish performance

Distribution pattern of antibiotic resistance genes in Escherichia coli isolated from colibacillosis cases in broiler farms of Egypt

Background and Aim: Multidrug resistance (MDR) of Escherichia coli has become an increasing concern in poultry farming worldwide. However, E. coli can accumulate resistance genes through gene transfer. The most problematic resistance mechanism in E. coli is the acquisition of genes encoding broad-spectrum β-lactamases, known as extended-spectrum β-lactamases, that confer resistance to broad-spectrum cephalosporins. Plasmid-mediated quinolone resistance genes (conferring resistance to quinolones) and mcr-1 genes (conferring resistance to colistin) also contribute to antimicrobial resistance. This study aimed to investigate the prevalence of antimicrobial susceptibility and to detect β-lactamase and colistin resistance genes of E. coli isolated from broiler farms in Egypt. Materials and Methods: Samples from 938 broiler farms were bacteriologically examined for E. coli isolation. The antimicrobial resistance profile was evaluated using disk diffusion, and several resistance genes were investigated through polymerase chain reaction amplification. Results: Escherichia coli was isolated and identified from 675/938 farms (72%) from the pooled internal organs (liver, heart, lung, spleen, and yolk) of broilers. Escherichia coli isolates from the most recent 3 years (2018–2020) were serotyped into 13 serotypes; the most prevalent serotype was O125 (n = 8). The highest phenotypic antibiotic resistance profiles during this period were against ampicillin, penicillin, tetracycline, and nalidixic acid. Escherichia coli was sensitive to clinically relevant antibiotics. Twenty-eight selected isolates from the most recent 3 years (2018–2020) were found to have MDR, where the prevalence of the antibiotic resistance genes ctx, tem, and shv was 46% and that of mcr-1 was 64%. Integrons were found in 93% of the isolates. Conclusion: The study showed a high prevalence of E. coli infection in broiler farms associated with MDR, which has a high public health significance because of its zoonotic relevance. These results strengthen the application of continuous surveillance programs

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge

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

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale <= 12 before intubation) who required mechanical ventilation (MV) >= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe