Diagnostic performance of alpha-fetoprotein, YKL40 and GP73 in hepatocellular carcinoma Egyptian patients

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is responsible for a large proportion of cancer deaths worldwide. Diagnosis of HCC often requires more sophisticated modalities and represents a challenge for physician.  Methods: This study aimed to compare the diagnostic performance of AFP, YKL40 and GP73 in patients' serum with hepatocellular carcinoma (HCC) in high-risk population in an attempt to justify the new, sensitive, specific and rapid measure for the diagnosis and detection of HCC. Serum YKL40, GP73 and alpha-fetoprotein (AFP) were compared in a total of 60 human subjects in this study, including 20 healthy adults, and 40 patients with HCC, The main outcome measures were the specificity and sensitivity of YKL40 and GP73 in patients at risk for the development of HCC.Results: Using 4.4 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 85% and 90% compared with 77% and 60% for YKL40 using 21.06 ng/ml as a cut-off value. On the same context, the sensitivity and specificity of serum AFP at 8.5ng/ml cut-off were 82% and 95%. While that for the AFP and GP73 combined detection was up to 92% and 96%, justifying that the combined detection could prevent the false negative diagnosis by any marker alone and significantly improve the detection rate of HCC.Conclusions: The current evidence indicates that serum GP73 has HCC diagnostic efficacy inferior to that of AFP and YKL40 and the clinical implementation of serum GP73 measurement as a standard test for HCC is recommended alone or in combination with AFP.

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

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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 years; 78.2% included were male with a median age of 37 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

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

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Diagnostic performance of alpha-fetoprotein, YKL40 and GP73 in hepatocellular carcinoma Egyptian patients

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is responsible for a large proportion of cancer deaths worldwide. Diagnosis of HCC often requires more sophisticated modalities and represents a challenge for physician. Methods: This study aimed to compare the diagnostic performance of AFP, YKL40 and GP73 in patients serum with hepatocellular carcinoma (HCC) in high-risk population in an attempt to justify the new, sensitive, specific and rapid measure for the diagnosis and detection of HCC. Serum YKL40, GP73 and alpha-fetoprotein (AFP) were compared in a total of 60 human subjects in this study, including 20 healthy adults, and 40 patients with HCC, The main outcome measures were the specificity and sensitivity of YKL40 and GP73 in patients at risk for the development of HCC. Results: Using 4.4 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 85% and 90% compared with 77% and 60% for YKL40 using 21.06 ng/ml as a cut-off value. On the same context, the sensitivity and specificity of serum AFP at 8.5ng/ml cut-off were 82% and 95%. While that for the AFP and GP73 combined detection was up to 92% and 96%, justifying that the combined detection could prevent the false negative diagnosis by any marker alone and significantly improve the detection rate of HCC. Conclusions: The current evidence indicates that serum GP73 has HCC diagnostic efficacy inferior to that of AFP and YKL40 and the clinical implementation of serum GP73 measurement as a standard test for HCC is recommended alone or in combination with AFP. [Int J Res Med Sci 2016; 4(4.000): 1086-1092

Association between adenosine receptor gene polymorphism and response to caffeine citrate treatment in apnea of prematurity; An Egyptian single-center study

Background: Caffeine citrate is the methyl-xanthine of choice used in controlling apnea of prematurity (AOP). Caffeine central effect is mediated via non-selective (A1) and selective (A2a) adenosine receptors antagonism. Variability in caffeine response had been frequently noticed in AOP, suggesting underlying genetic predisposition. Aim of the study: We evaluated the role of adenosine receptor A1 [ADORA1] and adenosine receptor A2a [ADORA2a] gene polymorphisms in the variability of caffeine response among Egyptian preemies with AOP. Patient and methods: In this case-control study, 43 preterm neonates with AOP were eligible as cases and 43 preterm babies free from apnea were taken as controls. Preterm neonates with AOP were further divided according to response to caffeine treatment into caffeine responder (n = 18) and caffeine non-responders (n = 25). ADORA1 [716 T > G] and ADORA2a [1976C > T] gene polymorphisms were genotyped by mean of PCR-based RFLP-assay. Results: There were significant increase in frequency distribution of ADORA2a [1976C > T] CT (62.7% vs 23.3%), TT (14% vs 4.7%) genotypes and T allele (34.3% vs 16.3%) in cases compared to controls with significant increased risk of AOP development with OR (95%CI); P-value of 8.37(3.03–23.1), P = 0.000; 9.3(1.61–53.61), P = 0.005 and 4.27(2.09–8.70), P = 0.000 respectively. Further, caffeine non-responders were associated with significant increase frequency of ADORA2a CT (80% vs 38.9%) and TT (16% vs 11.1%) genotypes and T allele (56% vs 30.6%) with OR (95%CI) and P-value of 21.38 (2.31–197.8), P = 0.001; 18 (1.24–260.9); P = 0.005 and 2.89(1.17–7.13), P = 0.019 respectively, when compared to caffeine responders. Patients with AOP who had ADORA2a CT and TT genotypes were associated with significant increase in duration of hospital stay and poor outcome. Genotype distribution frequency of studied polymorphisms did not deviate from Hardy Weinberg (HW) equilibrium among controls. Conclusion: ADORA2a [1976C > T] polymorphism has a significant role in AOP development and variation in caffeine response among preterm babies. Keywords: ADORA2a polymorphism, Adenosine receptor, Apnea of prematurity, Caffeine citrate, Caffeine respons