LC3B globular structures correlate with survival in esophageal adenocarcinoma

Background: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome. Previous studies have indicated that induction of autophagy can influence various aspects of tumor cell biology, including chemosensitivity. The objective of this study was to assess whether expression of the autophagy marker (LC3B) correlated with patient outcome. Methods: Esophageal adenocarcinoma tumor tissue from two independent sites, was examined retrospectively. Tumors from 104 neoadjuvant naïve patients and 48 patients post neoadjuvant therapy were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess impact of LC3B expression on survival. Cox regression was used to examine association with clinical risk factors. Results: A distinct globular pattern of LC3B expression was found to be predictive of outcome in both patient groups, irrespective of treatment (p < 0.001). Multivariate analysis found that this was a strong independent predictor of poor prognosis (p < 0.001). Conclusions: This distinctive staining pattern of LC3B represents a novel prognostic marker for resectable esophageal adenocarcinoma

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

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

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

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

Second-hand smoking among intermediate and secondary school students

Background and objectives. Second-hand smoke (SHS) is an important public health problem worldwide. The study aimed to estimate the prevalence of SHS exposure and its associated risk factors among intermediate and secondary school students. Methods. A cross-sectional study was conducted in 2013 among 3400 students from 34 intermediate and secondary schools in Madinah City, Saudi Arabia. Data about sociodemographic and smoking-related factors and SHS exposure were collected using a self-administered questionnaire. Results. Of the 3210 students analyzed, the prevalence of SHS exposure was 32.7% 49.3%, and 25% inside, outside, and both inside and outside the home, respectively. The highest risk of SHS exposure was associated with the adolescent&apos;s smoking status, parental smoking, close friends smoking, and family structure. The risk was markedly increased in association with parental smoking for exposure inside the home (OR = 6.49; 95% CI = 5.44-7.73) and with close friends smoking for exposure outside the home (OR = 4.16;. The risk of SHS, however, was lower among adolescents having knowledge about smoking and highly educated parents. Conclusion. The study revealed a considerably high prevalence of SHS both inside and outside the home among adolescents. Knowledge and beliefs about SHS exposure are the main preventable approach

Second-Hand Smoking among Intermediate and Secondary School Students in Madinah, Saudi Arabia

Background and objectives. Second-hand smoke (SHS) is an important public health problem worldwide. The study aimed to estimate the prevalence of SHS exposure and its associated risk factors among intermediate and secondary school students. Methods. A cross-sectional study was conducted in 2013 among 3400 students from 34 intermediate and secondary schools in Madinah City, Saudi Arabia. Data about sociodemographic and smoking-related factors and SHS exposure were collected using a self-administered questionnaire. Results. Of the 3210 students analyzed, the prevalence of SHS exposure was 32.7% 49.3%, and 25% inside, outside, and both inside and outside the home, respectively. The highest risk of SHS exposure was associated with the adolescent’s smoking status, parental smoking, close friends smoking, and family structure. The risk was markedly increased in association with parental smoking for exposure inside the home (OR = 6.49; 95% CI = 5.44–7.73) and with close friends smoking for exposure outside the home (OR = 4.16; 95% CI = 3.54–4.77). The risk of SHS, however, was lower among adolescents having knowledge about smoking and highly educated parents. Conclusion. The study revealed a considerably high prevalence of SHS both inside and outside the home among adolescents. Knowledge and beliefs about SHS exposure are the main preventable approach

Correlations of folic acid, vitamin B12, homocysteine, and thrombopoietin to platelet count in HCV infection

IntroductionThe platelet count is known to decrease in proportion to the advancement of the stage of liver disease in chronic hepatitis C (CHC) viral infection. The platelet count is currently used as an index for fibrosis staging. The pathophysiology of thrombocytopenia (TCP) in patients with hepatitis C virus (HCV) infection is not completely understood. PurposeThis work aimed to study the correlations of folic acid (FA), vitamin B12 (Vit B12), homocysteine (Hcy), and thrombopoietin to the platelet count in HCV infection. Patients and methods Sixty-seven patients (51 men and 16 women) with HCV infection were included in this study. All patients were sero-negative for hepatitis B viral markers. In addition, 20 healthy volunteers, matched for sex and age, were included as a control group. All patients and control individuals were subjected to the following: assessment of medical history, thorough clinical examination, and laboratory investigations including the following: complete blood cell counts, viral hepatitis markers, liver and renal function tests, HCV-RNA by quantitative PCR, serum folate, Vit B12, thrombopoietin, and plasma Hcy. Abdominal ultrasonography and ultrasound-guided liver biopsy for histopathologic examinations were carried out for the patients. Patients were divided into two groups of 36 patients with CHC and 31 patients with cirrhosis with HCV liver cirrhosis (LC). Results The Results indicated a significant decrease in the platelet count in CHC and LC patients compared with the healthy control group. There was a highly significant decrease in the FA level in CHC and LC patients compared with the control group; also, a significant decrease in the platelet count was found in LC patients compared with CHC patients. Hcy was significantly increased in CHC and LC patients. There was a nonsignificant decrease in Vit B12 in CHC patients, whereas it was significantly increased in LC patients. There was a nonsignificant decrease in thrombopoietin in CHC patients compared with the control group, whereas in LC patients, there was a highly significant decrease. There was a highly significant positive correlation between the platelet count and FA, but an insignificant correlation between the platelet count and Hcy, Vit B12, thrombopoietin, and viral load. Conclusion This study concluded that TCP in HCV-related chronic liver diseases is multifactorial and decreased FA is involved in its pathogenesis as an independent risk factor. Increased Hcy may cause TCP through platelet activation and endothelial dysfunction

Expression of SSX-1 and SSX-5 genes in the peripheral blood of patients with hepatocellular carcinoma

Background: Liver cancer is the fifth most common cancer in men and the seventh in women. Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality in patients with liver cirrhosis and accounts for 90% of primary liver cancer. Synovial sarcoma X chromosome (SSX) genes belong to cancer testis antigens (CTA) family; expressed only in germ cell tumors. There have been some studies about the SSX genes expression in the HCC. To the best of our knowledge no reports included these genes expression in the Egyptian patients with HCC. Aim: This study aims to evaluate the SSX-1 and SSX-5 mRNA expression in tumor cells circulating in the peripheral blood (PB) of a cohort of Egyptian patients with HCC and to find out any possible associations between these genes expression and different clinical/laboratory parameters. Subjects and methods: This study included 100 subjects; 52 HCC cases, 25 with post viral hepatitis liver cirrhosis and 23 apparently healthy controls. Expression of SSX-1 and SSX-5 mRNA in PB was tested by reverse transcription polymerase chain reaction (RT-PCR). Results: SSX-1 and SSX-5 mRNA were expressed in 40.4% and 36.5% of the HCC patients, respectively. SSX-1 and/or SSX-5 were not detected in healthy controls or cirrhotic patients. Neither SSX-1 nor SSX-5 expression showed an association with Alfa-Fetoprotein (AFP) levels, tumor size, tumor differentiation, hepatitis B infection and Bilharziasis (P > 0.05). Conclusion: SSX-1 and SSX-5 mRNA are specifically expressed in tumor cells circulating in PB of HCC patients and thus could be used as easy access, simple method molecular markers for early diagnosis of HCC patients in Egypt