High-incidence Regions Research Articles

Healthcare system delay and utilization in tuberculosis patients in Portuguese high-incidence region

Abstract Background In Portugal, the Tâmega e Sousa region (TeS) has a high incidence of tuberculosis (TB) [27.4 and 43.8 per 100.000 inhabitants in sub-regions Baixo Tâmega (BxT) and Vale do Sousa Sul (VSS), 2017]. Delay in TB diagnosis leads to increased transmission, which may lead to more people infected. This study aimed to describe healthcare system delay among TB patients and healthcare utilization from symptoms onset to diagnosis in TeS. Methods We analysed pulmonary TB cases notified in BxT and VSS in 2014-7 in the national surveillance system (SVIG-TB). Concomitantly, we analysed healthcare utilisation from patients in a retrospective study (URBAN-TB) about TB delays in 2019-20. We characterised demographics of patients from each data source and comorbidities from SVIG-TB. We calculated median overall delay until diagnosis (days); and healthcare delay overall and by patient characteristics, for each sub-region. Delay was calculated only when relevant dates were recorded. Healthcare utilisation from symptoms onset to diagnosis was described using the frequency of each first contact provider and the average number of visits until diagnosis. Results Included 139 patients from BxT and 206 from VSS (83% male, 53% aged 40-59y, and 17% with silicosis). Global delays were 48 and 75 days (n = 57/132; BxT and VSS). Healthcare delays were 7 and 8 days (n = 76/180; BxT and VSS). In both ACES, healthcare delays were longer for patients aged 60-79y, with COPD and aged 0-19y. Healthcare utilisation analysis included 38 patients (89% male; 55% aged 40-59y; n = 17/21). Primary care (n = 15; 39%) and emergency department (ED) (n = 9; 24%) were frequent points of first contact. The average number of visits until diagnosis was higher for patients from ED (3.9) and lower for patients from TB specialised units (1.3). Conclusions Our results suggest that in TeS it is important to avoid ED as a point of first contact of TB patients and to facilitate the diagnosis in young, older and COPD patients. Key messages Emergency department is a relevant point of first contact and may be included in efforts to reduce tuberculosis delay. Policies to reduce tuberculosis delay may target younger, older and COPD patients.

CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma

Purpose The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. Methods The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case–control studies, each of which included a population-based set and a hospital-based set. Results The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (p < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23–2.60 and 1.10–4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (p > 0.05). Conclusions The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.

Spatial autocorrelation study of fatal yellowing in organic oil palm in the eastern Amazon

The oil palm (Elaeis guineensis) is a very important source of vegetable oil worldwide. While oil palm cultivation is not currently economically significant in Brazil, there is immense growth potential for this crop in the Amazon region, with no need for deforestation. Fatal yellowing (FY) is a major phytosanitary barrier to the development of oil palm cultivation in the region. Many plantations have been devastated by FY, but its causes are unknown. The objective of this study was to analyze the spatial autocorrelation of FY in the oil palm crop by applying Moran’s Index (I). The experiment was carried out on a large farm (>8000 ha) in the municipality of Acará, in the state of Pará (Brazil), with 139 plots of oil palm of different genetic materials and ages. The number of diseased plants per plot has been recorded since 2001 and used in the analysis. A positive autocorrelation of disease incidence was calculated based on the observations of the current study. By calculation of the Local Moran’s I it was possible to identify the presence of high-incidence regions in the northeast and the central-west areas of the farm and low-incidence areas in the south and the north and in outlying plots. The approach described in this study was useful in identifying regions with the highest occurrence of FY, and could be useful in the management of this disease.

Understanding consumer and clinician perceptions of a potential Lyme disease vaccine.

Each year, over 450 000 Lyme disease diagnoses are estimated to occur in the United States, and current preventive measures have been insufficient to stem the rising incidence. An effective human Lyme disease vaccine could be a powerful intervention for population-level impact. In advance of new Lyme disease vaccines coming to market, this study explored barriers to acceptability and motivations for the uptake of a new Lyme disease vaccine. Researchers conducted 9 online focus groups among consumers who may potentially benefit from the vaccine and 30 in-depth interviews among clinician groups who may provide the vaccine. All participants were recruited from three US regions of high Lyme disease incidence. Researchers found that participants shared common motivators to either recommend (clinicians) or accept (consumers) a Lyme disease vaccine, largely driven by perceived benefits of the vaccine, the lack of current effective preventive measures and a greater peace of mind. The concern about the challenges associated with diagnosing and treating Lyme disease is a primary motivator for clinicians to recommend the vaccine, while the concern about getting Lyme disease is a primary motivator for consumers to desire the vaccine.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study

BackgroundDespite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions.MethodsWe performed an endoscopic examination of 44,857 individuals aged 40–69 years from five high incidence regions of China in 2017–2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors.ResultsWe identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52–3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03–3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05–1.37) was essential risk factor of LGIN.ConclusionsAmong individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Epidemiological and Clinical Characteristics of Melioidosis Caused by Gentamicin-Susceptible Burkholderia pseudomallei in Sarawak, Malaysia.

Background Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a broad range of antibiotics, including aminoglycosides. In Sarawak, Malaysia, a high proportion of melioidosis cases are caused by gentamicin-susceptible isolates. There are limited epidemiological and clinical data on these infections.MethodsWe conducted a retrospective study of culture-confirmed melioidosis among adults admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2016.ResultsOne hundred forty-eight adults with culture-confirmed melioidosis were identified. Of 129 (87%) tested, 84 (65%) had gentamicin-susceptible B pseudomallei. The average annual incidence of melioidosis was 12.3 per 100 000 population, with marked variation between districts ranging from 5.8 to 29.3 per 100 000 population. Rural districts had higher incidences of melioidosis and overwhelmingly larger proportions of gentamicin-susceptible B pseudomallei infection. Significantly more patients with gentamicin-susceptible infection had no identified risk factors, with diabetes less frequently present in this group. Ninety-eight percent had acute presentations. Pneumonia, reported in 71%, was the most common presentation. Splenic abscesses were found in 54% of those imaged. Bacteremia was present in 88%; septic shock occurred in 47%. Forty-five (35%) patients died. No differences in clinical, laboratory, or outcome characteristics were noted between gentamicin-susceptible and gentamicin-resistant infections.ConclusionsGentamicin-susceptible B pseudomallei infections are common in Sarawak and dominate in the high-incidence rural interior regions. Clinical manifestations and outcomes are the same as for gentamicin-resistant B pseudomallei infections. Further studies are required to determine if all gentamicin-susceptible B pseudomallei infections in Sarawak are clonal and to ascertain their environmental drivers and niches.

Shifting paradigm toward minimally invasive gastrectomy for gastric cancer--China's contribution

Surgery is the cornerstone of gastric cancer treatment. However, the traditional open surgery, which has been followed for more than 100 years, has restricted the development of gastric cancer surgery due to its "major trauma" defects. Therefore, how to scientifically develop laparoscopic and minimally invasive surgery (MIS) has become the main research orientation and focus worldwide for the development of gastric cancer surgery in recent 30 years, especially in China, a region of high incidence of gastric cancer. In the past 30 years, our Chinese colleagues in gastric cancer surgery have carried out systematic researches on key issues, and offered new theories of minimally invasive anatomy, new techniques for MIS, and new evidence of MIS for advanced gastric cancer. The system of the key surgical technology innovation for gastric cancer MIS was established, promoting a crucial move in the development of gastric cancer surgery. This article aims to commemorate the 30-year development of laparoscopic surgery in China and pay tribute to the strength produced by all the Chinese minimally invasive surgeons.

In-flight transmission of wild-type SARS-CoV-2 and the outbreak potential of imported clusters of COVID-19: a review of published evidence

International air travel has been highlighted as a concern since the beginning of the COVID-19 pandemic with respect to importation of cases. We summarise the available evidence for in-flight transmission of wild type SARS-CoV-2 during 2020, and for imported COVID-19 clusters to cause outbreaks. This paper provides a data baseline prior to the emergence of new mutations causing SARS-CoV-2 variants of concern, whose characteristics may increase the potential risk of in-flight transmission and imported outbreaks. The evidence on in-flight transmission of wild-type SARS-CoV-2 is limited, and is described in a small number of published reports. Most of the available evidence pertains to the early phase of the COVID-19 pandemic, during a period without non-pharmaceutical interventions such as distancing and in-flight mask wearing. There is considerable potential for outbreaks of COVID-19 from imported cases or clusters when public health guidance around quarantine of travellers and self-isolation of cases is not adhered to. Risks can be mitigated by measures such as: avoiding non-essential travel, targeted testing and quarantine of travellers from high incidence regions or regions of concern, managed quarantine processes, and protocols for rapid investigation and control of transmission from a possible variant of concern. Measures should be dynamically assessed and proportionate to the level of risk.Graphical abstract

Absence of Francisella tularensis in Finnish Ixodes ricinus and Ixodes persulcatus ticks

Francisella tularensis subsp. holarctica is the causative agent of tularaemia in Europe. Finland is a high-incidence region for tularaemia, with mosquito bites as the most common sources of infection. However, in Central and Western Europe, ticks (Acari: Ixodidae) have been suggested as the main vectors. Indeed, several studies have reported the pathogen from the locally most common human-biting tick species, Ixodes ricinus. In Finland, the occurrence of the pathogen in ticks has started receiving attention only recently. Here, we collate previous tick screening data from Finland regarding F. tularensis as well as present the results from a novel screening of roughly 15 000 I. ricinus and I. persulcatus collected from across the country.In total, 14 878 ticks collected between 2015 and 2020 were screened for F. tularensis using a TaqMan-based qPCR assay targeting the 23 KDa gene. The combined screening efforts of the current and previous studies, encompassing roughly 20 000 ticks, did not find any positive ticks. Given the negative results despite the considerable sample size, it appears that the pathogen is not circulating in local tick populations in Finland. We discuss some possible reasons for the lack of the bacterium in ticks in this high-incidence region of tularaemia.

A genome epidemiological study of mycobacterium tuberculosis in subpopulations with high and low incidence rate in Guangxi, South China

BackgroundTuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). China is the third in top 8 high TB burden countries and Guangxi is one of the high incidence areas in South China. Determine bacterial factors that affected TB incidence rate is a step toward Ending the TB epidemic.ResultsGenomes of M. tuberculosis cultures from a relatively high and low incidence region in Guangxi have been sequenced. 347 of 358(96.9%) were identified as M. tuberculosis. All the strains belong to Lineage 2 and Lineage 4, except for one in Lineage 1. We found that the genetic structure of the M. tuberculosis population in each county varies enormously. Low incidence rate regions have a lower prevalence of Beijing genotypes than other regions. Four isolates which harbored mutT4-48 also had mutT2-58 mutations. It is suggested that strains from the ancestors of modern Beijing lineage is circulating in Guangxi. Strains of modern Beijing lineage (OR=2.04) were more likely to acquire drug resistances than Lineage 4. Most of the lineage differentiation SNPs are related to cell wall biosynthetic pathways.ConclusionsThese results provided a higher resolution to better understand the history of transmission of M. tuberculosis from/to South China. And the incidence rate of tuberculosis might be affected by bacterial population structure shaped by demographic history. Our findings also support the hypothesis that Modern Beijing lineage originated in South China.

Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus.

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer in univariate models as well as models adjusted for age, sex, and CagA serostatus. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T allele at rs1927914.

Gastric cancer: lessons learned from high-incidence geographic regions.

Gastric cancer is a global health concern. There is a marked geographical variability in the incidence of gastric cancer, with higher incidence in East and Central Asia followed by Latin America and Eastern Europe. Survival rates in gastric cancer are low and strongly stage dependent. Due to the limited survival benefit achieved from currently available therapeutic options, prevention and early diagnosis are essential to minimize morbidity and mortality from this disease. Countries with high incidence of gastric cancer have pioneered the development and implementation of prevention and screening programs. Helicobacter pylori (H. pylori) eradication and dietary modifications are the main preventive strategies. Upper gastrointestinal (UGI) endoscopy is the mainstay screening strategy for early diagnosis. In this article, we review the lessons learned for gastric cancer diagnosis and treatment from high-incidence areas and discuss their applicability for treatment in the Western world to reduce morbidity and mortality from this disease.

Gastric Cancer in Iran: An Overview of Risk Factors and Preventive Measures.

Despite all recent treatment advances and the worldwide decline in the incidence rate, gastric cancer (GC) remains an ongoing global health challenge and one of the major leading causes of cancer-specific deaths, particularly in high-incidence regions including Iran. Since GC is often diagnosed in advanced stages, the best action may be to enable early diagnosis of the disease or even prevent it in the first place through identification and control of the underlying risk factors. Endoscopy, as the gold standard method, is both expensive and invasive, making it an unfavorable device in this regard. Therefore, it is crucial to implement a reliable region-specific screening and surveillance program to identify high-risk individuals with more efficient screening modalities. Here, in addition to a review of current GC knowledge, we presented the data of newly-established Population-based Cancer Registries (PBCRs) in Iran. Our assessment confirmed earlier reports of a very high GC incidence rate in the northwestern and northern provinces of Iran, most notably Ardabil. Along with the important role of conventional risk factors such as Helicobacter pylori (HP) infection and high dietary intake of salt, of more interest, we highlighted new region-specific risk factors, namely hookah, and opium. In conclusion, it seems the best results in reducing GC incidence and mortality rates on larger scales arise from modifying behavioral and environmental risk factors and advancing genetic and molecular biomarkers in order to supersede endoscopy. Regular endoscopic screening and antibiotic chemoprophylaxis against HP are still more appropriate in high-risk groups with specified criteria.

МОЖЛИВОСТІ ДЛЯ РОЗВИТКУ НАУКИ ПІД ЧАС ПАНДЕМІЇ COVID-19

Dear reader, The 21st year of the 21st century will go down in history as the boundary that divided the coronavirus (COVID-19) pandemic and post-pandemic world. It is the efforts of medical academic institutions and the dedicated medical professionals all around the world that have demonstrated a high readiness to overcome the modern challenges of the pandemic that has engulfed all the humanity. The world has received a new vector in the development of science to understand the strategy to combat the "plague" of the 21st century. First, it is the creation of specific prevention of COVID-19 at a record pace: on January 10, 2020, the information on the sequencing of SARS-CoV-2 virus (also known as 2019-nCoV) was received, and on December 11, 2020, vaccination against COVID-19 started among healthcare professionals in the United States. Currently, more than 2 billion people worldwide have been vaccinated against SARS-CoV-2 [1]. No deaths have been reported in the UK for 25 days (as of June 3, 2021), nevertheless changes in the SARS-CoV-2 genome and the emergence of new virus strains continue, and reports from high-incidence regions such as India are still alarming. The pandemic of the SARS-CoV-2 virus, which as of today has infected more than 171 million and killed more than 3.5 million people globally, has been a major test for newer vaccines that differ from the previous ones. The organization and conduct of clinical research are becoming more important than ever. The article by Andriy Cherkas is dedicated to this topic [2]. Pfizer, Moderna, AstraZeneca and Johnson-Johnson vaccines developed and tested in clinical trials were made possible following the results of fundamental research by Katalin Karikó and Drew Weisman, which began almost 30 years ago [2] and ushered in the fifth era of vaccination [3, 4].

A Statewide Multi-Institutional Study of Asymptomatic Pretreatment Testing of Radiation Therapy Patients for SARS-CoV-2 in a High-Incidence Region of the United States

PurposeOur purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. Methods and MaterialsBetween April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. ResultsOver a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. ConclusionsBroad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Occupational exposures and risk of nasopharyngeal carcinoma in a high‐risk area: A population‐based case‐control study

The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.

Validation of Differentially Expressed Immune Biomarkers in Latent and Active Tuberculosis by Real-Time PCR.

Tuberculosis (TB) remains a major global threat and diagnosis of active TB ((ATB) both extra-pulmonary (EPTB), pulmonary (PTB)) and latent TB (LTBI) infection remains challenging, particularly in high-burden countries which still rely heavily on conventional methods. Although molecular diagnostic methods are available, e.g., Cepheid GeneXpert, they are not universally available in all high TB burden countries. There is intense focus on immune biomarkers for use in TB diagnosis, which could provide alternative low-cost, rapid diagnostic solutions. In our previous gene expression studies, we identified peripheral blood leukocyte (PBL) mRNA biomarkers in a non-human primate TB aerosol-challenge model. Here, we describe a study to further validate select mRNA biomarkers from this prior study in new cohorts of patients and controls, as a prerequisite for further development. Whole blood mRNA was purified from ATB patients recruited in the UK and India, LTBI and two groups of controls from the UK (i) a low TB incidence region (CNTRLA) and (ii) individuals variably-domiciled in the UK and Asia ((CNTRLB), the latter TB high incidence regions). Seventy-two mRNA biomarker gene targets were analyzed by qPCR using the Roche Lightcycler 480 qPCR platform and data analyzed using GeneSpring™ 14.9 bioinformatics software. Differential expression of fifty-three biomarkers was confirmed between MTB infected, LTBI groups and controls, seventeen of which were significant using analysis of variance (ANOVA): CALCOCO2, CD52, GBP1, GBP2, GBP5, HLA-B, IFIT3, IFITM3, IRF1, LOC400759 (GBP1P1), NCF1C, PF4V1, SAMD9L, S100A11, TAF10, TAPBP, and TRIM25. These were analyzed using receiver operating characteristic (ROC) curve analysis. Single biomarkers and biomarker combinations were further assessed using simple arithmetic algorithms. Minimal combination biomarker panels were delineated for primary diagnosis of ATB (both PTB and EPTB), LTBI and identifying LTBI individuals at high risk of progression which showed good performance characteristics. These were assessed for suitability for progression against the standards for new TB diagnostic tests delineated in the published World Health Organization (WHO) technology product profiles (TPPs).

Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region

Laboratory testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of two pillars: the detection of viral RNA via rt-PCR as the diagnostic gold standard in acute cases, and the detection of antibodies against SARS-CoV-2. However, concerning the latter, questions remain about their diagnostic and prognostic value and it is not clear whether all patients develop detectable antibodies. We examined sera from 347 Spanish COVID-19 patients, collected during the peak of the epidemic outbreak in Spain, for the presence of IgA and IgG antibodies against SARS-CoV-2 and evaluated possible associations with age, sex and disease severity (as measured by duration of hospitalization, kind of respiratory support, treatment in ICU and death). The presence and to some degree the levels of anti-SARS-CoV-2 antibodies depended mainly on the amount of time between onset of symptoms and the collection of serum. A subgroup of patients did not develop antibodies at the time of sample collection. Compared to the patients that did, no differences were found. The presence and level of antibodies was not associated with age, sex, duration of hospitalization, treatment in the ICU or death. The case-fatality rate increased exponentially with older age. Neither the presence, nor the levels of anti-SARS-CoV-2 antibodies served as prognostic markers in our cohort. This is discussed as a possible consequence of the timing of the sample collection. Age is the most important risk factor for an adverse outcome in our cohort. Some patients appear not to develop antibodies within a reasonable time frame. It is unclear, however, why that is, as these patients differ in no respect examined by us from those who developed antibodies.

Incidence and Mortality of Prostate Cancer in Canada during 1992-2010.

In Canada, prostate cancer is the most common reportable malignancy in men. We assessed the temporal trends of prostate cancer to gain insight into the geographic incidence and mortality trends of this disease. Three independent population-based cancer registries were used to retrospectively analyze demographic data on Canadian men diagnosed with prostate cancer and men who died of prostate cancer between the years of 1992 and 2010. The incidence and mortality rates were calculated at the provincial, city, and forward sortation area (FSA) postal code levels by using population counts that were obtained from the Canadian Census of Population. The Canadian average incidence rate was 113.57 cases per 100,000 males. There has been an overall increasing trend in crude prostate cancer incidence between 1992 and 2010 with three peaks, in 1993, 2001, and 2007. However, age-adjusted incidence rates showed no significant increase over time. The national mortality rate was calculated to be 24.13 deaths per 100,000 males per year. A decrease was noted in crude and age-adjusted mortality rates between 1992 and 2010. Several provinces, cities, and FSAs had higher incidence/mortality rates than the national average. Several of the FSA postal codes with the highest incidence/mortality rates were adjacent to one another. Several Canadian regions of high incidence for prostate cancer have been identified through this study and temporal trends are consistent with those reported in the literature. These results will serve as a foundation for future studies that will seek to identify new regional risk factors and etiologic agents.