Highest Annual Incidence Research Articles

Aplastic Anemia in Thailand: Incidence and Treatment Outcome from a Prospective Nationwide Population-Based Study

Background: Incidence of Aplastic Anemia (AA) in Asia tends to be higher than in western countries, but contemporary real-world incidence and outcomes of AA in Asia remain limited. This study aimed to explore the incidence across the country regions and to evaluate the patient outcomes according to age, the severity of disease, and treatment modalities. Method: This is a prospective multicenter nationwide population-based observational study of patients with AA aged over 15 years old, diagnosed between August 1st, 2014 to July 31st, 2016, with a longitudinal follow-up period over 2 years, from 30 medical centers. Patients with suspected hypocellular MDS and congenital bone marrow failure syndrome were excluded. Results: During the study period of 2 years, there were 348 newly diagnosed patients with aplastic anemia, giving the annual incidence of 4.6 per million inhabitants. There was a higher annual incidence of severe (SAA) and very severe aplastic anemia (VSAA) (3.8 per million) than non-severe aplastic anemia (NSAA) (0.8 per million). The incidence was greater among older patients with a peak incidence in patients aged 60-89 years old. (Figure 1) There was a high variation in the geographic incidences across country regions, ranging from 2.6 to 6.6 per million per year. (Figure 2) The 2-year overall survival (OS) for NSAA, SAA, and VSAA were 65.5%, 49.3%, and 20.1%, respectively (P < 0.001). Patients aged older than 60 years had the worst OS (42.6% as compared with 47.7% for the age 41-60 years and 64.5% for the age 15-40 years, P = 0.002). Among patients with SAA and VSAA (n = 280), the overall response rate (ORR) among patients treated with rabbit anti-thymocyte globulin and/or cyclosporin A (rATG±CsA) was significantly superior than those treated with CsA-based therapy and those treated with anabolic steroid (44.4% vs. 36.4% and 31.2%, respectively, P < 0.001). Among evaluable patients, ORR after the 1st treatment with rATG±CsA at 3, 6, 12 and 24 months were 23.9%, 43.8%, 68.4% and 89.2%, respectively. The 2-year OS among SAA/VSAA patients treated with rATG±CsA, CsA-based therapy, and anabolic steroid were 54.8%, 54.5%, and 37.6% (P = 0.037), respectively (Figure 3). From multivariate analysis, age > 60 years (HR 1.63, 95%CI, 1.14-2.33, P = 0.007), VSAA (HR 2.24, 95% CI, 1.45-3.46, P < 0.001) and not receiving immunosuppressive therapy or anabolic steroid (HR 4.96, 95%CI, 2.88-8.54, P <0.001), were independently associated with inferior OS among patients with SAA/VSAA. Conclusion: The incidence rate of AA in Thailand from this contemporary nationwide population-based study is high, especially in the elderly. Patients treated with rATG±CsA had superior survival than those receiving anabolic steroid. The real-world outcome of patients with SAA/VSAA, especially in those aged over 60 years, is substantially poor. Figure 1 Disclosures No relevant conflicts of interest to declare.

Abstract 4105: Co-existing ESR1 D538G mutation and ESR1-CCDC170 fusion in a patient with metastatic hormone receptor positive breast cancer with progression after hormonal therapy

Abstract Breast cancer has a high annual incidence among females in India, with an age adjusted rate of 25.8 cases per 100,000 women and a mortality rate of 12.7 per 100,000 women1. Approximately 75% of breast cancers are estrogen receptor positive (ER+), and unfortunately, a significant number will develop resistance to first line hormonal therapy. Although several mechanisms have been linked to hormonal therapy resistance, no biomarker in clinical use currently exists to predict hormonal therapy resistance in a reliable manner. Comprehensive genomic profiling (CGP) is not routinely performed for metastatic breast carcinoma (MBC) in a relapsed setting in India. This research highlights utility of CGP on a MBC sample combined with interpretation by Watson™ for Genomics (WfG), an artificial-intelligence (AI)-based decision-support system (DSS), when a patient in a middle-income country developed resistance to endocrine therapy. A 33-year-old Indian female was diagnosed with ER+, progesterone-receptor-negative (PR-), human-epidermal-receptor-2-negative (HER2-) breast cancer. Two years later, she noted an axillary mass which was biopsied and revealed an ER+, PR-, HER2- MBC metastasis. CGP was performed with a panel from Illumina designed to detect genomic alterations in 170 genes, including 148 genes for substitutions and indels, 55 genes for fusion and splice variants, and 59 genes for copy number variation detection. Variant annotation and interpretation performed using WfG revealed co-existing ESR1 D538G mutation and ESR1-CCDC170 fusion. In addition, alterations in CCND1 resulting in activation of the CDK signaling pathway, an oncogenic mutation in MTOR resulting in activation of the MTOR/PI3K signaling pathway, and amplification of FGFR1, a poor prognostic factor in MBC, were also identified. While ESR1 D538 and ESR1-CCDC170 fusion individually have been reported to confer resistance to endocrine therapy, to the best of our knowledge, our report is the first HR+ MBC case with these two oncogenic alterations co-occurring in a metastatic tumor suggesting a synergistic role. CGP in this patient revealed a possible mechanism of resistance to endocrine therapy informing the physician to change treatment to a generic mTOR inhibitor based on the oncogenic MTOR mutation. In conclusion, assessment of DNA/RNA tumor variants in one assay along with a robust AI-based DSS can provide relevant information for consideration by the clinician when developing a treatment plan, may create efficiencies in tumor sample usage, time, and cost of treatment. Further research is needed to explore the functional synergy of the oncogenic ESR1 mutation and fusion detected in this patient's tumor and the role of identifying these pathogenic variants through circulating tumor cell or cell-free DNA assays to detect minimal residual disease. Citation Format: Ravindra Kolhe, Ashis Mondal, Nikhil Sahajpal, Meenakshi Ahluwalia, Yull Arriaga, Allan Njau, David Brotman, Jane Snowdon, Gretchen Jackson, Dilhan Weeraratne. Co-existing ESR1 D538G mutation and ESR1-CCDC170 fusion in a patient with metastatic hormone receptor positive breast cancer with progression after hormonal therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4105.

Spatio-temporal clustering of hepatitis A in Gansu provice, 2004-2018

Objective: To understand the characteristics of spatiotemporal clustering on hepatitis A in Gansu province and to provide evidence for hepatitis A prevention and control. Methods: Data related to hepatitis A were retrieved from National Notifiable Disease Report System, ArcGIS 10.3 and SaTScan 9.1 in Gansu province from 2004 to 2018. Results: The annual average report incidence rate of hepatitis A was 10.91/100 000, showing a descending trend with no periodic or seasonal features. After the implementation of national expanded immunization program, high annual incidence rates had been seen in Linxia Hui autonomous prefecture and Gannan Tibetan autonomous prefecture. From 2004 to 2012, the lowest RR value appeared in the 0-9 age group (P=0.000) while the highest RR value was in the over 60 age group during 2013-2018 except for the age 0-9 group in 2015. The annual average incidence rate was increasing from south to north and west to east, across the territory. Results from the temporal scanning program revealed that the incidence of hepatitis A was temporally aggregated from 2004 to 2018. For spatio-temporal scanning of 2004-2008, data showed one most likely cluster area (radius: 91.95 km, Time frame: 2004-2005), apparel mainly in Linxia and Longnan cities. Results from the spatio-temporal scanning program of 2009-2018 also showed that the most likely cluster areas (radius: 183.26 km, Time frame: 2009-2012) were in Gannan, Linxia, Dingxi and Longnan areas. Conclusions: The reported incidence rates of hepatitis A were declining, without significant periodic or seasonal pattern in Gansu province from 2004 to 2018. In the 0-9 years-old group, the incidence rate showed the lowest, while the highest was in the 60 year-olds group. Spatio-temporal clustering of hepatitis A was observed in Gansu province from 2004 to 2018. Strategies on prevention and control of the disease should be targeted in the southwest regions of the province.

Hepatitis víricas: virus de la hepatitis A, B y E

Viral hepatitises are an important worldwide health challenge, with high annual prevalence and incidence rates. Diagnosis and management require necessarily to know its clinical features. The most common and with higher morbidity and mortality, in its chronic infections (causing liver cirrhosis and hepatocarcinoma), is hepatitis B. In recent years its incidence has decreased thanks to vaccination. In last years, in developed countries outbreaks of Hepatitis A have been detected; hence differential diagnosis requires taking it into account. Usually, clinical course is benign and self-limited. In last decade, epidemiology of hepatitis E has undergone a change. Although hepatitis E has been always considered an infection in developing countries, recently it has been identified as common zoonosis in Europe and other countries.

Human myiasis in Ecuador.

We review epidemiological and clinical data on human myiasis from Ecuador, based on data from the Ministry of Public Health (MPH) and a review of the available literature for clinical cases. The larvae of four flies, Dermatobia hominis, Cochliomyia hominivorax, Sarcophaga haemorrhoidalis, and Lucilia eximia, were identified as the causative agents in 39 reported clinical cases. The obligate D. hominis, causing furuncular lesions, caused 17 (43.5%) cases distributed along the tropical Pacific coast and the Amazon regions. The facultative C. hominivorax was identified in 15 (38%) clinical cases, infesting wound and cavitary lesions including orbital, nasal, aural and vaginal, and occurred in both subtropical and Andean regions. C. hominivorax was also identified in a nosocomial hospital-acquired wound. Single infestations were reported for S. haemorrhoidalis and L. eximia. Of the 39 clinical cases, 8 (21%) occurred in tourists. Ivermectin, when it became available, was used to treat furuncular, wound, and cavitary lesions successfully. MPH data for 2013–2015 registered 2,187 cases of which 54% were reported in men; 46% occurred in the tropical Pacific coast, 30% in the temperate Andes, 24% in the tropical Amazon, and 0.2% in the Galapagos Islands. The highest annual incidence was reported in the Amazon (23 cases/100,000 population), followed by Coast (5.1/100,000) and Andes (4.7/100,000). Human myiasis is a neglected and understudied ectoparasitic infestation, being endemic in both temperate and tropical regions of Ecuador. Improved education and awareness among populations living in, visitors to, and health personnel working in high-risk regions, is required for improved epidemiological surveillance, prevention, and correct diagnosis and treatment.

RETRAIT : Seroprevalence of cystic echinococcosis in the provinces of Ifrane and El Hajeb in Morocco

Abstract Objectives Cystic echinococcosis (CE) is a cosmopolitan zoonosis caused by Echinococcus granulosus. The highest annual incidence in humans in Morocco is recorded in the provinces of Ifrane and El Hajeb. Hospital statistics underestimate the prevalence of this infection because a proportion of cases is not recorded on official registers and does not reach medical care. We aimed to estimate the actual prevalence of abdominal hydatidosis in these provinces of the Middle Atlas of Morocco. Materials and methods We performed a cross-sectional descriptive study of prevalence between September 2013 and February 2015 in the two towns of Timahdite and Ain Leuh in the province of Ifrane and the towns of Bouderbala and Sebt Jahjouh in the province of El Hajeb. This was a mass screening survey of liver hydatid cysts coupled with serological diagnosis. Results A total of 5367 participants underwent abdominal ultrasound, and 102 were selected. CE prevalence was 1.9%; 69 patients were screened in the province of Ifrane and 33 in the province of El Hajeb. The M/F sex ratio was 0.52 and the mean age was 39.6 ± 18 years. Conclusion Our results indicated a high prevalence and continuous transmission of hydatidosis in the provinces of Ifrane and El Hajeb of the Middle Atlas in Morocco. Mass screening campaigns are useful for evaluating the baseline prevalence, evolution of transmission, and risk factors for hydatidosis in endemic areas.

Incidence in Ph-Negative Myeloproliferative Neoplasms in Armenia from 2005 to 2019

Introduction: Enhancements of laboratory diagnostics and the emergence of new therapies had a significant impact on the incidence, prevalence and survival of patients with myeloproliferative neoplasms (MPN). Published epidemiology data are scarce, and multiple sources are needed to assess the disease burden. The aim of our work was to identify the patterns and trends of incidence, prevalence and survival of patients with MPN in the Republic of Armenia (RA) for the period 2005-2019. Methods: The data from Hematology Center blood diseases register, Oncological Center cancer register, as well as the data from death registration were the basis of our research. Demographic data were obtained from National Statistical Office of RA. Results: Analysis of the data obtained has shown that during the reporting period the average annual incidence of MPN was 1.84 per 100.000 inhabitants, including 2.1 for males and 1.64 for females. Analysis of incidence rates of MPN in relation to sex and age in the period under study revealed high rates in patients in groups 65 - 74 (8.3) and 55 - 64 (5.12 per 100 thousand years), respectively. According to the data obtained in the group of patients with MPN, the high annual average incidence rates are noted in primary myelofibrosis (PMF) (1.09 in 2018) and polycythemia vera (PV) (0.89 in 2016), the lowest for essential thrombocythemia (ET) (0.7 in 2016) per 100.000 population, respectively. In comparing our data to those obtained for 1966-1971 and 1998-2004 periods, one may detect a statistically significant increase in the total incidence of PMF and PV (p < 0.001). Conclusions: Analysis of the incidence rate in MPNs adjusted for age and gender shown the prevalence in group 65 - 74 (8.3) and in group 55 - 64 (5.13) per 100,000 inhabitants. The peak of incidence rate for both males and females was the age 65 - 74 and the male female incidence ratio in this age group was 11.3:6.2. The increasing incidence rate in MPNs in Armenia depends on the improvement of laboratory diagnosis. Thrombotic complications are observed in patients with an MPN in 45.3% of cases. In most cases, thrombosis is the first clinical symptom of an MPN, which determines the need for the introduction into clinical practice of molecular genetic testing methods among patients with thrombosis, an increase in blood levels, splenomegaly for the early diagnosis of clonal hematopoiesis and the use of a targeted drug.

A Comparison of Biannual Two-Phase Low-Dose Liver CT and US for HCC Surveillance in a Group at High Risk of HCC Development

Background and Aims: Biannual ultrasonography (US) is a current recommendation for hepatocellular carcinoma (HCC) surveillance in a high-risk group. The sensitivity of US, however, has been low in patients with a high risk of developing HCC. We aimed to compare sensitivity for HCC of biannual US and two-phase low-dose computed tomography (LDCT) in patients with a high risk of HCC. Methods: In this prospective single-arm study, participants with an annual risk of HCC greater than 5% (based on a risk index of ≥2.33) and who did not have a history of HCC were enrolled from November 2014 to July 2016. Participants underwent paired biannual US and two-phase LDCT 1–3 times. Two-phase LDCT included arterial and 3-min delayed phases. The sensitivity, specificity, and positive predictive value of HCC detection using US and two-phase LDCT were compared using a composite algorithm as a standard of reference. Results: Of the 139 enrolled participants, 137 underwent both the biannual US and two-phase LDCT at least once and had follow-up images. Among them, 27 cases of HCC (mean size: 14 ± 4 mm) developed in 24 participants over 1.5 years. Two-phase LDCT showed a significantly higher sensitivity (83.3% [20/24] vs. 29.2% [7/24], p < 0.001) and specificity (95.6% [108/113] vs. 87.7% [99/113], p =0.03) than US. A false-positive result was reported in 14 participants at US and 5 participants at two-phase LDCT, resulting in a significantly higher positive predictive value of two-phase LDCT (33.3% [7/21] vs. 80% [20/25], p < 0.001). Conclusions: Patients with a risk index ≥2.33 showed a high annual incidence of HCC development in our study, and two-phase LDCT showed significantly higher sensitivity and specificity for HCC detection than US.

Early Pediatric Fractures in a Universally Insured Population within the United States

BackgroundMusculoskeletal injury, including fracture, is one of the most common causes of morbidity in pediatric patients. The purpose of this epidemiologic study is to determine the prevalence and risk factors for fracture in a large cohort of pediatric patients under the age of 5.ResultsOf the 233,869 patients included in the study, 13,698 fractures were identified in 10,889 patients. The highest annual incidence was in the 4 year old age group with a rate of 24.2 fractures per 1000 children. The annual incidence within all age groups was 11.7 fractures per 1000 children. The two most common fractures were forearm and humerus fractures. Fracture incidence was increased in male children, patients who live outside the US, and in Caucasian patients. An increase in rate of fracture was also identified in children of officers when compared with children of enlisted service members. There were 35 abuse related fractures in our cohort, with 19 of them occurring in children less than 1 year old. Only three children in our cohort had Osteogenesis Imperfecta.ConclusionFractures are common injuries in young children with an incidence over the first 5 years of life of 5.86%. Multiple risk factors were also identified including age, race, geographic location and socioeconomic status. The results of this study are an important contribution to epidemiologic and public health literature and serve to characterize the incidence of and risk factors for sustaining an early childhood fracture.

COCAINE-INDUCED THROMBOTIC STORM

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cocaine is associated with a wide array of complications through a number of different mechanisms. Although majority of cocaine related morbidity has been attributed to complications in arterial vasculature, the deleterious impact of venous complications appears to be largely unrepresented in current literature as well as clinical practice despite emerging evidence of the high prevalence and annual incidence of DVT in illicit drug users CASE PRESENTATION: 27-year-old previously healthy male presented to the ED with new onset difficulty speaking and facial droop hours after using cocaine. He was afebrile with vitals 98.5 °F, BP 142/97, HR 94 and RR 16. Examination was remarkable for expressive aphasia and right facial droop with no other focal neurological finding. CT scan of head showed thrombosed left MCA with infarct in left frontal lobe and basal ganglia. Labs were significant for a troponin of 14 md/dl and CK-MB 34. CBC and metabolic panel were unremarkable. Urine toxicology was positive for cocaine and opiates. EKG showed T wave inversion with ST depression in V1-V4 II and aVF. CTA of chest revealed bilateral segmental and subsegmental PE without any acute pulmonary disease. CTA of head and neck showed complete abrupt occlusion of proximal left internal carotid artery with distal reconstitution at the segment M1 of MCA and an intraluminal thrombus in the M1 segment. A doppler of lower extremities revealed deep venous thrombosis in left peroneal and posterior tibial veins. An ECHO failed to reveal an intracardiac shunt precluding the possibility of paradoxical thrombosis. He was continued on heparin for 10 days before being switched to Xarelto. He experienced improvement in word finding ability and is currently in rehab. Hypercoagulability work-up including prothrombin gene mutation, factor V Leiden deficiency, APLA and anti-thrombin deficiency was negative. DISCUSSION: This case illustrates an uncharacteristic presentation of cocaine-related widespread thrombotic cascade involving both arterial and venous circulations causing significant morbidity. The complex pathophysiology of widespread prothrombotic state caused by cocaine includes endothelial damage promoting increase of fibrinogen and Von Willebrand factor to platelet aggregation and clot formation. It is important to identify the impact cocaine induced venous thrombosis can mount, especially in the form of potentially fatal complications like pulmonary embolism. CONCLUSIONS: Although recent studies have focused on increased incidence and prevalence of venous thrombosis in setting of cocaine abuse, ours is the first case of documented pulmonary embolism caused by cocaine related venous thrombosis. Further studies are needed to identify patients at higher risk for this complication like rare thrombotic disorders Reference #1: 1. Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013. Reference #2: Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality (formerly the Office of Applied Studies). The DAWN Report: Highlights of the 2009 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. Rockville, MD, December 28, 2010. Reference #3: . Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Drug Abuse Warning Network: Detailed Tables: National Estimates, Drug-Related Emergency Department Visits for 2004–2009. Rockville, MD, December 28, 2010. DISCLOSURES: no disclosure on file for Erika Cappelluti; No relevant relationships by Manish Kumar, source=Web Response No relevant relationships by Alain Rizkallah, source=Web Response No relevant relationships by Nihar Shah, source=Web Response No relevant relationships by Toishi Sharma, source=Web Response

Abstracts of Oral Presentations

Introduction: Snakebite envenoming affects 4.5-5.4 million people and kills 81,000-138,000 victims yearly according to the World Health Orga- nization (WHO), but estimates are extrapolations, and community-based country-wide studies are very scarce. Aim: To measure the impact of snakebite on human and animal health (incidence, mortality, disability) and livelihoods in Cameroon and Nepal. Methods: This epidemiological study is part of the SNAKE-BYTE project that aims at understanding the impact of snakebite in Cameroon and Nepal through one-health, health economy, and epidemiology using digital epidemiology and geo-health tools (Kobo-collect®, Stata® qGIS®, Guru-Maps®, AccesMod®). Based on minimal expected snakebite inci- dence of 100/100,000/year, 0.05% confidence limit, design effect of 2.0, 99% confidence level, 15% non-response margin, sample size was 61,000 people per country, i.e. 11,700 households in Cameroon and 13,800 in Nepal (respectively 5.2 and 4.4 persons per household). Households were preselected from satellite images, among 500 (2x250) randomly prese- lected administrative areas, where six mobile survey teams conducted the e-questionnaires. After ethical approval by Cameroonian, Nepalese, and Swiss authorities, surveys started in November 2018. Results: Interim data analysis on 5045 households in Cameroon and 10,163 in Nepal, showed respectively 120 victims per 29,537 persons- year and 141 victims per 46,888 persons-year. National snakebite inci- dence rates per 100,000 persons-year translate to 406.3 (95%CI: 338.3, 484.0) or 65,008 victims in rural Cameroon (population 16 million), and 300.7 (95%CI: 254.1, 353.5) or 39,993 victims in Nepal’s Terai lowlands (population 13.3 million). Victims were young adults (median 30/31y), often farmers, predominantly males in Cameroon (54.5%) and females in Nepal (66.4%), and 22.5% were children <15y. Snakes were seen by victims in 66%-71.2% cases, indoors or outdoors. Snakebite case-fatality ratios were high: 5.8% (n=7/120) in Cameroon, and 6.6% (n=9/141) in Nepal. About 10% received some injections, likely antivenom. Only 46.0% and 50.4% were taken to medical facilities. Multivariate analysis will model “hotspots” including demographic, clinical, ecological and socio- economic variables, and animals lost. Conclusion: This first country-wide community-based study shows very high annual snakebite incidence and mortality in rural Cameroon and Nepal. It should help health authorities to estimate antivenom needs by geographical area.

Epidemiological Study of Cutaneous Leishmaniasis in Neyshabur County, East of Iran (2011-2017).

BACKGROUND:Cutaneous Leishmaniasis (CL) isn’t a lethal disease, but it has always been taken into consideration due to more involvement of patients with skin ulcers and its long-term treatment. Various factors can play an intervening role in increasing the rate of disease. The present study aimed to evaluate the prevalence and associated factors of disease from 2011-2017 and provide appropriate control strategies for reducing its incidence in Neyshabur county.METHODS:All patients with CL, who had medical records in the health centres of Neyshabur from 2011 to 2017, were examined for conducting this cross-sectional analytical study. Data were analyzed by descriptive statistics and chi-square test at a 0.05 using Statistical Package for the Social Sciences (SPSS V.22).RESULTS:Findings indicated that the highest annual incidence was in 2016 (229 patients), and the least incidence was in 2014 (100 patients). The majority of patients were under 10 years of age and 51.7% of patients were male. About 59.5% of patients were living in cities and 35% of them were living in North of Neyshabur city. Hands were the most affected part of the body (56.0%) followed by trunk (1.3%). Most patients (69.9%) were treated with topical regimens.CONCLUSION:This study showed that CL was hypo-endemic in Neyshabur. Also, the disease was more prevalent in urban areas. Therefore, appropriate health measures to improve environmental conditions, public health educations, and the public awareness of the positive impact of early diagnosis of disease in the success of treatment (especially for inhabitance suburbanite) are essential.

Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA-derived circular RNA.

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types, with a high annual incidence. Although chemotherapy contributes to suppressing OSCC tumorigenesis, the available treatments result in poor prognosis because of local recurrence and regional lymph node metastasis. Thus, it is necessary to discover novel and safe drugs with greater effectiveness and fewer side effects. Fucoidan is a component of the cell wall of brown seaweed that has been shown to produce a wide range of biological activities. The present study aimed to investigate the effectiveness of fucoidan in treating OSCC. In in vitro studies, we found that fucoidan inhibited OSCC growth and suppressed migration and invasion of OSCC cells. In addition, the potential interaction between fucoidan and filamin A (FLNA)-derived circular RNA (circFLNA) was predicted using bioinformatics databases and then confirmed in OSCC samples and cell lines. Indeed, fucoidan increased the expression of circFLNA in OSCC cell lines. Furthermore, both fucoidan and circFLNA could mediate the expression of key proteins related to cell growth, apoptosis, migration, and invasion. In conclusion, our research demonstrated that fucoidan might be considered as a potential natural drug in the treatment of OSCC patients by targeting circFLNA.

Spatiotemporal epidemiology, environmental correlates, and demography of malaria in Tak Province, Thailand (2012\u20132015)

BackgroundTak Province, at the Thai–Myanmar border, is one of three high malaria incidence areas in Thailand. This study aimed to describe and identify possible factors driving the spatiotemporal trends of disease incidence from 2012 to 2015.MethodsClimate variables and forest cover were correlated with malaria incidence using Pearson’s r. Statistically significant clusters of high (hot spots) and low (cold spots) annual parasite incidence per 1000 population (API) were identified using Getis-Ord Gi* statistic.ResultsThe total number of confirmed cases declined by 76% from 2012 to 2015 (Plasmodium falciparum by 81%, Plasmodium vivax by 73%). Incidence was highly seasonal with two main annual peaks. Most cases were male (62.75%), ≥ 15 years (56.07%), and of Myanmar (56.64%) or Thai (39.25%) nationality. Median temperature (1- and 2-month lags), average temperature (1- and 2-month lags) and average relative humidity (2- and 3-month lags) correlated positively with monthly total, P. falciparum and P. vivax API. Total rainfall in the same month correlated with API for total cases and P. vivax but not P. falciparum. At sub-district level, percentage forest cover had a low positive correlation with P. falciparum, P. vivax, and total API in most years. There was a decrease in API in most sub-districts for both P. falciparum and P. vivax. Sub-districts with the highest API were in the Tha Song Yang and Umphang Districts along the Thai–Myanmar border. Annual hot spots were mostly in the extreme north and south of the province.ConclusionsThere has been a large decline in reported clinical malaria from 2012 to 2015 in Tak Province. API was correlated with monthly climate and annual forest cover but these did not account for the trends over time. Ongoing elimination interventions on one or both sides of the border are more likely to have been the cause but it was not possible to assess this due to a lack of suitable data. Two main hot spot areas were identified that could be targeted for intensified elimination activities.

Dry eye disease ranking among common reasons for seeking eye care in a large US claims database.

ObjectivesDry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care.MethodsIn this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003–2015) and annual incidence (2008–2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions.ResultsIn 2003–2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%).ConclusionThis study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment.

Prevalence, characteristics, and predictors of tuberculosis associated anemia.

Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. It is one of the deadliest disease and a major burden on the healthcare system in India. India, a second most populous country in the world, has a very high global annual incidence of tuberculosis. Multiple hematological changes have been reported in patients with tuberculosis such as iron deficiency anemia, folate deficiency, and sideroblastic anemia.Aims and Objectives:The present study was planned to find the prevalence and characteristics of anemia in the new cases of pulmonary tuberculosis. The secondary objective was to assess the predictors of anemia in new cases of pulmonary tuberculosis.Methods:The retrospective study was carried out at a tertiary care hospital of Uttarakhand and included all the new cases of tuberculosis aged more than 18 years attending medicine outpatient and inpatient departments over a period of 1 year. Detailed demographic, clinical, and biochemical data were obtained from the hospital record section and tabulated.Results:Most patients with tuberculosis and anemia were more than 50 years of age. Clearly, males outnumbered females. Approximately, 80% patients were illiterates. A majority (71, 39.2%) of the patients had BMI within the range of 18.5 to 24.9 kg/m2. The most common symptoms of tubercular patients with and without anemia were cough, fever, breathlessness, and hemoptysis. However, pallor was the most common sign. Clearly, hematological indices were lower in patients with anemia. In total, 112 (60%) patients had mild anemia and 103 (56.9%) patients had normocytic normochromic anemia. Significant association was found between Body Mass Index (BMI) and anemia in patients with pulmonary tuberculosis. Similarly, severity of anemia co-related significantly with BMI of patients with pulmonary tuberculosis. BMI showed a significant correlation with hemoglobin, packed cell volume, mean corpuscular cell volume, and red cell distribution width (RDW). In addition, age showed a significant correlation with hemoglobin and RDW.Conclusion:Normocytic normochromic anemia is a common hematological abnormality in patients with pulmonary tuberculosis. Thus, it warrants frequent screening for anemia in all the cases of pulmonary tuberculosis to improve morbidity and mortality in these patients.

Screening-level microbial risk assessment of acute gastrointestinal illness attributable to wastewater treatment systems in Nunavut, Canada

Most arctic communities use primary wastewater treatment systems that are capable of only low levels of pathogen removal. Effluent potentially containing fecally derived microorganisms is released into wetlands and marine waters that may simultaneously serve as recreation or food harvesting locations for local populations. The purpose of this study is to provide the first estimates of acute gastrointestinal illness (AGI) attributable to wastewater treatment systems in Arctic Canada. A screening-level, point estimate quantitative microbial risk assessment model was developed to evaluate worst-case scenarios across an array of exposure pathways in five case study locations. A high annual AGI incidence rate of 5.0 cases per person is estimated in Pangnirtung, where a mechanical treatment plant discharges directly to marine waters, with all cases occurring during low tide conditions. The probability of AGI per person per single exposure during this period ranges between 1.0 × 10−1 (shore recreation) and 6.0 × 10−1 (shellfish consumption). A moderate incidence rate of 1.2 episodes of AGI per person is estimated in Naujaat, where a treatment system consisting of a pond and tundra wetland is used, with the majority of cases occurring during spring. The pathway with the highest individual probability of AGI per single exposure event is wetland travel at 6.0 × 10−1. All other risk probabilities per single exposure are <1.0 × 10−1. The AGI incidence rates estimated for the other three case study locations are <0.1. These findings suggest that wastewater treatment sites may be contributing to elevated rates of AGI in some arctic Canadian communities. Absolute risk values, however, should be weighed with caution based on the exploratory nature of this study design. These results can be used to inform future risk assessment and epidemiological research as well as support public health and sanitation decisions in the region.

SIS-ECM Laden with GMSC-Derived Exosomes Promote Taste Bud Regeneration

Oral cancer has a high annual incidence rate all over the world, and the tongue is the most frequently affected anatomic structure. The current standard care is ablative surgery of malignant neoplasm, followed by tongue reconstruction with free flap. However, such reconstructive modalities with postsurgery radiotherapy or chemotherapy can hardly support the functional recovery of the tongue—particularly, functional taste bud regeneration—in reconstructed areas, thus seriously affecting patients’ prognosis and life quality. Using a critical-sized tongue defect model in rats, we show that combinatory transplantation of small intestinal submucosa–extracellular matrix (SIS-ECM) with gingival mesenchymal stem cells (GMSCs) or their derivative exosomes promoted tongue lingual papillae recovery and taste bud regeneration as evidenced by increased expression of CK14, CK8, and markers for type I, II, and III taste bud cells (NTPdase 2, PLC-β2, and AADC, respectively). In addition, our results indicate that GMSCs or their derivative exosomes could increase BDNF expression, a growth factor that plays an important role in the proliferation and differentiation of epithelial basal progenitor cells into taste bud cells. Meanwhile, we showed an elevated expression level of Shh—which is essential for development, homeostasis, and maintenance of the taste bud organ—in wounded areas of the tongue among animals treated with GMSC/SIS-ECM or exosome/SIS-ECM as compared with SIS-ECM control. Moreover, our data show that GMSCs or their derivative exosomes promoted innervation of regenerated taste buds, as evidenced by elevated expressions of neurofilament and P2X3 at the injury areas. Together, our findings indicate that GMSC/SIS-ECM and exosome/SIS-ECM constructs can facilitate taste bud regeneration and reinnervation with promising potential application in postsurgery tongue reconstruction of patients with tongue cancer.

Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis

More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients' inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5-95.4), 80.3% (95% CI 76.9-83.9), and 3.2% (95% CI 1.6-4.8) respectively. This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening.

Molecular detection of Leishmania infantum DNA and host blood meal identification in Phlebotomus in a hypoendemic focus of human leishmaniasis in northern Algeria.

BackgroundLeishmania parasites are transmitted by female phlebotomine sand flies that maintain the enzootic cycle by circulating between sylvatic and domestic mammals. Humans are part of this cycle as accidental hosts due to the vector’s search for a source of blood. In Algeria, Human Leishmaniases (HL) are endemic and represent a serious public health problem because of their high annual incidence and their spread across the country. The aim of this study is to identify sand fly species fauna (vectors of Leishmania), determine their infection rate and identify their feeding preferences using molecular tools in a hypoendemic focus of HL located in the province of Tipaza, northern Algeria.Methodology/Principal findingsAn entomological survey using CDC light traps was conducted between July and October of 2015 in four HL affected peri-urban locations in the province of Tipaza, northern Algeria. Sand flies were identified using the morphological criteria of the genitalia for the males and spermathecae for the females. Leishmania DNA was detected in pooled female sand flies (N = 81 pools with 8–10 specimens per pool) using quantitative real-time polymerase chain reaction (qPCR) targeting two different genes: kDNA-PCR and 18S rRNA. To identify their blood meal sources, blood-fed female sand flies were analyzed by PCR-sequencing targeting the vertebrate cytochrome c oxidase I (COI) gene. A total of 4,045 sand flies were caught, of which 3,727 specimens were morphologically identified. Seven species were recorded: P. (L.) perniciosus (50.28%), P. (L.) perfiliewi (26.13%), P. (L.) longicuspis (21.92%), Sergentomyia (S.) minuta (0.85%), P. (P.) papatasi (0.42%), P. (L.) langeroni (0.32%) and P. (L.) ariasi (0.05%). Afterwards, 740 female specimens were randomly selected and divided into 81 pools and were then screened to investigate the presence of Leishmania spp. L. infantum DNA was detected in three pools, corresponding to three sand fly specimens (one each). The infection rate was 0.33% (2/600) for P. (L.) perniciosus and 2.56% (1/39) for P. (L.) perfiliewi. Analysis of the blood feeding sources (N = 88 specimens) revealed that sand flies belonging to Larroussius subgenera, mainly (71.5%) feed on small ruminants. Human blood is the second feeding source (17%), eight specimens (9%) were found to feed on equines and no domestic reservoir (dog) blood was found.Conclusions/SignificanceThe presence of human leishmaniasis cases, the high abundance of Phlebotomus (Larroussius) species which are proven or suspected vectors of L. infantum, and the detection of L. infantum DNA from its natural vectors (P. (L.) perniciosus, P. (L.) perfiliewi), in addition to the blood-feeding of positive females for L. infantum on humans blood, prove that the major elements of the epidemiological transmission cycle of L. infantum are present and indicate risk factors for an outbreak of the disease in the province of Tipaza.