Positive Test Group Research Articles

Clinical and metagenomic predicted antimicrobial resistance in pediatric critically ill patients with infectious diseases in a single center of Zhejiang

BackgroundAntimicrobial resistance (AMR) poses a significant threat to pediatric health; therefore, precise identification of pathogens as well as AMR is imperative. This study aimed at comprehending antibiotic resistance patterns among critically ill children with infectious diseases admitted to pediatric intensive care unit (PICU) and to clarify the impact of drug-resistant bacteria on the prognosis of children.MethodsThis study retrospectively collected clinical data, identified pathogens and AMR from 113 children’s who performed metagenomic next-generation sequencing for pathogen and antibiotic resistance genes identification, and compared the clinical characteristic difference and prognostic effects between children with and without AMR detected.ResultsBased on the presence or absence of AMR test results, the 113 patients were divided into Antimicrobial resistance test positive group (AMRT+, n = 44) and Antimicrobial resistance test negative group (AMRT-, n = 69). Immunocompromised patients (50% vs. 28.99%, P = 0.0242) and patients with underlying diseases (70.45% vs. 40.58%, P = 0.0019) were more likely to develop resistance to antibiotics. Children in the AMRT + group showed significantly increased C-reaction protein, score of pediatric sequential organ failure assessment and pediatric risk of mortality of children and longer hospital stay and ICU stay in the AMRT + group compared to the AMRT+- group (P < 0.05). Detection rate of Gram-negative bacteria was significantly higher in the AMRT + group rather than Gram-positive bacteria (n = 45 vs. 31), in contrast to the AMRT- group (n = 10 vs. 36). Cephalosporins, β-lactams/β-Lactamase inhibitors, carbapenems and sulfonamides emerged as the most common types of drug resistance in children. Resistance rates to these antibiotics exhibited considerable variation across common pathogens, including Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.ConclusionsThe development of drug resistance in bacteria will significantly affect the prognosis of patients. The significant differences in drug resistance of common pathogenic bacteria indicate that identification of drug resistance is important for the rational use of antibiotics and patient prognosis.

Utility of Supine Stress Test to Anticipate Spinal Anaesthesia Induced Hypotension in Patients Undergoing Elective Cesarean Section

INTRODUCTION Reduction in venous return caused by compression of the inferior vena cava by the gravid uterus, known as the supine hypotensive syndrome of pregnancy, is one of the reasons for particular susceptibility to hypotension at cesarean delivery. The hypotensive effect of spinal anaesthesia further exacerbates maternal hypotension in the supine position in term parturients. This study was conducted with the objective to evaluate the ability of supine stress test to predict spinal anaesthesia induced hypotension in patients undergoing elective cesarean section. MATERIAL AND METHODS A prospective observational study was done among 232 singleton parturients scheduled for elective cesarean delivery under spinal anaesthesia in Universal College of Medical Sciences Teaching Hospital. Patients were subjected preoperatively to supine stress test and divided into two group of 116 patients each. SBP, DBP, MAP, HR were compared between two groups. Descriptive as well as inferential statistics were used to analyze the data. RESULTS Supine stress test was positive by heart rate criteria in 50% of positive patient. The incidence of hypotension in positive test group was 73.3%, while it was 11.2% in negative test group, which was statistically significant (p&lt;0.001). CONCLUSION This study demonstrates supine stress test preferably can easily identify parturients in risk of developing hypotension during cesarean section under spinal anaesthesia.

Risk factors for colorectal cancer in a fecal immunochemical test-positive group: The National Health Insurance Service-National Health Screening Cohort.

Colorectal cancer (CRC) was the fourth most common cancer in Republic of Korea in 2019. It has a gradually increasing mortality rate, indicating the importance of screening for CRC. Among the various CRC screening test, fecal immunochemical test (FIT) is a simple yet most commonly used. Neverthelss, there have been only few long-term studies on subjects with FIT-positive. Therefore, in this study, we aimed to investigate the risk factors for CRC in FIT-positive patients using the National Health Insurance Service Bigdata database. Among 1737633 individuals with a FIT screening result for CRC in 2009, 101143 (5.82%) were confirmed to be FIT positive. The CRC incidence over 10years (up to 2018) of these participants was investigated using the National Cancer Registry. Out of the 101143 FIT-positive participants, 4395 (4.35%) were diagnosed with CRC. The FIT-positive patients who underwent a second round of screening showed a 5-year cumulative CRC incidence of approximately 1.25%, whereas those who did not showed an incidence of approximately 3.75%. Among the FIT-positive patients, the CRC incidence in the non-compliance group for the second round of screening was 2.8 times higher than that in the compliance group. In FIT-positive participants, non-compliance with the second round of screening was identified as a major risk factor for CRC development. It is necessary to establish appropriate strategies for managing risk factors for CRC in FIT-positive patients to increase the rate of compliance with the second round of CRC screening.

The importance of mean platelet volume lymphocyte ratio and mean platelet volume platelet ratio in COVID-19 patients

Objective: The mean platelet volume lymphocyte ratio (MPVLR) and mean platelet volume platelet ratio (MPVPR) reflect inflammation more effectively and strongly than MPV, lymphocyte, platelet, and neutrophil counts separately, we aimed to evaluate the importance of MPVLR and MPVPR in COVID-19 patients. Material and Methods: Patients with COVID-19 were divided into two groups based on whether their RT-PCR test resulted in a positive or negative result. MPVLR, MPVPR, neutrophil, lymphocyte, platelet, MPV and RDW levels were compared between these two groups. In addition, the changes in MPVLR, MPVPR, neutrophil, lymphocyte, platelet, MPV, and RDW levels before and after treatment were compared in the whole patient population. Results: There were 113 patients diagnosed with COVID-19 with a positive PCR test and 79 patients with a negative PCR test. Before treatment, the MPVLR level was 7.2±0.85 in the PCR test positive group and 5.4±0.29 in the PCR test negative group (p=0.04). Post-treatment MPVLR levels were 5.7±0.4 and 4.9±0.26 in the PCR positive and negative groups, respectively (p=0.09). The MPVPR level before treatment was 0.046±0.002 in the PCR test positive group and 0.035±0.001 in the PCR test negative group (p=0.003). After treatment, the MPVPR level was 0.040±0.002 in the PCR-positive group and 0.032±0.001 in the PCR-negative group (p=0.023) Conclusion: This study is the first to demonstrate high MPVLR and MPVPR in PCR-positive COVID-19 patients. Patients with negative PCR test and high MPVLR and MPVPR should be evaluated with radiological and clinical symptoms.

Mechanism of Action of Clove and Ginger Herbal Formulation-Mediated TiO2 Nanoparticles Against Lactobacillus Species: An In Vitro Study

Introduction: With its numerous practical applications, the usage of nanotechnology in the medical profession has been a godsend in our modern technological era. Titanium dioxide (TiO2) is a semiconducting metal oxide with superior inherent qualities which can be utilized in various applications across various fields. Taking into account all of the above information, the current study focused on the mechanism of action of TiO2 nanoparticles mediated by clove and ginger herbal formulations against Lactobacillus species. Materials and Methods: Extract of clove and ginger herbal formulation-mediated TiO2 nanoparticles was obtained with acetone in the ratio of 10:1, yielding 9 mg/mL. After overnight incubation and further serial dilutions, the solution was introduced into microplate wells with cultured Lactobacillus species for 4 hours. A 5% of test solution was added into Kimble tubes containing Muller-Hinton broth along with the plant extract, followed by recording of minimum inhibitory concentrations at certain time intervals. The number of samples used for each concentration was 4 using the convenience method. The grouping sample was 3, i.e. test group, antibiotic and positive control group. The results were statistically analysed following one-way analysis of variances using SPSS software version 22. Result: Optical density determines the degree of scattering of light that is produced by a bacterium within a culture plate. The more the bacteria, the more the light is scattered. The results ( P &lt; .005) show that as the concentration increases, the value of optical density decreases which proves that there occurs a bactericidal process that results in the reduced bacterial count. Conclusion: The results of this study suggest that TiO2 nanoparticles enhanced with clove and ginger might be used as an antibacterial agent against Lactobacillus species.

Determination of the frequency of influenza-A and B antigens in swab samples in differentiating the diagnosis of influenza infection from other causes of upper respiratory tract infection

Aim: The present study aimed to determine the frequency of influenza-A and B antigens in swab samples and to examine their potential changes at the time of initial diagnosis in differentiating the diagnosis of influenza infection from other causes of upper respiratory tract infection by physical examination and vital clinical signs in the emergency room.Material and Method: This retrospective cross-sectional descriptive research analyzed 113 patients with Influenza-A (n:8) and B (n:15) over the age of 18 who applied to the emergency department in the last three years, were diagnosed with acute upper respiratory tract and underwent nasopharyngeal swab sampling were included in the study. The data of the patients were accessed digitally from the University hospital database.Results: The headache score was higher, while there was no difference between vital clinical signs and those with positive or negative swab tests (p&amp;gt;0.05). White blood cells in blood count parameters were lower in the Influenza test-positive group (p&amp;lt;0.0001), platelet distribution width (p=0.006), and monocyte counts (p=0.008) were significantly higher in Influenza positive patients than negative ones. The influenza swab test was not positive in any patient with tonsillar crypt (p&amp;gt;0.05).Conclusion: Influenza infections should be examined in detail in terms of costs to both public health and social security institutions, considering the burdens of diagnosis and treatment.

P437 Diagnostic utility of serum beta D glucan test to prescribe antifungal treatment and its effect on patient's outcome: a study from a tertiary care center in Western India

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMSerum Beta D glucan has 75%-80% sensitivity and 80% specificity to make a diagnosis of invasive candidiasis.ObjectivesThis study was designed to understand real-world diagnostic utility of S. Beta D Glucan (BDG) on antifungal prescription patterns associated patient outcomes.MethodsStudy design: Retrospective cohort studyStudy Population: All consecutive patients who underwent BDG (fungitell assay) testing with conclusive (positive or negative) results in the intensive care unit (ICU) setting between January 1, 2021 to December 31, 2021 at a tertiary care center in western India.Statistical Methods: We assessed the difference in continuous variables across compared groups using the independent samples t-test and binary logistic regression for categorical variables. We summarize the summary results as odds ratio and 95% confidence intervals. All P-values are 2-sided and set at 5% for all comparisons. All data analyses were performed using IBM SPSS ver 28.ResultsA total of 4481 patients were admitted in the ICU, of which 198 patients underwent BDG testing. Of the 198, 113 tested positive and 61 negative and formed the denominator for the study. Patients with intermediate BDG [24 (12.1%)] were excluded from the analysis. The mean (SD) age for the study cohort was 57.5 (14.7) years with 30.8% female. All the patients were receiving broad-spectrum antibiotics at the time of BDG collection. A total of 24 study patients had a positive blood culture (23 bacterial isolates and 1 Candida parapsilosis). The groups, positive and negative test results for BDG, were comparable for ventilator usage (P = .737), vasopressor prescription (P = .270), history of surgery (P = .791) central line placement (P = .403), liver disease (P = .144), CKD (P = .424), COVID-19 positivity (P = .238), WBC count (P = .137), CRP (P = .769), and serum procalcitonin (P = .784). Patients with ischemic heart diseases (IHD) (P = .013) and acute kidney injury requiring hemodialysis (AKI/HD) (P = .017) were significantly higher in the test positive group. Test negative group patients received early BDG testing, mean (SD) stay of 3.33 (3.77) days as compared to 5.61 for test positive (6.59) days P = .004). More test-positive patients received antifungal therapy (P <.0001), while 20.4% didn't receive antifungals. Caspofungin (25.9%), fluconazole (18.4%), anidulafungin (7.5%), voriconazole (6.9%), and combination antifungal were used in 10.9% of study patients. Logistic regression model showed no difference in mortality between the two groups (P = .413) with higher Odds of mortality in test-positive patients (1.357, 95% CI 0.705- 2.609). Treatment with caspofungin was associated with higher Odds of mortality (3.497; 95% CI 1.324–9.239, P = .012) as compared with fluconazole. Similar trend was observed with anidulafungin (OR: 4.089 95% CI 1.052-15.888, P = .042) as compared to fluconazole. This significance remained for caspofungin [OR 3.607 (1.262 -10.311) P = .017] while anidulafungin [OR: 3.934 (0.965-16.032) P = .56] didn't show significance with the multivariate model.ConclusionProbable invasive candidiasis as diagnosed with positive BDG test doesn't increase the risk of mortality. Patients treated with fluconazole were associated with better survival as compared with caspofungin.

Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents

The postacute sequelae of SARS-CoV-2 infection (PASC) has emerged as a long-term complication in adults, but current understanding of the clinical presentation of PASC in children is limited. To identify diagnosed symptoms, diagnosed health conditions, and medications associated with PASC in children. This retrospective cohort study used electronic health records from 9 US children's hospitals for individuals younger than 21 years who underwent antigen or reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 between March 1, 2020, and October 31, 2021, and had at least 1 encounter in the 3 years before testing. SARS-CoV-2 positivity by viral test (antigen or RT-PCR). Syndromic (symptoms), systemic (conditions), and medication PASC features were identified in the 28 to 179 days following the initial test date. Adjusted hazard ratios (aHRs) were obtained for 151 clinically predicted PASC features by contrasting viral test-positive groups with viral test-negative groups using proportional hazards models, adjusting for site, age, sex, testing location, race and ethnicity, and time period of cohort entrance. The incidence proportion for any syndromic, systemic, or medication PASC feature was estimated in the 2 groups to obtain a burden of PASC estimate. Among 659 286 children in the study sample, 348 091 (52.8%) were male, and the mean (SD) age was 8.1 (5.7) years. A total of 59 893 (9.1%) tested positive by viral test for SARS-CoV-2, and 599 393 (90.9%) tested negative. Most were tested in outpatient testing facility settings (322 813 [50.3%]) or office settings (162 138 [24.6%]). The most common syndromic, systemic, and medication features were loss of taste or smell (aHR, 1.96; 95% CI, 1.16-3.32), myocarditis (aHR, 3.10; 95% CI, 1.94-4.96), and cough and cold preparations (aHR, 1.52; 95% CI, 1.18-1.96), respectively. The incidence of at least 1 systemic, syndromic, or medication feature of PASC was 41.9% (95% CI, 41.4-42.4) among viral test-positive children vs 38.2% (95% CI, 38.1-38.4) among viral test-negative children, with an incidence proportion difference of 3.7% (95% CI, 3.2-4.2). A higher strength of association for PASC was identified in those cared for in the intensive care unit during the acute illness phase, children younger than 5 years, and individuals with complex chronic conditions. In this large-scale, exploratory study, the burden of pediatric PASC that presented to health systems was low. Myocarditis was the most commonly diagnosed PASC-associated condition. Acute illness severity, young age, and comorbid complex chronic disease increased the risk of PASC.

Evaluation of methacholine challenge test results in patients with chronic unexplained cough

Introduction: Asthma is one of the most common chronic diseases in adults characterized by variable airway obstruction. Asthma is diagnosed with wheezing and shortness of breath, however it sometimes manifests as a chronic cough that is difficult to diagnose and requires spirometry stimulation tests. Objectives: This study aimed to investigate the relationship between methacholine test results and respiratory symptoms in patients with chronic unexplained cough. Patients and Methods: In this cross-sectional study, 102 patients with chronic cough and normal basal spirometry were included. All patients underwent a methacholine challenge test, and their airway irritabilities were assessed. Then, the relationship between methacholine test results and clinical symptoms and also demographic characteristics were investigated. Results: Of 102 patients, 69 (67.6 %) and 33 (32.4%) were female and male, respectively. Most of patients were non-smoker (90.2%). Around 25 (24.5%) patients had a positive methacholine test. Rhinitis had a statistically significant difference between patients with positive and negative tests (positive test group: 48%, negative test group: 23.4%; P = 0.01). Postnasal discharge was reported in 60% of positive methacholine test patients, which was significant compared to the negative group (36.4%; P = 0.03). Most patients who had positive tests were housewives (76%). Logistic regression showed that female gender (OR: 7.75, 95% CI: 1.7-35.2), postnasal discharge (OR: 3.19, 95% CI: 1.25-8.2), rhinitis (OR: 3.02, 95% CI: 1.17-7.79), and allergy symptoms OR: 3.51, 95% CI: 1.35-9.18) were directly associated with a positive methacholine test. Conclusion: The presence of airway hypersensitivity, postnasal discharge, allergic rhinitis, female gender and the housewife’s job were strongly associated with a positive methacholine test.

Gut Microbiota Signatures in Tumor, Para-Cancerous, Normal Mucosa, and Feces in Colorectal Cancer Patients

Background: Association studies have linked microbiome alterations with colorectal cancer (CRC). However, differences in tumor, para-cancerous, normal mucosal, and fecal microbiota remain to be strengthened. Methods: We performed a study on the ecologically rich and taxonomically diverse of gut microbiota using three types of colorectal mucosa (tumor mucosa, para-cancerous mucosa, normal mucosa) and feces from 98 CRC patients. Additionally, we profiled the microbiota in the fecal occult blood test (FOBT) positive and negative groups at different sampling sites. Results: We found striking variations between tumor mucosal microbiota and normal mucosal microbiota. However, there was no significant difference between tumor and para-cancerous mucosal microbiota, as well as between para-cancerous and normal mucosal microbiota, revealing that the para-cancerous mucosal microbiota was a transitional state between the tumor and normal mucosal microbiota. And the substantial shifts in the fecal microbiota compared to mucosal microbiota indicated the risk of using fecal microbiota to define mucosal microbiota. A strong correlation between FOBT positive and Fusobacterium was discovered, indicating this adherent-invasive genus was closely related to intestinal bleeding. Furthermore, we identified six key genera, including Fusobacterium, Gemella, Campylobacter, Peptostreptococcus, Alloprevotella, and Parvimonas, which appear to be consistently over-represented in tumor mucosa compared to normal mucosa and/or in mucosa compared to feces. Conclusion: Compositional alterations in the microbiota existed in three types of colorectal mucosa and feces in CRC patients. Six key genera may contribute to the topographic variances in the microbiota of tumor-bearing colorectum.

Platelet Count and IgE Level in Chronic Idiopathic Urticaria: A Case-control Study.

Chronic Urticaria is an allergic disorder that affects about 0.5 to 5% of the population in different communities. The disease's chronic course and long-term onset impose high economic and psychological costs on communities, adversely affecting individual and social life. Platelets play a role in various pathophysiological processes, including inflammation and immunology. Growing evidence suggests that platelets are actively involved in the pathogenesis of various inflammatory disorders, including inflammatory skin diseases. This study investigated the relationship between platelet and immunoglobulin-E markers and chronic idiopathic urticaria. In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements. 100 patients and 100 healthy persons were evaluated in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001). The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

Relationship between white matter lesions and theresponse of cerebral spinal fluid tap test and clinical features in the patients with idiopathic normal pressure hydrocephalus

Objective: To explore the relationship between white matter lesions and clinical features and response of cerebral spinal fluid (CSF) tap test in patients with idiopathic normal pressure hydrocephalus(iNPH). Methods: Possible iNPH patients were enrolled from outpatients and inpatients in Peking Union Medical College Hospital between 2014 and 2019. All patients underwent detailed neuropsychological and walking assessments, CSF tap test, as well as head magnetic resonance imaging. The Fazekas score of white matter lesions, the fractional anisotropy (FA)and mean diffusivity (MD) values of regions of interest by means ofdiffusion tensor imaging (DTI) were compared between CSF tap test positive and negative response groups. The correlation between DTI parameters and clinical characteristics was analyzed. Results: Forty-three patients (29 male and 14 female, age range: 52-79 years] wererecruited.Compared with the negative group, patients in the positive group tended to have higher Fazekas score of periventricular white matter(U=108.00, P=0.03), higher MD value of the region near anterior horn of left lateral ventricles[(1.14±0.27)×10-9mm2/s vs (0.85±0.08) ×10-9mm2/s, P=0.003], lower FA value of the region near anterior horn of the right lateral ventricles[(0.20±0.07)vs(0.27±0.09), P=0.058], and higher MD value near the posterior horn of right lateral ventricle [(1.17±0.34)×10-9mm2/s vs (0.95±0.01)×10-9mm2/s, P=0.003]. FA and MD were significantly correlated with motor function, cognitive and functional scores, and iNPH grading scale (iNPHGS) scores(all P<0.05). Conclusions: The white matter lesions might be one of the pathogeneses of lNPH and apathological changewhich can be reversed by CSF drainage. More white matter lesions should not be the contraindication of CSF drainage surgery.

Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study

SummaryBackgroundWe describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11–17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status.MethodsIn this national cohort study, adolescents aged 11–17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192).Findings23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4–31·7) for the test-positive group and 19·3% (17·7–21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35–1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15–17 years than those aged 11–14 years, and in those with lower pretest physical and mental health.InterpretationAdolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.FundingUK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation.

Risk for Colorectal Cancer in Patients with Serially Positive Fecal Immunochemistry Test in an Annual Screening Program.

Objectives: There are patients who do not undergo colonoscopy even if the fecal immunochemistry test (FIT) results are positive and even with repeated positive test results the following year. We aimed to investigate colorectal cancer (CRC) risk in examinees with positive FIT results in our annual screening program. Methods: We analyzed patients who underwent initial colonoscopy from April 2010 to March 2017 because of positive FIT results using an endoscopy database in our hospital. We investigated the difference in the risk of advanced colorectal neoplasia as a surrogate marker of CRC between those who had an initial positive test and those who had repeated positive tests. Results: A total of 748 patients were included in this analysis. The advanced neoplasia detection rates were 7.6% (50/656) and 18.5% (17/92) for the initial and repeated positive test groups, respectively. Subgroup analysis of those with repeated positive tests revealed that the detection rates in examinees with positive tests 1-2 and >2 years ago were 16.7% (6/36) and 19.6% (11/56), respectively. The odds ratios for advanced neoplasia detection in patients with positive tests 1-2 and >2 years ago compared with those in the initial positive test group were 2.72 (95% confidence interval [CI], 1.04-7.10) and 3.09 (95% CI, 1.47-6.48), respectively. Conclusions: The risk of CRC appears more than doubled in patients with a repeated positive FIT result. Prompt colonoscopy is recommended for FIT-positive cases.

Nine year experience of the Northern Ireland Inherited Cardiac Conditions Service (NI ICC of slow vs. rapid ajmaline infusion protocols for the diagnosis of Brugada syndrome (BrS)

Abstract Background BrS is diagnosed in patients with ST-segment elevation with type1 morphology ≥2mm in one or more leads among the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (ie. ajmaline, flecainide, procainamide or pilsicainide). The specific protocol for Ajmaline provocation testing for diagnosis of BrS has been debated between ICC services worldwide. Concerns regarding safety and false positive rates are perceived to be associated with a more rapid infusion protocol. This retrospective observational cohort study describes the safety and positivity rates for patients undergoing ajmaline provocation challenge by both protocols over nine years. Method Consecutive adults undergoing ajmaline challenge test from Mach 2011 to Feb 2020 were retrospectively collected. Data on patient demographics, indication for testing, genetic information, adverse events and positivity rates were compared by test protocol used. Slow protocol was defined as total dose of 1mg/kg ajmaline capped at 100mg given at rate of 10mg/min over 10 minutes. Rapid protocol was defined as 1mg/kg ajmaline capped at 100mg given over 5 minutes. Results A total of 350 ajmaline challenges were included (275 (73%) slow vs. 75 (27%) rapid protocol) [Mean age 40±15 years; 53% male]. Indication for conducting the test was a) Family history of Brugada syndrome 164 (43%) b) Family history of SADS/SUD 103 (28%), c) OOHCA 22 (6%) d) abnormal ECG 39 (11%) and e) syncope 22 (6%). Among the positive test group, average time for test positivity is 5.92 minutes and average dose was 55mgs (p&amp;lt;0.05). There were no differences between positivity rate between the two protocols, group A vs. group B, p=0.45, ns. Comparison between all patients with positive vs. negative results regardless of the protocol, showed no statistical differences. Predominantly male in both groups (p=0.71, ns) and mean age of patients in their 40's (p=0.93, ns). There is a trend that positive patients likely to have family history of BrS p=0.08, ns). 2 patients had experience jaundice at later stage which resolved. Conclusion In NI ICC service to date, we have performed 350 Ajmaline test over the last nine years. Our positivity rate was 21% (75/350). We did not identify any significant evidence of ventricular dysrhythmia (0) or QRS broadening (2) that resulting in early termination of the protocol. Abnormal ECG with absence of symptoms yields low. Therefore we will continue fast protocol in our service for efficiency in our unit. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Belfast Health and Social Care TrustCormac Felowship

Immunogenicity of a new enhanced tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine against Bordetella pertussis in a murine model

BackgroundThe necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the vaccine, GC3111, produced previously in 2010 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, immunogenicity and efficacy of the enhanced Tdap vaccine compared and evaluated with two Tdap vaccines, GC3111 vaccine produced in 2010 previously and commercially available Tdap vaccine in a murine model.MethodsTwo tests groups and positive control group of Balb/c mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 9 week using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The enhanced GC3111 generated similar humoral response compare to the commercial vaccine for filamentous hemagglutinin (FHA). The interferon gamma (IFN-γ) (Th1), interleukin 5 (IL-5) (Th2) and interleukin 17 (IL-17) (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens (hBp + antigen). A bacterial challenge test was performed 4 weeks after booster vaccination.ResultsRegarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between two test groups and positive control group. All the vaccinated groups indicated a Th1 or Th1/Th2 response. On Day 5 post-bacterial challenge, B. pertussis colonies were absent in the lungs in two test groups and positive control group.ConclusionsOur results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.

Which skin prick test wheal size detects true allergy to Salsola kali?

Background. Sensitization to Salsola kali (Sk) weed pollen allergen is the most common cause of seasonal allergic rhinitis (SAR) in Middle East countries. Aim. To identify Salsola kali skin prick test (SkSPT) wheal size cut-off, able to determine true allergy among adult patients with moderate to severe SAR, who are in need of Salsola kali allergen specific immunotherapy (SkAIT). Methods. In 151 adults with moderate to severe SAR, mean age 32.79 ± 10.79 years, of both gender (females: 43.05%), with a positive SkSPT, (i.e., cut off wheal longest diameter of 3 mm) and one or more other local weed pollens, Salsola kali nasal provocation test (SkNPT) was carried out. Response was assessed both subjectively, with scores, and objectively, by measuring peak nasal inspiratory flow (PNIF). Safety profile of SkNPT was assessed using peak expiratory flow rate (PEF) measurements. Results. SkNPT positive response was found in 125 patients (82.78%). Mean skin prick test (SPT) wheal size to Sk was bigger in the nasal provocatin test (NPT) positive group (9 mm) compared to the NPT negative patients (5 mm), p less than 0.0001. ROC analysis showed that a SPT wheal size to Sk at the threshold of > 7.5 mm enabled identification of SkNPT positivity with a sensitivity of 73.6% and specificity of 100.0% (area under the curve 0.9498, standard error 0.01808; 95% confidence interval (CI): 0.9144 to 0.9853; p less than 0.0001). Conclusions. SPT wheal size of 3 mm might overestimate the presence of real allergy to Sk in a desert environment. A SPT wheal size > 7.5 mm for Sk appears to distinguish individuals who develop disease from those who does not. Physicians should select the proper SPT wheal size value as an appropriate criterion according to the allergen than using a uniform cut off value in patients eligible for SkAIT.

P1. Efficacy of a calcium phosphate collagen matrix bone graft with needle-shaped submicron surface topography in a rabbit posterolateral lumbar spine fusion model

<h3>BACKGROUND CONTEXT</h3> Synthetic bone grafts are a promising alternative for the treatment of degenerative spine conditions and are available without the added drawbacks associated autografts including limited availability and donor-site morbidity. Of these synthetic materials, calcium phosphate (CaP) with a characteristic needle-shaped submicron surface topography (BCP<µm) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine [1,2]. Previous in vitro and ex-vivo data presented by van Dijk LA [3] and Yuan H [4] at NASS, 2020 demonstrated that these specific surface characteristics drive a favorable response from the innate immune system. <h3>PURPOSE</h3> This study was to evaluate the efficacy of a novel synthetic bone graft using a clinically-relevant "Boden" rabbit posterolateral spine fusion model. The synthetic bone graft comprised of CaP granules with a needle-shaped submicron surface structure (BCP<µm) embedded in a highly porous and fibrillar bovine type I collagen matrix (col-BCP<µm). The fibrillar collagen was introduced as a carrier, designed to facilitate admixing of the graft with biological fluids perioperatively and to minimize graft migration postoperatively. <h3>STUDY DESIGN/SETTING</h3> The novel synthetic bone graft was first mixed in a 1:1 volume ratio with autologous bone (ABG). Subsequently, grafts were implanted in the rabbit posterolateral spine environment for 3 days, 6, 9 and 12 weeks. An autologous bone graft group was used as a positive control in this study. Outcomes for the test article were additionally compared to historical data for the same material (BCP<µm) implanted alone, without the fibrillar collagen carrier. <h3>OUTCOME MEASURES</h3> Spinal fusion was determined by manual palpation (MP), X-ray and µCT imaging (based on the Lenke scale), mechanical testing (range of motion testing at 12 weeks only) and histology (decalcified and undecalcified). <h3>METHODS</h3> Forty skeletally mature New Zealand white rabbits were divided into two groups and underwent single-level bilateral posterolateral intertransverse process spine arthrodesis at L4-5. Animals were euthanized after 3 days, 6, 9 and 12 weeks. <h3>RESULTS</h3> Based on all endpoints, the test group and positive control group showed an equivalent and gradual progression in bone formation and implant resorption over time, leading to mature fusion masses at 12 weeks. No adverse reactions were observed in any of the groups. Bilateral fusion rates by MP were consistent with the literature (0-40% at 6 weeks; 60-70% at 12 weeks) and similar trends were seen by histological and radiographic assessment (both X-ray and µCT). Flexion-extension and lateral bending results at 12 weeks demonstrated fusion of the treated level consistent with the MP results. The results observed for the test group were consistent with those seen historically for the same material implanted without the fibrillar collagen carrier. <h3>CONCLUSIONS</h3> These results show that BCP with needle-shaped submicron-scale surface topography (BCP<µm) combined with a fibrillar collagen matrix (col-BCP<µm) could achieve equivalent fusion rates to ABG when used as a bone graft extender in a clinically relevant single level rabbit intertransverse process posterolateral lumbar fusion model. Over time, a progression in bone healing, graft resorption and remodeling were seen with all experimental endpoints, with equivalency between the groups. The results for col-BCP<µm were consistent with those previously seen for BCP<µm alone, confirming that the fibrillar collagen carrier improved handling properties but was not detrimental to the bone-forming capacity of the BCP<µm. <h3>FDA DEVICE/DRUG STATUS</h3> Col-BCP<µm (Investigational/Not approved)

The Relationship between Pre-Pandemic Interferon Gamma Release Assay Test Results and COVID-19 Infection: Potential Prognostic Value of Indeterminate IFN-γ Release Assay Results

Objective To reveal the relationship between interferon-gamma release assay (IGRA) test (Standard ETB-Feron ELISA (TBF)) results performed within 12 months before the COVID-19 pandemic and the frequency of COVID-19 infections and the severity of COVID-19. Methods The retrospective TBF test results and contact information of 684 patients aged over 18 years who underwent TBF testing between March 11th, 2019, and March 10th, 2020, were obtained. Of the 684 patients contacted by phone, 365 agreed to participate in the study and were enrolled. The patients were divided into three groups (TBF test positive, negative, and indeterminate). The data obtained from the questionnaire were compared statistically. Results According to the TBF test results, positive (n = 51, 14%), negative (n = 286, 78.3%), and indeterminate (n = 28, 7.7%) groups were compared. The frequency of COVID-19 infections in the indeterminate group was found significantly higher than that in the positive and negative groups (p=0.005). When the group with COVID-19 (n = 46, 12.6%) was compared with the group without (n = 319, 87.4%), no difference was found in terms of age, sex, body mass index, smoking history and number of cigarettes smoked, TB history, diabetes mellitus, hypertension, coronary artery disease, and biologic and corticosteroid therapy use. Only the frequency of obstructive pulmonary disease was significantly higher in the group without COVID-19 (p=0.033). Conclusion The frequency of COVID-19 infection was increased in patients with indeterminate TBF test results. Indeterminate TBF test results may be a guide in terms of risk stratification in groups at risk for COVID-19.

Discriminatory Value of Self-reported Olfactory Dysfunction in the Prediction of Coronavirus Disease 2019.

Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.