Asymptomatic Healthy Controls Research Articles

Biomarkers for febrile urinary tract infection in children.

The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

The characteristics, disabilities, and spinal alignment of women with double crush syndrome: a case-control study

Aims Double crush syndrome is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The aims were to investigate the characteristics and disabilities of women with double crush syndrome, to compare the spinal alignment to healthy women, and to determine the cut-offs for the spinal alignment characteristics. Methods Twenty women with double crush syndrome (age: 49.50 ± 8.64 years) and 21 asymptomatic healthy controls (age: 44.76 ± 7.82 years) were included in the study. The physical characteristics, pain intensity, and symptoms were questioned. Disability with Disability of Arm and Shoulder Questionnaire and Neck Disability Index and spinal alignment with Spinal Mouse® (Idiag, Fehraltorf, Switzerland) were assessed. Results The pain intensity at rest, night, and during activity was 3.70 ± 3.25, 6.01 ± 2.77, and 7.15 ± 2.68 cm, respectively. The most bothersome symptom was numbness (65%). The symptoms were seen in hands and/or fingers (55%), arms (15%), shoulder blade (15%), and neck (15%). The Disability of Arm and Shoulder Questionnaire and Neck Disability Index scores were 58.64 ± 15.41 and 19.55 ± 6.37, respectively. The sagittal thoracic curvature (p: .011) and lumbar curvature (p: .049) increased, and the overall spine mobility (p<.001) decreased in the double crush syndrome patients. The cut-off points were detected as 54.5° (area under the curve: 0.680, p: .049, 40% sensitivity, 99.9% specificity) for the thoracic spinal curvature, and 113.5° (area under the curve: 0.667, p<.000, 65% sensitivity, 99.9% specificity) for the overall spine mobility. Conclusions The double crush syndrome patients had moderate to severe pain and disability, increased thoracic and lumbar curvature, and decreased spine mobility. The cut-off values were found as 54.5° for thoracic curvature and 113.5° for spine mobility.

Predicting cardiac disease from interactions of simultaneously-acquired hemodynamic and cardiac signals

Background and ObjectiveCoronary artery disease (CAD) and heart failure are the most common cardiovascular diseases. Non-invasive diagnostic testing for CAD requires radiation, heart rate acceleration, and imaging infrastructure. Early detection of left ventricular dysfunction is critical in heart failure management, the best measure of which is an elevated left ventricular end-diastolic pressure (LVEDP) that can only be measured using invasive cardiac catheterization. There exists a need for non-invasive, safe, and fast diagnostic testing for CAD and elevated LVEDP. This research employs nonlinear dynamics to assess for significant CAD and elevated LVEDP using non-invasively acquired photoplethysmographic (PPG) and three-dimensional orthogonal voltage gradient (OVG) signals. PPG (variations of the blood volume perfusing the tissue) and OVG (mechano-electrical activity of the heart) signals represent the dynamics of the cardiovascular system. MethodsPPG and OVG were simultaneously acquired from two cohorts, (i) symptomatic subjects that underwent invasive cardiac catheterization, the gold standard test (408 CAD positive with stenosis≥ 70% and 186 with LVEDP≥ 20 mmHg) and (ii) asymptomatic healthy controls (676). A set of Poincaré-based synchrony features were developed to characterize the interactions between the OVG and PPG signals. The extracted features were employed to train machine learning models for CAD and LVEDP. Five-fold cross-validation was used and the best model was selected based on the average area under the receiver operating characteristic curve (AUC) across 100 runs, then assessed using a hold-out test set. ResultsThe Elastic Net model developed on the synchrony features can effectively classify CAD positive subjects from healthy controls with an average validation AUC=0.90±0.03 and an AUC= 0.89 on the test set. The developed model for LVEDP can discriminate subjects with elevated LVEDP from healthy controls with an average validation AUC=0.89±0.03 and an AUC=0.89 on the test set. The feature contributions results showed that the selection of a proper registration point for Poincaré analysis is essential for the development of predictive models for different disease targets. ConclusionsNonlinear features from simultaneously-acquired signals used as inputs to machine learning can assess CAD and LVEDP safely and accurately with an easy-to-use, portable device, utilized at the point-of-care without radiation, contrast, or patient preparation.

Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis

ObjectivesAn increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of...

Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1\u2013associated adult T-cell leukemia: a pilot study

BackgroundAdult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease.MethodsSmall-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL.ResultsThe sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients.ConclusionsOur findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

Multiple rapid swallows and rapid drink challenge in patients with esophagogastric junction outflow obstruction on high‐resolution manometry

Esophagogastric junction outflow obstruction (EGJOO) as defined by Chicago Classification of esophageal motility disorders (CCv3.0) encompasses a broad range of diagnoses, thus posing clinical challenges. Our aims were to evaluate multiple rapid swallow (MRS) and rapid drink challenge (RDC) during high-resolution manometry (HRM) to aid identifying clinically relevant EGJOO. Patients with a HRM diagnosis of EGJOO based on CCv3.0 that also completed MRS and RDC during HRM and barium esophagram were retrospectively identified. Radiographic EGJOO (RAD-EGJOO) was defined by either liquid barium retention or delayed passage of a barium tablet on barium esophagram. Thirty healthy asymptomatic controls that completed HRM were also included. MRS involved drinking 2mL for 5 successive swallows. RDC involved rapid drinking of 200mL liquid. Integrated relaxation pressure (IRP) and presence of panesophageal pressurization (PEP) during MRS and RDC were assessed. One hundred one patients, mean (SD) age 56 (16) years, were included; 32% had RAD-EGJOO, 68% did not. RAD-EGJOO patients more frequently had elevated (>12mmHg) upright IRP (100%), MRS-IRP (56%), RDC-IRP (53%), and PEP during RDC (66%) than both controls [17%; 0%; 7%; 3%] and patients without RAD-EGJOO [83%; 35%; 39%; 41%] Having IRP >12mmHg during both MRS and RDC was twice as likely to be associated with RAD-EGJOO (19%) than those without RAD-EGJOO (9%) among patients with upright IRP >12mmHg. Adjunctive HRM maneuvers MRS and RDC appear to help identify clinically significant EGJOO. While future outcome studies are needed, comprehensive multimodal evaluation helps clarify relevance of EGJOO on HRM.

Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma

SummaryTumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74–0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95–0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70–1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

Objective To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. Methods sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP–, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP– (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. Results sNfL levels were increased both in 10 AL/PNP+ patients (p < .001) and in 10 AL/PNP– patients (p < .005) compared to 10 HC/AL individuals. sNfL levels were higher in AL/PNP+ patients than in AL/PNP– patients (p < .005). sNfL levels were also increased in 15 ATTRv/PNP+ patients, compared to both 15 HC/TTRv (p < .0001) and 15 TTRv carriers (p < .0001). ATTRv/PNP+ patients with progressive PNP (PND-score > I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. Conclusion sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis.

Influenza-like illness is associated with high pneumococcal carriage density in Malawian children

High pneumococcal carriage density is a risk factor for invasive pneumococcal disease (IPD) and transmission, but factors that increase pneumococcal carriage density are still unclear. We undertook a cross-sectional study to evaluate the microbial composition, cytokine levels and pneumococcal carriage densities in samples from children presenting with an influenza-like illness (ILI) and asymptomatic healthy controls (HC). The proportion of children harbouring viral organisms (Relative risk (RR) 1.4, p = 0.0222) or ≥ 4 microbes at a time (RR 1.9, p < 0.0001), was higher in ILI patients than HC. ILI patients had higher IL-8 levels in nasal aspirates than HC (median [IQR], 265.7 [0 - 452.3] vs. 0 [0 - 127.3] pg/ml; p = 0.0154). Having an ILI was associated with higher pneumococcal carriage densities compared to HC (RR 4.2, p < 0.0001). These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community.

Response to multiple rapid swallows shows impaired inhibitory pathways in distal esophageal spasm patients with and without concomitant esophagogastric junction outflow obstruction.

Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. The normal response to multiple rapid swallows (MRS) is deglutitive inhibition of the esophageal body during the MRS sequence. Our aim was to compare the response to MRS in DES patients and healthy control subjects. Response to MRS during HRM was evaluated in 19 DES patients (8 with and 11 without concomitant esophagogastric junction outflow obstruction [EGJOO]) and 24 asymptomatic healthy controls. Patients with prior gastroesophageal surgery, peroral endoscopic myotomy, pneumatic dilation, esophageal botulinum toxin injection within 6months of HRM, opioid medication use, and esophageal stricture were excluded. Response to MRS was evaluated for complete versus impaired inhibition (esophageal body contractility with distal contractile integral [DCI] > 100mmHg-sec-cm during MRS), presence of post-MRS contraction augmentation (DCI post MRS greater than single swallow mean DCI), and integrated relaxation pressure (IRP). Impaired deglutitive inhibition during MRS was significantly more frequent in DES compared to controls (89% vs. 0%, P < 0.001), and frequency was similar for DES with versus without concomitant EGJOO (100% vs. 82%, P =0.48). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs. 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3360.0 vs. 1238.9, P = 0.009). IRP was lower during MRS compared to single swallows in all patients, and IRP during MRS was normal in 5 of 8 patients with DES and EGJOO. Our study suggests that impaired deglutitive inhibition during MRS is present in the majority of patients with DES regardless of whether they have concomitant EGJOO, and future studies should explore the usefulness of incorporating response to MRS in the diagnosis of DES.

The relationship between dectin-1 and mast cells in patients with diarrhea-predominant irritable bowel syndrome

Background/Aims: Currently, the role of the microbiome GBA is being widely studied in the pathogenesis of visceral hypersensitivity in IBS. To investigate the role of fungus, the current study aimed to i) investigate the expression of Syk/CARD9-coupled Dectin-1 receptors in the ileocecal mucosa in D-IBS patients and (ii) explore the relationships between Dectin-1 and plasma MCT levels as well as anorectal sensory function in patients with D-IBS.Methods: Thirty-eight D-IBS patients who met the Rome III criteria and 2 groups of age- and sex-matched asymptomatic healthy controls were recruited from March 2015 to January 2017. Anorectal sensory function was quantified by HR-ARM. Plasma MCT titers were identified by ELISA, while the expression of Syk/CARD9 Dectin-1 receptors in ileocecal mucosa was identified by RT-qPCR.Results: (i) The expression of Syk/CARD9-coupled Dectin-1 receptors was significantly higher in D-IBS patients than in controls (p < .001). ii) The threshold values of first sensation and desire to defecate were significantly lower in D-IBS patientsthan in controls (the P value was0.007 and 0.001 respectively). (iii) There were negative correlations between plasma MCT levels and first sensation thresholds in D-IBS patients (r = −0.513, p = .012) and the desire to defecate thresholds (r = −0.423, p = .044). (iiii) There was a positive correlation between plasma MCT titers and the expression of Dectin-1 receptors in D-IBS patients (r = 0.565, p = .005).Conclusions: These results suggested that fungi may partially participate in the genesis of visceral hypersensitivity by activating mast cells, which is mediated by activation of the Dectin-1 receptor-mediated Syk/CARD9 signaling pathway.

Clinical Value of Ultrasonographic Assessment in Lateral Epicondylitis Versus Asymptomatic Healthy Controls

Background: Ultrasonography (US) is often used in the assessment of lateral epicondylitis (LE). The strength of evidence supporting its role is, however, not well-documented. Purpose: To describe and compare the US tendinopathic changes observed in patients with LE and the general population, including any correlation between patient characteristics and US outcomes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Tendon thickness, color Doppler activity, and bone spur were assessed by US in 264 participants with healthy elbows and 60 patients with chronic LE. In addition to patient characteristics, Patient-Rated Tennis Elbow Evaluation (PRTEE) score, pain, and disability were recorded. Results: Depending on the measurement technique used, mean LE tendon thickness increased by 0.53 mm (10.2%) or 0.70 mm (14.5%) as compared with the contralateral arm and 0.40 mm (7.9%) or 0.41 mm (8.5%) as compared with the general population. Mean color Doppler activity (scale, 0-4) was 3.47 in the LE arm versus 0.13 in the contralateral asymptomatic arm and 0.26 in the general population. Bone spur was observed in 78% of the LE arms as opposed to 45% in the contralateral arms and 50% in the general population. In the LE group and the general population, the prevalence of bone spur increases with age. No correlations were observed with pain, disability, PRTEE, and disease duration. Conclusion: Increased common extensor tendon thickness is part of the tendinopathic changes observed in LE. However, given the marked variation in natural tendon thickness and small increases in tendon thickness in patients with LE, this technique cannot be used as a stand-alone diagnostic tool but rather as a supplement to the overall assessment. The contralateral elbow (if asymptomatic) is a better tendon thickness comparator than a general population mean value. Color Doppler activity is an indicator of ongoing tendinopathy and supports the LE diagnosis, but it is not pathognomonic for the condition. Absence of Doppler activity in a patient with suspected LE should raise suspicion of other diagnoses. Identification of a bone spur is of very limited clinical value given the high prevalence in the general population. The important outcomes of pain, disability, PRTEE, and disease duration did not correlate with any of the investigated US techniques.

Clivus length distinguishes between asymptomatic healthy controls and symptomatic adult women with Chiari malformation type I

While the presence of cerebellar tonsillar descent in radiological images has been used as evidence of Chiari malformation type I (CMI), tonsillar ectopia alone is insufficient to identify individuals with symptomatic CMI. This study sought to identify differences in brain morphology between symptomatic CMI and healthy controls in adult females. Two hundred and ten adult females with symptomatic CMI and 90 age- and body mass index-matched asymptomatic female controls were compared using seven brain morphometric measures visible on magnetic resonance images. The CMI and control groups were divided into four subgroups based on the tonsillar position (TP) relative to the foramen magnum: group 1 was made up of healthy controls with normal TP (TP < 0mm); group 2 was comprised of control individuals with low-lying TP (1-5mm); group 3 was comprised of symptomatic CMI patients with low-lying TP (1-5mm); group 4 contained symptomatic CMI patients with severe tonsillar descent (6-13mm). All morphometrics for symptomatic CMI with severe tonsillar descent were significantly different than those for both control groups. The CMI group with low-lying TP was significantly different for four measures when compared to controls with normal TP. However, only clivus length was statistically different between the CMI and healthy control groups with low-lying TP. This study demonstrates that clivus length distinguishes adult female healthy individuals with low-lying tonsils from those with symptomatic CMI. Further investigation is required to understand the importance of a shorter clivus length on CMI symptomatology and pathophysiology.

Evaluation of plantar fasciopathy shear wave elastography: a comparison between patients and healthy subjects.

The aim of this study is to compare elasticity features between patients with plantar fasciitis (PFis) and an asymptomatic healthy control group using shear wave elastography (SWE) and to correlate SWE values with clinical scores. Consecutive patients diagnosed with PFis and asymptomatic subjects were enrolled in the present study. Both groups underwent clinical, ultrasound (US), and SWE evaluation. A plantar fascia thickness > 4mm was considered pathognomonic of PFis. SWE stiffness elasticity (Young's modulus in kPa and shear wave velocity in m/s) was measured 1cm distally from the calcaneal insertion. Correlations with VAS and the 17-Italian Foot Function Index (17-FFI) were determined. A total of 19 patients satisfied the inclusion criteria for the patient group and were enrolled in the study, and 21 healthy subjects were used as a control group. Statistically significant differences were found for shear wave velocity between the patient and the control group, with SWE findings of 3.8 (5.1; 1.5) m/s and 4.7 (4.07; 7.04) m/s, respectively (p = 0.006). Strong positive correlations were found between the SWE findings and both the pain and the functional scale (VAS: p = 0.001; FFI: p = 0.012). SWE allows quantitative assessment of the stiffness of the plantar fascia and can show PFis alterations, increasing the diagnostic performance of B-mode US. In addition, SWE shows a strong correlation with clinical scores, improving patient assessment and follow-up.

Labral tears with axial plane disorders.

Objectives This study aims to determine if there is an axial plane coverage insufficiency in patients with symptomatic labral tears compared to the contralateral asymptomatic side and healthy control subjects.Patients and methods This retrospective study was conducted between December 2017 and January 2019. Thirty patients (21 males, 9 females; mean age 28 years; range, 20 to 36 years) operated due to unilateral symptomatic acetabular labral tears secondary to femoroacetabular impingement were evaluated. Twenty asymptomatic patients (13 males, 7 females; mean age 27±9 years; range, 19 to 36 years) were included in the control group. The relationship between acetabular morphology and labral tear was investigated with the comparison of unilateral symptomatic hips with contralateral asymptomatic hips and the control group by using radiological parameters on plain radiographs and computed tomography.Results When the patient group symptomatic side was compared to the control group, acetabular anteversion angle (A A A) and alpha (a) angle were higher, while posterior acetabular sector angle and horizontal acetabular sector angle were lower. When the asymptomatic side was compared to the control group, AAA was higher in the patient group. There was no difference between the symptomatic and asymptomatic sides in the patient group; the symptomatic side yielded a higher α angle.ConclusionPosterior axial plane coverage deficiency in combination with cam deformity (increased a angle) seems to play a role in the pathogenesis of symptomatic acetabular labral tears, even creating a side-to-side difference in some individuals.

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.

Evaluate the Intestinal Microbiome in Patients With Erosive Gastroesophageal Reflux Disease and in Asymptomatic Healthy Controls

Evaluate the Intestinal Microbiome in Patients With Erosive Gastroesophageal Reflux Disease and in Asymptomatic Healthy Controls

Serum CXCL12/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity.

This study aimed to examine whether stromal cell-derived factor-1 (SDF-1) or C-X-C chemokine ligand 12 (CXCL12) participates in the development of lumbar disc degeneration, as implicated earlier by the level of CXCL12 correlating with this disease. It enrolled 145 patients with symptomatic lumbar intervertebral disc degeneration (IDD) and 130 asymptomatic healthy controls with no indication of IDD. Radiological assessment of the IDD patients was targeted at the lumbar vertebra region, based on Pfirrmann grade. Degeneration of the multifidus and psoas major muscles was evaluated using Goutallier classification. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were obtained for assessing the severity of manifestation. The levels of serum CXCL12, IL-6 and TNF-α were determined by ROC curve analysis, resulting in their prognostic value for Pfirrmann grading. Higher levels of serum CXCL12 were found in patients with IDD than in asymptomatic individuals, and were positively related to the Pfirrmann grade as well as multifidus muscle degeneration. Furthermore, serum CXCL12 concentration showed a significant correlation with the VAS and ODI scores. In addition, elevated serum CXCL12 levels were related to serum levels of TNF-α and IL-6. The ROC curve analysis implicated that CXCL12 could function as a biomarker of the early-mediate phase of IDD development. In summary, the serum CXCL12/SDF-1 level is positively related with lumbar IDD and its clinical severity.

A Snapshot of The Tumor Microenvironment in Colorectal Cancer: The Liquid Biopsy.

The molecular profile of liquid biopsies is emerging as an alternative to tissue biopsies in the clinical management of malignant diseases. In colorectal cancer, significant liquid biopsy-based biomarkers have demonstrated an ability to discriminate between asymptomatic cancer patients and healthy controls. Furthermore, this non-invasive approach appears to provide relevant information regarding the stratification of tumors with different prognoses and the monitoring of treatment responses. This review focuses on the tumor microenvironment components which are detected in blood samples of colorectal cancer patients and might represent potential biomarkers. Exosomes released by tumor and stromal cells play a major role in the modulation of cancer progression in the primary tumor microenvironment and in the formation of an inflammatory pre-metastatic niche. Stromal cells-derived exosomes are involved in driving mechanisms that promote tumor growth, migration, metastasis, and drug resistance, therefore representing substantial signaling mediators in the tumor-stroma interaction. Besides, recent findings of specifically packaged exosome cargo in Cancer-Associated Fibroblasts of colorectal cancer patients identify novel exosomal biomarkers with potential clinical applicability. Furthermore, additional different signals emitted from the tumor microenvironment and also detectable in the blood, such as soluble factors and non-tumoral circulating cells, arise as novel promising biomarkers for cancer diagnosis, prognosis, and treatment response prediction. The therapeutic potential of these factors is still limited, and studies are in their infancy. However, innovative strategies aiming at the inhibition of tumor progression by systemic exosome depletion, exosome-mediated circulating tumor cell capturing, and exosome-drug delivery systems are currently being studied and may provide considerable advantages in the near future.

2185. Group A Streptococcus (GAS) Detection by PCR in Children with Viral Acute Respiratory Illness and Healthy Children

BackgroundAcute pharyngitis is mostly of viral etiology; GAS, the leading bacterial cause, comprises 20%–30% of pediatric pharyngitis. Patients with pharyngitis and additional acute respiratory illness (ARI) symptoms more suggestive of viral etiology, including cough, rhinorrhea and conjunctivitis, are not recommended for GAS testing. The use of highly sensitive GAS PCR assays in patients with sore throat and viral ARI symptoms may detect GAS colonization and lead to antibiotic overuse. We evaluated GAS PCR in viral ARI inpatients and asymptomatic healthy controls (HC) to illustrate the potential negative impact of offering GAS PCR test in poorly selected patients.MethodsIn November 2015–June 2016, 458 ARI inpatients (< 18 years) and 205 HC (< 5 years, no ARI symptoms within 72 hours) in Kansas City were enrolled in the New Vaccine Surveillance Network study. Mid-turbinate and throat swabs were tested by multiplex respiratory panel PCR and leftover nucleic acid extracts were further tested by real-time GAS PCR. Presenting symptoms of cough, rhinorrhea and/or conjunctivitis, plus sore throat were assessed by parent interview.ResultsOverall, 6.3% of HC < 5 years old and 8.7% of ARI subjects < 18 years were GAS (+); mostly in the 3–15 year old age group (25/40, 62.5%). Among 3–15 year old GAS (+) ARI subjects, 92.8% had cough, 76.2% rhinorrhea and 37.2% conjunctivitis; 80% had > 2 of 3 symptoms noted above. Among 40 GAS (+) ARI subjects, a virus was co-detected in 34 (85%), among which Rhinovirus/Enterovirus were predominant 22/34 (55%). Of the 130 (28%) ARI subjects with sore throat, more tested positive for viruses (107/130, 82.3%) than for GAS (9/130, 6.9%). All GAS (+) HC (13/205, 6.3% overall) were < 3 year olds.ConclusionPCR detected GAS in 6.3% HC < 5 years old and 8.7% ARI subjects < 18 years old; mostly in 3- to 15-year-old ARI subjects. Most GAS (+) ARI children had cough, rhinorrhea or conjunctivitis and/or virus co-detection suggesting GAS carriage. Our data demonstrate that GAS may be detected in patients with a low clinical suspicion for acute GAS pharyngitis. These findings highlight the need to review patient selection and exercise caution in implementing highly sensitive GAS PCR assays especially in such clinical settings. Disclosures All authors: No reported disclosures.