scholarly journals Dynamic Changes of Th1 Cytokines and the Clinical Significance of the IFN-γ/TNF-α Ratio in Acute Brucellosis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Guang Xu ◽  
Peng Zhang ◽  
Rongjing Dang ◽  
Yanfang Jiang ◽  
Feng Wang ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Clinical Decision Making ◽  
Clinical Symptoms ◽  
Clinical Decision ◽  
Serum Levels ◽  
Post Treatment ◽  
Clinical Severity ◽  
Th1 Cells ◽  
Dynamic Changes ◽  
Necrosis Factor Alpha

Background. T-helper type 1 (Th1) cells and Th1-produced cytokines play essential roles in the immune response to foreign pathogens, such as Brucella spp. The aim of this study was to evaluate the dynamic changes of Th1 cells and Th1-produced cytokines in patients with acute brucellosis and their impact on clinical decision-making. Methods. Fifty-one individuals with acute brucellosis and 17 healthy subjects were enrolled in this study. The brucellosis patients were diagnosed based on clinical symptoms, laboratory tests, and clinical examination. The levels of serum gamma-interferon (IFN-γ) and tumor necrosis factor-alpha (TNF-α), along with the percentage of Th1 cells, were determined by flow cytometry bead arrays (CBA). Results. The frequency of Th1 cells, along with the levels of IFN-γ and TNF-α, was negatively correlated with the clinical parameters. The mean serum levels of IFN-γ and TNF-α and the frequency of Th1 cells were significantly higher in the brucellosis patients in comparison with the healthy subjects (p<0.05). Besides, the cytokine levels were not significantly different between the positive and negative blood culture groups. IFN-γ levels significantly decreased from 6 months to 12 months post treatment (p<0.05). However, the IFN-γ levels remained higher than those of the healthy subjects by 12 months post treatment (p<0.05). The IFN-γ/TNF-α ratio was significantly higher in severe cases than in nonsevere cases (p<0.05). Conclusions. The IFN-γ levels secreted by Th1 cells remain significantly higher than those of healthy subjects more than 12 months after treatment with antibiotics. This finding is different from similar studies. The IFN-γ/TNF-α ratio may be a feasible parameter for assessing clinical severity, yet further longitudinal studies of the immunization and inflammatory reaction of brucellosis are needed in larger patient populations.

scholarly journals The systemic nature of mustard lung: Comparison with COPD patients

2017 ◽  
Vol 10 (3) ◽  
pp. 114-127 ◽  
Author(s):  
Alireza Shahriary ◽  
Mostafa Ghanei ◽  
Hossein Rahmani
Keyword(s):  
Clinical Symptoms ◽  
Airway Remodeling ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Chemical Warfare Agent ◽  
Pulmonary Complications ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Copd Patients ◽  
Systemic Nature

AbstractSulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas inhalation is mustard lung which is discussed as a phenotype of chronic obstructive pulmonary disease (COPD). In this complication, there are clinical symptoms close to COPD with common etiologies, such as in smokers. Based on information gradually obtained by conducting the studies on mustard lung patients, systemic symptoms along with pulmonary disorders have attracted the attention of researchers. Changes in serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), matrix metalloproteinases (MMPs), interleukin (IL), chemokines, selectins, immunoglobulins, and signs of imbalance in oxidant-antioxidant system at serum level, present the systemic changes in these patients. In addition to these, reports of extra-pulmonary complications, such as osteoporosis and cardiovascular disease are also presented. In this study, the chance of developing the systemic nature of this lung disease have been followed on using the comparative study of changes in the mentioned markers in mustard lung and COPD patients at stable phases and the mechanisms of pathogenesis and phenomena, such as airway remodeling in these patients.

scholarly journals Host Inflammatory Biomarkers of Disease Severity in Pediatric Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

2019 ◽  
Vol 6 (12) ◽  
Author(s):  
Catarina D Fernandes ◽  
María B Arriaga ◽  
Maria Carolina M Costa ◽  
Maria Clara M Costa ◽  
Maria Heloina M Costa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Clinical Decision Making ◽  
Meta Analysis ◽  
Clinical Decision ◽  
Serum Levels ◽  
Community Acquired Pneumonia ◽  
Inflammatory Biomarkers ◽  
Cross Sectional ◽  
Cell Counts

Abstract Background Community-acquired pneumonia (CAP) is the leading cause of death in children. Identification of reliable biomarkers offers the potential to develop a severity quantitative score to assist in clinical decision-making and improve outcomes. Methods A systematic review and meta-analysis was performed in PubMed and EMBASE on November 13, 2018, to examine the association between host inflammatory biomarkers and CAP severity in children. The inclusion criteria were case–control, cross-sectional, and cohort studies that examined candidate serum biomarkers. We extracted outcomes of interest, means, and standardized mean differences (SMDs) of plasma and serum levels of biomarkers together with information on disease severity. Meta-analysis was performed. This review was registered in the PROSPERO international registry (CRD42019123351). Results Two hundred seventy-two abstracts were identified, and 17 studies were included. Among the biomarkers evaluated, levels of C-reactive protein (CRP; SMD, 0.63; 95% confidence interval [CI], 0.35 to 0.91), interleukin (IL)-6 (SMD, 0.46; 95% CI, 0.25 to 0.66), IL-8 (SMD, 0.72; 95% CI, 0.15 to 1.29), neutrophil count (SMD, 0.27; 95% CI, 0.07 to 0.47), and procalcitonin (SMD, 0.68; 95% CI, 0.20 to 1.15) were substantially increased in severe CAP. In contrast, IL-2 concentrations (SMD, –0.24; 95% CI, –0.45 to –0.03) were higher in nonsevere CAP. Study heterogeneity was reported to be high (I2 &gt; 75%), except for IL-2, IL-5, IL-6, and IL-12p70, which were classified as moderate (I2 = 50%–74%). Only neutrophil and white blood cell counts were described by studies exhibiting a low level of heterogeneity. Conclusions Our results suggest that host biomarkers, and especially CRP, IL-6, IL-8, and procalcitonin levels, have the potential to predict severe CAP in pediatric populations.

Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae

2006 ◽  
Vol 111 (4) ◽  
pp. 253-263 ◽  
Author(s):  
Shyi-Jou Chen ◽  
Mong-Ling Chu ◽  
Chia-Jen Wang ◽  
Ching-Len Liao ◽  
Shie-Liang Hsieh ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Haemophilus Influenzae ◽  
Clinical Symptoms ◽  
Specific Antigen ◽  
Clinical Severity ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th2 Response ◽  
Ifn Γ

To investigate the kinetic Th1/Th2 immunopathogenic mechanisms of Haemophilus influenzae meningitis, we established a murine experimental model of meningitis and elucidated the Th1/Th2 immune responses in T1/T2 doubly transgenic mice based on a BALB/c background under the control of the IFN-γ (interferon-γ)/IL-4 (interleukin-4) promoters respectively. NTHi (non-typeable Haemophilus influenzae) meningitis was induced in these mice by inoculation with either a colonized (CNTHi) or invasive (INTHi) strain of NTHi. Mice inoculated with CNTHi displayed a less severe degree of disease in terms of clinical symptoms, mortality rate and brain histopathology. Conversely, INTHi-inoculated mice had more severe clinical symptoms. CNTHi-inoculated mice had a more significant Th1 response in terms of a higher percentage and longer maintenance of Th1 cells, and more production of IFN-γ from strain-specific antigen-stimulated splenocytes than INTHi-inoculated mice. In contrast, INTHi-inoculated mice had a more significant Th2 response. This was due to a significant increase in IL-4-producing CD4+ T-cells (Th2 cells) and more production of IL-4 from strain-specific antigen-stimulated splenocytes accompanied by a rapid decline of Th1 cells in INTHi-inoculated mice. In conclusion, the preferential Th1/Th2 trend in this murine model of NTHi meningitis is correlated with clinical severity as well as isolated characteristics of the pathogens themselves.

scholarly journals Return to Play after Cervical Spine Injuries: A Consensus of Opinion

2016 ◽  
Vol 6 (8) ◽  
pp. 792-797 ◽  
Author(s):  
John C. France ◽  
Michael Karsy ◽  
James S. Harrop ◽  
Andrew T. Dailey
Keyword(s):  
Decision Making ◽  
Cervical Spine ◽  
Clinical Decision Making ◽  
Clinical Symptoms ◽  
Clinical Decision ◽  
Return To Play ◽  
Spine Injury ◽  
Cervical Cord ◽  
Clinical Scenarios ◽  
Cord Injury

Study Design Survey. Objective Sports-related spinal cord injury (SCI) represents a growing proportion of total SCIs but lacks evidence or guidelines to guide clinical decision-making on return to play (RTP). Our objective is to offer the treating physician a consensus analysis of expert opinion regarding RTP that can be incorporated with the unique factors of a case for clinical decision-making. Methods Ten common clinical scenarios involving neurapraxia and stenosis, atlantoaxial injury, subaxial injury, and general cervical spine injury were presented to 25 spine surgeons from level 1 trauma centers for whom spine trauma is a significant component of their practice. We evaluated responses to questions about patient RTP, level of contact, imaging required for a clinical decision, and time to return for each scenario. The chi-square test was used for statistical analysis, with p < 0.05 considered significant. Results Evaluation of the surgeons’ responses to these cases showed significant consensus regarding return to high-contact sports in cases of cervical cord neurapraxia without symptoms or stenosis, surgically repaired herniated disks, and nonoperatively healed C1 ring or C2 hangman's fractures. Greater variability was found in recommendations for patients showing persistent clinical symptomatology. Conclusion This survey suggests a consensus among surgeons for allowing patients with relatively normal imaging and resolution of symptoms to return to high-contact activities; however, patients with cervical stenosis or clinical symptoms continue to be a challenge for management. This survey may serve as a basis for future clinical trials and consensus guidelines.

scholarly journals Precision physiology and rescue of brain ion channel disorders

2017 ◽  
Vol 149 (5) ◽  
pp. 533-546 ◽  
Author(s):  
Jeffrey Noebels
Keyword(s):  
Ion Channel ◽  
Clinical Utility ◽  
Clinical Decision Making ◽  
Central Nervous System Disease ◽  
Clinical Decision ◽  
Channel Structure ◽  
Clinical Severity ◽  
Developmental Relationships ◽  
System Disease ◽  
Phenotypic Spectrum

Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution. Future gains in the clinical utility of variants as biomarkers integral to clinical decision making and drug discovery depend on our ability to unravel complex developmental relationships bridging single ion channel structure and human physiology.

scholarly journals Prolactin ≤1 ng/mL predicts macroprolactinoma reduction after cabergoline therapy

2020 ◽  
Vol 182 (2) ◽  
pp. 177-183
Author(s):  
Daham Kim ◽  
Cheol Ryong Ku ◽  
Kyungwon Kim ◽  
Hyein Jung ◽  
Eun Jig Lee
Keyword(s):  
Tumor Size ◽  
Prolactin Level ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Post Treatment ◽  
Size Reduction ◽  
Multivariable Logistic Regression Analysis ◽  
High Dose ◽  
Pituitary Hormone ◽  
Level 1

Objective The association between prolactin level variation and prolactinoma size reduction remains unclear. This study aimed to determine the prolactin level cut-off predictive of a tumor size reduction. Design Retrospective cohort study. Methods We reviewed medical records of patients with prolactinoma who received primary cabergoline therapy and for whom complete data on pituitary hormone assays and sellar MRI at baseline and 3 months post treatment were available. We tested whether the certain prolactin level after 3 months post treatment predicted better response. Results Prolactin levels normalized in 109 (88.6%) of 123 included macroprolactinoma patients. The mean tumor size reduction was 22.9%, and patients in the lowest prolactin tertile (≤0.7) had the highest frequency of tumor size reductions of ≥20% (73.7 vs 52.9% and 45.9% in tertiles 2 (>0.7 to 2.6) and 3 (>2.6 to 20), P = 0.015). Patients with prolactin levels ≤1 ng/mL exhibited larger tumor size reductions vs those with prolactin levels of 1–20 (27.2 ± 18.3% vs 19.5 ± 13.9%, P = 0.014), 1–10 (19.3 ± 13.7%, P = 0.017) and 1–5 ng/mL (19.2 ± 14.3%, P = 0.039). A multivariable logistic regression analysis revealed that a prolactin level ≤1 ng/mL at 3 months and high-dose cabergoline therapy were significantly associated with tumor size reductions of ≥20% (odds ratio (OR): 2.8, 95% confidence interval (CI): 1.2–6.7, P = 0.017; OR: 2.0, 95% CI: 1.0–3.9, P = 0.043). Conclusions A prolactin level ≤1 ng/mL at 3 months after cabergoline treatment was correlated with a significant tumor size reduction in patients with macroprolactinoma. This finding may help clinical decision making when treating macroprolactinoma patients.

Investigation in respiratory disease

2018 ◽  
Author(s):  
Pranabashis Haldar
Keyword(s):  
Respiratory Disease ◽  
Disease Severity ◽  
Clinical Decision Making ◽  
Clinical Symptoms ◽  
Clinical Decision ◽  
Respiratory Medicine ◽  
Clinical Expression ◽  
Serial Measurement ◽  
Non Invasive ◽  
Limited Spectrum

Investigation in respiratory disease may be broadly classified as (1) tests that aid with diagnosis; (2) tests that assess disease severity—these are usually measures of respiratory function and inform prognosis; and (3) tests that assess disease activity—these are usually non-invasive biomarkers, enabling serial measurement, and may inform therapy. One of the challenges of respiratory medicine is the limited spectrum of clinical expression associated with a diverse spectrum of pathologies. Clinical symptoms in respiratory medicine are often of poor specificity for securing a diagnosis or assessing disease severity. Investigations, therefore, necessarily form a critical part of assessment. The most appropriate choice of investigation is an important component of clinical decision-making that affects patient care and may be influenced by a number of different questions that the clinician will need to consider.

How clinicians make decisions regarding surveillance and treatment of colorectal cancer (CRC) patients.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 263-263 ◽  
Author(s):  
Amanda Cuddy ◽  
Katherine Van Loon ◽  
Y. Nancy You ◽  
Chung-Yuan Hu ◽  
Amanda Beth Francescatti ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Clinical Decision Making ◽  
Palliative Chemotherapy ◽  
Salvage Surgery ◽  
Patient Characteristics ◽  
Clinical Decision ◽  
Salvage Treatment ◽  
Post Treatment ◽  
Convenience Sample ◽  
The Impact

263 Background: The goal of post-treatment surveillance of CRC patients is to identify recurrences among patients eligible for salvage surgery or palliative chemotherapy. However, patient ineligibility for treatment of recurrence may contribute to variation in surveillance practices. The aim of this study was to evaluate patient factors that affect clinician decisions regarding surveillance and salvage treatment eligibility among CRC patients. Methods: A custom 41-item survey was developed, incorporating modified criteria for adult comorbidity evaluation. A convenience sample of physicians who treat CRC was recruited from the ALLIANCE GI Cancer Committee. All participants completed an anonymous written survey of objective and subjective information about salvage treatment eligibility and the impact on surveillance in these patients. Results: Respondents were medical oncologists (n = 16; n = 11 with > 10 yrs experience) and surgical oncologists (n = 4). Patients with average comorbidity were considered ineligible for curative salvage surgery at median age 85 yrs (IQR: 80, 90), life expectancy 3 yrs (IQR: 2, 4.8) or ECOG ≥ 2 (IQR: 2,3). Patients were considered ineligible for palliative chemotherapy at median age 90 (IQR: 80, 92.5), life expectancy ≤ 2 years (IQR: 1.5, 3) or ECOG status ≤ 3 (IQR: 3, 3). Patients with above average comorbidity were considered ineligible for salvage surgery at median age 80 yrs (IQR: 75, 80) and palliative chemotherapy at median age 80 yrs (IQR: 75, 85). 8 comorbidities were identified by > 75% of the respondents as determinants of treatment ineligibility. 12 respondents (60%) indicated follow-up of patients ineligible for treatment should be continued based on patient desire, ongoing management of late effects, and continuity of care. However, a majority (n = 15) responded that clinic visits only should be continued without further testing. Conclusions: Considerable agreement was observed regarding patient characteristics that lead to ineligibility for treatment of recurrent disease. This information can aid shared clinical decision-making for post-treatment surveillance strategies and may potentially reduce variation in surveillance practice.

Novel biomarker signatures for idiopathic REM sleep behavior disorder

Neurology ◽  
2018 ◽  
Vol 91 (18) ◽  
pp. e1710-e1715 ◽  
Author(s):  
Stefania Mondello ◽  
Firas Kobeissy ◽  
Yehia Mechref ◽  
Jingfu Zhao ◽  
Farid R. Talih ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clinical Decision Making ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical Decision ◽  
Serum Levels ◽  
Serum Samples ◽  
Proteomics Analysis ◽  
Sleep Behavior ◽  
Altered Expression

ObjectiveTo perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.MethodsSerum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.ResultsWe identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.ConclusionsOur results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Chickpea supplementation prior to colitis onset reduces inflammation in dextran sodium sulfate-treated C57Bl/6 male mice

2018 ◽  
Vol 43 (9) ◽  
pp. 893-901 ◽  
Author(s):  
Jennifer M. Monk ◽  
Wenqing Wu ◽  
Laurel H. McGillis ◽  
Hannah R. Wellings ◽  
Amber L. Hutchinson ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Sodium Sulfate ◽  
Clinical Symptoms ◽  
Basal Diet ◽  
Serum Levels ◽  
Dextran Sodium Sulfate ◽  
Male Mice ◽  
Acute Colitis ◽  
Colon Tissue ◽  
Necrosis Factor Alpha

The potential for a chickpea-supplemented diet (rich in fermentable nondigestible carbohydrates and phenolic compounds) to modify the colonic microenvironment and attenuate the severity of acute colonic inflammation was investigated. C57Bl/6 male mice were fed a control basal diet or basal diet supplemented with 20% cooked chickpea flour for 3 weeks prior to acute colitis onset induced by 7-day exposure to dextran sodium sulfate (DSS; 2% w/v in drinking water) and colon and serum levels of inflammatory mediators were assessed. Despite an equal degree of DSS-induced epithelial barrier histological damage and clinical symptoms between dietary groups, biomarkers of the ensuing inflammatory response were attenuated by chickpea pre-feeding, including reduced colon tissue activation of nuclear factor kappa B and inflammatory cytokine production (tumor necrosis factor alpha and interleukin (IL)-18). Additionally, colon protein expression of anti-inflammatory (IL-10) and epithelial repair (IL-22 and IL-27) cytokines were increased by chickpea pre-feeding. Furthermore, during acute colitis, chickpea pre-feeding increased markers of enhanced colonic function, including Relmβ and IgA gene expression. Collectively, chickpea pre-feeding modulated the baseline function of the colonic microenvironment, whereby upon induction of acute colitis, the severity of the inflammatory response was attenuated.

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