Randomized controlled trial to evaluate the utility of suction and inner-stylet of EBUS-TBNA for mediastinal and hilar lymphadenopathy

Background

The optimal procedure for maximizing the diagnostic yield and minimizing the procedural complexity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is controversial. We conducted a prospective randomized controlled trial to determine the optimal procedure of EBUS-TBNA for mediastinal and hilar lymphadenopathy, with a particular focus on the roles of the inner-stylet and suction.

Methods

Consecutive patients with enlarged mediastinal and hilar lymph nodes (LNs), detected by computed tomography (CT) or positron emission tomography-CT (PET-CT), who underwent EBUS-TBNA were included. Each LN was sampled with three needle passes using suction–stylet, suction–no stylet, and stylet–no suction procedures. The samples were smeared onto glass slides for cytological evaluation. A single, blinded cytopathologist evaluated each set of slides. The primary outcomes were cytological specimen adequacy rate and diagnostic yield of malignant LNs. The secondary outcomes were tissue-core acquisition rate, procedural time, and the amount of bleeding.

Results

This study evaluated 97 patients with a total of 255 LNs. The final LN diagnosis was benign in 144, malignant in 104, and inadequate in 7 cases. There were no significant differences among the suction–stylet, suction–no stylet, and stylet–no suction groups in specimen adequacy rate (87.1, 88.2, 85.9%, respectively) or diagnostic yield of malignancy (32.2, 31.8, 31.0%, respectively). However, the use of suction was associated with an increase in tissue-core acquisition rate (P?<? 0.001). The no-stylet procedure decreased the average procedural time by 14?s (P?<? 0.001). There was no significant difference in the amount of bleeding among the procedures.

Conclusions

The use of suction or non-use of an inner-stylet does not make a significant difference in cytological specimen adequacy or diagnostic yield when performing EBUS-TBNA. While omitting the stylet can simplify the procedure, applying suction can increase the tissue-core acquisition rate. These findings may assist endoscopic physicians in determining the optimal EBUS-TBNA procedure and warrant clinical verification in a future multicentre study.

Trial registration

Trial registration: (ChiCTR-IOR-17010616). Retrospective registered date: 12th February, 2017.

     

Making Mock-FNA Smears from Fresh Surgical Pathology Specimens to Improve Smear Preparation Technique and to Create Cytohistological Correlation Series

Background

Fine needle aspiration (FNA) cytology is a well-established diagnostic method based on the microscopic interpretation of often scant cytological material; therefore, experience, good technique and smear quality are equally important in obtaining satisfactory results.

Aims of Study

We studied the use of fresh surgical pathology specimens for making so-called mock-FNA smears with the potential of cytohistological correlation. Additionally, we studied how this process aids the improvement of preparation technique and smear quality.

Methods

Cytological aspirates from 32 fresh biopsy specimens from various sites: lung (20), lymph nodes (6), and breast (6) were obtained, all with a clinical diagnosis of tumor. Aspiration was performed from grossly palpable tumors. 25G needle and Cameco-type syringe holder was used with minimal or no suction.

Results

Unfixed surgical specimens provided sufficient cytological material that resulted in good quality smears. After standard processing of specimens into microscopic sections from paraffin embedded tissues, cytohistological case-series were created. No significant alteration was reported in tissue architecture on hematoxylin-eosin stained sections after the aspiration procedure. A gradual, but steady improvement was observed in smear quality just after a few preparations.

Discussions and Conclusions

Our study proved that surgical specimens may be used as a source of cytological material to create cytohistological correlation studies and also to improve FNA cytology skills. The use of very fine gauge needle (25G, 0,6 mm diameter) during the sampling process does not alter tissue architecture therefore the final histopathological diagnosis is not compromised. We conclude that by using fresh surgical specimens useful cytohistological collections can be created both as a teaching resource and as improving experience.     

Persistent High IgG Phase I Antibody Levels against Coxiella burnetii among Veterinarians Compared to Patients Previously Diagnosed with Acute Q Fever after Three Years of Follow-Up

Background

Little is known about the development of chronic Q fever in occupational risk groups. The aim of this study was to perform long-term follow-up of Coxiella burnetii seropositive veterinarians and investigate the course of IgG phase I and phase II antibodies against C. burnetii antigens and to compare this course with that in patients previously diagnosed with acute Q fever.

Methods

Veterinarians with IgG phase I ≥1:256 (immunofluorescence assay) that participated in a previous seroprevalence study were asked to provide a second blood sample three years later. IgG antibody profiles were compared to a group of acute Q fever patients who had IgG phase I ≥1:256 twelve months after diagnosis.

Results

IgG phase I was detected in all veterinarians (n = 76) and in 85% of Q fever patients (n = 98) after three years (p<0.001). IgG phase I ≥1:1,024, indicating possible chronic Q fever, was found in 36% of veterinarians and 12% of patients (OR 3.95, 95% CI: 1.84–8.49).

Conclusions

IgG phase I persists among veterinarians presumably because of continuous exposure to C. burnetii during their work. Serological and clinical follow-up of occupationally exposed risk groups should be considered.     

Diagnostic value of EBUS-TBNA for lung cancer with non-enlarged lymph nodes: a study in a tuberculosis-endemic country

Background

In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET.

Methods

We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA.

Results

The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET.

Conclusion

In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.     

Efficacy of Sorafenib Monotherapy versus Sorafenib-Based Loco-Regional Treatments in Advanced Hepatocellular Carcinoma

Background

Although sorafenib is accepted as the standard of care in advanced hepatocellular carcinoma (HCC), its therapeutic benefit is marginal. Here, we aimed to compare the efficacy and safety of sorafenib monotherapy (S-M) and sorafenib-based loco-regional treatments (S-LRTs) in advanced HCC.

Methods

From 2007 to 2012, 290 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) with S-M (n = 226) or S-LRTs (n = 64) were reviewed retrospectively. Survival outcomes and treatment-related toxicities between two groups were analyzed.

Results

Variables related to tumor burden and liver function were similar between the groups (all P > 0.05). Within the entire population, the S-LRTs group had both longer median overall survival (OS) (8.5 vs 5.5 months, P = 0.001) and progression-free survival (PFS) (5.3 vs 3.0 months, P = 0.002) than the S-M group. Furthermore, the S-LRTs group had longer Os than the S-M group in a subgroup with neither extrahepatic spread (EHS) nor regional nodal involvement (RNI) (18.0 vs 7.8 months, P = 0.019) and in a subgroup with EHS and/or RNI (8.3 vs 4.8 months, P = 0.028). In addition, the S-LRTs group had longer PFS than the S-M group in the subgroup with neither EHS nor RNI (9.6 vs 3.2 months, P = 0.027).

Treatment

Related toxicity was similar between two groups.

Conclusion

Combined use of sorafenib and LRTs may provide better treatment outcomes without significantly increasing treatment-related toxicities, even in patients with EHS and/or RNI. Therefore, addition of active LRTs might be considered, if feasible.     

High Postoperative Serum Cortisol Level Is Associated with Increased Risk of Cognitive Dysfunction Early after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study

Context

Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction.

Objective

To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery.

Design

Prospective cohort study.

Setting

Two teaching hospitals.

Patients

One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009.

Intervention

None.

Main Outcome Measures

Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction.

Results

Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016).

Conclusions

High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.     

Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala,Uganda: A Cross-Sectional Study

Introduction

Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions.

Objective

To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala.

Methods

Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria.

Results

Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant.

Conclusion

At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment.     

Can K-ras Gene Mutation Be Utilized as Prognostic Biomarker for Colorectal Cancer Patients Receiving Chemotherapy? A Meta-Analysis and Systematic Review

Introduction

K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear.

Objective

Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence.

Method

Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated.

Principal Findings

7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49).

Conclusions

K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy.     

Effect of the +781C/T Polymorphism in the Interleukin-8 Gene on Atherosclerotic Cerebral Infarction,and Its Interaction with Smoking and Drinking

Objective

The aims of this study were to investigate the association between the +781C/T polymorphism of interleukin-8 (IL-8) and atherosclerotic cerebral infarction and the interaction between the +781C/T polymorphism and smoking or drinking in cerebral infarction in the Han Chinese population.

Methods

We investigated the +781C/T polymorphism of IL-8 in 308 consecutive Han Chinese patients who were diagnosed with atherosclerotic cerebral infarction and in 294 age- and gender-matched healthy control subjects. The patients were classified using the Oxfordshire Community Stroke Project (OCSP) classification. The patients and subjects’ histories of smoking and drinking were recorded, and atherosclerosis (AS) of the internal carotid artery (ICA) was evaluated in the patients. The +781C/T polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

The +781C/T polymorphism and allele frequencies were not significantly different between the patients and controls and were not significantly associated with the OCSP classifications. We found that the 781C allele was significantly associated with AS of the ICA in the patients (p = 0.017), and the CT genotype was more prevalent in patients without AS of the ICA (p = 0.035). No interactions were observed between the +781C/T polymorphism and smoking or drinking.

Conclusion

Our results demonstrated that the +781C/T polymorphism of IL-8 did not play a role and had no interaction with smoking or drinking in the occurrence of cerebral infarction in the Han Chinese population. However, the C allele and the CT genotype might be associated with AS of the ICA in patients with ischemic stroke.     

Ratio of Intratumoral Macrophage Phenotypes Is a Prognostic Factor in Epithelioid Malignant Pleural Mesothelioma

Hypothesis

The tumor micro-environment and especially the different macrophage phenotypes appear to be of great influence on the behavior of multiple tumor types. M1 skewed macrophages possess anti-tumoral capacities, while the M2 polarized macrophages have pro-tumoral capacities. We analyzed if the macrophage count and the M2 to total macrophage ratio is a discriminative marker for outcome after surgery in malignant pleural mesothelioma (MPM) and studied the prognostic value of these immunological cells.

Methods

8 MPM patients who received induction chemotherapy and surgical treatment were matched on age, sex, tumor histology, TNM stage and EORTC score with 8 patients who received chemotherapy only. CD8 positive T-cells and the total macrophage count, using the CD68 pan-macrophage marker, and CD163 positive M2 macrophage count were determined in tumor specimens prior to treatment.

Results

The number of CD68 and CD163 cells was comparable between the surgery and the non-surgery group, and was not related to overall survival (OS) in both the surgery and non-surgery group. However, the CD163/CD68 ratio did correlate with OS in both in the total patient group (Pearson r −0.72, p<0.05). No correlation between the number of CD8 cells and prognosis was found.

Conclusions

The total number of macrophages in tumor tissue did not correlate with OS in both groups, however, the CD163/CD68 ratio correlates with OS in the total patient group. Our data revealed that the CD163/CD68 ratio is a potential prognostic marker in epithelioid mesothelioma patients independent of treatment but cannot be used as a predictive marker for outcome after surgery.     

Specific Diurnal EMG Activity Pattern Observed in Occlusal Collapse Patients: Relationship between Diurnal Bruxism and Tooth Loss Progression

Aim

The role of parafunctional masticatory muscle activity in tooth loss has not been fully clarified. This study aimed to reveal the characteristic activity of masseter muscles in bite collapse patients while awake and asleep.

Materials and Methods

Six progressive bite collapse patients (PBC group), six age- and gender-matched control subjects (MC group), and six young control subjects (YC group) were enrolled. Electromyograms (EMG) of the masseter muscles were continuously recorded with an ambulatory EMG recorder while patients were awake and asleep. Diurnal and nocturnal parafunctional EMG activity was classified as phasic, tonic, or mixed using an EMG threshold of 20% maximal voluntary clenching.

Results

Highly extended diurnal phasic activity was observed only in the PBC group. The three groups had significantly different mean diurnal phasic episodes per hour, with 13.29±7.18 per hour in the PBC group, 0.95±0.97 per hour in the MC group, and 0.87±0.98 per hour in the YC group (p<0.01). ROC curve analysis suggested that the number of diurnal phasic episodes might be used to predict bite collapsing tooth loss.

Conclusion

Extensive bite loss might be related to diurnal masticatory muscle parafunction but not to parafunction during sleep.

Clinical Relevance: Scientific rationale for study

Although mandibular parafunction has been implicated in stomatognathic system breakdown, a causal relationship has not been established because scientific modalities to evaluate parafunctional activity have been lacking.

Principal findings

This study used a newly developed EMG recording system that evaluates masseter muscle activity throughout the day. Our results challenge the stereotypical idea of nocturnal bruxism as a strong destructive force. We found that diurnal phasic masticatory muscle activity was most characteristic in patients with progressive bite collapse.

Practical implications

The incidence of diurnal phasic contractions could be used for the prognostic evaluation of stomatognathic system stability.     

Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphism and Left Ventricular Function in Early Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.

Methods

140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.

Results

The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).

Conclusions

eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.     

Bronchial Smooth Muscle Cells of Asthmatics Promote Angiogenesis through Elevated Secretion of CXC-Chemokines (ENA-78, GRO-α, and IL-8)

Background

Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors.

Objective

To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors.

Methods

Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay.

Results

Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p < 0.001). Levels of ENA-78, GRO-α and IL-8 were significantly elevated in CM of BSMC from asthma patients (p < 0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 (CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC.

Conclusions

BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-α and IL-8) produced by BSMC.

Implications

CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients. Counteracting the CXCR2-mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma.     

CASP8 SNP D302H (rs1045485) Is Associated with Worse Survival in MYCN-Amplified Neuroblastoma Patients

Background

Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.

Patients and Methods

We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.

Results and Conclusion

We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.     

Identification of Locally Advanced Rectal Cancer with Low Risk of Local Recurrence

Background

The routine application of neoadjuvant chemoradiotherapy for T3N0 rectal cancer remains controversial. The aim of this study was to use clinical, Magnetic resonance imaging, and pathological parameters to identify a subgroup of patients with low risk of local recurrence who might be precluded from neoadjuvant chemoradiotherapy.

Methods

We retrospectively reviewed a prospectively maintained database of consecutive rectal cancer patients who underwent curative resection. 166 pathologic confirmed T3N0 rectal cancer patients with tumor located 5–12cm above the anal verge and preoperative circumferential resection margin>1mm were included in analysis. The primary outcomes measured were3- and 5-year local recurrence rates.

Results

Local recurrence was demonstrated during follow-up in 5 patients; the actuarial overall 3- and 5-year local recurrence rates were 2.5% and 3.4%, respectively. Inadequate sampling of lymph nodes (≤12) was associated with higher local recurrence (P = 0.03) in this group of patients.

Conclusion

For upper and middle T3N0 rectal cancer with preoperative circumferential resection margin>1mm, local recurrence rate after total mesorectal excision is low and surgery alone may be enough for this group of patients.     

Blueberry and Mulberry Juice Prevent Obesity Development in C57BL/6 Mice

Objectives

To establish whether blueberry (Vaccinium ashei) and mulberry (Morus australis Poir) juice, anthocyanin rich fruit juice, may help counteract obesity.

Design

And Methods: Four-week-old C57BL/6 mice were fed a high-fat diet (HFD) with or without blueberry and mulberry juice for 12 weeks. Body weight, serum and hepatic lipids, liver and adipose tissues morphology, insulin and leptin were assessed.

Results

Mice fed HFD exhibited increased body weight, insulin resistance, serum and hepatic lipids. In comparison, blueberry and mulberry juice inhibited body weight gain, decreased the serum cholesterol, reduced the resistance to insulin, attenuated lipid accumulation and decreased the leptin secretin.

Conclusion

These results indicate that blueberry and mulberry juice may help counteract obesity.     

Prevalence and Global Initiative for Chronic Obstructive Lung Disease Group Distribution of Chronic Obstructive Pulmonary Disease Detected by Preoperative Pulmonary Function Test

Background

Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea. The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD.

Methods

We reviewed the medical records of adults (age, ≥40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea. COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7. We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test.

Results

Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44–93 years) were diagnosed with COPD. Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%). The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D.

Conclusions

The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease. Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.     

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

Background

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients.

Methods

In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex.

Results

Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls.

Conclusion

TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.     

Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo

Background

Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.

Methods

Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections.

Results

In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity.

Conclusion

In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC.