High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis

Purpose

This study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting.

Methods

One hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1 = 84) and a non-AFB smear-positive, pulmonary infection group (G2 = 99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions.

Results

Utilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96 ± 0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively.

Conclusion

The use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients.     

Thyroid autoantibodies and dysfunction do not impact the treatment efficacy of peginterferon and ribavirin combination therapy in chronic hepatitis C

Aims

Thyroid disorders, such as the emergence of thyroid autoantibodies (TAs) and thyroid dysfunction (TD), are not uncommon in chronic hepatitis C (CHC) patients. The study aimed to investigate the impact of TAs and dysfunction on the treatment response to pegylated interferon-?? plus ribavirin (PegIFN/RBV) combination therapy in CHC patients. The association between interleukin-28B (IL-28B) genetic variants and occurrence of TAs and dysfunction was also analyzed.

Methods

A total of 449 treatment-naive Taiwanese CHC patients with euthyroid status were consecutively enrolled. They received PegIFN/RBV combination therapy with current recommendation. TAs, TD, and IL-28B genetic variants were measured before treatment. Monitoring of TD was done at 3-month intervals during treatment, at end of treatment, and at end of follow-up (EOF).

Results

The development of TAs was detected in 42 (9.4%) patients before treatment, and the incidence of TD during or at EOF was 20%. Of 287 patients with IL-28B rs8099917 TT genotype, 29 (10.1%) had TAs before treatment, whereas the patients with other genotypes did not have TAs (P?=?0.04). There was no significant difference of TD incidence during treatment or at EOF between the patients with different IL-28B genotypes. There was also no significant difference of sustained virologic response according to the presence of TAs, TD, or different manifestations of TD.

Conclusion

Taiwanese CHC patients with rs8099917 TT genotype had a higher incidence of TAs. The development of TAs and TD did not impact the treatment efficacy of PegIFN/RBV combination therapy.     

FDG PET/CT of a late-term pregnant woman with breast cancer

A 38-year-old pregnant woman at 26-week gestation with left breast cancer requested an FDG PET/CT scan for more detailed staging of her breast cancer before treatment. After discussing the potential radiation-related risk and estimating possible absorbed dose to fetus, she consented for examination. By using a low-radiation-dose CT protocol and administration of routine 370-MBq FDG without diuresis, the resultant calculated (using existing models to predict fetal radiation exposure) fetal dose from CT and FDG would be 3.60 mGy and 6.29 mGy, respectively. In contrast to the existing few literatures, our case also demonstrated previously unreported uptake in the fetal kidneys.     

New drugs and the growth of health expenditure: evidence from diabetic patients in Taiwan

This paper contributes to the growing body of literature that debates whether the adoption of pharmaceutical innovation increases the overall expenditure on health care. By examining data obtained from Taiwan and focusing on diabetic patients, we use a new class of drugs, namely, thiazolidinediones, as an example to investigate the effect on health expenditure of prescribing new drugs to patients by focusing on the impact of treatment substitution and treatment expansion. Overall, our results indicate that the introduction of new drugs mainly impacts the outpatient drug expenditure and does not give rise to any offsetting effect on other outpatient and inpatient health expenditures. This suggests that the adoption of pharmaceutical innovation in treating diabetic patients is expenditure-increasing. In addition, we find evidence that the treatment substitution channel has a more significant impact on the level of health expenditure than the treatment expansion channel. An important policy implication for our finding is that the justification for increasing health expenditure on the treatment of diabetes is not conditional upon a lowering in the demand for other types of health-care services. By contrast, it is conditional upon the increased health benefits per se.     

Lactobacillus gasseri suppresses Th17 pro-inflammatory response and attenuates allergen-induced airway inflammation in a mouse model of allergic asthma

Probiotics are normal inhabitants of the gastrointestinal tract of man and are widely considered to exert a number of beneficial effects in many diseases. But the mechanism by which they modulate the immune system is poorly understood. The present study was planned to explore the anti-allergic effect of Lactobacillus gasseri on a mouse model of allergic asthma. Dermatophoides pteronyssinus (Der p) sensitised and challenged BALB/c mice were orally administered via oral administration with three different doses of L. gasseri (low, 1 × 10(6) colony-forming units (CFU); medium, 2 × 10(6) CFU; high, 4 × 10(6) CFU), in 700 μl of PBS daily, starting from 2 weeks before Der p sensitisation for 4 weeks. After the allergen challenge, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage (BAL) fluids and splenocytes culture were assessed. Our results showed that oral administration of a high dose of L. gasseri (4 × 10(6) CFU) decreased airway responsiveness to methacholine, attenuated the influx of inflammatory cells to the airways and reduced the levels of TNF-α, thymus and activation-regulated chemokine (TARC) and IL-17A in BAL fluids of Der p-sensitised and -challenged mice. Moreover, L. gasseri decreased IL-17A production in transforming growth factor-α and IL-6 stimulated splenocytes and cell numbers of IL-17 producing alveolar macrophages in L. gasseri-treated mice as compared to non-treated, Der p-sensitised and -challenged mice. In conclusion, oral administration with L. gasseri can attenuate major characteristics of allergen-induced airway inflammation and IL-17 pro-inflammatory immune response in a mouse model of allergic asthma, which may have clinical implication in the preventive or therapeutic potential in allergic asthma.     

Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in heterologous prime–boost vaccination against cancer

Studies have shown that an enhanced CD8+ T cell response and better tumor protection can be achieved by heterologous prime–boost vaccination in mice. Such heterologous vaccination can be more immunogenic than the homologous setting. We previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell (Treg)-directed suppression. In the present study, we assessed the combination of this approach with plasmid DNA vaccination, in a prime–boost immunization strategy. E. coli-LLO bacteria expressing ovalbumin (OVA) and plasmid pcDNA-encoding OVA were used to vaccinate naive or B16-OVA tumor-bearing C57B6 mice. The anticancer activity was measured in a tumor prevention or therapeutic model. Higher OVA-specific CD8+ T cell responses and greater tumor inhibition were seen in the bacterial-prime/plasmid–boost setting than with the homologous and reversed sequences. This tumor protection effect from heterologous prime–boost remained in the therapeutic model. When examining the Treg effect during the prime–boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. Our studies offer the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced antitumor effect in conjunction with DNA in a heterologous prime–boost protocol, and suggest that early Treg inhibition is crucial to a successful immunization against cancer.     

The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer

A combination of four-dimensional computed tomography with ¹⁸F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTV_PET) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTV_PET and CT-based GTV (GTV_CT) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTV_CT values. The decision coefficient (R²) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTV_CT was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.