Dissociable Contributions of Basolateral Amygdala and Ventrolateral Orbitofrontal Cortex to Flexible Learning Under Uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

An IFN-γ and TNF-α dual release fluorospot assay for diagnosing active tuberculosis.

OBJECTIVES: Currently available interferon (IFN)-γ-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-α-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-γ- and/or TNF-α-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-γ and TNF-α dual release fluorospot assay for active TB. METHODS: Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-γ- and TNF-α-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. RESULTS: A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70-93) and 70% (95% CI 61-79), respectively. The IFN-γ/TNF-α dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-γ single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). CONCLUSIONS: The fluorospot-based IFN-γ/TNF-α dual release assay appears to be a simple and useful test for diagnosing active TB.

Cosmetic outcome of implantation of cross-linked human acellular dermal matrix after parotidectomy.

Although skin depression after parotidectomy affects the patient's satisfaction with cosmesis we know of little research about it, so we attempted to alleviate it by inserting human acellular dermal matrix (hADM) after the operation. We made a retrospective analysis of the casenotes of 63 patients who were diagnosed with parotid tumours and were operated on between January 2015 and December 2016. Factors that affect satisfaction with cosmesis, including the use of hADM, sex, age, incision, size of tumour, sample size, complications, and the name of the surgeon were recorded and evaluated on a scale from 1 (most unsatisfactory) to 10 (very satisfactory), and the satisfaction according to each factor was compared. The mean (SD) follow-up period was 13 (6) months, and 19 of the 63 patients developed complications. Satisfaction was significantly better when hADM had been inserted (p=0.0008), when the patient was female (p=0.033), or there were no complications p=0.0161). On linear regression analysis, all three factors showed a significant causal relation with satisfactory cosmesis. Insertion of hADM after operations on the parotid gland seems to be effective in improving this by preventing skin depression.

Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease in Korea and China. Although there is previous evidence of person-to-person transmission via direct contact with body fluids, the role of environmental contamination by SFTS virus (SFTSV) in healthcare settings has not been established. We therefore investigated the contamination of the healthcare environment by SFTSV. METHODS: We investigated the possible contamination of hospital air and surfaces with SFTSV transmission by collecting air and swabbing environmental surface samples in two hospitals treating six SFTS patients between March and September 2017. The samples were tested using real-time RT-PCR for SFTS M and S segments. RESULTS: Of the six SFTS patients, four received mechanical ventilation and three died. Five rooms were occupied by those using mechanical ventilation or total plasma exchange therapy in isolation rooms without negative pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained from fomites including stethoscopes, and 9 of 43 were obtained from fixed structures including doorknobs and bed guardrails. Some samples from fixed structures such as television monitors and sink tables were obtained in areas remote from the patients. SFTSV RNA was not detected in five air samples from three patients' rooms. CONCLUSIONS: Our data suggest that SFTSV contamination was extensive in surrounding environments in SFTS patients' rooms. Therefore, more strict isolation methods and disinfecting procedures should be considered when managing SFTS patients.

Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) virus has a variety of central nervous system (CNS) manifestations. However, there are limited data regarding SFTS-associated encephalopathy/encephalitis (SFTSAE) and its mechanism. METHODS: All patients with confirmed SFTS who underwent cerebrospinal fluid (CSF) examination due to suspected acute encephalopathy were enrolled in three referral hospitals between January 2013 and October 2016. Real-time RT-PCR for SFTS virus and chemokine/cytokines levels from blood and CSF were analysed. RESULTS: Of 41 patients with confirmed SFTS by RT-PCR for SFTS virus using blood samples, 14 (34%) underwent CSF examination due to suspected SFTSAE. All 14 patients with SFTSE revealed normal protein and glucose levels in CSF, and CSF pleocytosis was uncommon (29%, 4/14). Of the eight patients whose CSF was available for further analysis, six (75%) yielded positive results for SFTS virus. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) level in CSF were significantly higher than those in serum (geometric mean 1889 pg/mL in CSF versus 264 pg/mL in serum for MCP-1, p = 0.01, and geometric mean 340 pg/mL in CSF versus 71 pg/mL in serum for IL-8, p = 0.004). CONCLUSIONS: The CNS manifestation of SFTS as acute encephalopathy/encephalitis is a common complication of SFTS. Although meningeal inflammation was infrequent in patients with SFTSAE, SFTS virus was frequently detected in CSF with elevated MCP-1 and IL-8. These findings indicate that possible direct invasion of the CNS by SFTS virus with the associated elevated cytokine levels in CSF may play an important role in the pathogenesis of SFTSAE.

Molecular epidemiology and environmental contamination during an outbreak of parainfluenza virus 3 in a haematology ward.

BACKGROUND: Although fomites or contaminated surfaces have been considered as transmission routes, the role of environmental contamination by human parainfluenza virus type 3 (hPIV-3) in healthcare settings is not established. AIM: To describe an hPIV-3 nosocomial outbreak and the results of environmental sampling to elucidate the source of nosocomial transmission and the role of environmental contamination. METHODS: During an hPIV-3 outbreak between May and June 2016, environmental surfaces in contact with clustered patients were swabbed and respiratory specimens used from infected patients and epidemiologically unlinked controls. The epidemiologic relatedness of hPIV-3 strains was investigated by sequencing of the haemagglutinin-neuraminidase and fusion protein genes. FINDINGS: Of 19 hPIV-3-infected patients, eight were haematopoietic stem cell recipients and one was a healthcare worker. In addition, four had upper and 12 had lower respiratory tract infections. Of the 19 patients, six (32%) were community-onset infections (symptom onset within <7 days of hospitalization) and 13 (68%) were hospital-onset infections (≥7 days of hospitalization). Phylogenetic analysis identified two major clusters: five patients, and three patients plus one healthcare worker. Therefore, seven (37%) were classified as nosocomial transmissions. hPIV-3 was detected in 21 (43%) of 49 environmental swabs up to 12 days after negative respiratory polymerase chain reaction conversion. CONCLUSION: At least one-third of a peak season nosocomial hPIV-3 outbreak originated from nosocomial transmission, with multiple importations of hPIV-3 from the community, providing experimental evidence for extensive environmental hPIV-3 contamination. Direct contact with the contaminated surfaces and fomites or indirect transmission from infected healthcare workers could be responsible for nosocomial transmission.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country.

Risk of stroke and transient ischaemic attack after herpes zoster.

We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person-years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person-years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85-1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year-olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age.

Electronic energy and electron transfer processes in photoexcited donor-acceptor dyad and triad molecular systems based on triphenylene and perylene diimide units.

We investigate the photophysical properties of organic donor-acceptor dyad and triad molecular systems based on triphenylene and perylene diimide units linked by a non-conjugated flexible bridge in solution using complementary optical spectroscopy techniques. When these molecules are diluted in dichloromethane solution, energy transfer from the triphenylene to the perylene diimide excited moieties is evidenced by time-resolved fluorescence measurements resulting in a quenching of the emission from the triphenylene moieties. Simultaneously, another quenching process that affects the emission from both donor and acceptor units is observed. Solution ultrafast transient absorption measurements provide evidence of photo-induced charge transfer from either the donor or the acceptor depending upon the excitation. Overall, the analysis of the detailed time-resolved spectroscopic measurements carried out in the dyad and triad systems as well as in the triphenylene and perylene diimide units alone provides useful information both to better understand the relations between energy and charge transfer processes with molecular structures, and for the design of future functional dyad and triad architectures based on donor and acceptor moieties for organic optoelectronic applications.

Late paradoxical lymph node enlargement during and after anti-tuberculosis treatment in non-HIV-infected patients.

SETTINGS: A tertiary referral centre in South Korea. OBJECTIVE: To investigate the incidence, clinical characteristics and outcomes of late paradoxical response (>4 months after the initiation of anti-tuberculosis treatment) during and after anti-tuberculosis treatment in non-human immunodeficiency virus (HIV) infected patients with lymph node tuberculosis (TB). DESIGN: We retrospectively reviewed the medical records of non-HIV-infected patients with lymph node TB between 1997 and 2007, and prospectively enrolled patients with newly diagnosed lymph node TB between 2008 and 2013. RESULTS: Of 467 patients with confirmed and probable lymph node TB, 83 (18%) displayed a paradoxical response: 57 of these (69%) were classified as early and 26 (31%) as late paradoxical response. Patients with late paradoxical response (median 12 months) received more prolonged anti-tuberculosis treatment than those with early (median 9 months, P < 0.001) or no paradoxical response (median 9 months, P < 0.001). The frequency of post-treatment lymph node enlargement increased progressively from those without any paradoxical response (6%), through those with an early response (12%) to those with a late response (23%). CONCLUSIONS: Paradoxical response presents late in about one third of non-HIV-infected patients with lymph node TB who experience a response. Although anti-tuberculosis treatment is commonly prolonged in patients with late paradoxical response, post-treatment lymph node enlargement is more frequent in these patients.

Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis.

Because there are no available molecular markers for pulmonary mucormycosis (PM), which has low culture sensitivity, early diagnosis and treatment rely heavily on imaging modes such as computed tomography (CT). However, there are limited data comparing CT findings for PM with those for invasive pulmonary aspergillosis (IPA). Adult patients who met the modified criteria for proven and probable PM (over an 11-year period) and IPA (over a 6-year period, owing to the availability of the galactomannan assay) according to the modified European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions were retrospectively enrolled. IPA cases were selected at a 1 : 4 (PM/IPA) ratio. Thoracic CT scans were reviewed by two experienced radiologists blinded to the patients' demographics and clinical outcomes. A total of 24 patients with PM, including 20 (83%) with proven PM and four (17%) with probable PM, and 96 patients with IPA, including 12 (13%) with proven IPA and 84 (87%) with probable IPA, were eventually analysed. The reverse halo sign was more common in patients with PM (54%) than in those with IPA (6%, p < 0.001), whereas some airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, were more common in patients with IPA (IPA 52% vs. PM 29%, p 0.04; IPA 49% vs. PM 21%, p 0.01; IPA 34% vs. PM 4%, p 0.003, respectively). The reverse halo sign was more common, and airway-invasive features were less common, in patients with PM than in those with IPA. These findings may help physicians to initiate Zygomycetes-active antifungal treatment earlier.

Comparison of the clinical characteristics of Mycobacterium tuberculosis and nontuberculous mycobacteria patients with joint involvement.

Nontuberculous mycobacteria (NTM) joint involvement is rare. However, the incidence of NTM disease is increasing and it is difficult to distinguish NTM from Mycobacterium tuberculosis (MTB). Here, the clinical characteristics of NTM joint involvement were compared with those of MTB. Distal joint involvement and precipitating factors were significantly more frequent for NTM joint infections. Because pathologic findings of NTM and MTB were similar, microbiological investigations are needed.

Prevalence of blaZ gene types and the cefazolin inoculum effect among methicillin-susceptible Staphylococcus aureus blood isolates and their association with multilocus sequence types and clinical outcome.

Cefazolin treatment failures have been described for bacteraemia caused by methicillin-susceptible Staphylococcus aureus (MSSA) with type A ß-lactamase and inoculum effect (InE). We investigated the prevalence of blaZ (ß-lactamase) gene types and a cefazolin InE among MSSA blood isolates in South Korea and evaluated their association with specific genotypes. The clinical impact of the cefazolin InE was also evaluated. A total of 220 MSSA isolates were collected from a prospective cohort study of S. aureus bacteraemia. A pronounced InE with cefazolin was defined as a ≥4-fold increase in the minimum inhibitory concentration (MIC) between a standard and high inoculum, resulting in a non-susceptible MIC. Sequencing of blaZ and multilocus sequence typing (MLST) were performed. Clinical outcomes were assessed in 77 patients treated with cefazolin. The blaZ gene was detected in 92 % of the 220 MSSA isolates. Type C ß-lactamase was the most common (53 %), followed by type B (20 %) and type A (17 %). Certain genotypes were significantly associated with specific ß-lactamase types (notably, ST30 and type A ß-lactamase). A pronounced cefazolin InE was observed in 13 % of isolates. Most of these (79 %) expressed type A ß-lactamase and ST30 was the predominant (55 %) clone amongst them. Cefazolin treatment failure was not observed in patients infected with strains exhibiting a pronounced InE. These strains had no impact on other clinical outcomes. In conclusion, the prevalence of a pronounced InE with cefazolin could be dependent upon distributions of MSSA genotypes. Cefazolin can likely be used for the treatment of MSSA bacteraemia (except endocarditis), without consideration of an InE.

Electro-optic switching in phase-discontinuity complementary metasurface twisted nematic cell.

Electro-optic switching of refraction is experimentally demonstrated in a phase-discontinuity complementary metasurface twisted nematic cell. The phase-discontinuity complementary metasurface is fabricated by focused-ion-beam milling, and a twisted nematic cell is constructed with complementary V-shape slot antenna metasurface. By application of an external voltage, switching is achieved between ordinary refraction and extraordinary refraction satisfying the generalized Snell's law. It has a strong implication for applications in spatial light modulation and wavelength division multiplexer/demultiplexer in a near-IR spectral range.

Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients.

BACKGROUND: Acute rejection (AR) after solid organ transplantation has been known to be a risk factor for cytomegalovirus (CMV) infection. However, data regarding the risk for CMV infection during and after anti-rejection therapy are limited. This study investigated whether the risk of CMV infection and disease within 6 months of kidney transplantation (KT) increases in CMV-seropositive KT recipients who develop AR. METHODS: A total of 992 seropositive KT recipients, including 75 patients (8%) who developed AR within 6 months after KT and 917 patients (92%) who did not, were recruited between May 2007 and April 2012. RESULTS: No significant difference was found in the incidence of CMV infection between the groups (AR group, 13% [10/75] vs. non-AR group, 10% [92/917], P = 0.37). The number of KT recipients in each group receiving preemptive therapy for CMV was similar (5% [4/75] vs. 6% [53/917], P > 0.99). While the incidence of CMV syndrome was comparable (0% [0/75] vs. 1% [12/917], P > 0.99), the incidence of tissue-invasive CMV disease (8% [6/75] vs. 3% [27/917], P = 0.04), particularly gastrointestinal CMV disease, was significantly greater in patients who experienced AR. No CMV-related mortality occurred in either group. AR (odds ratio, 2.81; 95% confidence interval, 1.08-7.29; P = 0.03) was an independent risk factor for tissue-invasive CMV disease within 6 months of KT. CONCLUSIONS: A high index of suspicion and active evaluation for tissue-invasive CMV disease in KT recipients suffering AR may be necessary to ensure appropriate treatment.

Diagnostic utility of diffusion tensor imaging in differentiating glioblastomas from brain metastases.

BACKGROUND AND PURPOSE: Differentiation of glioblastomas and solitary brain metastases is an important clinical problem because the treatment strategy can differ significantly. The purpose of this study was to investigate the potential added value of DTI metrics in differentiating glioblastomas from brain metastases. MATERIALS AND METHODS: One hundred twenty-eight patients with glioblastomas and 93 with brain metastases were retrospectively identified. Fractional anisotropy and mean diffusivity values were measured from the enhancing and peritumoral regions of the tumor. Two experienced neuroradiologists independently rated all cases by using conventional MR imaging and DTI. The diagnostic performances of the 2 raters and a DTI-based model were assessed individually and combined. RESULTS: The fractional anisotropy values from the enhancing region of glioblastomas were significantly higher than those of brain metastases (P < .01). There was no difference in mean diffusivity between the 2 tumor types. A classification model based on fractional anisotropy and mean diffusivity from the enhancing regions differentiated glioblastomas from brain metastases with an area under the receiver operating characteristic curve of 0.86, close to those obtained by 2 neuroradiologists using routine clinical images and DTI parameter maps (area under the curve = 0.90 and 0.85). The areas under the curve of the 2 radiologists were further improved to 0.96 and 0.93 by the addition of the DTI classification model. CONCLUSIONS: Classification models based on fractional anisotropy and mean diffusivity from the enhancing regions of the tumor can improve diagnostic performance in differentiating glioblastomas from brain metastases.

Reflection resonance switching in metamaterial twisted nematics cell.

Electric switching of reflection resonances at near-IR spectral range is experimentally demonstrated in a reflective metamaterial twisted nematic liquid crystal cell. Reflective metamaterial composed of nano-sized double-split ring resonator aperture is fabricated by a focused ion beam milling. Two-fold rotational symmetry of double-split ring resonators allows for two orthogonal polarization-dependent reflection resonances in the reflective metamaterial. With an external voltage of 10V across 12µm cell gap, a full switching is achieved between two reflection resonances. Dynamic measurements show the time constants of switch-on and switch-off are in the order of 100ms and 10ms, respectively.

Risk factors for false-negative results of T-SPOT.TB and tuberculin skin test in extrapulmonary tuberculosis.

PURPOSE: T-SPOT.TB, a recently developed T cell-based assay, has shown promise in diagnosing extrapulmonary tuberculosis (EPTB). However, a limited number of reports have compared the risk factors for false-negative results of tuberculin skin tests (TSTs) and T-SPOT.TB assays in patients with EPTB. We, thus, conducted a prospective, blinded, observational study to evaluate the risk factors for false-negative T-SPOT.TB and TST results in patients with EPTB. METHODS: Between April 2008 and November 2011, all adult patients with suspected EPTB were prospectively enrolled at Asan Medical Center, Seoul, South Korea (an intermediate TB-burden country). Only patients with confirmed and probable EPTB who underwent TST and T-SPOT.TB were included in the final analysis. RESULTS: Of the 324 patients who underwent both TST and T-SPOT.TB testing, 128 patients with 96 (75 %) culture- or polymerase chain reaction (PCR)-confirmed and 32 (25 %) probable EPTB were finally analyzed. T-SPOT.TB assays were less likely to yield false-negative results than TSTs [17 % (22/128) vs. 54 % (69/128), p < 0.001]. In a multivariate analysis, miliary TB was associated with false-negative TSTs [odds ratio (OR) = 5.3; 95 % confidence interval (CI) 1.7-16.1], while immunosuppression showed a trend toward false-negative TSTs (OR = 2.5; 95 % CI 0.9-6.8). Conversely, lymph node TB (OR = 0.2; 95 % CI 0.1-0.5) and skeletal TB (OR = 0.2; 95 % CI 0.1-0.5) were associated with true-positive TST results. The only risk factor for false-negative T-SPOT.TB results was TB meningitis (OR = 2.6; 95 % CI 1.0-6.6). CONCLUSIONS: Our findings suggest that T-SPOT.TB has a better sensitivity to diagnose EPTB than TST, especially in patients with immunosuppression or miliary TB.