Oral uracil-tegafur compared with intravenous chemotherapy as adjuvant therapy for resected early-stage non-small cell lung cancer patients.

BACKGROUND: Studies comparing the effectiveness of either adjuvant oral uracil-tegafur (UFT) or intravenous chemotherapy on early-stage (stage I and II) non-small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. METHODS: From January 2011 to December 2017, patients with early-stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse-free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. RESULTS: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49-0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61-0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score-matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48-1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72-1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non-drinker (HR: 0.66, 95% CI: 0.34-0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42-0.97, p = 0.0341). CONCLUSIONS: This population-based study in the real-world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early-stage NSCLC patients after surgery.

Toll-like receptor and matrix metalloproteinase single-nucleotide polymorphisms, haplotypes, and polygenic risk score differentiated between tuberculosis disease and infection.

OBJECTIVES: The association of toll-like receptors (TLRs) and matrix metalloproteinases (MMPs) single-nucleotide polymorphisms (SNPs) among latent tuberculosis (TB) infection and active TB remained less studied. METHODS: We recruited participants with TB disease (active TB) (n = 400) and TB infection (latent TB infection) (n = 203) in this study. We genotyped SNPs in TLR1, TLR2, TLR4, MMP1, MMP8, MMP9, MMP12, and tissue inhibitor of MMP2. Single-variant analysis and haplotype analysis were performed, and a polygenic risk score (PRS) was created. RESULTS: We found that SNPs in TLR1 (rs5743580, rs5743551), TLR2 (rs3804100), and MMP8 (rs2508383) were associated with different TB disease status risks. TLR1 rs5743580 was associated with a higher risk of TB disease status in genotypic, recessive, and additive models. TLR2 rs3804100 polymorphisms demonstrated significant association with TB disease status in genotypic, dominant, and additive models. In the haplotype analysis, the TLR1 haplotype was associated with a higher risk of TB disease, and the MMP12 haplotype was associated with a lower risk of TB disease. A PRS using 3 SNPs was associated with a higher risk of TB disease. CONCLUSION: This study revealed that SNP variants in TLR1, TLR2, and MMP8 differed among TB infection and disease. Haplotypes and PRS could potentially help predict TB disease status.

Association of changes in NT-proBNP, hsTnT and uric acid levels with haemodynamic changes after targeted medical therapies in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: During pulmonary arterial hypertension (PAH)-targeted therapies for patients with idiopathic pulmonary arterial hypertension (IPAH), regular follow up to evaluate treatment efficacy is essential. Serum biomarkers can reflect various pathobiological processes in IPAH and have the advantages of being non-invasive, simple to carry out and low cost. The aim of our study was to evaluate whether serum biomarkers could serve as non-invasive markers to reflect haemodynamic changes after PAH-targeted therapies in patients with IPAH. METHODS: A total of 31 eligible patients aged 38.1 ± 12.1 years (25 were female) were included in this study. Changes in haemodynamic parameters and several serum biomarkers (cardiac markers, serum uric acid, high-sensitivity C-reactive protein, hepatic and kidney function markers) were compared before and after at least six months of PAH-targeted therapies. The time interval between the blood assays and right heart catheterisation was within five days. RESULTS: After at least six months of PAH-targeted therapies, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level decreased from 579 (191-905) to 135 pg/ml (60-395) (p < 0.01), high-sensitivity cardiac troponin T (hsTnT) level decreased from 0.009 (0.006-0.012) to 0.007 ng/ml (0.005-0.01) (p < 0.01), and serum uric acid level decreased from 381.5 ± 131.4 to 327.2 ± 110.0 µmol7sol;l (p = 0.011). The change in NT-proBNP level was positively correlated with changes in pulmonary vascular resistance (r = 0.538, p < 0.01) and mean pulmonary arterial pressure (r = 0.440, p = 0.013). The change in hsTnT level was positively correlated with the change in mean right atrium pressure (r = 0.504, p < 0.01). The change in serum uric acid level was negatively correlated with that of cardiac index (r = -0.471, p < 0.01). CONCLUSION: NT-proBNP, hsTnT and serum uric acid levels can be used as non-invasive tools for evaluating the efficacy of PAH-targeted medications for IPAH patients. The role of these biomarkers in the follow up should be emphasised.

Evaluating the efficacy of endoscopic sphincterotomy on biliary-type sphincter of Oddi dysfunction: A retrospective clinical trial.

BACKGROUND: Although endoscopic sphincterotomy (EST) has a positive therapeutic effect on biliary-type sphincter of Oddi dysfunction (SOD), some patients still have little relief after EST, which implies that other functional abdominal pain may also be present with biliary-type SOD and interfere with the diagnosis and treatment of it. AIM: To retrospectively assess EST as a treatment for biliary-type SOD and analyze the importance of functional gastrointestinal disorder (FGID) in guiding endoscopic treatment of SOD. METHODS: Clinical data of 79 patients with biliary-type SOD (type I and type II) treated with EST at Affiliated Hospital of Guizhou Medical University from January 2014 to January 2019 were retrospectively collected to evaluate the clinical therapeutic effect of EST. The significance of relationship between FGID and biliary-type SOD was analyzed. RESULTS: Seventy-nine patients with biliary-type SOD received EST, including 29 type 1 patients and 50 type 2 patients. The verbal rating scale-5 (VRS-5) scores before EST were all 3 or 4 points, and the scores decreased after EST; the difference was statistically significant (P < 0.05). After EST, the serum indexes of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin in biliary-type SOD were significantly lower than before (P < 0.05). After EST, 67 (84.8%) and 8 (10.1%) of the 79 patients with biliary-type SOD had obviously effective (VRS-5 = 0 points) and effective treatment (VRS-5 = 1-2 points), with an overall effectiveness rate of 94.9% (75/79). There was no difference in VRS-5 scores between biliary-type SOD patients with or without FGID before EST (P > 0.05). Of 12 biliary-type SOD (with FGID) patients, 11 had abdominal pain after EST; of 67 biliary-type SOD (without FGID) patients, 0 had abdominal pain after EST. The difference was statistically significant (P <0.05). The 11 biliary-type SOD (with FGID) patients with recurrence of symptoms, the recurrence time was about half a year after the EST, and the symptoms were significantly relieved after regular medical treatment. There were 4 cases of post-endoscopic retrograde cholangiopancreatography pancreatitis (5.1%), and no cholangitis, bleeding or perforation occurred. Patients were followed up for 1 year to 5 years after EST, with an average follow-up time of 2.34 years, and there were no long-term adverse events such as sphincter of Oddi restenosis or cholangitis caused by intestinal bile reflux during the follow-up. CONCLUSION: EST is a safe and effective treatment for SOD. For patients with type I and II SOD combined with FGID, single EST or medical treatment has limited efficacy. It is recommended that EST and medicine be combined to improve the cure rate of such patients.

PeakPETCO2 combined with FEV1/FVC predicts vasodilator-responsive patients with idiopathic pulmonary arterial hypertension.

Cardiopulmonary exercise testing and pulmonary function test are important methods for detecting human cardio-pulmonary function. Whether they could screen vasoresponsiveness in idiopathic pulmonary artery hypertension (IPAH) patients remains undefined. One hundred thirty-two IPAH patients with complete data were retrospectively enrolled. Patients were classified as vasodilator-responsive (VR) group and vasodilator-nonresponsive (VNR) group on the basis of the acute vasodilator test. Pulmonary function test and cardiopulmonary exercise testing were assessed subsequently and all patients were confirmed by right heart catheterization. We analyzed cardiopulmonary exercise testing and pulmonary function test data and derived a prediction rule to screen vasodilator-responsive patients in IPAH. Nineteen of VR-IPAH and 113 of VNR-IPAH patients were retrospectively enrolled. Compared with VNR-IPAH patients, VR-IPAH patients had less severe hemodynamic effects (lower RAP, m PAP, PAWP, and PVR). And VR-IPAH patients had higher anaerobic threshold (AT), peak partial pressure of end-tidal carbon dioxide (PETCO2), oxygen uptake efficiency (OUEP), and FEV1/FVC (P all <0.05), while lower peak partial pressure of end-tidal oxygen (PETO2) and minute ventilation (VE)/carbon dioxide output (VCO2) slope (P all <0.05). FEV1/FVC (Odds Ratio [OR]: 1.14, 95% confidence interval [CI]: 1.02-1.26, P = 0.02) and PeakPETCO2 (OR: 1.13, 95% CI: 1.01-1.26, P = 0.04) were independent predictors of VR adjusted for age, sex, and body mass index. A novel formula (=-16.17 + 0.123 × PeakPETCO2 + 0.127×FEV1/FVC) reached a high area under the curve value of 0.8 (P = 0.003). Combined with these parameters, the optimal cutoff value of this model for detection of VR is -1.06, with a specificity of 91% and sensitivity of 67%. Compared with VNR-IPAH patients, VR-IPAH patients had less severe hemodynamic effects. Higher FEV1/FVC and higher peak PETCO2 were associated with increased odds for vasoresponsiveness. A novel score combining PeakPETCO2 and FEV1/FVC provides high specificity to predict VR patients among IPAH.

Sjögren's syndrome with nodular pulmonary amyloidosis.

We report a case of Sjögren's syndrome with nodular pulmonary amyloidosis. Amyloidosis is a heterogeneous group of diseases caused by aggregation of autologous protein and its extracellular deposition as fibrils. Most cases of nodular pulmonary amyloidosis are the result of an underlying disorder such as mucosa-associated lymphoid tissue lymphoma, rheumatoid arthritis, or multiple myeloma. Nodular pulmonary amyloidosis with Sjögren's syndrome is very rare. The clinical outcome of patients with nodular pulmonary amyloidosis is good if the underlying disease can be controlled.

Successful Management of a ROS1-Rearranged Pulmonary Pleomorphic Carcinoma Using Serial Tyrosine Kinase Inhibitors.

Pulmonary pleomorphic carcinoma (PPC) generally lacks actionable driver mutations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase or c-ros oncogene 1 (ROS1) rearrangements. The response to crizotinib, ceritinib, brigatinib, and lorlatinib in ROS1-positive advanced non-small cell lung carcinoma is well established; however, there is little mention of their successful administration in pulmonary pleomorphic carcinoma cases. We report a case of a stage II PPC with recurrence after surgical resection and developed multiple distant metastasis. The tumor was refractory to chemotherapy and immunotherapy with progressive disease. EZR-ROS1 fusion was detected by next-generation sequencing and showed a good response to serial ROS1 inhibitors combined with surgery and radiotherapy. Now under lorlatinib, all her lesions responded well during the follow-up with sustained partial remission for more than 18 months. A sustainable treatment effect can be achieved in pulmonary pleomorphic carcinoma with driver mutations with tyrosine kinase inhibitor treatment. Driver mutations should be regularly tested in pulmonary pleomorphic carcinomas.

Kinetics of oxygen uptake during unassisted breathing trials in prolonged mechanical ventilation: a prospective pilot study.

Few studies have investigated the measurement of oxygen uptake ([Formula: see text]O2) in tracheostomized patients undergoing unassisted breathing trials (UBTs) for liberation from mechanical ventilation (MV). Using an open-circuit, breath-to-breath method, we continuously measured [Formula: see text]O2 and relevant parameters during 120-min UBTs via a T-tube in 49 tracheostomized patients with prolonged MV, and calculated mean values in the first and last 5-min periods. Forty-one (84%) patients successfully completed the UBTs. The median [Formula: see text]O2 increased significantly (from 235.8 to 298.2 ml/min; P = 0.025) in the failure group, but there was no significant change in the success group (from 223.1 to 221.6 ml/min; P = 0.505). In multivariate logistic regression analysis, an increase in [Formula: see text]O2 > 17% from the beginning period (odds ratio [OR] 0.084; 95% confidence interval [CI] 0.012-0.600; P = 0.014) and a peak inspiratory pressure greater than - 30 cmH2O (OR 11.083; 95% CI 1.117-109.944; P = 0.04) were significantly associated with the success of 120-min UBT. A refined prediction model combining heart rate, energy expenditure, end-tidal CO2 and oxygen equivalent showed a modest increase in the area under the receiver operating characteristic curve of 0.788 (P = 0.578) and lower Akaike information criterion score of 41.83 compared to the traditional prediction model including heart rate and respiratory rate for achieving 48 h of unassisted breathing. Our findings show the potential of monitoring [Formula: see text]O2 in the final phase of weaning in tracheostomized patients with prolonged MV.

[Association of oxygen uptake efficiency in exercise test with exercise capacity in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To explore the characteristics of oxygen uptake efficiency (OUE) in patients with chronic obstructive pulmonary disease (COPD), and to analyze the relationship between OUE and the exercise capacity. METHODS: Pulmonary function test and cardiopulmonary exercise test were performed in 59 patients with stable COPD (grade I, n = 15; grade II, n = 16; grade III, n = 19; grade IV, n = 9) and 29 healthy volunteers of the same age. Their successive breathing respiratory exchange parameters were collected and analyzed. t test and χ(2) test were used for 2 sample comparison, while multiple comparisons among groups were performed by using single factor analysis of variance. Correlation analysis was done by Pearson correlation test. RESULTS: Compared with the normal control group [(2.2 ± 0.4) L·min(-1)·lg(L·min(-1))(-1); (35 ± 4) ml/L], the OUES and OUEP of the COPD patient group [(1.9 ± 0.3) L·min(-1)·lg(L·min(-1))(-1); (31 ± 5) ml/L]were significantly lower (t = 4.57, 3.39, all P < 0.01) . The OUE of the grade I patients showed no significant difference compared with the normal control group (t = 0.36-1.49, all P > 0.05), while the OUES of the grade II-IV patients [(2.05 ± 0.26), (1.76 ± 0.28) and (1.63 ± 0.19) L·min(-1)·lg(L·min(-1))(-1)] decreased significantly compared to the normal control group [(2.23 ± 0.39) L·min(-1)·lg(L·min(-1))(-1); t = 2.42-5.26, all P < 0.05]. The OUEP and the OUE at the anaerobic threshold of the grade II-III patients [(31 ± 4) and (31 ± 5), (29 ± 5) and (29 ± 5) ml/L] decreased significantly compared to the normal control group [(35 ± 4) and (34 ± 4) ml/L, t = 2.18-4.83, all P < 0.05]. The OUES, OUEP and the OUE at the anaerobic threshold in COPD patients were correlated (r = 0.500-0.625, all P < 0.01) positively with the exercise tolerance (peak VO2% pred). CONCLUSIONS: The oxygen uptake efficiency of patients with COPD is significantly reduced compared to that of the normal subjects, and is correlated positively with the exercise capacity.

Development of NTU standard Chinese Brain Template: morphologic and functional comparison with MNI template using magnetic resonance imaging.

BACKGROUND AND PURPOSE: The brain structure mismatch between western and eastern people may lead to an inappropriate interpretation of neurocognitive studies. To minimize this interracial misinterpretation, we developed the National Taiwan University Chinese Brain Template (NTU-CBT). METHODS: 102 (M/F = 55/47) healthy Chinese subjects were recruited and received 3T MR brain scans. The template development processes were based on the construction process of Montreal Neurological Institute (MNI) template. Further pilot functional magnetic resonance imaging (fMRI) studies with blocked design visual stimulation and foot tapping task were performed on 3 volunteers and applied to both MNI template and NTU-CBT for analyses. RESULTS: 7 subjects were excluded due to motion artifacts. The average brain size of 95 (M/F = 50/45) subjects was 16.0 cm in length, 13.9 cm in width and 11.3 cm in height, which was 88.9%, 97.9% and 84.3% of the size of MNI template, respectively. Maximum dimensional differences came from the height of superior brain and the length of posterior brain. The average activation voxel volume of the fMRI studies applying to NTU-CBT was 80.7% of that to MNI template in visual stimulation, and 72.8% in foot tapping task. Noticeable mismatches were noted between interpolating original data to NTU-CBT and MNI template. CONCLUSIONS: Morphologic differences between MNI template and NTU-CBT do lead to spatial mismatch in functional studies, especially at cortical regions of superior and posterior brain. With the development of NTU-CBT, we look forward to more accurate interpretation in neurocognitive studies for Chinese subjects.

Brain activation in patients with idiopathic hyperacusis.

The neural network associated with idiopathic hyperacusis is still not well known. We studied the brain activation of 3 middle-aged patients with mild to moderate hyperacusis by functional magnetic resonance imaging while they were listening to white noise binaurally. In addition to the temporal lobes, in all patients, sound elicited activation in the frontal lobes (superior, middle, or inferior frontal gyri) and occipital lobes (precuneus, cuneus, superior occipital gyrus, lingual gyrus, or fusiform gyrus). The parahippocampus was activated in 2 of 3 patients. Furthermore, the precentral and postcentral gyri, superior and inferior parietal lobules, thalamus, midbrain, claustrum, insula, posterior cingulated gyrus, and orbital and rectal gyrus were also activated in one patient. The neural network associated with idiopathic hyperacusis might be associated with the frontal lobes and parahippocampus.

Protein preparation, crystallization and preliminary X-ray crystallographic analysis of N-acetylglutamate kinase from Streptococcus mutans.

The N-acetylglutamate kinase from Streptococcus mutans was expressed in Escherichia coli in soluble form and purified to homogeneity. Crystals suitable for X-ray diffraction were obtained by hanging-drop vapor diffusion method and diffracted to 2.06 A. The crystal belonged to space group P2(1)2(1)2, with unit cell parameters a = 57.19 A, b =94.76 A, c =47.58 A. The gel filtration and initial phasing results showed that the enzyme exists as a monomer, which is different from previously reported N-acetylglutamate kinases.

Brain activation in patients with congenital bilateral hearing impairment.

Twelve patients with idiopathic, congenital, symmetric, moderate-to-severe sensorineural hearing loss participated in this study. Functional magnetic resonance imaging was performed while speech sounds were presented to each patient monaurally. Notable blood oxygenation level-dependent responses were clustered mainly in the superior temporal gyrus and transverse temporal gyrus of both hemispheres during right and left ear stimulation. In addition, the middle temporal gyrus of the right hemisphere was activated during right ear stimulation. The activation pattern was very similar to that of participants with normal hearing. Thus, as long as peripheral acoustic stimulation has not been totally absent from childhood, the classical activation pattern can be elicited in patients with congenital bilateral hearing impairment.

Aging effects on the activation of the auditory cortex during binaural speech listening in white noise: an fMRI study.

The functional significance of age-related pathology of the auditory cortex is not well established. The purpose of this study was to elucidate the activation pattern of the auditory cortex in aged subjects in response to speech signals. Functional magnetic resonance imaging was performed on 12 elderly subjects with normal hearing acuity during selective listening with both ears to speech sounds in quiet and in white noise. Twelve young, normal-hearing subjects served as controls. Our results showed that activation of the auditory cortex during selective listening to speech decreased in elderly subjects compared to young subjects, especially in noise. Reduced activation occurred in the anterior and posterior regions of the bilateral superior temporal gyrus (STG), but mainly in the posterior part of the left STG. In addition, background noise had a greater masking effect on speech perception in the elderly subjects than in the young ones. These findings suggest that early functional changes associated with central presbycusis occur mainly in the posterior part of the left STG.

Changes in activation of the auditory cortex following long-term amplification: an fMRI study.

CONCLUSION: Speech-elicited activation decreased after monaural amplification bilaterally during unaided or aided ear stimulation, but tended to recover later at the contralateral hemisphere during aided ear stimulation. OBJECTIVES: The purpose of this study was to investigate the changes in the activation pattern of auditory cortex following long-term monoaural amplification. PATIENTS AND METHODS: Serial functional magnetic resonance images were obtained while speech sounds were presented to the aided (right) and unaided (left) ears of eight hearing-impaired subjects before, 3 months, and 9 months after beginning the use of a single hearing aid. The results were analyzed by group analysis. RESULTS: Before hearing aid fitting, we found that activation patterns of the auditory cortex were somewhat segmented in the left hemisphere, regardless of whether the speech sounds were delivered to right or left ear. Cross projection was lost in response to right ear stimulation. After hearing aid fitting, on the unaided side stimulation, the activation tended to decrease progressively on both sides 3 months and 9 months after beginning monoaural amplification. On the aided side stimulation, activation also decreased 3 months after amplification bilaterally, but tended to recover at the contralateral hemisphere after 9 months of amplification. Cross projection was restored in response to right ear stimulation.

Dissociated roles of the middle frontal gyri in the processing of Chinese characters.

The present study examined a hypothesis that the right middle frontal gyrus participates in processing orthography of Chinese characters, while the left middle frontal gyrus mediates access to phonology and semantics. Brain activation during three character tasks, which required processing orthography, phonology, or semantics of Chinese characters, respectively, was measured by functional magnetic resonance imaging. Comparable neural activity in the right middle frontal gyrus was observed in all three character tasks that always demand orthographical processing. In contrast, the left middle frontal gyrus showed greater activation in the phonological and semantic tasks than in the orthographic task. These results suggest that the right and left middle frontal gyrus have dissociable functions in achieving Chinese character recognition.

The effects of masking on the activation of auditory-associated cortex during speech listening in white noise.

CONCLUSIONS: Noise-induced masking has different effects on the two hemispheres during speech listening. Auditory-associated cortices in the left hemisphere were more affected by masking than the right side. However, activation of primary and secondary auditory cortices was not affected in both sides under the masking with high signal to noise ratio. OBJECTIVES: The purpose of this study was to investigate the effects of masking on the central auditory system during speech listening in white noise. MATERIALS AND METHODS: Twelve healthy young subjects with normal hearing participated in this study. Functional magnetic resonance imaging (fMRI) was performed while subjects were listening to speech sounds alone and speech plus white noise binaurally. RESULTS: In humans, the activation of several regions including the middle parts of the superior and middle temporal gyri, parahippocampal gyrus, cuneus and thalamus of the left hemisphere was significantly reduced under the masking paradigm with +5 dB signal to noise ratio. In addition, reduced activation was also found at the lingual gyrus, anterior and middle parts of the superior temporal gyrus (STG), uncus, fusiform gyrus, and inferior frontal gyrus of the right hemisphere during masking.

Hemispheric difference in activation patterns of human auditory-associated cortex: an FMRI study.

The purpose of this study was to demonstrate interhemispheric differences in activation patterns of the auditory-associated cortex elicited by a series of sounds. Functional magnetic resonance imaging was performed while different sounds were presented binaurally to 10 healthy subjects with normal hearing. Characteristic activation patterns were elicited although variability was shown between subjects. The activation number was significantly higher on the right than on the left side for non-speech (but not for speech) stimulations. As stimulation increased in complexity (from a pure tone to white noise to ocean wave sounds to classical music), the activation pattern of the superior temporal lobe became more pronounced in both hemispheres while that of the auditory cortex tended to become more sustained and concentrated on the right rather than on the left side. No hemispheric differences in activation pattern were seen in response to speech.