The differential impact of Type D personality on the prognosis of patients with stable coronary artery disease.

OBJECTIVE: This study investigated the association between Type D personality and prognoses in stable coronary artery disease (CAD) patients by mode of endpoints, age, and methodological debates to explain substantial heterogeneity among Type D studies. DESIGN: The prospective study was designed to recruit 590 stable CAD patients in Taiwan. Main outcome measures: Demographic and clinical characteristics, and the 14-item Type D scale-Taiwanese version were recorded at discharge. RESULTS: Hierarchical logistic regression analyses showed, regardless of the methodological debates, Type D personality was significantly associated with MACEs though not non-cardiac outcomes in stable CAD patients after adjusting for possible confounders. Furthermore, Type D personality was especially associated with MACEs in stable CAD patients with younger age (<65 y), rather than older age (≥65 y). Subgroup analysis also showed the adverse effect of Type D personality on MACEs was larger among males, those living in the rural region, those with PTCA or stent, those with heart failure, hypertension, diabetes, and those who were smokers. CONCLUSIONS: Regardless of whether the methodological debate is dichotomous or continuous, Type D personality was significantly associated with MACEs in stable CAD patients, some of whom had younger age, were males, smokers, or had comorbidities.

A robust approach for endotracheal tube localization in chest radiographs.

Precise detection and localization of the Endotracheal tube (ETT) is essential for patients receiving chest radiographs. A robust deep learning model based on U-Net++ architecture is presented for accurate segmentation and localization of the ETT. Different types of loss functions related to distribution and region-based loss functions are evaluated in this paper. Then, various integrations of distribution and region-based loss functions (compound loss function) have been applied to obtain the best intersection over union (IOU) for ETT segmentation. The main purpose of the presented study is to maximize IOU for ETT segmentation, and also minimize the error range that needs to be considered during calculation of distance between the real and predicted ETT by obtaining the best integration of the distribution and region loss functions (compound loss function) for training the U-Net++ model. We analyzed the performance of our model using chest radiograph from the Dalin Tzu Chi Hospital in Taiwan. The results of applying the integration of distribution-based and region-based loss functions on the Dalin Tzu Chi Hospital dataset show enhanced segmentation performance compared to other single loss functions. Moreover, according to the obtained results, the combination of Matthews Correlation Coefficient (MCC) and Tversky loss functions, which is a hybrid loss function, has shown the best performance on ETT segmentation based on its ground truth with an IOU value of 0.8683.

Targeting YAP1 ameliorates progesterone resistance in endometriosis.

STUDY QUESTION: Does YAP1 inhibition alleviate progesterone resistance in endometriosis? SUMMARY ANSWER: YAP1 inhibition reduces progesterone resistance in vitro and in vivo. WHAT IS KNOWN ALREADY: Progesterone resistance not only causes treatment failure for endometriosis but also inhibits eutopic endometrial cell proliferation, dysregulates decidualization, and reduces the success rates of pregnancy. Hippo/yes-associated protein 1 (YAP1) signaling pathway plays an important role in the pathogenesis of endometriosis. STUDY DESIGN, SIZE, DURATION: Paraffin-embedded tissues containing paired endometriotic and endometrial specimens (n = 42) and serum samples isolated from normal controls (n = 15) or endometriotic patients with (n = 25) or without (n = 21) prior dienogest treatment were analyzed. A mouse model of endometriosis was also used to evaluate the effects of YAP1 inhibition on progesterone resistance. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary endometriotic and endometrial stromal cells treated with YAP1 inhibitor or miR-21 mimic/inhibitor were used for the in vitro studies including decidualization induction, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation. Tissue specimens and serum from human and mouse were used for immunohistochemistry staining, exosome isolation, and microRNA (miRNA) quantification, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Herein, we report, by using ChIP-PCR and RNA-IP, that YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. Upregulation of miR-21-5p not only reduces PGR expression but also inhibits endometrial stromal cell decidualization. Indeed, levels of YAP1 and miR-21-5p are inversely correlated with the level of PGR in human endometrial samples. In contrast, knockdown of YAP1 or treatment with verteporfin (VP), a YAP1 inhibitor, reduces miR-21-5p expression, thus leading to an increase in PGR expression in ectopic endometriotic stromal cells. In the mouse model of endometriosis, treatment with VP increases PGR expression and enhances decidualization. More importantly, VP synergistically increases the treatment effect of progestin in causing the regression of endometriotic lesions and improves the decidualization capability of the endometrium. Interestingly, treatment with dienogest, a synthetic progestin, reduces YAP1 and miR-21-5p expression in human cells and in the mouse model of endometriosis. Patients who received dienogest treatment for 6 months show a significant decrease in serum extracellular vesicle-associated miR-21-5p level. LARGE SCALE DATA: A public dataset (GSE51981) containing a large cohort of endometriotic tissues is available from the Gene Expression Omnibus (GEO). LIMITATIONS, REASONS FOR CAUTION: A large cohort of clinical samples is needed to verify the current diagnostic value of miR-21-5p in future studies. WIDER IMPLICATIONS OF THE FINDINGS: The reciprocal regulation of YAP1 and PGR suggests that combined YAP1 inhibitor and progestin may be a better therapeutic approach for treating endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Ministry of Science and Technology, Taiwan (MOST-111-2636-B-006-012, MOST-111-2314-B-006-075-MY3, and MOST-106-2320-B-006-072-MY3). The authors have no conflict of interest to disclose.

Type D Personality as a Risk Factor for Adverse Outcome in Patients With Cardiovascular Disease: An Individual Patient-Data Meta-analysis.

OBJECTIVE: Type D personality, a joint tendency toward negative affectivity and social inhibition, has been linked to adverse events in patients with heart disease, although with inconsistent findings. Here, we apply an individual patient-data meta-analysis to data from 19 prospective cohort studies ( N = 11,151) to investigate the prediction of adverse outcomes by type D personality in patients with acquired cardiovascular disease. METHOD: For each outcome (all-cause mortality, cardiac mortality, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiac event, any adverse event), we estimated type D's prognostic influence and the moderation by age, sex, and disease type. RESULTS: In patients with cardiovascular disease, evidence for a type D effect in terms of the Bayes factor (BF) was strong for major adverse cardiac event (BF = 42.5; odds ratio [OR] = 1.14) and any adverse event (BF = 129.4; OR = 1.15). Evidence for the null hypothesis was found for all-cause mortality (BF = 45.9; OR = 1.03), cardiac mortality (BF = 23.7; OR = 0.99), and myocardial infarction (BF = 16.9; OR = 1.12), suggesting that type D had no effect on these outcomes. This evidence was similar in the subset of patients with coronary artery disease (CAD), but inconclusive for patients with heart failure (HF). Positive effects were found for negative affectivity on cardiac and all-cause mortality, with the latter being more pronounced in male than female patients. CONCLUSION: Across 19 prospective cohort studies, type D predicts adverse events in patients with CAD, whereas evidence in patients with HF was inconclusive. In both patients with CAD and HF, we found evidence for a null effect of type D on cardiac and all-cause mortality.

Alterations of sympathetic dynamics after atrial fibrillation ablation by analysis sympathetic nerve activity provide prognostic value for recurrence and mechanistic insights into ablation.

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Success is associated with autonomic function modulation; however, the relationship between the changes after ablation is not fully understood. We aimed to investigate the effect of ablation on autonomic modulation by skin sympathetic nerve activity (SKNA) using conventional electrocardiogram (ECG) electrodes and to predict the treatment success. Methods: We enrolled 79 patients. We recorded neuECG for 10 min at 10 kHz before and after ablation. The NeuECG was bandpass-filtered (500-1,000 Hz) and integrated at intervals of 100 ms (iSKNA). iSKNA was averaged over different time windows (1-, 5-,10-s; aSKNAs), and burst analyses were derived from aSKNAs to quantify the dynamics of sympathetic activities. AF recurrence after 3 months was defined as the study endpoint. Results: Sixteen patients experienced AF recurrence after the ablation. For burst analysis of 1-s aSKNA, the recurrence group had a higher bursting frequency than the non-recurrence group (0.074 ± 0.055 vs. 0.109 ± 0.067; p < 0.05) before ablation. The differences between pre- and post-ablation of firing duration longer than 2 s were more in the non-recurrence group (2.75 ± 6.41 vs. -1.41 ± 5.14; p < 0.05), while no significant changes were observed in the percentage of duration longer than 10 s using 5-s aSKNA. In addition, decreases in differences in firing frequency and percentage of both overall firing duration and longer firing duration (> 2 s) between pre- and post-ablation were independently associated with AF recurrence and more area under receiver operating characteristics (ROC) curve in combination with CHADS2 score (0.833). Conclusion: We demonstrated the applicability of neuECG for determining sympathetic modulation during AF ablation. Decreasing sympathetic activity is the key to successful ablation.

Different Characteristics and Clinical Outcomes between Early-Onset and Late-Onset Asthma: A Prospective Cohort Study.

Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan's National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (<40 years). Of the consecutive 101 patients with asthma, 21 patients (20.7%) had EOA and 80 (79.3%) had LOA. In the 12-month period, patients with EOA had higher declines in forced expiratory volume in one second (FEV1; −2.1 ± 8.4 vs. 6.8 ± 13.1, % of predicted value, p = 0.037) and forced vital capacity (FVC; −4.6 ± 12.0 vs. 6.1 ± 13.6, % of predicted value, p = 0.023) than patients with LOA. Patients with nonatopic EOA had a significantly higher exacerbation rate at 12 months than patients with nonatopic LOA (50% vs. 11.8%, p = 0.012). Identification of different phenotypes of asthma is important in clinical practice because treatment responses may differ.

Prospective cohort study of psoriatic arthritis risk in patients with psoriasis in a real-world psoriasis registry.

BACKGROUND: The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment. OBJECTIVE: To develop a model to predict the 2-year risk of developing PsA among patients with PsO. METHODS: This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%). LIMITATIONS: PsA misclassification bias by dermatologists. CONCLUSION: PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.

Cardiometabolic multimorbidity is common among patients with psoriasis and is associated with poorer outcomes compared to those without comorbidity.

BACKGROUND: Associations between cardiometabolic multimorbidity and response to therapy in psoriasis are unknown. OBJECTIVE: Determine the associations of multimorbidity with response to biologic treatment in psoriasis patients. METHODS: CorEvitas Psoriasis Registry participants who initiated biologic therapy and had 6-month follow-up were stratified by 0, 1, 2+ comorbidities (diabetes, hypertension, hyperlipidemia). Adjusted odds ratios (95% CIs) were calculated overall and separately by biologic class (TNFi, IL-17i, IL-12/23i + IL-23i), to assess the likelihood of achieving response for the 1 and 2+ groups vs. 0. RESULTS: Of 2,923 patients, 49.5%, 24.7% and 25.8% reported 0, 1 and 2+ comorbidities, respectively. Overall, likelihood of PASI75 was 18% (OR = 0.82; 95%CI: 0.67, 1.00) and 23% (OR = 0.77; 95%CI: 0.63, 0.96) lower in those with 1 and 2+ comorbidities, respectively, vs. 0. In those who initiated IL-17i, odds of PASI75 and PAS90 were 34% (OR = 0.66; 95%CI: 0.48-0.91) and 35% (OR = 0.65; 95%CI: 0.47-0.91) lower in the 2+ multimorbidity cohort. No significant associations were found among users of TNFi or IL-12/23i + IL-23i groups in the multimorbidity group. LIMITATIONS: Patients may not be representative of all psoriasis patients. CONCLUSION: Multimorbidity in psoriasis may decrease the likelihood of achieving treatment response to biologic therapy and should be considered when discussing treatment expectations with patients.

Early Diagnosis and Intervention of Acute Renal Infarction with Catheter-Directed Thrombolytic Therapy.

Background: Acute renal infarction is a rare and under-diagnosed disease for which the optimal treatment is unknown. Objectives: This study aimed to determine the utility of catheter-directed thrombolysis (CDT) to treat acute renal infarction. Methods: From November 2010 to September 2017, 13 patients with acute renal infarction were treated with CDT. The diagnosis was confirmed by contrast-enhanced computed tomography and renal angiography. Results: The most common symptoms and signs were flank pain (53.8%) and abdominal pain (30.8%). More than two-thirds of the patients (69.2%) had atrial fibrillation. In successful reperfusion cases, the median time from symptom onset to diagnosis was 6 hours, and the average time from diagnosis to treatment was 3.5 hours. Complete resolution of thrombi in the renal artery was achieved in 10 of the 13 patients (76.9%) and partial resolution in two patients (15.4%). Only one patient (7.7%) failed to respond to treatment. Compared with admission, renal function was significantly improved at 6 months. No major complications occurred during the course of CDT therapy. Conclusions: CDT offers an alternative to surgical intervention and can achieve good angiographic results with an early diagnosis and intervention. It is relatively safe and can restore at least partial renal function.

The impact of sources of perceived social support on readmissions in patients with heart failure.

BACKGROUND: Lower levels of perceived social support have been known as an independent predictor of hospital readmissions in patients with heart failure (HF). However, the impact of sources of perceived social support on readmissions remain unexplored. PURPOSE: The main purpose of this study was to investigate and compare the relative importance of social support from significant other, family, and friends on all-cause readmission and cardiac readmission in patients with HF. METHODS: The prospective cohort study was used to recruit a total of 299 patients with HF in Taiwan between May 2012 and December 2014. Demographic and clinical characteristics, Multidimensional Perceived Social Support Scale (MPSSS), and 18-month follow-up readmissions were recorded during the hospital stay. Univariate and multivariate logistic regressions were constructed to determine the impact of levels and sources of perceived social support with all-cause readmission and cardiac readmission. RESULTS: A total of 158 patients (52.8%) and 118 patients (39.5%), respectively, had all-cause readmission and cardiac readmissions within 18 months. Multivariate logistic regression yielded inverse associations between levels of perceived social support and readmissions by 18-months. Importantly, social support from significant other was significantly associated with a lower risk of readmissions, both of all-cause readmission and cardiac readmission, in patients with HF, even after controlling for possible covariates, social support from family and friends. CONCLUSIONS: Social support from significant other, rather than from family and friends, was relatively and inversely associated with 18-month all-cause readmission and cardiac readmission in patients with HF, which is consistent with the hierarchical compensatory model.

Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry.

BACKGROUND: Psoriasis is associated with comorbid systemic metabolic disease. OBJECTIVE: To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry. METHODS: Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each. RESULTS: Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group. LIMITATIONS: The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences. CONCLUSION: Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.

Assessing the change in disease severity based on depressive symptoms in real-world psoriasis patients.

Aim: To evaluate whether the presence of a history of depression hinders psoriasis response to systemic therapies and to delineate baseline characteristics of patients whose depressive symptoms improved on systemic treatment. Methods: We studied patients within the Corrona® Psoriasis Registry, a prospective, multicenter observational disease-based registry, that were enrolled through September 2018, comparing changes from enrollment to 12-month visit. Results: There was a statistically significant improvement in all disease characteristics and most patient-reported outcomes in patients reporting a history of depression and in those that did not while there was no statistically significant difference in the degree of change comparing these two cohorts. Patients who noted improvement in depressive symptoms had more severe baseline disease characteristics and reported overall worse baseline patient-reported outcomes. Conclusions: History of depression does not portend a differential response to systemic treatment. Patients with improvement in depressive symptoms had worse baseline characteristics.

Unique clinical features and long term follow up of survivors of sudden cardiac death in an Asian multicenter study.

There has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia-Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy.

The Association Between Traditional Chinese Medicine Body Constitution Deviation and Essential Hypertension: A Case-Control Study.

BACKGROUND: The prevention and treatment of hypertension is valued globally. The World Health Organization advocates combining traditional medicines in the prevention and treatment of diseases. Traditional Chinese medicine (TCM) assumes that diseases originate from the attenuation of one's body constitution. A few studies have found that hypertension is correlated with TCM body constitution. However, body constitution is also affected by living environment. Therefore, investigating the correlation between deviations in body constitution and essential hypertension in different living environments is necessary to provide the basis for using TCM in combination with conventional Western medicine to prevent and treat hypertension. PURPOSE: The aim of this study was to explore the association between TCM body constitution deviation and essential hypertension. METHODS: A case-control study was designed. Participants were selected from the outpatient clinics and neighboring communities of a regional teaching hospital in southern Taiwan. The study included 210 hypertension and 210 nonhypertension cases. Blood pressures were measured using an electronic sphygmomanometer to confirm the presence or absence of hypertension. The TCM Body Constitution Questionnaire, demographic datasheet, and hypertension-related factors questionnaire were used to collect data. RESULTS: A higher proportion of patients with body constitution deviation were found in the hypertension group than the nonhypertension group. The proportions of patients with Yin-Xu, Yang-Xu, and stasis constitution were 44.8%, 32.4%, and 30.6%, respectively, in the hypertension group and 28.6%, 25.2%, and 19.6%, respectively, in the nonhypertension group. After performing univariate analysis, the results showed significant differences between the two groups in terms of average body mass index; emotional traits of anger, worry, and fear; hyperlipidemia; hyperuricemia; Yin-Xu constitution; and stasis constitution. However, the multivariate analysis revealed having a Yin-Xu constitution to be a risk factor of essential hypertension after adjusting for age, gender, body mass index, emotional traits, drinking habit, hyperlipidemia, and hyperuricemia. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results suggest that Yin-Xu and stasis constitutions are respectively associated with essential hypertension. The findings offer a valuable reference to governments and healthcare professionals to prevent the risk of essential hypertension. Screening and healthcare measures for TCM Yin-Xu or stasis constitution may be included in related prevention plans to minimize public exposure to the risk factors of essential hypertension.

Systemic lupus erythematosus is associated with impaired autophagic degradation via interleukin-6 in macrophages.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with dysregulated interleukin (IL)-6 and autophagy. Although such disturbances are increasingly recognized in patients with SLE and animal models of the disease, little is known about the specific role of IL-6 and autophagy in SLE macrophages. Here, we investigated alterations in the IL-6 axis and autophagy in macrophages derived from patients with SLE and determined whether IL-6 modulates autophagy using human macrophage models. Serum IL-6 detected by ELISA was higher in SLE patients (n = 19) than in normal controls (n = 19, p < 0.001). Levels of the IL-6 receptor (IL-6R) and autophagic markers LC3B and p62 in SLE and normal macrophages were assessed by real-time PCR, western blotting, and immunofluorescence. Compared with normal macrophages, SLE macrophages not only overexpressed IL-6Rs but also exhibited impaired autophagic degradation as evidenced by elevated levels of LC3B and p62. In vitro analyses using macrophage models revealed that prolonged exposure to exogenous recombinant human IL-6 induced a marked impairment of autophagic degradation indicated by elevated levels of LC3B and p62 in both primary macrophages and transformed macrophages. Pretreatment with tocilizumab, a humanized anti-IL-6R monoclonal antibody, restored autophagic degradation and reversed p62 accumulation in a paracrine manner in macrophages. These findings demonstrate that SLE involves IL-6-induced impairment of autophagic degradation through augmentation of IL-6R in human macrophages.

Negative Affectivity Is Associated with a Higher Systolic and Diastolic Blood Pressure in Normotensive Middle-Aged and Older Adults: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: Type D personality, characterized by two stable traits (social inhibition and negative affectivity), is associated with adverse cardiovascular events. A possible mediating factor for this association could be hypertension. Previous research has shown that individuals with Type D personality were associated with an increased risk of hypertension. However, the association of negative affectivity and social inhibition on blood pressure in normotensive individuals has not yet been reported. Therefore, the aim of this study was to investigate whether negative affectivity and social inhibition were associated with systolic and diastolic blood pressure in normotensive middle-aged and older Taiwanese adults. MATERIALS AND METHODS: A cross-sectional study design was used. Individuals attending general health examination at a regional hospital in southern Taiwan who were 40 to 75 years old were recruited. Patients with self-reported hypertension or currently receiving antihypertensive medication were excluded. Negative affectivity and social inhibition were assessed with the 14-item Type D Scale-Taiwanese version. Multiple linear regression analyses were conducted to determine the association of Z-score transformed negative affectivity and social inhibition on blood pressure. RESULTS: A total of 92 patients with a mean age of 51.5 years were included in the study, and 15 (16.3%) were defined as having a Type D personality. The Z-score transformed negative affectivity score (p = 0.035, effect size = 0.18) and Z-score transformed social inhibition score (p = 0.054, effect size = 0.17) were significantly associated with a higher systolic blood pressure. In addition, the Z-score transformed negative affectivity score (p = 0.036, effect size = 0.28) and Z-score transformed social inhibition score (p = 0.154, effect size = 0.24) were significantly associated with a higher diastolic blood pressure. CONCLUSIONS: Negative affectivity of the Type D personality was significantly associated with higher systolic and diastolic blood pressure, with a medium effect size, in apparently healthy middle-aged and older adults. Assessment of negative affectivity may be clinically useful in identifying individuals at risk of hypertension.

Oral vinorelbine plus cisplatin with concomitant radiotherapy as induction therapy for stage III non-small cell lung cancer: Results of a single-arm prospective cohort study.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is an optimal recommended treatment for stage III non-small cell lung cancer (NSCLC). Herein, we aimed to investigate the efficacy and safety of oral vinorelbine plus cisplatin with concomitant radiotherapy for stage III NSCLC. METHODS: This prospective, open-label, single-arm, observational cohort study was performed between January 2010 and September 2016. Patients were treated with two cycles of chemotherapy with 60 mg/m2 intravenous cisplatin on day 1 and 50 mg/m2 oral vinorelbine on days 1, 8, and 15; radiotherapy was administered concurrently from day 1 when chemotherapy was initiated. A total dose of 66-70 Gy radiotherapy was delivered in daily fractions of 2 Gy for 6.5-7 consecutive weeks. The tumor response was assessed after completing concomitant treatment. RESULTS: A total of 58 patients were enrolled and analyzed; 31 patients had stage IIIA NSCLC and 27 had stage IIIB NSCLC. After induction CCRT, 31 patients achieved an objective response (complete response in one and partial response in 30; the response rate was 53.4%). The median progression-free survival was 6.73 months (95% confidence interval [CI], 5.42-7.91), duration of response was 12.30 months (95% CI, 5.59-19.01), and overall survival was 24.83 months (95% CI, 19.26-30.21). No treatment-related mortality was observed, and neutropenia was the most common grade 3 and 4 treatment-related toxicity (11 patients; 18.9%). CONCLUSIONS: CCRT with the weekly regimen of oral vinorelbine plus triweekly cisplatin was effective and safe for stage III NSCLC.

Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib.

BACKGROUND: The first (1G) and second (2G) generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) show differential inhibitory capacities towards EGFR T790M-mutated non-small-cell lung cancer (NSCLC) cells. OBJECTIVE: To assess the ratio of the allele fractions of T790M (AFT790M) to EGFR-activating mutations (AFmEGFR) in patients treated with 1G and 2G EGFR TKIs who acquired T790M-mediated resistance and to determine the relationship between AF and the later efficacy of osimertinib. PATIENTS AND METHODS: The efficacy of osimertinib was reviewed for 54 T790M-positive EGFR-mutated NSCLC patients grouped by the generation of prior EGFR TKI use (1G vs. 2G). AFmEGFR and AFT790M were determined by QuantStudio digital PCR using tissues obtained upon acquired resistance. RESULTS: The progression-free survival (PFS; 20.3 vs. 11.6 months, p = 0.031) and the 1-year PFS rate (63.2 vs. 37.5%, p = 0.029) for osimertinib were significantly better for group 1G compared to group 2G. The ratio of AFT790M to AFmEGFR in group 1G was significantly higher than in group 2G (46.16 ± 5.40% vs. 25.86 ± 4.25%, p = 0.009). An unbiased analysis revealed three AF-associated clusters (ARCs) suggesting the ratio of AFT790M to AFmEGFR correlates with the efficacy of osimertinib. We found all patients in ARC2 having the highest ratio of AFT790M to AFmEGFR to have previously been treated with a 1G EGFR TKI and to show the longest osimertinib PFS compared to ARC3 (NR vs. 11.9 months, p = 0.060) and ARC1 (NR vs. 12.4 month, p = 0.045). CONCLUSIONS: Acquired T790M fraction of EGFR-mutated NSCLC is linked to different generations of prior EGFR TKI use and the later efficacy of osimertinib.