PURPOSE: Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. MATERIALS AND METHODS: Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. RESULTS: A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome. CONCLUSION: Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.
Adenocarcinoma ; Biopsy ; Disease-Free Survival* ; Humans ; Lung ; Prescriptions ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Age is a traditional risk factor for open-heart surgery. The efficacy and safety of transcatheter edge-to-edge mitral valve repair, using MitraClip (Abbott Vascular), has been demonstrated in patients with severe mitral regurgitation (MR). Since octogenarians or older patients are usually deferred to receive open-heart surgery, the main interest of this study is to elucidate the procedural safety and long-term clinical impact of MitraClip in elderly patients. METHODS: Patients with symptomatic severe MR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before, 1-month, 6-months, and 1 year after index procedure. RESULTS: A total of 46 consecutive patients receiving MitraClip procedure were enrolled. Nineteen patients (84.2±4.0 years) were over 80-year-old and 27 (73.4±11.1 years) were younger than 80. Compare to baseline, the significant reduction in MR severity was achieved after the procedure and sustained. All the patients benefited from significant improvement in New York Heart Association functional class. The 6-minute walk test (6MWT) increased from 259±114 to 319±92 meters (p=0.03) at 1 year. The overall 1-year survival rate was 80% in the elderly and 88% in those <80 years, p=0.590. Baseline 6MWT was a predictor for all-cause mortality (odds ratio, 0.99; 95% confidence interval, 0.982–0.999; p=0.026) after the MitraClip procedure. CONCLUSIONS: Trans-catheter edge-to-edge mitral valve repairs are safe and have positive clinical impact in subjects with severe MR, even in advanced age.
Aged ; Aged, 80 and over ; Echocardiography ; Heart ; Hematologic Tests ; Humans ; Mitral Valve Insufficiency ; Mitral Valve ; Mortality ; Risk Factors ; Survival Rate

Purpose: To investigate urothelial cell proliferation, cytoskeleton, inflammation, and barrier function protein expressions in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) after intravesical platelet-rich plasma (PRP) injections Methods: A total of 19 patients with IC/BPS underwent 4 monthly intravesical PRP injections. Bladder biopsies were taken at the first and fourth PRP treatment. The bladder specimens were analyzed using the Western blot and immunochemical staining for progenitor cell markers for sonic hedgehog (Shh), CD34, and cytoskeleton proteins cytokeratin 5 (CK5), CK14, CK20; barrier function markers for zonula occludens-1 (ZO-1), E-cadherin, and intercellular adhesive molecule-1, tryptase and transforming growth factor-β (TGF-β). Global response assessment (GRA) was used to evaluate treatment outcomes. Results: The mean age of patients was 55.6 years. After PRP injections, the functional bladder capacity and maximum flow rate increased, and the visual analogue scale (VAS) of pain, interstitial cystitis (IC) symptom index, IC problem index, O’Leary-Sant symptom score, and GRA improved in all patients. Urothelium Shh, CK5, ZO-1, E-cadherin, and TGF-β expressions increased significantly after repeated PRP injections. By subgrouping, according to PRP treatment outcomes, significant increases in Shh, E-cadherin, and ZO-1 expressions were noted only in patients with GRA ≥1 or improved VAS, but not in patients with GRA=0 and no improvement in VAS. Conclusions The level of urothelial barrier function protein and cell proliferation protein expression in the patients with IC/BPS was increased after repeat intravesical PRP injections. Intravesical repeat PRP injections may have potential to improve urothelial health and result in symptoms improvement in the patients with IC/BPS.

BACKGROUND AND OBJECTIVES: Age is a traditional risk factor for open-heart surgery. The efficacy and safety of transcatheter edge-to-edge mitral valve repair, using MitraClip (Abbott Vascular), has been demonstrated in patients with severe mitral regurgitation (MR). Since octogenarians or older patients are usually deferred to receive open-heart surgery, the main interest of this study is to elucidate the procedural safety and long-term clinical impact of MitraClip in elderly patients. METHODS: Patients with symptomatic severe MR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before, 1-month, 6-months, and 1 year after index procedure. RESULTS: A total of 46 consecutive patients receiving MitraClip procedure were enrolled. Nineteen patients (84.2±4.0 years) were over 80-year-old and 27 (73.4±11.1 years) were younger than 80. Compare to baseline, the significant reduction in MR severity was achieved after the procedure and sustained. All the patients benefited from significant improvement in New York Heart Association functional class. The 6-minute walk test (6MWT) increased from 259±114 to 319±92 meters (p=0.03) at 1 year. The overall 1-year survival rate was 80% in the elderly and 88% in those <80 years, p=0.590. Baseline 6MWT was a predictor for all-cause mortality (odds ratio, 0.99; 95% confidence interval, 0.982–0.999; p=0.026) after the MitraClip procedure. CONCLUSIONS Trans-catheter edge-to-edge mitral valve repairs are safe and have positive clinical impact in subjects with severe MR, even in advanced age.

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.
Adenocarcinoma* ; Disease-Free Survival ; Epidermal Growth Factor* ; Exons ; Humans ; Lung Neoplasms ; Lung* ; Mutation Rate ; Odds Ratio ; Phosphotransferases ; Point Mutation ; Prevalence ; Receptor, Epidermal Growth Factor* ; Sequence Deletion

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset ( ≥ 40 years) Ps patients was significantly higher in type I than in types II and III (P = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P = 0.086). The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications (P = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Child ; China ; Cornified Envelope Proline-Rich Proteins ; genetics ; DNA Copy Number Variations ; DNA Methylation ; Female ; Genetic Predisposition to Disease ; Humans ; Interleukins ; genetics ; Male ; Middle Aged ; Psoriasis ; classification ; genetics ; Risk Factors ; Young Adult ; beta-Defensins ; genetics

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.
Aged ; Aged, 80 and over ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Glucose Intolerance/epidemiology* ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Skin Diseases/epidemiology*

BACKGROUND: Particulate matter (PM) < 2.5 μm (PM METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM RESULTS: DLEC1 methylation and PM CONCLUSIONS We found significant positive associations between PM
Adult ; Aged ; Air Pollutants/adverse effects* ; DNA Methylation/drug effects* ; Environmental Exposure/adverse effects* ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Particulate Matter/adverse effects* ; Taiwan ; Tumor Suppressor Proteins/metabolism*