Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR-mutated advanced non-small-cell lung.

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.

5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells. METHOD: The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells. RESULT: Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone. CONCLUSIONS: In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.

SiMAIM: identifying sockpuppets and puppetmasters on a single forum-oriented social media site.

With the Internet becoming indispensable in our lives, social media has become an integral part of our lives. However, with this has come the phenomenon of a single user registering multiple accounts (sockpuppets) to advertise, spam, or cause controversy on social media sites, where the user is called the puppetmaster. This phenomenon is even more evident on forum-oriented social media sites. Identifying sockpuppets is a critical step in stopping the above-mentioned malicious acts. The identification of sockpuppets on a single forum-oriented social media site has seldom been addressed. This paper proposes a Single-site Multiple Accounts Identification Model (SiMAIM) framework to address this research gap. We used Mobile01, Taiwan's most popular forum-oriented social media site, to validate SiMAIM's performance. SiMAIM achieved F1 scores between 0.6 and 0.9 on identifying sockpuppets and puppetmasters under different datasets and settings. SiMAIM also outperformed the compared methods by 6-38% in F1 score.

Local Consolidative Therapy May Have Prominent Clinical Efficacy in Patients with EGFR-Mutant Advanced Lung Adenocarcinoma Treated with First-Line Afatinib.

Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26-0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12-0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.

Chromatin Remodeling Enzyme Cluster Predicts Prognosis and Clinical Benefit of Therapeutic Strategy in Breast Cancer.

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for the heterogeneity of breast cancer. Recent studies have shown that epigenetic modifications contribute to tumorigenesis through alterations in the expression of tumor suppressor genes. Our aim was to investigate the role of epigenetic modifications in genes involved in breast cancer. A total of 486 patients from The Cancer Genome Atlas Pan-cancer BRCA project were enrolled in our study. Hierarchical agglomerative clustering analysis further divided the 31 candidate genes into 2 clusters according to the optimal number. Kaplan-Meier plots showed worse progression-free survival (PFS) in the high-risk group of gene cluster 1 (GC1). In addition, the high-risk group showed worse PFS in GC1 with lymph node invasion, which also presented a trend of better PFS when chemotherapy was combined with radiotherapy than when chemotherapy was administered alone. In conclusion, we developed a novel panel using hierarchical clustering that high-risk groups of GC1 may be promising predictive biomarkers in the clinical treatment of patients with breast cancer.

Evaluation and subsequent treatment for superficial peroneal entrapment and hypertrophic scar using high-resolution ultrasound.

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Mouth opening/breathing is common in sleep apnea and linked to more nocturnal water loss.

BACKGROUND: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)_the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023). CONCLUSION: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.

Real-world treatment pattern and prognostic factors of stage IV lung squamous cell carcinoma patients.

Lung squamous cell carcinoma (LUSC) represents a minor proportion of nonsmall cell lung cancer (NSCLC) harboring a poor prognosis. Herein, retrospective medical record research was performed to investigate real-world treatment patterns and identify the prognostic factors among LUSC patients. A total of 173 patients with a median age of 68 years were enrolled for analysis. Males were predominant (n = 143, 83%) and current or ex-smokers contributed to 78% of the entire cohort. Pleura and lung were the most common metastatic sites, whereas brain metastasis was only 7%. After diagnosis, however, only 107 patients (62%) had received first-line chemotherapy. In the chemotherapy cohort, median progression-free survival (PFS) and overall survival (OS) were 3.9 and 11.1 months, respectively. After multivariable analysis, bone metastasis and the use of first-line single-agent chemotherapy independently predicted shorter PFS. For baseline characteristics, male sex, metastasis to lung, pleura, liver, and bone independently predicted worse OS. Regarding the treatment pattern, patients who had undergone standard first-line doublet therapy and employed targeted therapies after disease progression linked to longer OS. In the real world, even those who underwent chemotherapy still had poor outcome. The findings may help clinicians to orchestrate the treatment strategies for LUSC patients and provide further direction of large-scale studies.

Impact of Smoking Status in Combination Treatment with EGFR Tyrosine Kinase Inhibitors and Anti-Angiogenic Agents in Advanced Non-Small Cell Lung Cancer Harboring Susceptible EGFR Mutations: Systematic Review and Meta-Analysis.

Patients with advanced non-small cell lung cancer (NSCLC) who harbor susceptible epidermal growth factor receptor (EGFR) mutations and are treated with EGFR tyrosine kinase inhibitors (TKIs) show longer progression-free survival (PFS) than those treated with chemotherapy. However, developed EGFR-TKI resistance limits PFS improvements. Currently, combination treatment with EGFR-TKIs and anti-angiogenic agents is considered a beneficial regimen for advanced-stage NSCLC harboring susceptible EGFR mutations. However, several trials reported osimertinib plus bevacizumab failed to show superior efficacy over osimertinib alone. However, subgroup analysis showed significantly longer PFS among patients with a history of smoking over those who never smoked. We performed a comprehensive systematic review and meta-analysis to evaluate the smoking status impact. At the end of the process, a total of 2068 patients from 11 randomized controlled trials (RCTs) were included in our meta-analysis. Overall, combination EGFR-TKI plus anti-angiogenic agent treatment showed significantly better PFS among patients with a smoking history (Hazard Ratio (HR) = 0.59, 95% confidence interval (CI) = 0.48-0.73). Erlotinib-based combination therapy showed positive PFS benefits regardless of smoking status (HR = 0.54, 95%CI = 0.41-0.71 for ever smoker, HR = 0.69, 95%CI = 0.54-0.87 for never smoker). Combination therapy prolonged PFS significantly regardless of ethnicity (HR: 0.64, 95% CI: 0.44-0.93 for Asian RCTs, HR: 0.55, 95% CI: 0.41-0.74 for global and non-Asian RCTs). PROSPERO registration number is CRD42022304198).

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes.

Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively).

Utilizing NPWT improving skin graft taking in reconstruction for extended breast skin defects following mastectomy.

NPWT fulfill graft taking in complex breast wounds.

Unusual paediatric sigmoid perivascular epithelioid cell tumour with regional lymph node metastasis treated using gemcitabine and docetaxel: a case report and literature review.

Perivascular epithelioid cell tumour (PEComa) is an extremely rare neoplasm with distinctive morphology and specific expression of immunohistochemical markers. The lesion is typically diagnosed in middle-aged women, with few reports of paediatric cases, and there is no standardized treatment for the tumour type. Here, the case of a 17-year-old female, who presented with painless haematochezia for 2 days and was diagnosed with gastrointestinal PEComa of the sigmoid colon with regional lymph node metastasis after serial examination, is presented. She was treated by surgical resection of the tumour and cytotoxic chemotherapy comprising 900 mg/m2 gemcitabine and 100 mg/m2 docetaxel every 3 weeks for six cycles. Haematochezia did not recur, and complete response was achieved, with progression-free survival at the 24-month follow-up examination. Surgical resection with adjuvant conventional cytotoxic chemotherapy may be considered as an option for treating gastrointestinal PEComa.

Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer.

Activin, a member of the TGF-ß superfamily, is involved in many physiological processes, such as embryonic development and follicle development, as well as in multiple human diseases including cancer. Genetic mutations in the activin signaling pathway have been reported in many cancer types, indicating that activin signaling plays a critical role in tumorigenesis. Recent evidence reveals that activin signaling may function as a tumor-suppressor in tumor initiation, and a promoter in the later progression and metastasis of tumors. This article reviews many aspects of activin, including the signaling cascade of activin, activin-related proteins, and its role in tumorigenesis, particularly in pancreatic cancer development. The mechanisms regulating its dual roles in tumorigenesis remain to be elucidated. Further understanding of the activin signaling pathway may identify potential therapeutic targets for human cancers and other diseases.

Microcirculatory Responses to Muscle and Tendon Exercises in Individuals With and Without Type 2 Diabetes Mellitus and the Association Between Microcirculatory and Exercise Performance.

Background: This study aimed to measure and compare (1) the microcirculation and microcirculatory responses of the muscles and tendons at rest and during isometric muscle contractions in participants with and without diabetes mellitus (DM) and (2) to determine correlations between microcirculation and muscle strength. Methods: Sixty-three participants with type 2 DM and 42 physically matched controls were recruited. Baseline measurements of the microcirculation of the rectus femoris (RF) and medial gastrocnemius (MG) muscles and patellar (PT) and Achilles tendons (AT), as well as their microcirculatory changes during maximal isometric exercises, were performed and recorded by using near-infrared spectroscopy and a red laser. Data on various laboratory tests (including glycated hemoglobin, triglyceride, high-density cholesterol), the monofilament test, and the ankle-brachial index were also obtained. Results: The baseline measurements indicated that, compared with the controls, the diabetic participants had lower oxygen saturation (SpO2) in their RF and MG muscles (both P < 0.001), and the total hemoglobin in the diabetic PT and AT was higher (P = 0.001 and P = 0.01). The minimal SpO2 levels in the aforementioned muscles during isometric contractions were lower in the diabetes group than in the control group (P ≤ 0.001). Furthermore, there were correlations between the microcirculatory change of the RF muscle and the knee extension force. Conclusions: This study demonstrated the effects of diabetes on the microcirculation of skeletal muscles and tendons during baseline measurements and responses to maximal isometric exercises. The results support the need for preventive strategies for diabetic muscles to prevent adverse complications when performing resistance training.

Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations.

BACKGROUND: Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. METHODS: We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. RESULTS: A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p < 0.0001). CONCLUSION: Patients receiving 30 mg afatinib daily as their initial treatment had similar RR, PFS, OS, but significantly fewer serious ADRs, as compared with those using 40 mg as their starting dose.

The Effect of Quasi-Spherical Gold Nanoparticles on Two-Photon Induced Reactive Oxygen Species for Cell Damage.

The performance of quasi-spherical gold nanoparticles (GNPs) on the generation of reactive oxygen species (ROS) to cause cell damage, as irradiated by a two-photon laser, is studied. In this mechanism, hot electrons are generated from GNPs as irradiated by the two-photon laser, reacting with the molecules in the medium to produce ROS. We used laser scanning confocal microscopy with a low-fluence femtosecond Ti:Sapphire laser of 800 nm to observe the generated ROS in A431 cells, which were incubated with GNPs in advance. Subsequently, the cell morphology, cytoskeleton, and viability were investigated. In comparison with the control (no GNPs), the expression of ROS in these GNP-treated cells was enhanced after irradiation by the two-photon laser. Additionally, the disruption of cytoskeletons and the follow-up apoptosis of these GNP-treated cells are significantly increased as the number of laser shots increases. Moreover, we used N-acetyl-L-cysteine (NAC), an antioxidant, to inhibit the formation of ROS, to clarify whether the cytoskeletal disruption is caused by ROS rather than photothermal effects. Our results show that after two-photon irradiation, the ROS expression in these cells treated with GNPs plus NAC was significantly reduced. In addition, the cytoskeletal damage of these cells treated with GNPs and NAC was less than that of those treated with GNPs but without NAC; their cell viability after three days was almost the same with the control. These results illustrate that the induced ROS from the two-photon excited GNPs is the main cause of cell damage. The study may pave a way for the use of GNPs as a photosensitized therapeutic agent for two-photon photodynamic therapy on tumor treatment.

Increased risk of major depressive disorder in sleep apnea patients in Taiwan.

The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p < 0.0001). Multivariable Cox regression analysis showed that SA remained an independent risk factor for incident MDD after adjusting for age, sex, residency, income level, and comorbidities (hazard ratio = 2.9 [95% CI 2.8-3.1], p < 0.0001). In summary, SA patients have an increased risk to develop MDD. Physicians caring for SA patients must pay attention to their psychosocial health status.

The Association between Temporomandibular Disorder and Sleep Apnea-A Nationwide Population-Based Cohort Study.

An increased incidence of temporomandibular disorders (TMD) among patients with sleep apnea (SA) has been reported. However, the association between TMD and SA has not been demonstrated in a large-scale study. This population-based cohort study with the Taiwan National Health Insurance (NHI) Research Database aimed to understand the association between SA and TMD. We identified adult patients with suspected SA (identified with diagnostic codes) and excluded those diagnosed with TMD prior to SA. Patients with SA diagnosis after polysomnography were also identified as probable SA patients. The index dates were the dates of their initial SA diagnosis. Ten control subjects were matched, by age and sex, to each SA patient, and were assigned the same index dates as the SA patients. In total, 10,408 suspected SA patients (including 4105 probable SA patients) matched to 104,080 control subjects (including 41,050 subjects matched to the probable SA patients) in this study. The TMD incidence rate was significantly higher in the SA patients than in the control subjects (2.8 vs. 1.0 per thousand-patient-year in probable SA patients vs. the corresponding control subjects, with an adjusted incidence rate ratio [95% confidence interval] = 2.5 [2.3-2.7], p < 0.0001). SA patients significantly showed a higher cumulative incidence of TMD than the corresponding control subjects (p < 0.0001). Multivariable Cox regression analysis revealed SA as an independent risk factor for the development of TMD (adjusted hazard ratio = 2.5 [1.7-3.7], p < 0.0001). In summary, this study confirmed an increased TMD incidence in the SA patients. While treating TMD patients, dentists should pay careful attention to the potential underlying SA.

High-frequency versus theta burst transcranial magnetic stimulation for the treatment of poststroke cognitive impairment in humans

Background: Because the reliability of repetitive transcranial magnetic stimulation (rTMS) in treating poststroke cognitive impairment has not been convincingly demonstrated, we systematically examined the effectiveness of this regimen with 2 protocols. Methods: We randomly allocated 41 patients with poststroke cognitive impairment to receive 5 Hz rTMS (n = 11), intermittent theta burst stimulation (iTBS; n = 15) or sham stimulation (n = 15). Each group received 10 stimulation sessions over the left dorsolateral prefrontal cortex. We performed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Beck Depression Inventory at baseline and after the intervention. Results: The 5 Hz rTMS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.006), attention (p = 0.001) and delayed memory (p < 0.001). The iTBS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.005) and delayed memory (p = 0.007). The 5 Hz rTMS group exhibited a superior modulating effect in attention compared to the iTBS group (p = 0.016). Patients without comorbid hypertension (p = 0.008) were predisposed to favourable therapeutic outcomes. Limitations: Although we included only patients with left hemispheric stroke, heterogeneity associated with cortical and subcortical implications existed. We did not investigate the remote effects of rTMS. Conclusion: Our results demonstrated that both 5 Hz rTMS and iTBS were effective for poststroke cognitive impairment in terms of global cognition, attention and memory function; the domain of attention was susceptible to 5 Hz modulation. Treatment with 5 Hz rTMS may slow cognitive decline, representing both a pivotal process in poststroke cognitive impairment and an aspect of neuroplasticity that contributes to disease-modifying strategies. Clinical trial registration: NCT02006615; clinicaltrials.gov/ct2/show/NCT02006615.

The Factors Predicting Concordant Epidermal Growth Factor Receptor (EGFR) Mutation Detected in Liquid/Tissue Biopsy and the Related Clinical Outcomes in Patients of Advanced Lung Adenocarcinoma with EGFR Mutations.

Liquid biopsy to identify epidermal growth factor receptor (EGFR) gene mutations from circulating tumor DNA (ctDNA) for lung adenocarcinoma is less invasive than traditional tissue biopsy. Most patients have concordant results in liquid/tissue biopsy, while the clinical significance of concordant results remains unclear. Our study aimed to evaluate the predicting factors and clinical outcomes associated with concordant results in liquid/tissue biopsy in newly diagnosed lung adenocarcinoma patients with EGFR mutations. In the 80 patients of stage III or IV lung adenocarcinoma, 51 patients had EGFR mutations detected in tissue samples, while 33 (65%) of them had concordant results shown in liquid biopsy. Multivariable regression analysis showed that lymph node involvement (adjusted odds ratio (95% CI): 8.71 (1.88-40.35), p = 0.0057) and bone metastasis (adjusted odds ratio (95% CI): 9.65 (1.72-54.05), p = 0.0099) were the independent predicting factors for concordant results. Forty of these 51 patients were stage IV and were treated with EGFR tyrosine kinase inhibitors (TKIs). The concordant results in liquid/tissue samples were associated with significantly poorer progression-free survival (PFS) in univariate analysis. However, multivariable analysis showed that lymph node involvement was the only independent predicting factor for poorer PFS, while concordant results in liquid/tissue samples were excluded during variable selection. The concordant results in liquid/tissue samples might indicate a larger tumor burden, which actually contributes to poorer PFS.