Salpingectomy for ectopic pregnancy reduces ovarian cancer risk-a nationwide study.

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

Purpose: To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Methods: Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). Results: A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Conclusion: Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

The landscape of investigator-initiated oncology trials conducted in mainland China during the past decade (2010-2019).

The number of clinical trials conducted in mainland China, including investigator-initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer-related IITs. We performed a comprehensive analysis of the landscape of cancer-related IITs in mainland China in the past decade. All cancer-related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer-related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double-blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer-related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015-2019 vs. 40.2% in 2010-2014, p < 0.001) and data monitoring committee use (44.5% vs. 40.0%, p = 0.001) and a decrease in randomization (51.5% vs. 62.7%, p < 0.001) and funding (36.4% vs. 56.3%, p < 0.001) between these periods. We also observed changes in intervention type (decrease in cytotoxic drug therapy [34.8% vs. 48.9%, p < 0.001]; increase in targeted therapy [17.8% vs. 14.2%, p = 0.004], immune checkpoint inhibitor therapy [6.6% vs. 0.0%, p < 0.001], and immune cell therapy [9.6% vs. 4.5%, p < 0.001]). Details of cancer-related IITs conducted during the past decade illustrate the merits of oncology research in mainland China. Although the increased quantity of IITs is encouraging, limitations remain regarding the quality of clinical trials, regional imbalances, and funding allocation.

Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sjögren syndrome.

AIM: Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease. METHODS: Whole-genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network-based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves. RESULTS: We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS. CONCLUSION: Clinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.

Photonic crystal enhanced immunofluorescence biosensor integrated with a lateral flow microchip: Toward rapid tear-based diabetic retinopathy screening.

Diabetic retinopathy (DR) has accounted for major loss of vision in chronic diabetes. Although clinical statistics have shown that early screening can procrastinate or improve the deterioration of the disease, the screening rate remains low worldwide because of the great inconvenience of conventional ophthalmoscopic examination. Instead, tear fluid that contains rich proteins caused by direct contact with eyeballs is an ideal substitute to monitor vision health. Herein, an immunofluorescence biosensor enhanced by a photonic crystal (PhC) is presented to handle the trace proteins suspended in the tear fluid. The PhC was constructed by self-assembled nanoparticles with a thin layer of gold coated on top of it. Then, the PC substrate was conjugated with antibodies and placed in a microchannel. When the capillary-driven tear sample flew over the PC substrate, the immunoassay enabled the formation of a sandwich antibody-antigen-antibody configuration for PhC-enhanced immunofluorescence. The use of PhC resulted in a concentration enhancement of more than tenfold compared to non-PhC, while achieving an equivalent signal intensity. The limit of detection for the target biomarker, lipocalin-1 (LCN-1), reached nearly 3 µg/ml, and the turnaround time of each detection was 15 min. Finally, a preclinical evaluation was conducted using ten tear samples. A clear trend was observed, showing that the concentrations of LCN-1 were at least twofold higher in individuals with chronic diabetes or DR than in healthy individuals. This trend was consistent with their medical conditions. The results provided a direct proof-of-concept for the proposed PhC biosensor in rapid tear-based DR screening.

Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study.

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04-4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98-5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13-10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.

[Evaluation of Low Concentration Dithiothreitol for Negating the Monoclonal Anti-CD38 Interference with Transfusion Compatibility Testing].

OBJECTIVE: To investigate the effectiveness and safety of low concentration dithiothreitol (DTT) in removing the interference of monoclonal anti-CD38 on transfusion compatibility testing, and develop a reasonable clinical transfusion strategy. METHODS: The blood type, direct antiglobulin testing (DAT) and antibody screening were tested according to standard methods. Antibody screening cells and donor's red blood cells were treated by DTT 0.2, 0.1, 0.05, 0.02, 0.01 and 0.005 mol/L, and antibody screening and cross-matching of serums after monoclonal anti-CD38 treatment were performed by anti-human globulin card. RESULTS: The 0.01 mol/L DTT at 37℃ for 30 minutes could remove the effect of monoclonal anti-CD38 on antibody screening and cross-matching, meanwhile retain their effectiveness in detecting anti-K, anti-LW, anti-JMH, anti-Lub, anti-e, anti-Dia and anti-Jka alloantibodies. All the 10 patients had no acute or delayed haemolytic transfusion reactions and their routine blood tests showed that the red blood cells transfusion was effective. CONCLUSION: The 0.01 mol/L DTT is a safe and effective method for removing the interference of monoclonal anti-CD38 with transfusion compatibility testing, while retaining the ability to detect most alloantibodies.

Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies.

BACKGROUND: To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity. METHOD: The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently. RESULT: Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well. CONCLUSION: CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.

Time Trends in Psoriasis and Psoriatic Arthritis Incidence from 2002 to 2016 in Taiwan: An Age-Period-Cohort Analysis.

BACKGROUND: Psoriatic disease is a chronic inflammatory disease that is associated with morbidity and a poor quality of life. However, studies on the trends of psoriatic disease incidence are limited. We examined trends in psoriasis and psoriatic arthritis from 2002 to 2016 in Taiwan and distinguished the effects of age, period, and cohort on those trends. METHODS: Data from the National Health Insurance Research Database were analyzed for the annual incidence of psoriasis and psoriatic arthritis. An age-period-cohort model was designed in order to investigate the effects of each age, period, and birth cohort on the incidence. RESULTS: From 2002 to 2016, the incidence of psoriasis significantly decreased from 43.33 to 23.14 per 100,000 persons. The incidence of psoriatic arthritis significantly increased from 3.57 to 5.22 per 100,000 persons. In the age-period-cohort analysis, the net age effect on the incidence of psoriasis and psoriatic arthritis increased with advancing age (6-fold and 7.7-fold difference, respectively). CONCLUSION: The age-period-cohort analysis revealed that the incidence of psoriasis and psoriatic arthritis is associated with older age and early birth cohorts. Elderly individuals in Taiwan may be at a higher risk of developing new-onset psoriasis and psoriatic arthritis.

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan.

Background: The incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults. Methods: This cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors. Results: Among 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50-2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02-76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26-2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85-2.90), aphasia (aHR, 1.77; 95% CI, 1.20-2.60), and malignancy (aHR, 2.05; 95% CI, 1.30-3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53-5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48-0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up. Conclusions: Stroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.

Association Between DPP-4 Inhibitors and Events of Colorectal and Liver Cancers in Patients With Diabetes Receiving Second-Line Agents: A Nested Case-Control Study.

Objective: Plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. Until now, whether DPP4is therapy affects the progression of liver cancer and colorectal cancer in patients with T2DM has not been well investigated. We investigated the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes. Materials and Methods: We identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan's National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is. Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32-0.75; P=0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32-2.61; P<0.001). No association between DPP4is use and liver cancer risk was observed. Conclusions: This nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. Therefore, the effects of long-term DPP4is use on colorectal cancer risk warrant further study.

Dysgraphia Phenotypes in Native Chinese Speakers With Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants. METHODS: This study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors. RESULTS: All PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively. DISCUSSION: The findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.

Tonal and orthographic analysis in a Cantonese-speaking individual with nonfluent/agrammatic variant primary progressive aphasia.

Clinical understanding of primary progressive aphasia (PPA) has been established based on English-speaking population. The lack of linguistic diversity in research hinders the diagnosis of PPA in non-English speaking patients. This case report describes the tonal and orthographic deficits of a multilingual native Cantonese-speaking woman with nonfluent/agrammatic variant PPA (nfvPPA) and progressive supranuclear palsy. Our findings suggest that Cantonese-speaking nfvPPA patients exhibit tone production impairments, tone perception deficits at the lexical selection processing, and linguistic dysgraphia errors unique to logographic script writer. These findings suggest that linguistic tailored approaches offer novel and effective tools in identifying non-English speaking PPA individuals.

The Symptoms and Factors Associated With Posttraumatic Stress Disorder for Burns Nurses: A Cross-Sectional Study From Guangdong Province in China.

The symptoms of posttraumatic stress disorder (PTSD) among medical staff have become a significant issue. Environments related to burns are highly stressful for nurses and can lead to PTSD, thus affecting their mental health. It is vital to consider that the quality of burns care, and the outcomes of such treatments, may be threatened if nurses experience PTSD. We evaluated PTSD symptoms in burns nurses and explored the correlations between demographic characteristics, work-related characteristics, professional identity, turnover intention, and PTSD symptoms. This was a cross-sectional study involving 273 nurses working in the burns unit from Guangdong, China, between July and August 2019. Nurses were recruited from 30 hospitals and completed three validated psychological questionnaires: Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Professional Identity Scale (PIS) for nurses, and Turnover Intention Questionnaire (TIQ). We also collated information relating to sociodemographic and work-related characteristics. The cutoff point for the PCL-C was defined as 38 points; 17.22% (n = 47) of participants scored higher than or equal to 38. The PCL-C score was negatively correlated with professional identity level (P < .01) and positively correlated with turnover intention (P < .01). The workplace, mean monthly income, experience of workplace violence, and professional identity level were important factors and all associated with the severity of PTSD. PTSD symptoms were common in burns nurses. Attention should be paid to the mental well-being of these staff. Screening processes need to be initiated to identify individuals suffering from PTSD and take appropriate early interventional action.

Risk Factors for Spine Reoperation and Joint Replacement Surgeries after Short-Segment Lumbar Spinal Surgeries for Lumbar Degenerative Disc Disease: A Population-Based Cohort Study.

BACKGROUND: Short-segment lumbar spinal surgery is the most performed procedure for treatment of degenerative disc disease. However, population-based data regarding reoperation and joint replacement surgeries after short-segment lumbar spinal surgery is limited. METHODS: The study was a retrospective cohort design using the Taiwan National Health Insurance Research Database for data collection. Patients selected were diagnosed with lumbar degenerative disc disease and undergone lumbar discectomy surgery between 2002 and 2013. The Kaplan-Meier method was used to estimate the incidence of 1-year spine reoperation and joint replacement surgeries, and the Cox proportional hazard regression was used to examine risk factors associated with the outcomes of interest. RESULTS: A total of 90,105 patients were included. Incidences of 1-year spine reoperation and joint replacement surgeries for the hip and knee were 0.27, 0.04, and 0.04 per 100 people/month. Compared to fusion with the fixation group, fusion without fixation and the non-fusion group had higher risks of spine reoperation. Risk factors associated with spine reoperation included fusion without fixation, non-fusion surgery, age ≥ 45 years old, male gender, diabetes, a Charlson Comorbidity Index = 0, lowest social economic status, and steroid use history. Spine surgeries were not risk factors for joint replacement surgeries. CONCLUSIONS: Non-fusion surgery and spinal fusion without fixation had higher risks for spine reoperation. Spine surgeries did not increase the risk for joint replacement surgeries.

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo.

Exploring the mechanism through which berberine (Ber) reverses the multidrug resistance (MDR) of breast cancer is of great importance. Herein, we used the methyl thiazolyl tetrazolium assay to determine the drug resistance and cytotoxicity of Ber and doxorubicin (DOX) alone or in combination on the breast cancer cell line MCF-7/DOXFluc. The results showed that Ber could synergistically enhance the inhibitory effect of DOX on tumor cell proliferation in vitro, and the optimal combination ratio was Ber/DOX = 2:1. Using a luciferase reporter assay system combined with the bioluminescence imaging technology, the efflux kinetics of d-luciferin potassium salt in MCF-7/DOXFluc cells treated with Ber in vivo was investigated. The results showed that Ber could significantly reduce the efflux of d-luciferin potassium salt in MCF-7/DOXFluc cells. In addition, western blot and immunohistochemistry experiments showed that the expression of P-glycoprotein (P-gp/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) in MCF-7/DOXFluc cells was downregulated upon Ber treatment. Finally, high-performance liquid chromatography was used to investigate the effect of Ber on DOX tissue distribution in vivo, and the results showed that the uptake of DOX in tumor tissues increased significantly when combined with Ber (P < 0.05). Thus, the results illustrated that Ber can reverse MDR by inhibiting the efflux function of ATP-binding cassette transporters and downregulating their expression levels.

Effectiveness and safety of rivaroxaban versus warfarin in Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation: A real-world nationwide cohort study.

BACKGROUND: The optimal anticoagulant for end-stage renal disease patients for stroke prophylaxis is unknown. The efficacy and safety of warfarin in this population are debatable. In addition, real-world evidence of direct oral anticoagulants in patients with end-stage renal disease is limited. The aim of this study was to evaluate the clinical outcomes of rivaroxaban compared with warfarin in Taiwanese patients with end-stage renal disease with nonvalvular atrial fibrillation in a real-world setting. METHODS AND RESULTS: This was a retrospective population-based cohort study conducted using Taiwan's National Health Insurance Research Database. Patients with nonvalvular atrial fibrillation and end-stage renal disease who started on rivaroxaban or warfarin between February 2013 and September 2017 were eligible to participate in the study. The inverse probability of treatment weighting approach was used to balance baseline characteristics. Bleeding and thromboembolic outcomes were compared using competing risk analyses. The study population consisted of 3358 patients (173 and 3185 patients on rivaroxaban and warfarin, respectively). In the rivaroxaban group, 50.8%, 38.7%, and 10.4% of the patients received 10, 15, and 20 mg of the drug, respectively. The cumulative incidence of major bleeding was similar between the two groups; however, the gastrointestinal bleeding rate was lower in the rivaroxaban group (adjusted subdistribution hazard ratio [SHR]: 0.56, 95% confidence interval [CI]: 0.34-0.91) than in the warfarin group. Furthermore, the composite risk of ischemic stroke or systemic embolism was significantly lower in the rivaroxaban group (adjusted SHR: 0.36, 95% CI: 0.17-0.79). Similar findings were observed for patients who received 10 mg of rivaroxaban. CONCLUSIONS: In Taiwanese patients with end-stage renal disease and nonvalvular atrial fibrillation, rivaroxaban may be associated with a similar risk of major bleeding but a lower risk of thromboembolism compared with warfarin. The potential benefit of 10 mg of rivaroxaban in this population requires further investigation.

Association of frailty with in-hospital outcomes in elderly patients with heart failure.

BACKGROUND: Frailty is prevalent in elderly patients with cardiovascular diseases. However, the association between frailty and in-hospital outcomes for elderly patients with heart failure and reduced ejection (HFrEF) remains unknown. AIM: To evaluate the predictive efficacy of frailty, compared with pre-frailty, for adverse events in these patients. METHODS: Elderly patients (≥ 60 years) with HFrEF were assessed. Frailty was evaluated with the Fried phenotype criteria, and physical performance was evaluated based on handgrip strength and the short physical performance battery (SPPB). The composite incidence of adverse events, including all-cause death, multiple organ failure, cardiac shock, and malignant arrhythmia, during hospitalization was recorded. RESULTS: Overall, 252 elderly individuals with HFrEF [mean age: 69.4 ± 6.7 years, male: 169 (67.0%)] were included. One hundred and thirty-five (53.6%) patients were frail and 93 (36.9%) were pre-frail. Frail patients were older, more likely to be female, to have a lower blood pressure, and to present with left ventricular thrombosis (P all < 0.05). Frail patients with HFrEF had a higher incidence of in-hospital mortality (11.9% vs 4.3%, P = 0.048). Multivariate analyses showed that female gender (OR = 0.422), aging (OR = 1.090), poor cardiac functional class (OR = 2.167), frailty (OR = 2.379), and lower handgrip strength (OR = 1.106) were independent predictors of in-hospital adverse events (P all < 0.05). CONCLUSION: Frailty may be associated with poor in-hospital outcomes for elderly patients with HFrEF. The influence of frailty on long-term prognosis in these patients deserves further investigation.

C5aR deficiency attenuates the breast cancer development via the p38/p21 axis.

Emerging evidence has shown activation of the complement component C5 to C5a in cancer tissues and C5aR expression in breast cancer cells relates to the tumor development and poor prognosis, suggesting the involvement of complement C5a/C5aR pathway in the breast cancer pathogenesis. In this study, we found that as compared to the non-tumoral tissues, both C5aR and MAPK/p38 showed an elevated expression, but p21/p-p21 showed lower expression, in the tumoral tissues of breast cancer patients. Mice deficient in C5aR or mice treated with the C5aR antagonist exhibited attenuation of breast cancer growth and reduction in the p38/p-p38 expression, but increase in p21/p-p21 expression, in the tumor tissues. Pre-treatment of the breast cancer cells with recombinant C5a resulted in reduced p21 expression, and MAPK/p38 inhibitors prevented C5a-induced reduction in p21 expression, suggesting the involvement of the MAPK/p38 signaling pathway in the C5a/C5aR-mediated suppression of p21/p-p21 expression. These results provide evidence that breast cancer development may rely on C5a/C5aR interaction, for which MAPK/p38 pathway participate in down-regulating the p21 expression. Inhibition of C5a/C5aR pathway is expected to be helpful for the treatment of patients with breast cancer.

Pharmaco-genetic inhibition of pyramidal neurons retards hippocampal kindling-induced epileptogenesis.

AIMS: Pharmaco-genetics emerges as a new promising approach for epileptic seizures. Whether it can modulate epileptogenesis is still unknown. METHODS: Here, parvalbumin neurons and pyramidal neurons of the seizure focus were transfected with engineered excitatory Gq-coupled human muscarinic receptor hM3Dq and engineered inhibitory Gi-coupled human muscarinic receptor hM4Di, respectively. And their therapeutic value in mouse hippocampal kindling-induced epileptogenesis was tested. RESULTS: Pharmaco-genetic activating parvalbumin neurons limitedly retarded the progression of behavioral seizure stage and afterdischarge duration (ADD) during epileptogenesis induced by kindling. Activating parvalbumin neurons delayed seizure development only in the early stage, but accelerated it in late stages. On the contrary, pharmaco-genetic inhibiting pyramidal neurons robustly retarded the progression of seizure stages and ADDs, which greatly delayed seizure development in both early and late stages. Although both pharmaco-genetic therapeutics efficiently alleviated the severity of acute kindling-induced seizures, pharmaco-genetic inhibiting pyramidal neurons were able to reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco-genetic activating parvalbumin neurons. CONCLUSION: Our results demonstrated that pharmaco-genetic inhibiting pyramidal neurons retard hippocampal kindling-induced epileptogenesis and reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco-genetic activating parvalbumin neurons. It suggests that pharmaco-genetics targeting pyramidal neurons may be a promising treatment for epileptogenesis.