Efficacy and Safety of Niraparib as First-Line Maintenance Treatment for Patients with Advanced Ovarian Cancer: Real-World Data from a Multicenter Study in China.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors are a new maintenance therapy option for patients with ovarian cancer (OC). OBJECTIVE: To evaluate the efficacy and influencing factors of the novel PARP inhibitor niraparib for maintenance treatment of Chinese patients with advanced OC. PATIENTS AND METHODS: In this retrospective multicenter real-world study patients with advanced OC from 15 hospitals throughout China were enrolled. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included the time to treatment discontinuation and safety. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify possible risk factors for PFS, after which a prediction model was established to evaluate the likelihood of achieving an 18-month PFS. The relationship between the dose of niraparib and PFS was also evaluated. RESULTS: The PFS rates of 199 patients at 6, 12, 18, 24, and 30 months were 87.4%, 75.9%, 63.6%, 56.1%, and 51.8%, respectively. LASSO regression model revealed that only age < 65 years (P = 0.011), BRCA mutations (P < 0.001), and R0 status after cytoreductive surgery (P = 0.01) were significant factors associated with prolonged PFS times. Based on the LASSO logistic regression analysis, a clinical prediction formula was developed: - 2.412 + 1.396Age≥65yr + 2.374BRCAwt + 1.387R1 + 0.793Interval≥12w + 0.178BMI>24kg/m2 which yielded a cut-off value of 0.091, an area under the curve (AUC) of 0.839 (0.763-0.916), a sensitivity of 94.3%, and an accuracy of 78.5%. A nomogram was then built to visualize the results. The major treatment-emergent adverse events of ≥ grade 3 included a platelet count decrease (19.1%), white blood cell count decrease (15.1%), neutrophil count decrease (13.1%), and anemia (18.6%). The 18-month PFS rates in patients treated with 200 mg niraparib were somewhat higher than in patients treated with 100 mg after 3-months of therapy. CONCLUSIONS: For Chinese OC patients, niraparib, particularly at a 200 mg individual starting dose, was an effective therapy with easily manageable safety.

Maintenance therapy with poly (ADP-ribose) polymerase inhibitors is a new option for patients with ovarian cancer (OC) after they have received platinum-based chemotherapy to reduce the recurrence or relapse rates, but it remains unclear whether there are any changes in efficacy and safety when different starting doses of niraparib are administrated to Chinese patients, who typically have a bodyweight < 77 kg. We found that niraparib exhibited satisfactory efficacy with tolerable safety during maintenance therapy for advanced OC whether administered at 100 mg or 200 mg doses. We believe these regimens can serve as a valuable addition to the previous results of randomized controlled trials.

Efficacy and Safety of Anti-HER2 Targeted Therapy for Metastatic HR-Positive and HER2-Positive Breast Cancer: A Bayesian Network Meta-Analysis.

Despite the development of HER2-targeted drugs, achieving favorable outcomes for patients with HR+/HER2+MBC remains challenging. This study utilized Bayesian Network Meta-analysis to compare the efficacy and safety of anti-HER2 combination regimens. The primary analysis focused on progression-free survival (PFS), while secondary analyses included objective response rate, overall survival (OS) and the incidence rate of grade 3/4 adverse events (AEs). A comprehensive search across seven databases identified 25 randomized controlled trials for inclusion in this meta-analysis. For patients eligible for endocrinotherapy, our findings revealed that dual-target combined endocrine therapy, such as Her2-mAb+Her2-mAb+Endo (HR = 0.38; 95%CrI: 0.16-0.88) and Her2-mAb+Her2-tki+Endo (HR = 0.45; 95%CrI: 0.23-0.89), significantly improved PFS compared to endocrine therapy alone. According to the surface under the cumulative ranking curves (SUCRAs), Her2-mAb+Her2-mAb+Endo and Her2-mAb+Her2-tki+Endo ranked highest in terms of PFS and OS, respectively. For patients unsuitable for endocrine therapy, anti-HER2 dual-target combined chemotherapy, such as Her2-mAb+Her2-mAb+Chem (HR = 0.76; 95%CrI: 0.6-0.96) and Her2-mAb+Her2-tki+Chem (HR = 0.48; 95%CrI: 0.29-0.81), demonstrated significant improvements in PFS compared to Her2-mAb+Chem. The results were the same when compared with Her2-tki+Chem. According to the SUCRAs, Her2-mAb+Her2-tki+Chem and Her2-mAb+Her2-mAb+Chem ranked highest for PFS and OS, respectively. Subgroup analyses consistently supported these overall findings, indicating that dual-target therapy was the optimal approach irrespective of treatment line.

Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study.

Purpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.

Primary healthcare workers' COVID-19 infection status following implementation of adjusted epidemic prevention and control strategies: a cross-sectional study in Jiangsu, China.

Introduction: In times of epidemic outbreaks, healthcare workers (HCWs) emerge as a particularly vulnerable group. This cross-sectional study endeavors to assess the COVID-19 infection rate among the primary HCWs in Jiangsu Province subsequent to the implementation of adjusted epidemic prevention and control strategies. Methods: From January 17 to February 2, 2023, an extensive survey was conducted among primary HCWs in Jiangsu Province, employing a self-designed questionnaire. Logistic regression analysis was utilized to identify the factors associated with COVID-19 infection. Results: The overall infection rate among primary HCWs stood at 81.05%, with a 95% confidence interval (CI) of 80.61-81.48%. Among those afflicted, cough, fatigue, and fever emerged as the three most prevalent symptoms, each with an incidence rate exceeding 80%. In the context of multivariate logistic regression, an elevated risk of COVID-19 infection was observed in correlation with female gender (adjusted odds ratio [aOR] = 1.12, 95% CI: 1.04-1.21), possessing a bachelor's degree or higher (aOR = 1.32, 95% CI: 1.23-1.41), accumulating over 10 years of work experience (aOR = 1.28, 95% CI: 1.11-1.47), holding a middle-level cadre position (aOR = 1.22, 95% CI: 1.11-1.35), assuming the role of a unit leader (aOR = 1.30, 95% CI: 1.11-1.54), and working in a fever clinic for 1 to 10 days per month (aOR = 1.42, 95% CI: 1.29-1.57). Conversely, advanced age (aOR = 0.76, 95% CI: 0.70-0.82), being underweight (aOR = 0.78, 95% CI: 0.69-0.90), current smoking (aOR = 0.64, 95% CI: 0.57-0.71), receiving 4 doses of COVID-19 vaccine (aOR = 0.49, 95% CI: 0.37-0.66), and pregnancy or perinatal status (aOR = 0.85, 95% CI: 0.72-0.99) were associated with a diminished risk of infection. Conclusion: Following the implementation of adjusted policies, a substantial proportion of primary HCWs in Jiangsu province contracted COVID-19. Female gender and younger age emerged as risk factors for COVID-19 infection, while no discernible link was established between professions and COVID-19 susceptibility. The receipt of COVID-19 vaccines demonstrated efficacy in curtailing the infection rate, underscoring the significance of bolstering prevention knowledge and heightening self-protective awareness among primary HCWs.

An Unsupervised Deep Learning-Based Model Using Multiomics Data to Predict Prognosis of Patients with Stomach Adenocarcinoma.

Methods: Patients (363 in total) with stomach adenocarcinoma from The Cancer Genome Atlas (TCGA) cohort were included. An autoencoder was constructed to integrate the RNA sequencing, miRNA sequencing, and methylation data. The features of the bottleneck layer were used to perform the k-means clustering algorithm to obtain different subgroups for evaluating the prognosis-related risk of stomach adenocarcinoma. The model's robustness was verified using a 10-fold cross-validation (CV). Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate Cox regression was used to estimate hazard risk. The model was validated in three independent cohorts with different endpoints. Results: The patients were divided into low-risk and high-risk groups according to the k-means clustering algorithm. The high-risk group had a significantly higher risk of poor survival (log-rank P value = 2.80e - 06; adjusted hazard ratio = 2.386, 95% confidence interval: 1.607~3.543), a concordance index (C-index) of 0.714, and a Brier score of 0.184. The model performed well both in the 10-fold CV procedure and three independent cohorts from the Gene Expression Omnibus (GEO) repository. Conclusions: A robust and generalizable model based on the autoencoder was proposed to integrate multiomics data and predict the prognosis of patients with stomach adenocarcinoma. The model demonstrates better performance than two alternative approaches on prognosis prediction. The results might provide the grounds for further exploring the potential biomarkers to predict the prognosis of patients with stomach adenocarcinoma.

Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure.

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.

Complete genomic sequence of crow-dipper mosaic-associated virus, a novel macluravirus infecting Pinellia ternata.

A new macluravirus infecting Pinellia ternata in China was identified by high-throughput sequencing (HTS) and tentatively named "crow-dipper mosaic-associated virus" (CrdMV). The complete genome sequence of CrdMV was determined by reverse transcription (RT) PCR and rapid amplification of cDNA ends (RACE) PCR. The genomic RNA of CrdMV consists of 8,454 nucleotides (nt), excluding the poly(A) tail at the 3' end. CrdMV has a genomic structure typical of macluraviruses, with large open reading frame encoding a polyprotein of 2,696 amino acids (aa). CrdMV shares 54.40%-59.37% nt sequence identity at the genome sequence level, 48.00%-58.58% aa sequence identity, at the polyprotein sequence level and 37.27%-49.22% aa sequence identity at the CP sequence level with other members of the genus Macluravirus. These values are well below the species demarcation threshold for the family Potyviridae. Phylogenetic analysis based on the amino acid sequences of polyproteins confirmed that CrdMV clusters closely with broad-leafed dock virus A (BDVA, GenBank accession no. KU053507). These results suggest that CrdMV should be considered a distinct member of the genus Macluravirus.

A novel individualized strategy for cryoballoon catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The optimal dosage for cryoablation of atrial fibrillation (Cryo-AF) is still unknown. To evaluate the efficacy of an individualized freeze duration, we compared the clinical outcome of patients treated with a time-to-pulmonary vein isolation (TT-PVI) or temperature-guided ablation protocol to the outcome of patients treated with a conventional ablation protocol. METHODS: A total of 164 consecutive patients were included in the study. One method employed was a conventional dosing protocol (at least 2 applications of 180 s each) (the Cryo-AFConventional group n = 84), and the second method had a shorter protocol that was based on the TT-PVI or achievement of - 40 °C within 60 s (the Cryo-AFDosing group n = 80) RESULTS: We treated 656 pulmonary veins (PVs) with 1420 cryotherapy applications. The mean number of applications per patient was 8.7 ± 0.8, with no difference between groups (Cryo-AFConventional, 8.7 ± 0.8 versus Cryo-AFDosing,8.6 ± 0.8; P = 0.359). The Cryo-AFDosing group required significantly less total cryotherapy application time (990.60 ± 137.77versus 1501.58 ± 89.60 s; P < 0.001) and left atrial dwell time (69.91 ± 6.91 versus 86.48 ± 7.03 min; P < 0.001) than the Cryo-AFConventional group. Additionally, the Cryo-AFDosing group required significantly less total procedure time (95.03 ± 6.50 versus 112.43 ± 7.11 min; P < 0.001). We observed acute ATP-induced or spontaneous vein electric reconnections in 13 veins (1.98%) after 20 min. The reconnection rates between the Cryo-AFConventional and Cryo-AFDosing groups were similar in that 2.98 and 0.94% of the initially isolated veins were reconnected, respectively, (P = 0.061). There was no difference in the recurrence rate of free atrial arrhythmia after a 1-year follow-up, which were 78.75% in the Cryo-AFDosing group versus 78.57% in the Cryo-AFConventional group (P = 0.978). CONCLUSION: A novel Cryo-AF dosing protocol guided by temperature or the TT-PVI can be used to individualize an ablation strategy. This new protocol can lead to a significant reduction in duration of the procedure, the cryoenergy dosage and the left atrial dwell time. The procedure had equal safety and similar acute and 1-year follow-up outcomes compared to the conventional approach.

Puerarin inhibits apoptosis and inflammation in myocardial cells via PPARα expression in rats with chronic heart failure.

Chronic heart failure affects myocardial energy metabolism and cardiac function. Puerarin has been reported to improve cardiac function through regulation of energy metabolism in mice with myocardial infarction. The aim of the current study was to determine whether puerarin can improve body weight and reduce inflammation and apoptosis in rats with chronic heart failure. Rats were divided into three groups: Puerarin, PBS and sham group. Transverse aortic constriction was performed to induce chronic heart failure in the puerarin an PBS groups. Cardiac function, apoptosis and inflammation were evaluated following a 4-week treatment in rats with chronic heart failure. The results demonstrated that puerarin significantly increased the survival rate of rats and improved cardiac function compared with the PBS group. In addition, puerarin decreased lactate dehydrogenase and succinate dehydrogenase activity compared with the PBS group. Puerarin treatment increased the expression levels of glucose transporter type 4 and decreased the expression levels of CD36. Additionally, puerarin decreased the levels inflammatory factors, including tumor necrosis factor α, interleukin (IL)-1ß and IL-6 in serum and myocardial tissue compared with the PBS group. Puerarin upregulated peroxisome proliferator-activated receptor α (PPARα) and its downstream target genes nuclear respiratory factor 1, FOS proto-oncogene, YY1 transcription factor, acetyl-coenzyme A carboxylase a, Fas cell surface death receptor, L-type pyruvate kinase and acetyl-coenzyme A dehydrogenase medium chain in myocardial cells from rats with chronic heart failure. These results demonstrated that puerarin inhibited apoptosis and inflammation in myocardial cells via the PPARα pathway. In conclusion, the present study indicated that puerarin may exhibit antiapoptotic and anti-inflammatory activity through the PPARα pathway in rats with chronic heart failure.

Cavotricuspid-Dependent Atrial Flutter in Patients With Prior Atriotomy: 12-Lead ECG Interpretation and Electroanatomical Characteristics.

BACKGROUND: The aim of this study was to describe the electrocardiogram (ECG) morphology and electroanatomical characteristics of counterclockwise tricuspid annular atrial flutter (CCWTA-AFL) in the patients with prior atriotomy. METHODS AND RESULTS: This retrospective study included 34 patients with CCWTA-AFL after cardiac surgery and 20 patients with typical CCWTA-AFL without prior surgery. For patients in the postsurgical group, 19 had single-loop CCWTA-AFL and 15 had a double loop CCWTA-AFL. For single loop CCWTA-AFL the F-wave in lead I was very flat in l7 of 19 patients. The F-wave morphology in the inferior leads and V1 were found to be similar to typical AFL in 14 of 19 patients. For double loop CCWTA-AFL, F-waves were positive in lead I in 13 out of 15 patients. A long isoelectric activation was measured between F-waves in most of the patients. The presence of isoelectric segments between F-waves suggested a double loop AFL, which had a sensitivity of 86.7% and a specificity of 100%. Moreover, flat F-waves in lead I suggested a single loop AFL, which had a sensitivity of 89.5% and specificity of 86.7%. All patients in the group without prior cardiac surgery had typical ECGs features of CCWTA-AFL. None of the patients showed isoelectric segments between F-waves in the inferior leads. The amplitudes of most of the leads were higher than those for single loop CCWTA-AFL in patients with prior surgery.

[Infection status of HBV, HCV and HIV in voluntary blood donors of Chinese Nanjing area during 2010-2013].

This study was purposed to understand the infection of HBV, HCV, HIV among the voluntary blood donors and the epidemic trend in infectious population in Chinese Nanjing area, and to guide the mobilization and recruitment of blood donors. A total of 199777 whole blood samples of voluntary blood donors were tested by ELISA, the nucleic acid technology (NAT) combined detection (HBV-DNA, HCV-RNA, HIV-RNA) was added for detection of the samples with HBsAg,anti-HCV, anti-HIV at least unilateral negative donors from June 10, 2010 to June 9, 2013 years, and these statistic data were analyzed. Every HIV reactive sample(HIV-antibody and/or HIV-RNA) was sent to be confirmed in the Centers for Disease Control and Prevention in Nanjing. The results showed that the voluntary donors' infection rate of HBsAg, anti-HCV, anti-HIV were 0.45%, 0.28%, 0.11% respectively; NAT positive rate was 0.07%, 32 cases were confirmed with anti-HIV positive, in which 30 cases were male (6 cases were repeated blood donors) and 2 cases were female, 3 cases were unconfirmed, in which 2 cases were males and 1 case was female. The statistical analysis demonstrated that the difference of unqualitative rate of HBsAg, anti-HCV, anti-HIV was statistically significant between the first-time and repeated blood donors.It is concluded that the positive rate of anti-HCV and anti-HIV displayed a declining trend year by year in Nanjing voluntary blood donation population from June 10,2010 to June 9, 2013 years. The unqualitative rate of HBsAg and NAT increased with the age increasing, while that of anti-HCV, anti-HIV decreased with age increasing. The unqualitative rate of the repeated blood donors is far lower than that of the first-time blood donors. The ELISA positive rate of anti-HIV testing in females is higher than that in males, but the confirmed positive rate of male is significantly higher than that of female. Therefore the consulting skills before donating should be improved, concerning the link of recruiting donors, focusing on strengthening the first-time donors' consultation, evaluating and developing the fixed voluntary blood donors, and vigorously popularizing NAT technology in blood screening to improve the blood safety effectively.

Intramyocardial autologous bone marrow cell transplantation for ischemic heart disease: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study was undertaken to evaluate the efficacy of intramyocardial bone marrow cell (BMC) transplant therapy for ischemic heart disease (IHD). METHODS: The PubMed, Embase, and Cochrane Library databases through October 2013 were searched for randomized clinical trials (RCTs) of intramyocardial BMCs to treat IHD. The primary endpoint was change in left ventricular ejection fraction (LVEF). Secondary endpoints were changes in left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). Weighted mean differences for the changes were estimated with a random-effects model. RESULTS: Eleven RCTs with 492 participants were included. Intramyocardial BMC transplantation increased LVEF (4.91%; 95% confidence interval [CI] 2.84%-6.99%; P<0.00001), reduced LVESV (10.66 mL; 95% CI, -18.92 mL to -2.41 mL; P=0.01), and showed a trend toward decreased LVEDV (-7.82 mL; 95% CI, -16.36 mL-0.71 mL; P=0.07). Patients suitable for revascularization with coronary artery bypass grafting had greater improvement in LVEF (7.60%; 95% CI, 4.74%-10.46%, P<0.00001) than those unsuitable for revascularization (3.76%; 95% CI, 2.20%-5.32%; P<0.00001). LVEDV reduction was also more significant in revascularizable IHD (-16.51 mL; 95% CI, -22.05 mL to -10.07 mL; P<0.00001) than non-revascularizable IHD (-0.89 mL; 95% CI, -8.44 mL-6.66 mL; P=0.82). CONCLUSION: Intramyocardial BMC injection contributes to improvement in left ventricular dysfunction and reduction in left ventricular volume. Patients with revascularizable IHD may benefit more from this therapy.