A novel nomogram integrated with PDL1 and CEA to predict the prognosis of patients with gastric cancer

Introduction This study aimed to develop a prognostic nomogram for patients with gastric cancer (GC) based on the levels of programmed death 1 ligand 1 (PDL1) and carcinoembryonic antigen (CEA). Methods The nomogram was developed using data from a primary cohort of 247 patients who had been clinicopathologically diagnosed with GC, as well as a validation cohort of 63 patients. Furthermore, the nomogram divided the patients into three different risk groups for overall survival (OS)—the low-risk, middle-risk, and high-risk groups. Univariate and multivariate Cox hazard analyses were used to determine all of the factors included in the model. Decision curve analysis and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram. Results The Kaplan–Meier survival analysis revealed that metastasis stage, clinical stage, and CEA and PDL1 levels were predictors for progress-free survival (PFS) and OS of patients with GC. Metastasis stage, clinical stage, and CEA and PDL1 levels were found to be independent risk factors for the PFS and OS of patients with GC in a multivariate analysis, and the nomogram was based on these factors. The concordance index of the nomogram was 0.763 [95% confidence interval (CI) 0.740–0.787]. The area under the concentration–time curve of the nomogram model was 0.81 (95% CI 0.780–0.900). According to the decision curve analysis and ROC curves, the nomogram model had a higher overall net efficiency in forecasting OS than clinical stage, CEA and PDL1 levels. Conclusion In conclusion, we proposed a novel nomogram that integrated PDL1 and CEA, and the proposed nomogram provided more accurate and useful prognostic predictions for patients with GC (AU)

Impact of Quality Control Circle on Patient Outcomes after Hepatocellular Carcinoma Intervention: A Meta-Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common clinical malignant tumors, and patients undergoing interventional treatment often experience emotional and physical distress in the postoperative period. This meta-analysis aimed to evaluate the effects of quality control circle (QCC) intervention on patient wareness of health education and postoperative complications following hepato-cellular carcinoma (HCC) intervention. METHODS: A systematic search was conducted to identify relevant controlled trials on the impact of QCC on patients' knowledge of health education and complications after HCC intervention. The search was conducted using various online databases from the earliest available date to July 2022. Following inclusion and exclusion criteria, data were analyzed using RevMan 5.3 software, and the heterogeneity of the studies was explored. RESULTS: A total of 120 articles were retrieved, and 11 controlled trials were included according to the inclusion and exclusion criteria. Meta-analysis showed that QCC reduced postinterventional fever (OR: 0.41, 95% CI: 0.26, 0.65, P = 0.0002), nausea and vomiting (OR: 0.36, 95% CI: 0.22, 0.58, P < 0.0001), abdominal pain (OR: 0.34, 95% CI: 0.20, 0.56, P < 0.0001), loss of appetite (OR: 0.37, 95% CI: 0.21, 0.68, P = 0.001), improved patient knowledge of health education (OR: 4.84, 95% CI: 3.03, 7.74, P < 0.0001), and increased patient satisfaction with nursing care (OR: 6.63, 95% CI: 4.21, 10.45, P < 0.00001). All differences were statistically significant. CONCLUSIONS: QCC after HCC intervention can reduce postoperative fever, nausea and vomiting, abdominal pain, and loss of appetite. It also improves patient knowledge of health education and satisfaction with care.

A novel nomogram integrated with PDL1 and CEA to predict the prognosis of patients with gastric cancer.

INTRODUCTION: This study aimed to develop a prognostic nomogram for patients with gastric cancer (GC) based on the levels of programmed death 1 ligand 1 (PDL1) and carcinoembryonic antigen (CEA). METHODS: The nomogram was developed using data from a primary cohort of 247 patients who had been clinicopathologically diagnosed with GC, as well as a validation cohort of 63 patients. Furthermore, the nomogram divided the patients into three different risk groups for overall survival (OS)-the low-risk, middle-risk, and high-risk groups. Univariate and multivariate Cox hazard analyses were used to determine all of the factors included in the model. Decision curve analysis and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram. RESULTS: The Kaplan-Meier survival analysis revealed that metastasis stage, clinical stage, and CEA and PDL1 levels were predictors for progress-free survival (PFS) and OS of patients with GC. Metastasis stage, clinical stage, and CEA and PDL1 levels were found to be independent risk factors for the PFS and OS of patients with GC in a multivariate analysis, and the nomogram was based on these factors. The concordance index of the nomogram was 0.763 [95% confidence interval (CI) 0.740-0.787]. The area under the concentration-time curve of the nomogram model was 0.81 (95% CI 0.780-0.900). According to the decision curve analysis and ROC curves, the nomogram model had a higher overall net efficiency in forecasting OS than clinical stage, CEA and PDL1 levels. CONCLUSION: In conclusion, we proposed a novel nomogram that integrated PDL1 and CEA, and the proposed nomogram provided more accurate and useful prognostic predictions for patients with GC.

Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial

Purpose Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. Methods We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK−PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. Results CD8+ T cells, PD-L1+ cells, and PANCK−PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK−PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). Conclusions Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK−PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. (AU)

Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial.

PURPOSE: Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. METHODS: We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK-PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. RESULTS: CD8+ T cells, PD-L1+ cells, and PANCK-PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK-PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). CONCLUSIONS: Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK-PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

The Hierarchical Sequence Requirements of the H1 Subtype-Specific Noncoding Regions of Influenza A Virus.

The genome of influenza A virus consists of eight single-stranded viral RNA (vRNA) segments. The nonconserved noncoding regions (NCRs) at the 3' and 5' termini of each segment show extremely low divergence and mutation rate. They appear as segment specific among the eight segments and also subtype specific among different subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments. In order to acquire in-depth knowledge on the sequence requirements of the segment-specific or subtype-specific NCRs (ssNCRs), we, in the context of WSN (H1N1) reverse genetics, designed a virus random nucleotide selection assay (vRNSA) in which we generated pHW2000-HA plasmid libraries with random nucleotides in each grouped nucleotide positions in the 3' and 5' H1-ssNCRs, followed by virus rescue, serial passage, and deep sequencing. The resulting sequence logos present a visualized dynamic overview of the hierarchical sequence requirements of the 3' and 5' H1-ssNCRs. It showed that, in the process of continuous passage, the 3' H1-ssNCR, in general, stabilized more quickly than the 5' H1-ssNCR. The nucleotides close to the highly conserved 3' and 5' promoter regions showed higher sequence stringency than nucleotides away from the promoter regions. All stabilized sequences displayed a common feature of high A/U ratios. Especially with our mutational function analyses, we demonstrate that the 3' promoter-proximal nucleotides could cooperatively exert a direct effect on the transcription and replication of the HA segment. Together, these results provide in-depth knowledge for understanding the NCRs of influenza A virus. IMPORTANCE The segment-specific and subtype-specific nonconserved noncoding regions (ssNCRs) at both 3' and 5' ends of viral RNA segments of influenza A virus are largely conserved among the same segments of different viruses. However, the function-related sequence requirements of these ssNCRs remain unclear. In this study, through a novel self-designed vRNSA approach, we present a visualized dynamic overview diagram directly reflecting the hierarchical sequence requirements within and between the 3' and 5' H1-ssNCRs. The in-depth functional mutagenesis analyses further revealed that specific nucleotides in the 3' promoter-proximal region could cooperatively exert a direct effect on viral RNA transcription and replication. This work further advanced our knowledge in understanding the nonconserved noncoding regions of influenza A viruses.

Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer.

OBJECTIVE: The role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS. METHODS: We retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS. RESULTS: In 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS. CONCLUSION: Lymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

Diagnostic performance of individual characteristics and anthropometric measurements in detecting elevated serum alanine aminotransferase among children and adolescents.

BACKGROUND: Screening for elevated serum alanine aminotransferase (ALAT) can help identifying individuals at the risks of chronic and metabolic diseases, but blood collection is invasive and cannot be widely used for investigations. Considered as simple and inexpensive screening indices, individual characteristics and anthropometric measurements can be measured in a large crowd and may be important surrogate markers for ALAT levels. This study aimed to examine the diagnostic performance of individual characteristics and anthropometric parameters as predictive factors for discerning an elevated ALAT activity among Shenzhen children and adolescents. METHODS: A school-based screening study was performed from 9 high schools in Shenzhen during February 2017 and June 2018. Receiver operating characteristic curve was used to examine the diagnostic performance of each variable for detecting elevated ALAT. RESULTS: Altogether 7271 students aged 9-17 years were involved. The proportion of elevated ALAT greatly increased with increasing classification of BMI-z. By the sex-specific cut-offs for elevated ALAT (30 U/L boys; 19 U/L girls), BMI showed the highest area under the curve of 0.789 (95% CI 0.765-0.812) and followed by weight (0.779 [0.755-0.802]), BMI-z (0.747 [0.722-0.772]), height (0.622 [0.597-0.647]), and age (0.608 [0.584-0.632]), while height-z was not capable. With the cut-off of 67.8 kg for weight and 22.6 kg/m2 for BMI, the accuracy to identify elevated ALAT was 87.1% for weight and 82.9% for BMI. CONCLUSIONS: The presence of elevated ALAT was more common in overweight or obese children and adolescents. BMI and weight had the superiority of detecting elevated ALAT, followed by BMI-z, height, and age.

Analysis of the perceptions and attitudes to participate in radical and palliative clinical trials among Chinese lymphoma and head/neck cancer patients.

Objective: The purpose of this prospective study was to investigate the perceptions and attitudes to participate in radical and palliative clinical trials among Chinese lymphoma and head/neck cancer patients. Patients and Methods: A self-developed questionnaire was administered to hospitalized patients in the Department of Medical Oncology in Sun Yat-Sen University Cancer Center between 20 September 2014 and 20 September 2015. This study included lymphoma patients who were enrolled into a radical treatment clinical trial, and head/neck cancer patients participating in a palliative clinical trial. Results: There were 136 lymphoma patients and 87 head/neck cancer patients who completed and returned the questionnaire. The questionnaire return rate was 100%. More than 90% of the patients in both groups showed trust and acceptance for medical care personnel, and more than 50% of the patients in both groups were in hope of trying new medication, receiving free medication, and receiving new treatment at an earlier rate. As compared with those in the radical trials, patients in the palliative clinical trials were more likely to hope to try new medication (P<0.001) and receive a new treatment at an earlier date (P=0.025), but less likely to hope to receive free medication (P=0.047). Conclusions: This study reveals several shared perceptions and needs of patients in both the radical (lymphoma) and palliative (head/neck cancer) settings and explores the differences in patients' attitudes between radical clinical trials and palliative clinical trials. These findings may provide a basis for improving recruitment of patients for different types of clinical trials and ensuring that patients have a better understanding of clinical trials.

Barriers and facilitators to participation in clinical trial among lymphoma patients from Sun Yat-sen University Cancer Center in China: An observation study.

Recruitment rate of clinical trials in cancer patients is pretty low in China. Little is known about factors influencing trial recruitment in Chinese cancer patients. The aim of present study is to evaluate the barriers and facilitators to participation in clinical trials among lymphoma patients in China.From December 2014 to August 2015, the survey was carried out in the Department of Medical Oncology in Sun Yat-sen University Cancer Center. A self-made questionnaire was used among lymphoma patients (N = 331) to evaluate their attitude toward clinical trials. The questionnaire included 2 parts: patients' basic information and whether they were willing to participate in future clinical trials and their reasons.There were 53.5% patients willing to participate in clinical trials. The most common reasons were thirst for new treatments, trust on hospital and doctors, the idea that clinical trials may be more effective than conventional therapy, and to get more management and monitoring. The following patients are more likely to participate in clinical trials: patients who have children (P = .019) or spouse (P = .037), cannot afford treatment cost (P = .019), have tumor relapse (P = .045), and cared about the medical development (P = .032). Patients who have little knowledge of clinical trials are less likely to participate in clinical trials (P = .047).Popularization of knowledge about clinical trial is helpful to improve clinical trial participation in Chinese lymphoma patients.