[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].

Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

[Value of (99)Tc(m)-MDP SPECT/CT in clinical decision-making for nasopharyngeal carcinoma and a comparison of the values of different imaging techniques for diagnosing skull-base bone invasion].

Objective: To analyze the clinical value of SPECT/CT in diagnosis of skull base bone invasion and clinical decision-making for nasopharyngeal carcinoma (NPC), and to compare their diagnostic value with SPECT/CT, CT, MRI, and MRI combined with SPECT (MRI-SPECT) for skull base bone invasion. Methods: Before treatment, among 348 newly diagnosed NPC patients, CT scan was performed in 186 patients (group A) and the remaining 162 patients received MRI scan (group B). Clinical doctors then made clinical management decisions according to the CT or MRI results. After that, all patients underwent (99)Tc(m)-MDP SPECT/CT examination for nasopharyngeal local tomography, and the results were provided to the clinical doctors to make clinical management decisions again. The changes between the two clinical management decisions were scored according to diagnosis, range of lesion, staging, treatment regimens, and auxiliary examination. The diagnostic value of CT scan, MRI scan, SPECT/CT and MRI-SPECT for skull base bone invasion was then evaluated and compared. Results: In terms of changes in scores of clinical management decisions, the score of group A was 1.387 and group B was 0.951, showing a significant difference between the two groups by Wilcoxon test (Z=6.570, P<0.001). By χ(2) test, there were correlations between CT and SPECT/CT (χ(2) =98.495, P<0.001), and between MRI and SPECT/CT (χ(2) =32.662, P<0.001). The consistency of CT and SPECT/CT (Kappa=0.713) was greater than MRI and SPECT (Kappa=0.449). The sensitivity of CT, MRI, SPECT/CT and MRI-SPECT was 67.1%, 84.5%, 90.8% and 100%, the specificity was 73.3%, 92.3%, 85.6% and 84.6%, and the area under the ROC curve was 0.702, 0.884, 0.882 and 0.923, respectively. Conclusions: SPECT/CT has important impact on clinical management decision for NPC. In the judgement of skull base invasion, the diagnostic value of SPECT/CT is significantly higher than CT and approximately equal to MRI. SPECT/CT should be one of the routine examination methods of nasopharyngeal carcinoma. In addition, in view of its greater diagnostic value, MRI combined with SPECT should be the focus of future imaging studies.

[Prognostic analysis of gastrointestinal stromal tumors complicated with gastrointestinal bleeding].

OBJECTIVE: To study the relationship between clinicopathological characteristics, prognosis and gastrointestinal bleeding in primary gastrointestinal stromal tumors (GIST). METHODS: The clinicopathological and follow-up data of 200 patients with gastrointestinal stromal tumors treated in our hospital from April 2008 to December 2014 were retrospectively reviewed. The correlation of gastrointestinal bleeding with gastrointestinal stromal tumor clinicopathological characteristics and prognosis were analyzed. RESULTS: The 200 GIST patients were divided into two groups according to the bleeding in the digestive tract, including 57 gastrointestinal bleeding patients and 143 non-bleeding patients. The mean tumor diameter was 6.5 cm (range 1.8-22 cm) in the bleeding group and 2.5 cm (range 0.4-18 cm) in the non-bleeding group (P<0.05). Of the 57 bleeding patients, 31 located in the stomach, 25 in the small intestine, and one had colorectal bleeding. Fifty patients had mitotic index (MI) ≤ 5/50 HPF, other 6 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Six GIST patients were complicated with tumor rapture. But in the non-bleeding group, 125 patients had gastric GIST, 8 in the small intestine, one colorectum, and 9 had esophageal or other GIST. 141 patients had MI ≤5/50 HPF, 1 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Only 1 GIST patients was complicated with tumor rapture. The gastrointestinal bleeding was closely associated with tumor size, mitotic index, tumor location, risk classifications, tumor rapture and tumor recurrence (P<0.05 for all). The 3-year and 5-year survival rates of the 200 patients were 96.5% and 86.8%, respectively. 16 patients developed recurrence or metastasis, and 11 died of GIST. The 5-year survival rate of patients with gastrointestinal bleeding was 76.2%, significantly lower than that of patients without gastrointestinal bleeding (91.6%, P<0.05). CONCLUSIONS: GIST patients complicated with gastrointestinal bleeding have poor prognosis, and attention should be paid to stratifying patients for therapy.

[Matching in observational research: from the directed acyclic graph perspective].

Matching is a standard method for selecting research objects regarding the observational research, which controls confounding factors and improves statistical efficiency. However, its role in controlling confounding is not consistent in different observational studies. Matching can eliminate the confounding bias of matching variables in cohort studies, but checking on itself cannot eliminate confounding bias in case-control studies. In matched case-control studies, researchers may not accurately judge whether the variable is a confounder. Sometimes the variables that are not confounders are mistakenly matched. In that case, it will result in overmatching, which will lead to the decline of statistical efficiency or the introduction of unavoidable bias or increase of workload. If the real confounding factors are omitted, it will cause confounding bias. Therefore, researchers should consider what kind of matching variable selection criteria should be formulated. A directed acyclic graph is a visual graphic language that can show the complicated causality among different epidemiological research designs. This article analyzes the role of Matching in different observational research designs from the perspective of the directed acyclic graph, formulates the selection criteria for matching variables in matched case-control studies, and provides some reference suggestions for future epidemiological research design.

[Epidemiological and Etiologic characteristics of Meningococcal meningitis in Xinjiang Uygur Autonomous Region,1960-2019].

Objective: To understand the epidemiological and etiologic characteristics of meningococcal meningitis in Xinjiang Uygur Autonomous Region (Xinjiang). Methods: The epidemiological data about the meningococcal meningitis cases in Xinjiang from 1960 to 2019 were collected from the China information system for disease control and prevention and the Center for Disease Control and Prevention of Xinjiang. The epidemiological characteristics were analyzed. Clinical specimens from suspected cases were cultured and tested by real-time PCR method. A survey on the carriage rate of Neisseria meningitides (Nm) in the healthy population was performed. The serogroups of isolates were determined by serum-agglutination and PCR methods. Multi-locus sequence typing was used for subtyping the isolates. Results: The incidence rates of meningococcal meningitis in Xinjiang from 1960 to 2019 were 0.02/100 000-81.32/100 000, with the mortality as 1.05%-20.78%. The five districts with the most cases were Kashi prefecture, Aksu prefecture, Urumqi city, Changji Hui autonomous prefecture, and Hotan prefecture. Before 1990, serogroup A (81.82%) was the commonest group for cases and contacts. After 1990, 14.00% of the cases were caused by serogroups B, C, W, and Y. There was no predominant serogroup for contacts with serogroups B, C, W, Y, and C accounting for 23.28%, 18.53%, 15.52%, 9.91% and 7.33% respectively. The general Nm carriage rate was 15.50%, with the population of 16 - 20 years age group having the highest rate (25.53%). Serogroups B (52.11%), W (20.66%), C (12.21%), and Y (9.39%) occupied 52.11%, 20.66%, 12.21% and 9.39% respectively. The commonest clonal lineages of Nm isolates were ST-4821, ST-175, and ST-5 clonal complexes, while the ST-5 and ST-4821 clonal complexes were the major ones for invasive strains. Conclusions: There appeared regional differences in the incidence rates of Xinjiang meningococcal meningitis, and the carriage rate of Nm was high. The serogroups have been changing. It is necessary to strengthen the prevention and control of meningococcal meningitis to prevent any potential outbreak.

[Co-prevalence relationship analysis on different metabolic syndrome scores and behavioral risk factors in adults from Urumqi based].

Objective: To investigate the influence of the prevalence and co-prevalence of risk factors for metabolic syndrome on the scores of different levels of metabolic syndrome in people receiving physical examination in Urumqi. Methods: Using the 2017 Xinjiang Health Examination Database, a total of 175 927 people from 7 districts and 1 county in Urumqi were selected as subjects. Face-to-face survey and body measurements were used to collect cardiovascular risk factors and metabolic syndrome scores. Metabolic syndrome scores were used. For the 0-5 points at 6 levels, χ(2), χ(2) trend test, correlation analysis of ordered variable Kendall's tau-b, and logistic regression analysis of ordered results were used to analyze the influence of prevalence and co-prevalence of behavioral risk factors on the MS scores. Results: The percentages of 6 metabolic syndrome scores in the sample population were 23.82%, 27.87%, 22.41%, 16.03%, 8.02%, and 1.85%, respectively. The scores of metabolic syndrome were different in different age groups, ethnic groups, groups with different drinking rates, and groups with different dietary types, with the differences all significant (P<0.05).The MS score in men increased with the increase of oil/salt rate and excessive drinking rate (P<0.01). The score in women increased with the increase of the current smoking rate, oil/salt rate, and increased with the decrease of physical activity (P≤0.01). There was no significant difference in the distribution of regular drinking rates between different score groups (P>0.05). The scores of metabolic syndrome increased with the increase of risk factors (P<0.05). Ordered results logistic analysis found that in the men with ≥3 risk factors and the metabolic syndrome score was 1.15 (1.06-1.26) times higher than that in the men without risk factor, as well as in women with 2 risk factors and≥3 risk factors. The metabolic syndrome scores were 1.38 (1.22-1.55), 2.02 (1.53-2.66) times higher than those in the women without risk factors. Conclusions: The physical examination group in Urumqi, the more the metabolic syndrome disease behavior risk factors clustered, the higher the metabolic syndrome score was. Therefore, comprehensive intervention measures should be taken to control the different forms of metabolic syndrome to prevent the occurrence and progress of the disease.

Prognostic Factors for Survival in Node-Negative Gastric Cancer Patients Who Underwent Curative Resection.

BACKGROUND AND AIM: Lymph node involvement is the strongest prognostic factor for patients with gastric cancer; patients with node-negative gastric cancer present with better survival. However, some patients develop recurrent gastric cancer. The aim of this study was to review the clinicopathological characteristics and factors for prognosis in patients with node-negative gastric cancer who underwent curative resection. METHODS: Between January 2004 and December 2015, the clinicopathological characteristics of 302 patients with node-negative gastric cancer who underwent curative gastrectomy in our hospital were retrospectively analyzed. RESULTS: The 1-, 3-, and 5-year overall survival rates for patients with node-negative gastric cancer were 80.0%, 69.0%, and 63.0%, respectively. Univariate analysis showed that tumor size, histologic type, and depth of invasion had significant effects on survival (p < 0.05). Multivariate analysis showed that tumor size (hazard ratio: 1.83%, 95.0% confidence interval: 1.13-2.96, p = 0.014), histologic type (hazard ratio: 1.57%, 95.0% confidence interval: 1.01-2.44, p = 0.042), and depth of invasion (hazard ratio: 1.38%, 95.0% confidence interval: 1.14-1.67, p = 0.001) were independent prognostic factors. CONCLUSION: Tumor size, histologic type, and depth of invasion are important prognostic factors in patients with node-negative gastric cancer. These parameters should be considered to stratify patients for therapy and follow-up strategies.