China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

血清Hcy、IGFBP-1联合预测多囊卵巢综合征患者孕早期自然流产的价值

目的探讨血清同型半胱氨酸(Hcy)、胰岛素样生长因子结合蛋白-1(IGFBP-1)联合检测对多囊卵巢综合征患者孕早期自然流产的预测价值。方法选取2018年3月—2020年5月行促排卵治疗并成功临床妊娠的多囊卵巢综合征165例,检测血清Hcy、IGFBP-1水平。根据孕早期自然流产发生情况分为孕早期自然流产组与未自然流产组,比较两组妊娠前一次促排卵后血清Hcy、IGFBP-1水平;多囊卵巢综合征患者孕早期自然流产的危险因素采用多因素Logistic回归分析,并采用受试者工作特征(ROC)曲线分析血清Hcy、IGFBP-1水平单项及联合检测对多囊卵巢综合征患者孕早期自然流产的预测价值。结果患者妊娠前一次促排卵后血清Hcy水平低于入院时,血清IGFBP-1水平高于入院时(P<0.01);自然流产组妊娠前一次促排卵后血清Hcy水平高于未自然流产组,血清IGFBP-1水平低于未自然流产组(P<0.01)。孕早期自然流产的发生率为28.48%。年龄≥35岁、多囊卵巢综合征分型、空腹胰岛素水平偏高、空腹血糖水平偏高、血清睾酮水平偏高、血清叶酸水平偏低、妊娠前一次促排卵后血清Hcy水平偏高及血清IGFBP-1水平偏低均是多囊卵巢综合征患者孕早期自然流产的危险因素(P<0.01)。妊娠前一次促排卵后血清Hcy水平联合血清IGFBP-1水平预测多囊卵巢综合征患者孕早期自然流产的敏感度、ROC曲线下面积均高于单独预测(P<0.01)。结论多囊卵巢综合征孕早期自然流产患者血清Hcy水平偏高,IGFBP-1水平偏低,二者均与多囊卵巢综合征患者孕早期自然流产密切相关,并对多囊卵巢综合征患者孕早期自然流产的发生具有较好的预测价值,联合检测时的预测效能更高。     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

IntroductionThe female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males.AimWe aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ET_A) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD).MethodsWe compared prevalence of ET-1 gene (Lys198Asn) and ET_A gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls.ResultsThe presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females.ConclusionsET-1 and ET_A gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.     

Seroprevalence and trends of transfusion transmissible infections among retrospective blood donors in Western Azerbaijan Regional Blood Transfusion Center,Iran: A ten-years evaluation

Transfusion transmissible infections (TTIs) have been a public health challenge for the accessibility, quality and safety of blood transfusion. The present study aimed to consider the prevalence and the trends of hepatitis B virus (HBV), hepatitis C virus (HCV), Human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV) and syphilis across the ten years among retrospective blood donors. A retrospective investigation of blood donors’ data covering the period from 22 May 2009 to 22 May 2019 was done. Data was accumulated and analyzed from Blood Transfusion Center records, pertaining to all donors who were screened for various TTIs using respective immunological techniques. Out of the 682,171 screened donors in the 2009–2019 study period, 2470 (0.36 %) were infected with at least one infectious agent. The overall prevalence of HBV, HCV, HTLV-1, HIV and syphilis were 1700 (0.25 %), 184 (0.027 %), 335 (0.05 %), 4 (0.0.05 %) and 247 (0.036 %), respectively. The study showed male dominated donor pool (96.79 %) with higher prevalence (0.34 %) of TTIs compared to female donors (0.02 %) with 3.21 % population. Despite the low prevalence of TTIs in our study, HBV, HCV, syphilis and HIV have remained a big threat to safe blood transfusion in Iran. Strict adherence to selection criteria, algorithm of donor screening, use of highly sensitive and specific methods for detection of TTIs, regular consultation and health education programs, prevention and sanitization strategies to reduce the risk of TTIs are recommended to reduce the risk of TTIs and ensure the safety of blood transfusion for recipient.     

Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction

Background and objective: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. Methods: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. Results: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). Conclusion: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.