Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review

BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.     

Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss

BACKGROUNDNucleos(t)ide analogs (NAs) cessation in chronic hepatitis B (CHB) patients remains a matter of debate in clinical practice. Current guidelines recommend that patients with hepatitis B e antigen (HBeAg) seroconversion discontinue NAs after relatively long-term consolidation therapy. However, many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen (HBsAg) loss occurs. It remains unclear whether NAs can be discontinued in this subset of patients.AIMTo investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss (without hepatitis B e antibody) after cessation of NAs.METHODSWe studied patients who discontinued NAs after achieving HBeAg loss. The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs. The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves; we confirmed the cut-off value of HBsAg according to a previous study. The log-rank test was used to compare cumulative relapse rates among groups. We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates. Propensity score matching analysis (PSM) was used to balance baseline characteristics between the groups.RESULTSWe included 83 patients with HBeAg loss. The mean age of these patients was 32.1 ± 9.5 years, and the majority was male (67.5%). Thirty-eight patients relapsed, and the cumulative relapse rate at months 3, 6, 12, 24, 36, 60, 120, and 180 were 22.9%, 36.1%, 41.0%, 43.5%, 45.0%, 45.0%, 45.0%, and 52.8%, respectively. Twenty-six (68.4%) patients relapsed in the first 3 mo after NAs cessation, and 35 patients (92.1%) relapsed in the first year after NAs cessation. Consolidation period (≥ 24 mo vs < 24 mo) (HR 0.506, P = 0.043) and HBsAg at cessation (≥ 100 IU/mL vs < 100 IU/mL) (HR 14.869, P = 0.008) were significant predictors in multivariate Cox regression. In the PSM cohort, which included 144 patients, there were lower cumulative relapse rates in patients with HBeAg seroconversion (P = 0.036).CONCLUSIONHBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation, especially in patients with HBsAg at cessation < 100 IU/mL. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.     

基质金属蛋白酶与出血性转化

溶栓能有效治疗缺血性卒中,但有导致出血性转化的风险.许多研究显示,出血性转化与基质金属蛋白酶参与血脑屏障破坏、增加血管通透性密切相关.血浆MMP-9水平增高可作为出血性转化的独立预测因素.脑缺血早期应用基质金属蛋白酶抑制剂,有可能降低出血性转化的发生率和严重程度,但尚需进一步验证.     

Radioiodinated anti-hepatocellular carcinoma (HCC) ferritin Targeting therapy,tumor imaging and anti-antibody response in HCC patients with hepatic arterial infusion

Summary Radioimmunoimaging and radioimmunotherapy with radioiodinated anti-(hepatocellular carcinoma ferritin) antibody (¹³¹I-or¹²⁵I-FtAb) have been applied in patients with primary liver cancer. A total of 41 patients with surgically unresectable hepatocellular carcinoma (HCC) and receiving hepatic artery ligation and cannulation during exploratory laparotomy were treated with this regimen by intrahepatic arterial infusion. Compared with the control group, a decline of serum -fetoprotein (65.7% versus 42.9%) and shrinkage of tumor (68.3% versus 33.9%) were observed in the treated group, and a higher second-look resection rate (31.7% versus 5.1%) and longer survival (1-year: 61.0% versus 37.3%, 3-year: 25.0% versus 6.9%) resulted. The administration of antibody through a hepatic arterial catheter (n=16) was compared with intravenous injection (n-17) in terms of the tumor-imaging sensitivity in 33 patients with liver cancer. The results indicated that hepatic arterial infusion was superior to intravenous injection. The sensitivity 7 days after the administration was 100% in the i.a. group and 76.5% in the i.v. group, the uptake ratio of tumor to liver being 1.74±0.57 in the former and 1.34±0.29 in the latter. Furthermore, intrahepatic arterial infusion revealed a lower anti-antibody detection rate than intravenous injection (0/14 versus 4/11).Abbreviations AFP -tetoprotein - FtAb ferritin antibody     

一氧化氮在心房颤动的应用

一氧化氮(nitricoxide,NO)作为一种新型信使分子,参与机体多种生理和病理过程,在心血管系统同样具有重要意义。心房颤动是一种常见的心律失常,机体发生特殊的病理生理变化,影响NO及相关产物表达和活性发挥;而NO的这些变化又对心房颤动中血栓的形成以及结构和功能重构都发挥重要作用。     

重症急性呼吸综合征患者中重症者早期预警指标研究

目的　探讨重症急性呼吸综合征 (SARS)患者中与重症发生相关的危险因素 ,寻找发生重症的早期预警指标。方法　对北京市SARS临床诊断病例数据库中转院资料完整 ,且在 2周内发生重症的 35 5例和始终未发生重症的 84 1例SARS患者进行单因素和多因素分析。结果　高龄、有基础病的患者发生重症的危险性明显增加。重症患者发生重症前表现出以下特点 :体温下降缓慢、脉搏加快、淋巴细胞计数持续 <0 9× 10 9/L、中性粒细胞高于 7 1× 10 9/L(80 % )、X线胸片异常进展较快等。采用Cox多元逐步回归发现 ,具有统计学显著性的早期预警重症发生的独立因素包括 :年龄偏大、有基础疾病、住院 2d后体温仍不能降至正常、住院 3d后中性粒细胞比值持续在 80 %以上、住院 4d后淋巴细胞计数仍持续 <0 9× 10 9/L和病程中出现脉搏持续加快达到 10 0次 /min。结论　根据SARS患者的年龄和基础病情况 ,结合临床对体温、脉搏、淋巴细胞绝对值以及中性粒细胞绝对值 (百分比 )的密切观察能够对重症SARS的发生进行早期预警。     

急性心力衰竭患儿血浆脑钠素变化及意义

为探讨急性心力衰竭患儿血浆脑钠素(BNP)的变化及其与心功能的关系,随机选取不同病因的充血性心力衰竭(CHF)患儿46例作为观察组,另选择肺炎患儿40例、先天性心脏病患儿31例、健康儿40例作对照组;所有病例均采用酶联免疫吸附法分别检测血浆BNP,心力衰竭患儿在心衰期和恢复期用多普勒超声测量心脏指数(CI)及左室射血分数(LVEF)。结果显示,CHF患儿心衰早期BNP即开始升高,心衰期达高峰,恢复期渐下降,但仍高于对照组(P<0.001);心衰时心脏CI、LVEF值均明显下降(P<0.01);CHF患儿心衰时升高的BNP水平与CI、LVEF呈负相关(P<0.05)。表明CHF患儿血BNP水平明显升高,且与心衰程度关系密切。     

Upregulation of alveolar epithelial active Na+ transport is dependent on beta2-adrenergic receptor signaling

Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechanisms are sufficient to regulate active transport is unknown. In this study, we report that mice with no beta1- or beta2-adrenergic receptors (beta1AR-/-/beta2AR-/-) have reduced distal lung Na,K-ATPase function and diminished basal and amiloride-sensitive AFC. Total lung water content in these animals was not different from wild-type controls, suggesting that betaAR signaling may not be required for alveolar fluid homeostasis in uninjured lungs. Comparison of isoproterenol-sensitive AFC in mice with beta1- but not beta2-adrenergic receptors to beta1AR-/-/beta2AR-/- mice indicates that the beta2AR mediates the bulk of beta-adrenergic-sensitive alveolar active Na+ transport. To test the necessity of betaAR signaling in acute lung injury, beta1AR-/-/beta2AR-/-, beta1AR+/+/beta2AR-/-, and beta1AR+/+/beta2AR+/+ mice were exposed to 100% oxygen for up to 204 hours. beta1AR-/-/beta2AR-/- and beta1AR+/+/beta2AR-/- mice had more lung water and worse survival from this form of acute lung injury than wild-type controls. Adenoviral-mediated rescue of beta2-adrenergic receptor (beta2AR) function into the alveolar epithelium of beta1AR-/-/beta2AR-/- and beta1AR+/+/beta2AR-/- mice normalized distal lung beta2AR function, alveolar epithelial active Na+ transport, and survival from hyperoxia. These findings indicate that betaAR signaling may not be necessary for basal AFC, and that beta2AR is essential for the adaptive physiological response needed to clear excess fluid from the alveolar airspace of normal and injured lungs.     

Pulmonary artery diastolic pressure: a simultaneous Doppler echocardiography and catheterization study

Pulmonary hypertension is an important determinant of the clinical presentation of and surgical approach to patients with heart disease. To confirm the utility of continuous wave Doppler echocardiography in assessing the pulmonary artery diastolic pressure in patients with pulmonary regurgitation, 51 patients representing the wide hemodynamic spectrum of pulmonary artery pressure underwent simultaneous determination of pulmonary artery diastolic pressure by continuous wave Doppler echocardiography and cardiac catheterization. Pulmonary artery diastolic pressure was estimated from the Doppler recordings by the end-diastolic pressure gradient obtained by the modified Bernoulli equation plus the estimated right atrial pressure. A correlation was observed (r = 0.935, SEE = 7.4 mmHg) between Doppler and catheterization pulmonary artery diastolic pressure. In addition, comparison between the mean diastolic pressure gradient across the pulmonary valve by Doppler and pulmonary artery diastolic pressure at catheterization yielded a high correlation (r = 0.947, SEE = 5.1 mmHg). These data demonstrate that continuous wave Doppler echocardiography is a useful noninvasive technique for evaluating the pulmonary artery diastolic pressure in patients with pulmonary regurgitation.     

Rickettsial and serologic evidence for prevalent spotted fever rickettsiosis in inner Mongolia

A field study in northeastern Inner Mongolia, People's Republic of China, in June of 1985 demonstrated a spotted fever group rickettsiosis. Two strains of spotted fever group rickettsiae were isolated. One strain was obtained from the blood of a patient with an eschar, regional lymphadenopathy, and history of a recent tick bite. The other strain originated from ova of ticks, Dermacentor nuttalli. These represent the second isolate of a spotted fever group rickettsia from a human and the first isolate from tick ova in the People's Republic of China. Antibodies to these rickettsiae were demonstrated by indirect immunofluorescence in the sera of 4% of healthy children and 34% of healthy human adults, in 58% of sheep, and in 76% of cattle in the same location. Hemolymph test revealed rickettsiae in 6 of 36 D. nuttalli examined.