Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Lysine analogue use during cancer surgery: a survey from a Canadian tertiary care centre

BackgroundWhen used during surgery, antifibrinolytic hemostatic agents such as lysine analogues are effective at reducing blood loss and the need for transfusions. Despite proven efficacy, use of hemostatic agents remains low during some surgeries. Our objective was to explore surgeon opinions about, and use of lysine analogues in, oncologic surgeries at a large tertiary care academic institution.MethodsWe administered a survey to surgeons who perform high-transfusion-risk oncologic surgeries at a large academic hospital in Ottawa, Ontario. Design and distribution of the survey followed a modified Dillman method. To ensure that the survey questionnaire was relevant, clear, and concise, we performed informant interviews, cognitive interviews, and pilot-testing. The final survey consisted of 19 questions divided into 3 sections: respondent demographics, use of hemostatic agents, and potential clinical trial opinions.ResultsOf 28 surgeons, 24 (86%) participated. When asked to indicate the frequency of lysine analogue use, “never” accounted for 46% of the responses, and “rarely” (<10% of the time) accounted for 23% of the responses. Reasons for never using included “unfamiliar with benefits” and “prefer alternatives.” Fifteen surgeons (63%) felt that a trial was needed to demonstrate the efficacy and safety of lysine analogues in their cancer field.ConclusionsOur survey found that lysine analogues are infrequently used during oncologic surgeries at our institution. Many surgeons are unfamiliar with the benefits and side effects of lysine analogues and, alternatively, use topical hemostatic agents. Our results demonstrate that future trials exploring the efficacy and safety of lysine analogues in oncologic surgery are needed.     

核苷(酸)类似物在经肝动脉介入治疗乙型肝炎病毒相关性肝细胞癌中的作用

目的探讨核苷(酸)类似物在乙型肝炎病毒(HBV)相关肝细胞癌(HCC)经肝动脉介入治疗(TAIT)中的应用价值。方法入组60例HBsAg阳性且不能手术切除的HCC患者,配对分为核苷(酸)类似物治疗组(A组)和常规保肝降酶组(B组),每组30例。对两组进行常规TAIT同时,给予常规保肝降酶治疗,A组同时联合核苷(酸)类药物行抗病毒治疗。比较两组的生存率,分析预后影响因素。结果 A组核苷(酸)类似物抗病毒初始治疗药物选择:恩替卡韦14例,拉米夫定8例,阿德福韦酯8例,其中4例患者出现病毒学突破,经加用另一核苷(酸)类似物后实现病毒持续抑制。B组中,13例(13/30,43.33%)患者分别在第1~9次TAIT后发生病毒学突破,中位突破时间为5.52个月(4次TAIT后)。两组共死亡48例,其中A组20例,B组28例,中位生存期分别为29.63、14.77个月(χ2=7.51,P=0.01)。A组和B组中BCLC分期C期患者中位生存期分别为23.63、8.07个月(2χ=7.11,P=0.01)。Cox回归模型分析显示:患者是否行核苷(酸)类似物抗病毒治疗、肝功能分级、肝癌BCLC分期影响患者预后。未发生核苷(酸)类药物相关严重不良反应。结论采用TAIT治疗HBV相关HCC时联合应用核苷(酸)类药物安全、有效。     

Interaction of structural isomers of sucrose in the reaction between sucrose and glucosyltransferases from mutans streptococci

Structural isomers of sucrose, i.e. disaccharides composed of glucose and fructose molecules with different glucosidic linkages, were examined for their effect on the reaction between sucrose and various glucosyltransferases (GTases) from Streptococcus mutans MT8148 and Streptococcus sobrinus 6715. Trehalulose (alpha 1-1), turanose (alpha 1-3), maltulose (alpha 1-4), and palatinose (alpha 1-6) were used as the sucrose analogues. Mutans streptococci were found not to utilize these sucrose analogues. Analysis of enzymatic products of GTase and sucrose with thin layer chromatography clearly revealed that glucan synthesis from [14C]sucrose by the various purified GTase preparations from S. mutans and S. sobrinus was inhibited in the presence of these sucrose analogues except turanose, resulting in the release of increased amounts of [14C]fructose and [14C]oligosaccharides. It was also found that the fructose residues in the oligosaccharides were derived from those of sucrose analogues but not sucrose itself. The Lineweaver-Burk plots of the substrate saturation kinetics of GTase vs sucrose indicated increased Km and Vmax in the presence of sucrose analogue, as compared with sucrose alone. Finally, these sucrose analogues except turanose inhibited sucrose dependent cellular adherence of S. sobrinus 6715 to a glass surface, while they scarcely inhibited the adherence of S. mutans MT8148. Among the analogues, maltulose appeared the most effective inhibitor against GTases in general.     

Synthesis of 4-aminoquinoline analogues and their platinum(II) complexes as new antileishmanial and antitubercular agents

A series of 4-amino-7-chloroquinoline derivatives were synthesized by the reaction of 4,7-dichloro-quinoline with the corresponding diamine and then with propargyl bromide. In addition, platinum(II) complexes were obtained by reacting some of the organic derivatives with K₂PtCl₄. Several of the synthesized compounds displayed antituberculosis activities. Compound 3 was 47.5 times more active than amphotericin B against Leishmania chagasi (IC₅₀ = 0.04 μg/mL). Compounds 5, 6, 7, 9, 10, 11 and 13 presented promising results against Mycobacterium tuberculosis, with MIC values ranging from 12.5 to 15.6 μg/mL, comparable to the “first and second line” drugs used to treat tuberculosis.     

Medications for weight reduction

Comparatively few drugs are available for the treatment of overweight patients, and their effectiveness is limited to palliation of the chronic disease of obesity. Nevertheless, drug development that is now underway is more rapid than in the past, and we anticipate the discovery of safe and effective pharmacologic strategies for the management of obesity and its serious complications.