Goal-directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A randomised,blinded trial (GODIF trial—First version)

Background

Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU patients with fluid overload.

Methods

We conducted a multicentre, randomised, stratified, parallel-group, blinded, placebo-controlled trial in clinically stable, adult ICU patients with at least 5% fluid overload. Participants were randomised to furosemide versus placebo infusion aiming at achieving neutral cumulative fluid balance as soon as possible. The primary outcome was the number of days alive and out of the hospital at 90 days.

Results

The trial was terminated after the enrolment of 41 of 1000 participants because clinicians had difficulties using cumulative fluid balance as the only estimate of fluid status (32% of participants had their initially registered cumulative fluid balance adjusted and 29% experienced one or more protocol violations). The baseline cumulative fluid balance was 6956 ml in the furosemide group and 6036 ml in the placebo group; on day three, the cumulative fluid balances were 1927 ml and 5139 ml. The median number of days alive and out of hospital at day 90 was 50 days in the furosemide group versus 45 days in the placebo group (mean difference 1 day, 95% CI -19 to 21, p-value .94).

Conclusions

The use of cumulative fluid balance as the only estimate of fluid status appeared too difficult to use in clinical practice. We were unable to provide precise estimates for any outcomes as only 4.1% of the planned sample size was randomised.     

整体护理联合加速康复外科应用于小儿尿道下裂修复术的效果

目的探讨整体护理联合加速康复外科(ERAS)措施应用于小儿尿道下裂修复术的效果。方法选择2019年3月至2021年5月中山市博爱医院收治的80例尿道下裂修复术的患儿作为研究对象,按照随机数字表法将其分为参照组(40例)与实验组(40例)。参照组采取传统护理方案,实验组采取整体护理联合ERAS,比较两组干预后并发症发生率、满意度及下床活动时间、切口愈合时间、术后首次排便时间、住院时间,使用儿童疼痛评估量表(FLACC)评估患儿疼痛程度。结果实验组并发症总发生率低于参照组,总满意度高于参照组,差异有统计学意义(P<0.05);实验组下床活动时间、切口愈合时间、术后首次排便时间、住院时间均短于参照组,10 d内排便次数低于参照组,差异有统计学意义(P<0.05)。护理前两组FLACC评分比较,差异无统计学意义(P>0.05);两组护理后FLACC评分低于护理前,且护理后实验组FLACC评分低于参照组,差异有统计学意义(P<0.05)。结论在小儿尿道下裂修复术中给予整体护理联合ERAS措施,可促进患儿尽快康复,减轻其疼痛程度,降低并发症发生率,缩短住院时间,提升患儿家属满意度,值得临床借鉴。     

Prenatal Substance Use and Perceptions of Parent and Partner Use Using the 4P’s Plus Screener

Maternal and Child Health Journal - Background Prenatal substance use screening is recommended. The 4 P’s Plus screener includes questions on perceived problematic substance use in parents...     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.     

剪切波成像对乳腺BI-RADS 4类肿块分类影响的研究

目的:探讨剪切波成像（shear wave elastography，SWE）对乳腺BI-RADS 4类肿块分类影响。方法:收集2017年9月至2019 年3月就诊于我院肿瘤科且常规超声定为BI-RADS 4类的乳腺肿瘤患者139例，共 157个病灶，在手术或穿刺活检前均进行SWE检查，以病理结果作为金标准，评估常规超声及SWE对乳腺肿块诊断的敏感度、特异度和准确性。结果:常规超声诊断4a类73个，4b类35个，4c类49个，常规超声诊断乳腺肿块的敏感性86.1%，特异性74.1%，准确性76.9%；SWE参数最大杨氏模量值（Emax）诊断乳腺良恶性病灶的临界值为94.15 kPa，以该值为诊断良恶性肿块的依据，SWE校正BI-RADS分类后诊断的敏感性87.5%，特异性90.6%，准确性90.4%。结论:SWE通过硬度信息评估，在常规超声的基础上矫正BI-RADS 4类肿块的亚分类，降低了误诊率，提高了诊断的准确性，有一定临床应用价值。     

左、右半结肠癌肝转移患者射频消融治疗疗效及生存的对比分析

目的:探讨原发部位分别位于左、右半结肠的结肠癌肝转移患者行超声引导下肝转移瘤射频消融术后的生存差异及预后影响因素分析。方法:回顾性分析2010年1月至2015年12月于我科行射频消融治疗的结肠癌肝转移患者100例，其中左半结肠癌62例，右半结肠癌38例，分析原发部位不同的结肠癌肝转移患者在进行超声引导下射频消融治疗后的生存情况。结果:左半结肠癌肝转移患者射频消融术后1、3、5年总体生存率及中位生存期均高于右半结肠癌肝转移患者（88.71% vs 73.68%、62.90% vs 30.02%、49.72% vs 26.33%、55个月 vs 23个月），且二者生存曲线差异具有统计学意义（P＜0.05）。经Log-rank检验及COX多因素分析，左、右半结肠癌肝转移患者射频消融治疗术后的生存情况存在差异。此外，原发灶淋巴结转移情况、患者术前CA199水平及原发灶分化程度是患者射频消融治疗术后生存情况的影响因素。结论:左半结肠癌肝转移患者射频消融术后整体生存率明显高于右半结肠癌肝转移患者，左半结肠癌与右半结肠癌肝转移患者在射频消融治疗术后生存状况存在明显差异。     

miR-145调控肝癌腹水模型Th9细胞升高的机制研究

目的:探讨miR-145调控肝癌腹水模型Th9细胞升高的作用机制。方法:构建小鼠H22肝癌腹水模型。造模两周后处死小鼠并分离出脾脏组织，流式细胞术分析肝癌腹水组（MA组）与正常对照组（Control 组）小鼠脾脏Th9细胞表达水平。ELISA法检测脾脏IL-9表达水平。RT-PCR法检测脾脏miR-145表达水平。Western Blot法检测脾脏中PI3K/Akt/mTOR/P70S6K/HIF-1α相关蛋白表达水平。分选小鼠脾脏CD4+T细胞，随机分为miR-145 mimics组和NC组，分别应用miR-145-5P mimics、阴性对照寡核苷酸（negative control，NC）进行转染，RT-PCR检测各组miR-145、HIF-1α mRNA及IL-9 mRNA表达水平。结果:与Control 组相比，MA组Th9细胞及其细胞因子IL-9表达均升高（P<0.05），miR-145表达降低（P<0.05），p-PI3K、p-Akt、mTOR、p-mTOR、p-P70S6K、HIF-1α蛋白均升高（P<0.05）。与NC组相比，miR-145 mimics组miR-145显著升高，HIF-1α mRNA及IL-9 mRNA表达下降。结论:肝癌腹水中Th9细胞升高可能与miR-145下降导致的PI3K/Akt/mTOR/P70S6K/HIF-1α通路激活有关。     

胃肠安丸对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠的治疗作用及机制

目的探讨胃肠安丸对葡聚糖硫酸钠(DSS)诱导溃疡性结肠炎小鼠的治疗作用及机制。方法SPF级C57BL/6小鼠60只,除正常对照组小鼠外,其余小鼠均给予2.5%DSS水溶液,自由饮用7 d制备溃疡性结肠炎模型,模型评价后再随机分为模型组、美沙拉嗪组及胃肠安丸高剂量组、中剂量组、低剂量组。胃肠安丸低、中、高剂量组分别给予0.015、0.03、0.06 g/(kg·d)胃肠安丸混悬液0.5 mL灌胃,1次/d;美沙拉嗪组给予0.52 g/(kg·d)美沙拉嗪混悬液0.5 mL灌胃,1次/d;正常对照组和模型组给予等体积纯水灌胃,均连续干预10 d。对比各组小鼠疾病活动指数(DAI)评分、结肠长度,用HE染色观察小鼠结肠组织病理形态学变化,用流式细胞术检测脾组织中Treg、Th17、CD4^+、CD8^+细胞百分比,ELISA法检测血清细胞因子TNF-α、IL-6、IL-8、IL-10、CRP水平。结果药物干预过程中,各组小鼠体质量均逐日增加,腹泻、便血、体质量下降等症状逐日缓解,与模型组相比,美沙拉嗪组和胃肠安丸高剂量组能更快地缓解上述症状,2组DAI评分逐日下降(P<0.05)。药物干预结束后,与模型组比较,胃肠安丸高剂量组和美沙拉嗪组小鼠结肠较长(P<0.05),结肠组织充血、间质水肿及炎性细胞浸润较轻,CD4^+、CD8^+、Treg细胞百分比及血清IL-10水平较高(P<0.05),Th17细胞百分比及血清TNF-α、IL-6、IL-8、CRP水平较低(P<0.05)。结论胃肠安丸对DSS诱导的小鼠肠道黏膜损伤有一定的修复作用,其作用机制可能与恢复Treg/Th17免疫平衡以及调节相关细胞因子水平有关。