Supine transfer test-induced changes in cardiac index predict fluid responsiveness in patients without intra-abdominal hypertension.

BACKGROUND: The reversible maneuver that mimics the fluid challenge is a widely used test for evaluating volume responsiveness. However, passive leg raising (PLR) does have certain limitations. The aim of the study is to determine whether the supine transfer test could predict fluid responsiveness in adult patients with acute circulatory failure who do not have intra-abdominal hypertension, by measuring changes in cardiac index (CI). METHODS: Single-center, prospective clinical study in a 25-bed surgery intensive care unit at the Fudan University Shanghai Cancer Center. Thirty-four patients who presented with acute circulatory failure and were scheduled for fluid therapy. Every patient underwent supine transfer test and fluid challenge with 500 mL saline for 15-30 min. There were four sequential steps in the protocol: (1) baseline-1: a semi-recumbent position with the head of the bed raised to 45°; (2) supine transfer test: patients were transferred from the 45° semi-recumbent position to the strict supine position; (3) baseline-2: return to baseline-1 position; and (4) fluid challenge: administration of 500 mL saline for 15-30 min. Hemodynamic parameters were recorded at each step with arterial pulse contour analysis (ProAQT/Pulsioflex). A fluid responder was defined as an increase in CI ≥ 15% after fluid challenge. The receiver operating characteristic curve and gray zone were defined for CI. RESULTS: Seventeen patients were fluid challenge. The r value of the linear correlations was 0.73 between the supine transfer test- and fluid challenge-induced relative CI changes. The relative changes in CI induced by supine transfer in predicting fluid responsiveness had an area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.72-0.97) and predicted a fluid responder with 76.5% (95% confidence interval 50.1-93.2) sensitivity and 88.2% (95% confidence interval 63.6-98.5) specificity, at a best threshold of 5.5%. Nineteen (55%) patients were in the gray zone (CI ranging from -3 and 8 L/min/m2). CONCLUSION: The supine transfer test can potentially assist in detecting fluid responsiveness in patients with acute circulatory failure without intra-abdominal hypertension. Nevertheless, the small threshold and the 55% gray zone were noteworthy limitation. TRIAL REGISTRATION: Predicting fluid responsiveness with supine transition test (ChiCTR2200058264). Registered 2022-04-04 and last refreshed on 2023-03-26, https://www.chictr.org.cn/showproj.html?proj=166175 .

Overexpression of the lncRNA HOTAIRM1 promotes lenvatinib resistance by downregulating miR-34a and activating autophagy in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers in humans and has a high fatality rate. Despite pharmacological advances such as sorafenib and lenvatinib approval, responses are seen only in a limited fraction of HCCs, and the majority of HCC patients do not benefit from this treatment. In recent years, researchers have verified that the long noncoding RNAs (lncRNAs) impact the efficiency of lenvatinib and the prognosis of patients with HCC. MATERIALS AND METHODS: This work obtained gene expression profile from an Arraystar lncRNA microarray. Expression of HOTAIRM1, Beclin-1, and p62 in HCC was characterized in clinical HCC tissues of 24 patients with HCC. Overexpression and knockdown experiments were performed in HCC cells to examine the effects of the HOTAIRM1 on lenvatinib sensitivity. The interactions between HOTAIRM1, miR-34a and Beclin-1 were predicted according to GSEA and CNC network. The effects of HOTAIRM1, autophagy and lenvatinib on tumor inhibit were validated in orthotopic tumor-bearing nude mouse model. RESULTS: Lenvatinib-resistant HCC cell lines were established using the concentration gradient method. Data from an Arraystar lncRNA microarray indicated that HOTAIRM1, a specific lncRNA located in an evolutionarily highly conserved HOX gene cluster, was differentially expressed between lenvatinib-resistant HCC cells and their parental cells. Expression of HOTAIRM1 and Beclin-1 in HCC was characterized in clinical HCC tissues of 24 patients who have different sensitivity to lenvatinib. Knocking down of HOTAIRM1 decreased the autophagy level in lenvatinib-resistant HCC cells and increased their sensitivity to lenvatinib, especially when combined with autophagy inhibitors both in vitro and in vivo. Further study indicated that knocking down HOTAIRM1 in lenvatinib-resistant cell lines increased the level of miR-34a and inhibited the expression of Beclin-1 in Huh7-R and HepG2-R cells. Investigation according to GSEA and CNC network, lncRNA and nearby coding gene and lncRNA-miRNA analyses demonstrated that the resistance of HCC to lenvatinib was affected by the HOTAIRM1-miR-34a-Beclin-1 regulatory axis. CONCLUSION: HOTAIRM1 is an independent drug resistance factor which significantly associated with the efficacy of lenvatinib in HCC. HOTAIRM1 may downregulation of miR-34a and upregulation of Beclin-1, leading to activation of autophagy, thereby inducing lenvatinib resistance in HCC.

Factors associated with outcomes of septic shock patients receiving high dose noradrenaline according to three primary infection sites.

OBJECTIVE: To identify factors associated with outcome of septic shock patients receiving high dose noradrenaline according to three primary infection sites. METHODS: This retrospective study was based on data from a publicly available ICU database (Medical Information Mart for Intensive Care [MIMIC] III. Septic shock patients receiving high dose (≥1 µg/kg per min) noradrenaline and ≥18 years were identified and their characteristics and outcomes were compared according to three primary infection sites (abdominal, respiratory and urinary tract). RESULTS: 154 septic shock patients who received high doses of noradrenaline were identified; (89 [58%] had a respiratory infection, 41 [27%] an abdominal infection and 24 [16%] a urinary infection). There were no differences among the three infection groups in duration/maximum dosage of noradrenaline, length of stay in the ICU/hospital, do not resuscitate (DNR) rates, hypertension and adequate antimicrobial therapy. Patients with urinary infections had a lower risk of death at 28-days compared with those with abdominal or respiratory infections. CONCLUSIONS: The prognosis for septic shock patients receiving high dose noradrenaline is poor. Patients with abdominal or respiratory infections are at higher risk of death compared with those with urinary infections.

Mechanism of long non-coding RNA MALAT1 in lipopolysaccharide-induced acute kidney injury is mediated by the miR-146a/NF-κB signaling pathway.

The present study aimed to examine the expression and function of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA (miR)-146a/nuclear factor (NF)-κB axis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The mRNA levels of MALAT1 and miR-146a in AKI tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction analysis. The NF-κB pathway proteins and cell viability were assessed using western blot analysis and the MTT method, respectively. The secretion of inflammatory factors was determined using the ELISA method. The present study also examined effects of the abnormal expression of MALAT1 and miR-146a on cytokines and the NF-κB pathway. A potential binding region between MALAT1 and miR-146a was confirmed via RNA immunoprecipitation. The results revealed that the upregulation of MALAT1 reduced the expression of miR­146a, and there was a negative linear correlation between MALAT1 and miR-146a in a RNA-induced silencing complex­dependent manner. The expression levels of miR-146a were lower in the kidney injury specimens and NRK-52E cells, compared with those in the controls. MALAT1 knockdown and the overexpression of miR-146a reduced the production of phosphorylated inhibitor of NF-κB and np65 protein. miR­146a was found to be transcriptionally induced by NF-κB, and miR-146a repressed the pro-inflammatory NF-κB pathway and downstream transcription factors. Taken together, these data indicated that the MALAT1/miR­146a/NF-κB pathway exerted key functions in LPS-induced AKI, and provided novel insights into the mechanisms of this therapeutic candidate for the treatment of the disease.

Tirofiban facilitates the reperfusion process during endovascular thrombectomy in ICAS.

The aim of the present study was to assess the use of tirofiban injections for rescue therapy following artery reocclusion due to intra-luminal thrombosis during endovascular thrombectomy in patients with acute ischemic stroke (AIS). A total of seven cases of patients treated with adjunctive tirofiban injections following failed endovascular thrombectomy due to instant intra-luminal thrombosis were retrospectively assessed. A Solitaire stent was used as the primary thrombectomy device in all patients. Tirofiban was injected intra-arterially via a temporarily deployed Solitaire stent with continuous intravenous infusion for the subsequent 24 h; half of the conventionally recommended dose was employed. Outcome measures included angiographic reperfusion (mTICI), symptomatic intracranial hemorrhage, mortality and functional independence at 90 days (modified Rankin Scale, 0-2). Six patients had occlusions in the middle cerebral artery and one patient had occlusions in the basilar artery. Of the seven patients, five exhibited successful reperfusion (mTICI 2b-3) and achieved functional independence following 90 days. Reperfusion failed in the remaining two patients, who succumbed within 90 days of therapy. No intracranial or extracranial hemorrhage cases were identified. The results of the present study suggest that tirofiban facilitates reperfusion and ameliorates long-term prognosis in patients with AIS undergoing endovascular thrombectomy, and may be safe for those receiving intravenous tissue plasminogen activator therapy.

The carina is approximately 1-2 cm above the pericardial reflection among Chinese patients.

BACKGROUND: Central venous catheters (CVCs) and central venous pressure (CVP) monitor is essential in fluid resuscitation and management for critically ill patients. Accuracy of the CVP is mainly dependent on the proper position of the catheter tip. Although the X-ray visible carina was generally recommended as the alternative of pericardial reflection (PR) to guide the placement of CVCs, few data was available with respect to the distance between the carina and PR among Chinese patients. The purpose of this study was to explore the topographic relationship between the trachea carina and PR among Chinese patients by using computed tomography (CT) images. METHODS: CT images of 172 patients who underwent CT pulmonary angiogram or CT angiogram for aorta from January 1, 2013 to November 30, 2013 were retrospectively reviewed. Distances between upper margin of the right clavicular notch, trachea carina, PR and atriocaval junction (ACJ) were calculated using the table positions on axial images. RESULTS: The mean length of extrapericardial superior vena cava (SVC) was 2.5 cm. For all patients, the PR was lower than the carina by average 1.6 cm. CONCLUSIONS: Given the PR was average 1.6 cm lower than the carina among Chinese patients, placing the CVCs tip approximate 1.6 cm lower the carina among Chinese patients would be more likely to result in a satisfactory placement.

Antihypertensive therapy with nicardipine for patients with aortic disease is associated with more esmolol usage than urapidil.

BACKGROUND: Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous ß-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients' outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease. METHODS: All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients' outcomes were evaluated with logistics regression. RESULTS: A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine (with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123). CONCLUSIONS: Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.

Good neurological recovery after rescue thrombolysis of presumed pulmonary embolism despite prior 100 minutes CPR.

We reported the case of a 70-year-old man who was admitted to neurologic wards for recurrent syncope for 3 years. Unfortunately, just 2 hours after his admission, he suddenly collapsed and failed to return of spontaneous circulation (ROSC) after a 100-minute standard cardiopulmonary resuscitation (CPR). Fortunately, he was timely suspected to have pulmonary embolism (PE) based on his sedentary lifestyle, elevated D-dimer and markedly enlarged right ventricle chamber on bedside echocardiography. After a rescue thrombolytic alteplase therapy, he was successfully resuscitated and good neurological recovery was achieved.