Clinical features and risk factors of severely and critically ill patients with COVID-19.

BACKGROUND: As of June 1, 2020, over 370000 coronavirus disease 2019 (COVID-19) deaths have been reported to the World Health Organization. However, the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear. AIM: To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19. METHODS: A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan. Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups: The moderate group, severe group and critically ill group. Epidemiological data, demographic data, clinical symptoms and outcomes, complications, laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups. RESULTS: A total of 126 patients were enrolled. There were 59 in the moderate group, 49 in the severe group, and 18 in the critically ill group. Multivariate logistic regression analysis showed that age [odd ratio (OR) = 1.055, 95% (confidence interval) CI: 1.099-1.104], elevated neutrophil-to-lymphocyte ratios (OR = 4.019, 95%CI: 1.045-15.467) and elevated high-sensitivity cardiac troponin I (OR = 10.126, 95%CI: 1.088 -94.247) were high-risk factors. CONCLUSION: The following indicators can help clinicians identify patients with severe COVID-19 at an early stage: age, an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.

Use of Low-Dose Recombinant Factor â ¦a for Uncontrolled Perioperative Bleeding.

BACKGROUND: Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients and has also been used for a diverse range of off-label indications in the context of massive uncontrolled blood loss; however, no convincing evidence exists regarding the optimal dose of rFVIIa to treat uncontrolled bleeding in surgical patients. AIM: To evaluate the effects and safety of a very low dose of rFⅦa in patients with uncontrolled perioperative bleeding in the surgical intensive care unit (ICU). METHODS: 55 patients from Beijing Hospital, who received rFⅦa between July 2004 and November 2018 for uncontrolled perioperative bleeding were included. The controls were matched for age, sex, severity, and operation type. The baseline demographics, survival, changes in bleeding and transfusion, coagulation parameters and complications were analyzed. RESULTS: A low dose of rFⅦa (2.0∼3.6 mg, with a median dose of 39.02 µg/kg) appears to be effective in controlling massive hemorrhage (with an effective rate of 74.55%), and can reduce volume of red blood cell transfusion, improve coagulation status, while has a relatively low risk of thromboembolic complications (3.6%). CONCLUSION: In patients with uncontrolled perioperative bleeding, a low dose of rFⅦa could be used when traditional methods are ineffective.

Aortic intimal intussusception during acute type B aortic dissection endovascular repair.

Aortic intimal intussusception (AoII) is rare, especially during the endovascular repair of acute uncomplicated type B aortic dissection. Here we present a case of 47-year-old man who suffered AoII during the endovascular repair of type B aortic dissection. An abdominal aortic stent was inserted to recanalize the aorta, but failed. He was immediately transferred to our department from the local hospital. Computed tomography angiography confirmed the AoII and showed thrombus in the abdominal aortic stent. Hybrid operation was performed. Final angiography showed patency of the aorta. His postoperative period was uneventful and was discharged on the postoperative 8th day. No complications happened during the 6th month follow-up.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.

Characteristics and treatment strategy of hepatic angiomyolipoma: a series of 94 patients collected from four institutions.

AIM: To report on a Chinese multicenter series of hepatic angiomyolipoma (HAML) patients and to study the characteristics and the treatment strategy of the disease. METHOD: Data of 94 patients diagnosed with HAML from four institutions of China between December 1997 and January 2008 were reviewed retrospectively. Immunohistochemical assays were performed on the surgical specimens and follow up studies were done in all the patients. RESULTS: 52 of 94 patients (55.3%) showed no significant clinical symptoms. There were no specific findings on laboratory examinations. The correct preoperative diagnostic rate of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) was 0% (0/94), 15.7% (11/70) and 22.7% (10/44), respectively. Regarding the treatment, 93 patients had a hepatectomy and 1 patient was treated by radiofrequency ablation. The postoperative pathology showed HAML in all the patients: 69 patients were studied with HMB-45 staining by immunohistochemistry and the positive rate was 100% . The postoperative follow-up rate was 91.5% (86/94), no sign of recurrence or metastasis was observed during the follow-up period. CONCLUSION: This is the largest HAML series reported in the literature. There are no specific signs and symptoms in HAML patients; the preoperative imaging diagnosis (including CT, MRI) is insensitive. The common pathological features include the basic histological components and expression of HMB-45. Conservative treatment is not suggested; surgical resection should be considered as a treatment choice for HAML.

[Regulatory mechanisms of Hedgehog signaling pathway for epithelial-mesenchymal transition in pancreatic cancer cells].

OBJECTIVE: To explore the blocking effects of hedgehog signaling pathway on the processes of cell migration, invasion and epithelial-mesenchymal transition (EMT) in human pancreatic cancer cells and elucidate its possible mechanisms. METHODS: The lentiviral expression vector for RNA interference of human Smoothened (SMO) gene was constructed to silence the expression of SMO. And RNAi against SMO was used to suppress the hedgehog signaling pathway in human pancreatic cancer Panc-1 cells. The in vitro invasion capacity in Panc-1 cells was assessed by Matrigel/Transwell chamber assay. Real-time PCR (polymerase chain reaction) and Western blot were used to detect the expressions of such EMT markers as E-cadherin, N-cadherin, ß-catenin, vimentin and fibronectin and such transcription factors as Snail, Slug, Twist1 and Sip1. RESULTS: The stable interference of SMO could suppress the hedgehog signaling activity in Panc-1 cells. The inhibition of hedgehog signaling reduced the in vitro invasion capacity significantly in Panc-1 cells. The expression of E-cadherin significantly increased while N-cadherin, vimentin and fibronectin were significantly down-regulated in the RNAi group. Compared to the control group, the expressions of Snail and Slug were significantly reduced in the SMO knock-down group. CONCLUSION: The inhibition of hedgehog signaling pathway reduces the in vitro invasion capacity in human pancreatic cancer cells. And the EMT process is significantly suppressed. The mechanism is partially correlated with the down-regulations of Snail and Slug.

[Influence of the venous catheter site on data of pulse indicator continuous cardiac output monitoring].

OBJECTIVE: To compare the use of subclavian vein catheter and femoral vein catheter, in monitoring pulse indicator continuous cardiac output (PiCCO) monitoring data cardiac index (CI), extravascular lung water index (EVLWI), and global end-diastolic volume index (GEDVI) with central venous injection of the bolus cold saline injection, in order to determine whether the femoral vein access, which is not typically used, could be used to obtain reliable data. METHODS: Thirteen patients in Beijing Hospital intensive care unit (ICU) were involved, from January 2007 to March 2009. Each patient was monitored with PiCCOplus device, after an injection of cold saline bolus via both femoral and subclavian venous catheter. Paired t-test and Bland-Altman analysis were used to compare CI, EVLWI and GEDVI values. RESULTS: Data of 39 measurements were collected. The bias between femoral injection and subclavian injection were CI (0.28+/-0.46) L x min(-1) x m(-2), EVLWI (1.05+/-1.89) ml/kg, GEDVI (195.2+/-105.7) ml/m(2), and they were statistically significant (P values was 0.000 5, 0.001 3, <0.0001, respectively). The Bland-Altman analysis showed an clinically overestimation of GEDVI after femoral injection (limit of concordance was -11.9, 402.3), compared with that after subclavian injection. CONCLUSION: Measurements with a cold saline bolus via a femoral catheter, compared to those via a subclavian catheter, lead to overestimation of CI, EVLWI and GEDVI values, and a great bias of GEDVI should be taken into account in clinical work.

[Study on safety and efficacy of concentrated potassium chloride infusions in critically ill patients with hypokalemia].

OBJECTIVE: To explore the safety and clinical efficacy of intravenous infusion of concentrated potassium chloride using micro-pumps in critically ill patients with hypokalemia. METHODS: One hundred and twenty-eight critically ill patients with hypokalemia, the endogenous creatinine clearance rate over 0.5 ml/second and the urine output over 50 ml/hour were randomly divided into the therapy group (n=64) and the control group (n=64). Patients in therapy group received 1,208 mmol/L (9%) KCl, while those in the control group received 201 mmol/L (1.5%) potassium chloride, intravenously with the aid of a micro-pump, with hourly equal quantity of KCl in both groups. Patients in both groups were monitored strictly, and the potassium infusion was stopped whenever the serum potassium exceeded or equal to 3.5 mmol/L. RESULTS: It took (15.55+/-3.22) hours and (14.18+/-4.93) hours for the therapy group and the control group to correct the hypokalemia respectively, and there was no significant difference (P>0.05). Potassium infusion brought larger amount of fluid in the control group than the therapy group [(124.36+/-25.79) ml vs. (680.83+/-236.70) ml, P<0.01]. All patients tolerated the infusion without evidence of hemodynamic change, hyperkalemia or acute heart dysfunction. For all the patients, renal function did not throw significant influence on the potassium infusion time. An inverse correlation was observed between preinfusion potassium concentration and the quantity of potassium infused (r= -0.259, P<0.01). CONCLUSION: Under meticulous monitoring, it is safe and effective to infuse concentrated potassium for the critically ill patients with hypokalemia. This strategy can also be followed in patients with mild renal dysfunction but without oliguria or anuria under careful monitoring.

Increased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma.

PURPOSE: Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. EXPERIMENTAL DESIGN: Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. RESULTS: Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001). CONCLUSIONS: WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.

[Risk factors for metastasis and recurrence of hepatocellular carcinoma at different stages].

OBJECTIVE: To analyze the risk factors for metastasis and recurrence of hepatocellular carcinoma (HCC) postoperatively. METHODS: Data of 270 cases of postoperative HCC were analyzed by SPSS software retrospectively. RESULTS: Out of the 270 cases, 162 got follow-up study and 136 showed metastasis and recurrence. Lots of risk factors induced the recurrence of HCC, such as AFP, tumor form, venous blood invasion, HBV infection, resection dimension and perioperative transfusion. There were different risk factors at different stages. CONCLUSION: The early recurrence of HCC may be mediated by macro- or micro-vessel blood invasion and metastasis, the late recurrence by multicentric carcinogenesis or introhepatic cacinoma de novo.

Determination of high mobility group A1 (HMGA1) expression in hepatocellular carcinoma: a potential prognostic marker.

Our objective was to investigate the expression of HMGA1 mRNA and protein in hepatocellular carcinoma (HCC) and the correlation between its expression and clinical pathological characteristics and prognosis. HMGA1 expression was determined at both the mRNA level and the protein level in 30 HCC tissues and their corresponding paracancer liver tissues (PCLTs) and 2 normal liver tissues by RT-PCR and IHC. Follow-up study was done on the 30 patients involved in this research. HMGA1 mRNA was detected in nine cases of HCC tissues and two PCLTs, for a positivity rate of 30% and 6.7%, respectively (P < 0.05), whereas no HMGA1 mRNA expression was found in normal liver tissues. Clinicopathological analysis revealed that HMGA1 mRNA expression was significantly correlated with Edmondson's grade (P < 0.05). HMGA1 protein was detected in four HCC tissues by IHC and located mainly in the nuclei; no positive staining was found in PCLTs. Follow-up study showed that HMGA1 mRNA-positive patients had a higher risk of recurrence/metastasis and a shorter survival than negative cases (P < 0.05). Our findings indicate that HMGA1 may be involved in the carcinogenesis and invasiveness of HCC and the determination of HMGA1 can be of great value in predicting the prognosis of patients with HCC.

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV.

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (< or =2 years) and late phase (>2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed. RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which "HBsAg, HBeAb, HbcAb" positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P<0.05). CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma de novo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.

Role of AFP mRNA expression in peripheral blood as a predictor for postsurgical recurrence of hepatocellular carcinoma: a systematic review and meta-analysis.

AIM: To identify the role of alpha-fetoprotein (AFP) mRNA expression in peripheral blood one week after surgery as a predictor for recurrence of hepatocellular carcinoma (HCC). METHODS: Published studies fulfilling the selection criteria were identified by searching several databases online. After a methodology assessment using a quality scale designed by European Lung Cancer Working Party, data in each research were aggregated by means of meta-analysis. RESULTS: Altogether 368 cases were included in the 9 selected studies, which fulfilled the selection criteria. The quality scores ranged from 35% to 84% with a median score of 55%. The 'design' subscore had the lowest median value (38%). By aggregating the data, a high chi2 value (77.576) was presented. The fail-safe number was 136 and 64 for P = 0.05 and 0.01, respectively. CONCLUSION: AFP mRNA expression in peripheral blood 1 wk after surgery correlated with the recurrence of HCC and was a good predictor for tumor recurrence.