The aim of this study was to investigate whether right ventricular longitudinal strain (RVLS) was independently predictive of higher mortality in patients with coronavirus disease-2019 .BACKGROUND RVLS obtained from 2-dimensional speckle-tracking echocardiography has been recently demonstrated to be a more accurate and sensitive tool to estimate right ventricular (RV) function. The prognostic value of RVLS in patients with COVID-19 remains unknown.METHODS One hundred twenty consecutive patients with COVID-19 who underwent echocardiographic examinations were enrolled in our study. Conventional RV functional parameters, including RV fractional area change, tricuspid annular plane systolic excursion, and tricuspid tissue Doppler annular velocity, were obtained. RVLS was determined using 2-dimensional speckle-tracking echocardiography. RV function was categorized in tertiles of RVLS.RESULTS Compared with patients in the highest RVLS tertile, those in the lowest tertile were more likely to have higher heart rate; elevated levels of D-dimer and C-reactive protein; more high-flow oxygen and invasive mechanical ventilation therapy; higher incidence of acute heart injury, acute respiratory distress syndrome, and deep vein thrombosis; and higher mortality. After a median follow-up period of 51 days, 18 patients died. Compared with survivors, nonsurvivors displayed enlarged right heart chambers, diminished RV function, and elevated pulmonary artery systolic pressure. Male sex, acute respiratory distress syndrome, RVLS, RV fractional area change, and tricuspid annular plane systolic excursion were significant univariate predictors of higher risk for mortality (p < 0.05 for all). A Cox model using RVLS (hazard ratio: 1.33; 95% confidence interval [CI]: 1.15 to 1.53; p < 0.001; Akaike information criterion ¼ 129; C-index ¼ 0.89) was found to predict higher mortality more accurately than a model with RV fractional area change (Akaike information criterion ¼ 142, Cindex ¼ 0.84) and tricuspid annular plane systolic excursion (Akaike information criterion ¼ 144, C-index ¼ 0.83). The best cutoff value of RVLS for prediction of outcome was À23% (AUC: 0.87; p < 0.001; sensitivity, 94.4%; specificity, 64.7%).CONCLUSIONS RVLS is a powerful predictor of higher mortality in patients with COVID-19. These results support the application of RVLS to identify higher risk patients with COVID-19.
Background: To investigate deep vein thrombosis (DVT) in hospitalized patients with coronavirus disease 2019 (COVID-19), we performed a single institutional study to evaluate its prevalence, risk factors, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center. Methods: We studied a total of 143 patients with COVID-19 from January 29, 2020 to February 29, 2020. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities, and outcome variables were obtained, and comparisons were made between groups with and without DVT. Results: Of the 143 patients hospitalized with COVID-19 (age 63±14 years, 74 [51.7%] men), 66 patients developed lower extremity DVT (46.1%: 23 [34.8%] with proximal DVT and 43 [65.2%] with distal DVT). Compared with patients who did not have DVT, patients with DVT were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis, including an increased proportion of deaths (23 [34.8%] versus 9 [11.7%]; P =0.001) and a decreased proportion of patients discharged (32 [48.5%] versus 60 [77.9%]; P <0.001). Multivariant analysis showed an association only between CURB-65 (confusion status, urea, respiratory rate, and blood pressure) score 3 to 5 (odds ratio, 6.122; P =0.031), Padua prediction score ≥4 (odds ratio, 4.016; P =0.04), D-dimer >1.0 μg/mL (odds ratio, 5.818; P <0.014), and DVT in this cohort, respectively. The combination of a CURB-65 score 3 to 5, a Padua prediction score ≥4, and D-dimer >1.0 μg/mL has a sensitivity of 88.52% and a specificity of 61.43% for screening for DVT. In the subgroup of patients with a Padua prediction score ≥4 and whose ultrasound scans were performed >72 hours after admission, DVT was present in 18 (34.0%) patients in the subgroup receiving venous thromboembolism prophylaxis versus 35 (66.0%) patients in the nonprophylaxis group ( P =0.010). Conclusions: The prevalence of DVT is high and is associated with adverse outcomes in hospitalized patients with COVID-19. Prophylaxis for venous thromboembolism may be protective in patients with a Padua protection score ≥4 after admission. Our data seem to suggest that COVID-19 is probably an additional risk factor for DVT in hospitalized patients.
Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.
This study evaluated potential of serum tumor markers to predict the incidence and intensity of pancreatic cancer metastasis as well as patient survival. Retrospective records from 905 patients and prospective data from 142 patients were collected from two high-volume institutions. The levels of eight serum tumor markers (CA19-9, CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) commonly used in gastroenterological cancer were analyzed in all stages of pancreatic cancer. Serum CA125 levels were the most strongly associated with pancreatic cancer metastasis and were higher in patients with metastatic disease than those without. CA125 levels increased with increasing metastasis to lymph nodes and distant organs, especially the liver. High baseline CA125 levels predicted early distant metastasis after pancreatectomy and were associated with the presence of occult metastasis before surgery. An optimal CA125 cut-off value of 18.4 U/mL was identified; patients with baseline CA125 levels of 18.4 U/mL or higher had poor surgical outcomes. In addition, high serum CA125 levels coincided with the expression of a metastasis-associated gene signature and with alterations in “driver” gene expression involved in pancreatic cancer metastasis. CA125 may therefore be a promising, noninvasive, metastasis-associated biomarker for monitoring pancreatic cancer prognosis.
Microvessel density (MVD) as an angiogenesis predictor is inefficient per se in cancer prognosis. We evaluated prognostic values of combining intratumoral alpha-smooth muscle actin (α-SMA)-positive stromal cell density and MVD after curative resection in hypervascular hepatocellular carcinoma (HCC) and hypovascular pancreatic cancer (PC). Tissue microarrays were constructed from tumors of 305 HCC and 57 PC patients who underwent curative resection and analyzed for α-SMA and CD34 expression by immunostaining. Prognostic values of these two proteins and other clinicopathological features were examined. Both low α-SMA density and high MVD-CD34 were associated in HCC with the presence of intrahepatic metastasis and microvascular invasion, and they were related to lymph node involvement and microvascular invasion in PC (p<0.05). Although CD34 alone, but not α-SMA, was an independent prognostic factor for overall survival and recurrence-free survival, the combination of low α-SMA and high CD34 was a predictor of worst prognosis for both types of tumors and had a better power to predict patient death and early recurrence (p<0.01). Furthermore, the results show that distribution of most of the α-SMA-positive cells and vascular endothelial cells overlap, showing major colocalization on vascular walls. Poor microvessel integrity, as indicated by high MVD, together with low perivascular α-SMA-positive cell coverage is associated with early recurrence, unfavorable metastasis, and short survival after tumor resection. This finding highlights the significance of vascular quality in tumor progression, which provides an optimized complement to vascular quantity in prognosis of postoperative patients.
PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevance The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4. This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.
MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC.
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