Reduced NOV expression correlates with disease progression in colorectal cancer and is associated with survival, invasion and chemoresistance of cancer cells

Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in certain malignancies. In the current study, we aim to investigate the role played by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of 359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was investigated using in vitro NOV knockdown and overexpression models. NOV transcripts were reduced in the CRC tumours compared with the paired adjacent normal colorectal tissues (p < 0.01) and was associated with distant metastases. NOV knockdown resulted in increased cell proliferation and invasion of RKO cells, whilst an opposite effect was seen in the HT115 NOV over expressing cells. A positive association between Caspase-3/-8 and NOV was seen in NOV knockdown and overexpression cell lines which contributed to the survival of serum deprived CRC cells. Further investigation showed that NOV regulated proliferation, survival and invasion through the JNK pathway. NOV knockdown in RKO cells reduced the responsiveness to 5-Fluorouracil treatment, whilst overexpression in HT115 cells exhibited a contrasting effect. Taken together, NOV is reduced in CRC tumours and this is associated with disease progression. NOV inhibits the proliferation and invasion of CRC cells in vitro. Inhibition of proliferation is mediated by a regulation of Caspase-3/-8, via the JNK pathway, which has potential for predicting and preventing chemoresistance

PaLM 2 Technical Report

We introduce PaLM 2, a new state-of-the-art language model that has better multilingual and reasoning capabilities and is more compute-efficient than its predecessor PaLM. PaLM 2 is a Transformer-based model trained using a mixture of objectives. Through extensive evaluations on English and multilingual language, and reasoning tasks, we demonstrate that PaLM 2 has significantly improved quality on downstream tasks across different model sizes, while simultaneously exhibiting faster and more efficient inference compared to PaLM. This improved efficiency enables broader deployment while also allowing the model to respond faster, for a more natural pace of interaction. PaLM 2 demonstrates robust reasoning capabilities exemplified by large improvements over PaLM on BIG-Bench and other reasoning tasks. PaLM 2 exhibits stable performance on a suite of responsible AI evaluations, and enables inference-time control over toxicity without additional overhead or impact on other capabilities. Overall, PaLM 2 achieves state-of-the-art performance across a diverse set of tasks and capabilities. When discussing the PaLM 2 family, it is important to distinguish between pre-trained models (of various sizes), fine-tuned variants of these models, and the user-facing products that use these models. In particular, user-facing products typically include additional pre- and post-processing steps. Additionally, the underlying models may evolve over time. Therefore, one should not expect the performance of user-facing products to exactly match the results reported in this report

Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P &lt; 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment

Vascular complications in adult postcardiotomy cardiogenic shock patients receiving venoarterial extracorporeal membrane oxygenation

Abstract Background The rate, prognostic impacts, and predisposing factors of major vascular complications (MVCs) in patients underwent venoarterial extracorporeal membrane oxygenation (VA-ECMO) by surgical cut-down are poorly understood. The purpose of this study was to identify these parameters in adult VA-ECMO patients. Methods Adult postcardiotomy cardiogenic shock (PCS) patients receiving VA-ECMO by femoral surgical cut-down cannulation from January 2004 to December 2015 were enrolled in this study. Patients were separated into two groups depending on the presence of MVCs. Multivariate logistic regression was performed to identify factors independently associated with MVCs. Results Of 432 patients with PCS treated with VA-ECMO, 252 patients (58.3%) were weaned off VA-ECMO and 153 patients (35.4%) survived to discharge. MVCs were seen in 72 patients (16.7%), including bleeding or hematoma in the cannulation site (8.6%), limb ischemia requiring fasciotomy (8.6%), femoral artery embolism (0.7%), and retroperitoneal bleeding (0.7%). The rate of survival to discharge was 16.7 and 39.2% in patients with or without MVCs, respectively (p < 0.001). Obesity, concomitant with intra-aortic balloon pump (IABP), Sequential Organ Failure Assessment (SOFA) score at 24 h post-ECMO, and hemostasis disorder were shown to be associated with MVCs. MVCs were an independent risk factor for in-hospital mortality by multivariate analysis (odds ratio 3.91; 95% confidence interval, 1.67–9.14; p = 0.013). Conclusions MVCs are common and associated with higher in-hospital mortality among adult PCS patients receiving peripheral VA-ECMO support. The obesity, concomitant with IABP, SOFA score at 24 h post-ECMO, and hemostasis disorder were independent risk factor of MVCs

Impact of renal complications on outcome in adult patients with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation: an analysis of nationwide CSECLS database in China

Abstract Background Limited data are available on renal complications in patients with acute fulminant myocarditis (AFM) receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in China. To evaluate the impact of renal complications on outcomes in adult patients with AFM supported with VA-ECMO. Methods Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Adult patients who were diagnosed with AFM receiving VA-ECMO support in the database were included. The primary outcome was 30-day mortality in patients with AFM supported with VA-ECMO. Logistic regression model was used to examine the impact of renal complications on 30-day mortality by adjusting confounders. Results A total of 202 patients were included. The median age was 38 years (IQR 29–48) and males (n = 103) represented 51.0% of the total accounted patients. The median ECMO duration was 142.9 h (IQR 112.1–188.8 h). 178 (88.1%) patients weaned from ECMO and 156 (71.9%) patients survived. 94(46.5%) patients developed renal complications while on ECMO course. Patients with renal complications had higher 30-day mortality (40.7% (37 of 94) vs 8.3% (9 of 108), P < 0.001) compared with those without. The development of renal complications was related to a 3.12-fold increase risk of 30-day mortality (adjusted OR 3.120, 95%CI 1.002–6.577, P = 0.049). Increasing age (adjusted OR1.025, 95% CI 1.008–1.298, P = 0.040) and higher SOFA score (adjusted OR 1.162, 95%CI 1.012–1.334, P = 0.034) were independent risk factors of renal complications. Conclusions Our findings demonstrated that patients with AFM receiving VA-ECMO at high risk of developing renal complications. Advancing age and higher SOFA score was associated with increased risk of developing renal complications. The onset of renal complications was significantly associated with 30-day mortality

Supplemental Material - A nomogram to predict nosocomial infection in patients on venoarterial extracorporeal membrane oxygenation after cardiac surgery

Supplemental Material for A nomogram to predict nosocomial infection in patients on venoarterial extracorporeal membrane oxygenation after cardiac surgery by Xiyuan Li, Liangshan Wang, Chenglong Li, Xiaomeng Wang, Xing Hao, Zhongtao Du, Haixiu Xie, Feng Yang, Hong Wang, and Xiaotong Hou in Perfusion</p

Intra‐aortic balloon pump impacts the regional haemodynamics of patients with cardiogenic shock treated with femoro‐femoral veno‐arterial extracorporeal membrane oxygenation

Abstract Aims To investigate the impact of intra‐aortic balloon pump (IABP) on the regional haemodynamics of patients with severe cardiogenic shock undergoing femoro‐femoral veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO). Methods and results From July 2017 to April 2018, a total of 39 adult patients with cardiogenic shock receiving both IABP and ECMO for circulatory support were enrolled consecutively in a university‐affiliated cardiac surgery intensive care unit. The blood flow rates (BFRs) of the bilateral femoral artery (IABP side: iFA, ECMO side: eFA) and carotid artery (left: LCA, right: RCA) and the velocity time integral (VTI) of aortic root were assessed by ultrasonography and compared when IABP was on and off. Seventeen of 39 (43.6%) patients survived to discharge, and 29 (74.4%) survived on ECMO. A total of 172 pairs of data (IABP on and off) were collected in this study, measured on the median of 2.0 (1.0, 4.5) days after patients received VA‐ECMO. The BFR on both sides of FA (iFA: 176.4 ± 104.5 vs. 152.2 ± 139.8 mL/min, P  3.5 L/min). Conclusions Concomitant IABP used in patients undergoing femoro‐femoral VA‐ECMO was associated with increased aortic VTI and BFR in bilateral FA. The change in CA BFR depended on cardiac function. A decreased LCA BFR was observed in patients with cardiac stunning when IABP was turned on, which might be compensated by a higher ECMO blood flow. Further study is needed to confirm the relationship between BFR and extremities and neurological complications

Additional file 1 of Impact of renal complications on outcome in adult patients with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation: an analysis of nationwide CSECLS database in China

Additional file 1. STROBE statement

Additional file 2 of Impact of renal complications on outcome in adult patients with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation: an analysis of nationwide CSECLS database in China

Additional file 2: Table S1 Diagnostic criteria for clinical suspected myocarditis. Figure S1 Receiver operating characteristic curve calculated for multivariable logistic regression of renal complications. Figure S2 Receiver operating characteristic curve calculated for multivariate logistic regression of 30-day mortality