RWMAs in critically ill patients with non-obstructed coronary arteries

Introduction

Left ventricular (LV) dysfunction is estimated to occur in 10%–25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population.

Methods

In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries.

Results

We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56–2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy.

Conclusion

RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.     

Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -