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AbstractIntroductionPatients with small‐cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long‐term survival. The objective of this study was to investigate factors and pattern of long‐term survival in patients with limited‐stage small cell lung cancer (LS‐SCLC) who achieved a complete response (CR) after chemoradiotherapy.Patient and MethodsThis was a single‐center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan–Meier model, and the results were reported as the median and interquartile range.ResultsWe identified 162 patients, median age was 64.7 (56.2–70.2) years, and 94 (58%) were females. Eighty‐one patients (50%) had recurrence during follow‐up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45–0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29–0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001).ConclusionsPatients with LS‐SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.

Abstract Chimeric antigen receptor (CAR)-T cell therapy is the next revolutionary advance in cancer therapy. By using ex vivo engineered T cells to specifically target antigens, a targeted immune reaction is induced. Chimeric antigen receptor-T cell therapy is approved for patients suffering from advanced and refractory B cell and plasma cell malignancies and is undergoing testing for various other haematologic and solid malignancies. In the process of triggering an anticancer immune reaction, a systemic inflammatory response can emerge as cytokine release syndrome (CRS). The severity of CRS is highly variable across patients, ranging from mild flu-like symptoms to fulminant hyperinflammatory states with excessive immune activation, associated multiorgan failure and high mortality risk. Cytokine release syndrome is also an important factor for adverse cardiovascular (CV) events. Sinus tachycardia and hypotension are the most common reflections, similar to what is seen with other systemic inflammatory response syndromes. Corrected QT interval prolongation and tachyarrhythmias, including ventricular arrhythmias and atrial fibrillation, also show a close link with CRS. Events of myocardial ischaemia and venous thromboembolism can be provoked during CAR-T cell therapy. Although not as closely related to CRS, changes in cardiac function can be observed to the point of heart failure and cardiogenic shock. This may also be encountered in patients with severe valvular heart disease in the setting of CRS. This review will discuss the pertinent CV risks of the growing field of CAR-T cell therapy for today’s cardiologists, including incidence, characteristics, and treatment options, and will conclude with an integrated management algorithm.

AbstractBackground and objectivePleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on‐site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy.MethodsA prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on‐site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross‐validated area under the receiver operating characteristic curve.ResultsOf the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17–131.14,p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85–35.16,p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97–22.1,p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross‐validated AUC of 0.94 (95% CI = 0.91–0.97).ConclusionA prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to date been anecdotal. Here, we conducted a phase 1 clinical trial of systemic OV therapy and investigated the mechanisms of action in responding T-cell lymphoma (TCL) patients. A single IV dose of VSV-IFNβ-NIS was administered to patients with relapsed refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DL). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication and immune responses. Fifteen patients received VSV-IFNβ-NIS (7 multiple myeloma, 7 TCL, 1 acute myeloid leukemia); 3 patients were treated at each DL1 through DL3 (0.05, 0.17, and 0.5 x 1011 TCID50), and 6 at DL4 (1.7 x 1011 TCID50). There were no dose limiting toxicities. 3 of 7 patients with TCL had RECIST responses: a 3-month PR at DL2, a 6-month PR and a durable CR ongoing at 20 months at DL4. Viremia peaked at the end of infusion and no infectious virus shedding was detected. Plasma interferon-β levels, a biomarker of VSV-IFNβ-NIS replication, peaked between 4h and 48h post infusion. The patient with CR had robust viral replication with increased ell free DNA in her plasma, a very high peak IFNβ level of 18,213 pg/ml, a strong anti-VSV neutralizing antibody response, and increased numbers of tumor reactive T-cells. VSV-IFNβ-NIS as a single agent was effective in patients with TCL resulting in durable disease remissions in heavily pretreated patients. Correlative analyses suggest that responses may be due to a combination of direct oncolytic tumor destruction and immune-mediated tumor control. Further clinical testing is warranted. (This trial is registered at www.clinicaltrials.gov as NCT03017820).

AbstractOptimal perioperative care contributes to improved patient outcomes, as demonstrated in the field of liver transplant (LT). The evolution in perioperative care over the past two decades has been driven by research in areas such as preoperative testing, coagulation management, and intraoperative monitoring. However, much of this research is driven by local institutional pressures and practices with a dearth of studies emanating from research consortia or other groups of experts within the field. To better characterize the top research questions in the field, we queried a group of 128 LT anesthesiologists representing 87 international liver transplant centers with a response from 71 practitioners (59.2%). Three experts then codified the responses into the top 20 questions, which were sent to the survey recipients as a second survey to rank order. Seventy‐five respondents (61.5%) provided responses, which were merged into a weighted ranked priority list and analyzed by respondent location and center size. The highest ranked question was, “What intraoperative anesthetic management/interventions affect graft outcome?” Most of the top research questions focused on preoperative risk factor management or optimization and intraoperative management techniques. In general, this priorities list may serve as a guide for transplant anesthesiology researchers to focus future research endeavors on shared interests that improve patient care.

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with an elevated mortality risk due to right ventricular failure. Pulmonary arterial pulsatility index (PAPi) based on invasively acquired parameters has emerged as a potentially valuable hemodynamic risk predictor. Whether non-invasively derived PAPi (PA pulse pressure/ RA pressure) is valuable is unclear. Purpose To assess whether PAPi measured non-invasively by transthoracic echocardiography acts as a prognostic hemodynamic biomarker of patient risk. Methods Consecutive patients undergoing transthoracic echocardiography for known or suspected PH over a one year period were included. PA systolic and diastolic pressure were estimated in standard fashion from peak tricuspid and end-pulmonary regurgitant Doppler profiles. Right atrial pressure was estimated based on 2D & Doppler assessment of the inferior vena cava hepatic vein. In those patients with PH (mean PA pressure &gt; 20 mm Hg), PAPi was divided into 3 groups based on prior publications with invasive data as &lt;1.5, 1.5 to 3 and &gt;3. Mortality was assessed over 5 years. Results Of 1,045 patients enrolled 64% had PH. Patients with the lowest PAPi (table) had higher NT-proBNP levels, larger right ventricles, worse right heart systolic function (cardiac output, TAPSE, systolic annular velocity, free wall systolic strain) and greater degrees of tricuspid regurgitation (Table). In patients with PH, PAPi was inversely associated with death (figure, p &lt; 0.0001) with each group of PAPi correlating with incrementally worse survival. Patients with a PAPi of &lt;1.5 had worst right heart size and dysfunction on echo (table) and worst survival (figure). Conclusions In patients with PH, low PAPi derived non-invasively by transthoracic echocardiography is associated with markers of right heart failure, right ventricular dysfunction and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with known or suspected PH and maybe a useful predictor of outcome. Abstract Table Abstract Figure

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.

Introduction: Patients with carotid stenosis may have silent cerebrovascular disease due to chronic hypoperfusion and atheroembolism. If so, progression of silent disease may be preventable through revascularization. We aim to evaluate the association between carotid stenosis/occlusion and cerebral small vessel disease (SVD) burden ipsilateral to the cervical carotid stenosis. Methods: Patients age ≥40 years with carotid stenosis or occlusion on carotid ultrasound who underwent MRI brain and intracranial angiogram with gradable SVD on MRI from 2011-2015 were included. Severity of carotid stenosis was defined using NASCET criteria as 50-69% (moderate), 70-99% (high-grade), or occluded. WMH volume was quantified using an automated artificial intelligence algorithm applied to axial T2 FLAIR images. Images were also scored for presence of chronic lacune, cerebral microbleeds (CMB), and silent infarcts using STRIVE criteria. Differences in WMD volume between hemispheres ipsilateral and contralateral to the carotid stenosis were calculated, and prevalence of SVD and silent infarct were compared across severities of carotid stenosis. Results: Of the 183 patients, mean age was 71±10 years and 38% were female. Moderate and severe stenosis was present in 36% and 46.5%, respectively, and 18% had carotid occlusion. Mean WMH volume was 7271±522mm 3 . Patients with carotid stenosis had greater WMH volume ipsilateral to the side of carotid stenosis than the contralateral side (mean difference 224±206mm 3 ), and higher severity of stenosis was associated with greater hemispheric difference in WMH volume (moderate vs high; 164±274mm 3 vs 743±309 mm 3 , p=0.009). Silent infarcts were more prevalent in high-grade carotid stenosis than moderate grade (moderate vs high, 10.8% vs 36.5%; p=0.002). There were no differences in either lacunae or CMBs across severities. Conclusions: Greater than one third of patients with high-grade carotid stenosis had ipsilateral silent brain infarction, and the volume of WMH was greater on the side of carotid stenosis. Future analyses should consider the potential yield of screening for carotid atherosclerosis in patients with varying degrees of hemispheric WMH asymmetry.