Independent Predictor Of Worse Survival Research Articles

#1439 Risk factors and significance of a reduction of serum albumin after start of PD

Abstract Background and Aims A reduction in the serum level of albumin following the initiation of peritoneal dialysis (PD) has been reported to associate with impaired survival. Our aim was to identify pre-PD risk factors of drop of serum albumin, and to estimate how a decrease in albumin level affects PD patients’ survival prognosis. Method We included all adult patients who had been on PD for at least half a year in the Helsinki area in Finland during the years 2004 to 2019. Patients who had a dialysis history longer than 1 year before transferal to PD were excluded. We analysed the serum albumin level at start of PD and the last available albumin level before 6 months after start of PD. A 20% reduction of serum albumin was considered significant. Logistic regression was used to assess the association between risk factors (age, sex, primary kidney disease, comorbidities, laboratory variables) and a 20% drop of serum albumin. Cox regression was employed to study the effect of albumin drop on survival with adjustment for confounders. Results Of 379 patients, 80 (21%) showed a reduction of serum albumin of at least 20% after start of PD. High age, high albumin level at start of PD, high level of HDL cholesterol and low level of ionized calcium all associated independently with the risk of an albumin drop in the logistic regression analysis. The albumin level at start (hazard ratio 0.94 per one g/l increment, 95% CI 0.89-0.98) and a 20% or larger drop of albumin level (HR 2.3, 95% CI 1.4-3.9) were connected to impaired survival irrespective of each other. Other independent predictors of worse survival were high age, peripheral vascular disease, a history of stroke, and diabetes. Conclusion A drop of serum albumin after start of PD is frequent and associates with impaired survival. Drop of albumin is more common among elderly patients and those with high values HDL cholesterol or low levels of ionized calcium.

Impact of Preoperative Tumor Size on Prognosis of Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinomas.

Tumor size (TS) is a well-established prognostic factor of pancreatic ductal adenocarcinoma (PDAC). However, whether a uniform treatment strategy can be applied for all resectable PDACs (R-PDACs) and borderline resectable PDACs (BR-PDACs), regardless of TS, remains unclear. This study aimed to investigate the impact of preoperative TS on surgical outcomes of patients with R-PDACs and BR-PDACs. Chart data from three institutions were reviewed to select patients who underwent pancreatectomy for R-PDACs and BR-PDACs between January 2006 and December 2020. The patients were divided into TSsmall and TSlarge groups according to a TS cutoff value determined for each of R- and BR-PDAC using the minimum P value approach for the risk of R1 resection. TS of 35 mm and 24 mm was the best cutoff value in R-PDAC and BR-PDAC, respectively. The R1 rate was higher in the TSlarge than TSsmall group, in both R- (n = 35, 37% versus n = 294, 19%; P = 0.011) and BR-PDAC (n = 89, 37% versus n = 27, 15%; P = 0.030). Overall survival was significantly better in the TSsmall than TSlarge group in R-PDAC (38.2 versus 12.1 months; P < 0.001), but comparable between the two groups in BR-DPAC (21.2 versus 22.7 months; P = 0.363). Multivariate analysis revealed TS > 35 mm as an independent predictor of worse survival in patients with R-PDAC. Larger TS was associated with a higher R1 rate and is a worse prognostic factor in patients with R-PDAC.

The Impact of Tumor Size on Node Involvement in Typical Lung Carcinoids

BackgroundObservation has been suggested as an alternative to surgical resection for small typical lung carcinoids. We sought to evaluate the potential impact of tumor growth and lymphatic spread during observation by examining predictors of node positivity and the impact of tumor size and node status on survival. MethodsNational Cancer Database cases of typical lung carcinoid resections from 2006 to 2016 were analyzed. Predictors of lymph node involvement and survival were determined. ResultsOverall, 1019 of 8257 patients who underwent typical carcinoid resection had at least 1 positive node (12.3%). The incidence of node positivity among the 921 patients with subcentimeter tumors was 5.4% (n = 50). Increasing tumor size was independently associated with nodal involvement. Patients with nodal involvement had significantly worse 5-year survival (89.5% vs 94.0%; P < .001). Increasing tumor size was not associated with worse survival in multivariable analysis, but node positivity did independently predict worse survival. ConclusionsMore than 5% of patients with subcentimeter typical carcinoids of the lung have nodal metastases, and node involvement is an independent predictor of worse survival, whereas tumor size is not. These data suggest that even patients with small tumors should generally undergo resection when diagnosed.

Survival Trends and Profiling of Gastric Mixed Adenoneuroendocrine Carcinoma (gMANEC) in the Current Era

Background: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a histopathologic diagnosis with at least 30% each of exocrine and endocrine components. Although prognosis is thought to be driven by the relative exocrine or endocrine dominance, gMANEC has been clinically treated as gastric adenocarcinoma (gAC). The overall survival of gMANEC as compared to gastric neuroendocrine carcinoma (gNEC) or gAC remains undefined. Methods: Using the National Cancer Database, patients with gastric tumors were queried from 2004 to 2016 for gMANEC, gNEC, and gAC histologies. Demographic and clinicopathologic features were recorded. Univariate and multivariate Cox proportional hazards analyses were performed to delineate factors associated with overall survival (OS). Results: Overall, 404 patients diagnosed with gMANEC were identified. Patients had a median age 68 years, were majority male, and predominantly Caucasian. Gastric MANEC was more frequently poorly differentiated (73%vs 52% (gAC) vs 20% (gNEC), P &lt; .001) with lymphovascular invasion (57%vs 38%vs 27%, P &lt; .001) and lymph node involvement (59%vs 49%vs 36%, P &lt; .001); these factors were associated with worse OS on univariable analysis. Finally, tumors &gt;5 cm and lymph node involvement were independent predictors of worse survival. The median OS of patients with gMANEC was 41.5 months. Conclusion: Gastric MANEC and gAC have a similarly dismal prognosis and thus should be continued to treat like gAC. Pathologic nodal metastasis, tumor size and grade are useful prognostic factors.

The ARETHA study: A phase 2 randomized control trial of eribulin with evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer (TNBC) and metabolic dysfunction.

TPS1131 Background: The prognosis for advanced/metastatic TNBC remains poor and novel therapeutic strategies are urgently needed. Insulin resistance and obesity contribute to TNBC progression and are independent predictors of worse survival. Methionine aminopeptidase 2 (MetAP2/p67) is overexpressed in many tumor types including breast. MetAP2 inhibitors exhibit broad anti-tumor activity and attenuate the effects of metabolic dysfunction on tumor growth. Evexomostat (SDX-7320) is a second-generation MetAP2 inhibitor that improved insulin sensitivity, reduced fat mass, and normalized adipokine levels in preclinical models of obesity and reduced tumor growth in TNBC preclinical models. In phase 1 trials, evexomostat monotherapy partially restored insulin sensitivity, reduced adipokines, and showed anti-metastatic effects in patients with advanced solid tumors. The goal of this phase 2 study is to test whether evexomostat prevents worsening of insulin resistance and augments tumor response in patients with metastatic TNBC and metabolic dysfunction in combination with eribulin chemotherapy, a standard of care treatment option after prior anthracycline and taxane exposure. Methods: This is a single-center phase 2 randomized control trial of evexomostat, a MetAP2 inhibitor, and eribulin chemotherapy. Key eligibility criteria include metastatic TNBC, measurable disease or ≥1 predominantly lytic bone lesion, baseline hemoglobin A1c &gt;5.5% and/or BMI ≥30 kg/m2, and ≤2 prior lines of therapy in the advanced/metastatic setting. Patients with uncontrolled or insulin-dependent type II diabetes, or who require combination antihyperglycemic therapy are excluded. During the safety run-in period, 15 patients will be assigned to receive evexomostat 49 mg/m2 Q2 weeks and eribulin 1.4 mg/m2 on days 1 &amp; 8 of a 21-day cycle. Upon safety confirmation, an additional 40 patients will be randomized 2:1 to receive evexomostat or placebo with eribulin. The primary endpoint is metabolic efficacy assessed by change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score. Secondary endpoints include objective response rate, progression-free survival, safety and tolerability, patient-reported outcomes, and changes in metabolic markers and body composition. Historically, HOMA-IR scores double during chemotherapy, and this trial will test whether evexomostat attenuates the expected HOMA-IR rise. This trial will have &gt;90% power to detect a difference between a 1.5-fold change in HOMA-IR in the control arm vs. no change in the evexomostat arm while controlling the Type I error at 5%. As of Feb 2022, 3 patients are enrolled; total accrual of 61 patients is planned with a goal of 55 evaluable patients. Clinical trial information: NCT05570253 .

Renal cell carcinoma in native kidneys before transplantation - When will we stop waiting?

Kidney transplantation requires immunosuppression, traditionally regarded as a risk factor for progression in all malignancies. Based on the Cincinnati Registry, a waiting period before transplantation is therefore mandatory. However, recent evidence suggests this increased risk is restricted to particular tumors, whereas others like renal cell carcinoma (RCC) are not negatively affected. We aimed to compare oncological outcomes of RCC in native kidneys of end-stage renal disease (ESRD) patients, according to their transplantation or dialysis status. Retrospective analysis of all ESRD patients diagnosed with RCC between 2010 and 2020 in our center. Recurrence-free survival (RFS) and overall survival (OS) were estimated with Kaplan-Meier curves. Multivariable Cox regression model was used to evaluate their association with kidney transplantation. Clinical and pathological characteristics were similar between groups. Kidney transplant recipients had similar risk of recurrence (hazard ratio [HR] 0.40, 95% confidence interval [CI) 0.04-4.46, p = 0.458) and overall survival (HR 0.34, 95%CI 0.07-1.77, p = 0.202) as dialyzed patients. On multivariable Cox regression model, presence or absence of transplantation was not significantly associated with RFS (p = 0.479) or OS (p = 0.236). Time on dialysis was the only independent predictor of worse survival (HR 1.86, 95%CI 1.18-2.93, p = 0.008). Most RCC in native kidneys of ESRD patients are low-grade, low-stage and exhibit favourable pathological and outcome features. Immunosuppression does not seem to have an impact on oncological outcomes, but an increased time on dialysis seems to be associated with worse overall survival. Therefore, waiting time for transplantation for these tumors could be reduced.

Prognostic factors and role of postoperative radiotherapy in surgically resected thymomas

ObjectiveTo investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. MethodsA total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan–Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. ResultsTumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. ConclusionsThe extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Abstract OT2-17-02: The ARETHA Study: A phase 2 randomized control trial of Eribulin with Evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer and metabolic dysfunction

Abstract Background: The prognosis for advanced/metastatic triple negative breast cancer (TNBC) remains poor and novel therapeutic strategies are urgently needed to improve outcomes. Insulin resistance and obesity contribute to cancer progression and are independent predictors of worse survival after TNBC diagnosis. Chemotherapy worsens insulin resistance, body mass index, and multiple other metabolic parameters which can paradoxically limit treatment efficacy and survival. Methionine aminopeptidase 2 (MetAP2/p67) is overexpressed in many tumor types and MetAP2 inhibitors exhibit broad anti-tumor activity. Additionally, MetAP2 inhibitors improve insulin resistance, reduce adiposity, and normalize levels of adipokines, attenuating the effects of metabolic dysfunction on tumor growth. Evexomostat (SDX-7320) is a second-generation MetAP2 inhibitor designed to improve drug-like properties and minimize central nervous system toxicities. Evexomostat improved insulin sensitivity, reduced fat mass and normalized adipokine levels in preclinical models of obesity, and reduced tumor growth in preclinical models of TNBC. In phase 1 trials, MetAP2 inhibition combined with chemotherapy was safe and well tolerated, while evexomostat monotherapy partially restored insulin sensitivity, reduced angiogenic factors as well as adipokines and showed anti-metastatic effects in patients with advanced solid tumors. The goal of this phase 2 study is to test whether evexomostat in combination with eribulin chemotherapy prevents worsening of insulin resistance and augments tumor response in patients with metastatic TNBC and concomitant metabolic dysfunction. Methods: This is a single-center, placebo-controlled phase 2 randomized control trial of evexomostat, a MetAP2 inhibitor, in combination with eribulin chemotherapy. Eligible patients must have histologically confirmed metastatic TNBC, measurable disease or ≥1 predominantly lytic bone lesion, baseline metabolic dysfunction defined as hemoglobin A1c &amp;gt;5.5% and/or BMI ≥30 kg/m2, have received ≤2 prior lines of therapy in the advanced/metastatic setting, have ECOG performance status ≤1, and adequate organ function. Patients with uncontrolled or insulin-dependent type II diabetes, or who require combination antihyperglycemic therapy are excluded. During the safety run-in period, 15 patients will be assigned to receive evexomostat 49 mg/m2 every 2 weeks in combination with eribulin 1.4 mg/m2 administered on days 1 and 8 of a 21-day cycle. Upon safety confirmation, an additional 40 patients will be randomized 2:1 to receive evexomostat or placebo in combination with eribulin. The primary endpoint is metabolic efficacy assessed by change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score. Secondary endpoints include objective response rate, progression-free survival, duration of response, safety and tolerability, patient-reported outcomes, changes in metabolic markers, and changes in body composition parameters. Historically, HOMA-IR scores double during chemotherapy, and this trial will test whether evexomostat will attenuate the expected rise in HOMA-IR. Specifically, the trial will have &amp;gt;90% power to detect a difference between a 1.5-fold change in HOMA-IR in the control arm versus no change in the investigational arm while controlling the Type I error at 5%. This trial opened to accrual in July 2022. A total accrual of 61 patients is planned with a goal of 55 evaluable patients. For any inquiries/questions, please contact Sherry Shen at shens1@mskcc.org. Clinical trial registry number: pending Funding, study drug evexomostat and other support provided by: SynDevRx, Inc. Citation Format: Sherry Shen, Anna Whalen, Mark E. Robson, Larry Norton, Tiffany A. Traina, Neil M. Iyengar. The ARETHA Study: A phase 2 randomized control trial of Eribulin with Evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer and metabolic dysfunction [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-17-02.

Influence of anterior tumor location on survival after resection of lung cancer invading the thoracic inlet (Pancoast tumors)

ObjectiveSuperior sulcus tumors are a challenging subset of non–small cell lung carcinomas invading the thoracic inlet. In this study, we determined whether the location of the tumor along the first rib had an influence on survival. MethodsWe performed a review of 92 consecutive patients undergoing surgery for non–small cell lung carcinomas invading the thoracic inlet between January 1996 and June 2021. Tumor location was categorized into anterior and posterior based on predefined zones. ResultsIn total, 21 tumors were located anteriorly (23%) and 71 posteriorly (77%). The rate of R0 resection (81% vs 87%; P = .4) and pathological complete response to induction therapy (33% vs 37%; P = .8) were similar between locations. After a median follow-up of 5.8 years (range, 0.8-24 years), 49 patients died for an overall survival of 48% (95% CI, 38%-59%) at 5 years. The 5-year survival was favorably influenced by R0 (vs R1) resection (51% vs 29%; P = .02), pathological complete response (vs no pathological complete response) (69% vs 31%; P = .03), posterior (vs anterior) location (56% vs 22%; P = .01), and ≤60 (vs >60) years of age (61% vs 37%; P = .007). Compared with posterior tumors, anterior tumors were associated with higher risk of systemic recurrence and significantly greater survival benefit from pathological complete response. Anterior tumors remained an independent predictor of worse survival in multivariate analysis (hazard ratio, 2.3; 95% CI, 1.2-4.5; P = .01). ConclusionsThe anatomical location of the tumor affects survival after resection of non–small cell lung carcinomas invading the thoracic inlet. Anterior tumors have greater propensity to metastasize and may derive greater benefit from optimal systemic therapy than posterior tumors.

Preoperative Rapid Weight Loss as a Prognostic Predictor After Surgical Resection for Pancreatic Cancer.

The aim of the study is to evaluate the influence of cachexia at the time of diagnosis of pancreatic ductal adenocarcinoma (PDAC) on prognosis in patients undergoing surgical resection. Patients with data on preoperative body weight (BW) change followed by surgical resection during 2008-2017 were selected. Large BW loss was defined as weight loss >5% or >2% in individuals with body mass index less than 20 kg/m2 within 1 year preoperatively. Influence of large BW loss, ΔBW defined as preoperative BW change (%) per month, prognostic nutrition index, and indices of sarcopenia. We evaluated 165 patients with PDAC. Preoperatively, 78 patients were categorized as having large BW loss. ΔBW was ≤ -1.34% per month (rapid) and > -1.34% per month (slow) in 95 and 70 patients, respectively. The median postoperative overall survival of rapid and slow ΔBW groups was 1.4 and 4.4 years, respectively (P < 0.001). In multivariate analyses rapid ΔBW (hazard ratio [HR], 3.88); intraoperative blood loss ≥430 mL (HR, 1.89); tumor size ≥2.9 cm (HR, 1.74); and R1/2 resection (HR, 1.77) were independent predictors of worse survival. Preoperative rapid BW loss ≥1.34% per month was an independent predictor of worse survival of patients with PDAC.

Association of Mu-Opioid Receptor Expression With Long-Term Survival and Perineural Nerve Invasion in Patients Undergoing Surgery for Ovarian Cancer

BackgroundOpioids are widely used during primary debulking surgery (PDS) for ovarian cancers, and a high mu-opioid receptor (MOR) expression predicts worse cancer outcomes. However, the impact of MOR expression on survival outcomes in ovarian cancers is still not clear.MethodsA retrospective cohort study was conducted in patients who underwent PDS in ovarian cancer patients. MOR expression was measured in tumor and normal tissue. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included perineural invasion (PNI), intraoperative sufentanil consumption, length of stay (LOS), and verbal numerical rating scale (VNRS) on postoperative day 1 (POD1), POD3, and POD5.ResultsAfter propensity score matching, a total of 366 patients were finally enrolled in this study. There were no significant differences in OS rates in patients with high versus low levels of MOR (1-year OS: 82.9% versus 83.3%, 3-year: 57.8% versus 59.1%, 5-year: 22.4% versus 23.1%,respectively) in the ovarian cancers. There were no significant differences in DFS between the groups. Intraoperative sufentanil consumption was higher in the MOR high-expression group compared with the MOR low-expression group. Tumors expressing high levels of MOR showed higher rates of PNI. VNRS in the MOR high-expression group was higher on POD1.ConclusionMOR is not an independent predictor of worse survival in ovarian cancers but is associated with high rates of perineural invasion.

Pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous tumor: Different prognostic factors for different overall survival.

It is unclear whether invasive intraductal papillary mucinous neoplasm (IPMN) has different clinical and prognostic characteristics, beyond histological factors, when compared to pancreatic ductal adenocarcinoma (PDAC). compare prognostic features of resected PDAC and invasive IPMN METHODS: A retrospective study of patients resected for PDAC or invasive IPMN realized at Humanitas Cancer Center's Pancreatic Surgery Unit, Milan, Italy, between 2010 and 2016. Data recorded included patient demographics, onset symptoms, preoperative health status, tumor features, histology and surgical characteristics. Overall survival was estimated using Kaplan-Meier and prognostic factors for survival were assessed by multivariate Cox regression. A total of 332 patients were included (PDAC, n=289; invasive IPMN, n=43). Patients with invasive IPMN had better overall survival than PDAC patients (median: 76.6 versus 25.6 months; 5-year OS rate: 65.4% vs. 14.2%; p<0.001). PDAC histology was associated with a significantly higher risk of death than IPMN (hazard ratio 1.815, 95% CI: 1.02, 3.24; p=0.044). Survival was also worse with PDAC in early-stage disease (IA-IB-IIA, N0). In multivariate analysis, independent predictors of worse survival included perineural invasion, preoperative ASA physical status ≥3 and pain at diagnosis. Patients with IPMN had a better prognosis than PDAC patients, regardless of disease stage.

Right and left ventricular assist devices are an option for bridge to heart transplant

BackgroundPatients with a left ventricular assist device with right ventricular failure are prioritized on the heart transplant waitlist; however, their post-transplant survival is less well characterized. We aimed to determine whether pretransplant right ventricular failure affects postoperative survival in patients with a left ventricular assist device as a bridge to transplant. MethodsWe performed a retrospective review of the 2005-2018 Organ Procurement and Transplantation Network/United Network for Organ Sharing registry for candidates aged 18 years or more waitlisted for first-time isolated heart transplantation after left ventricular assist device implantation. Candidates were stratified on the basis of having right ventricular failure, defined as the need for right ventricular assist device or intravenous inotropes. Baseline demographic and clinical characteristics were compared among the 3 groups, and post-transplant survival was assessed. ResultsOur cohort included 5605 candidates who met inclusion criteria, including 450 patients with right ventricular failure, 344 patients with a left ventricular assist device and intravenous inotropes as a bridge to transplant, 106 patients with a left ventricular assist device and right ventricular assist device, and 5155 patients with a left ventricular assist device as a bridge to transplant without the need for right side support. Compared with patients without right ventricular failure, patients with a left ventricular assist device as a bridge to transplant with right ventricular failure were younger (median age 51 years, 55 vs 56 years, P < .001) and waited less time for organs (median 51 days, 93.5 vs 125 days, P < .001). These patients also had longer post-transplant length of stay (median 18 days, 20 vs 16 days, P < .001). Right ventricular failure was not associated with decreased post-transplant long-term survival on unadjusted Kaplan–Meier analysis (P = .18). Neither preoperative right ventricular assist device nor intravenous inotropes independently predicted worse survival on multivariate Cox proportional hazards analysis. However, pretransplant liver dysfunction (total bilirubin >2) was an independent predictor of worse survival (hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P < .001), specifically in the left ventricular assist device group and not in the left ventricular assist device + right ventricular assist device/intravenous inotropes group. ConclusionsPatients with biventricular failure are prioritized on the waiting list, because their critical pretransplant condition has limited impact on their post-transplant survival (short-term effect only); thus, surgeons should be confident to perform transplantation in these severely ill patients. Because liver dysfunction (a surrogate marker of right ventricular failure) was found to affect long-term survival in patients with a left ventricular assist device, surgeons should be encouraged to perform transplantation in these severely ill patients after a recipient's optimization by inotropes or a right ventricular assist device because even when the bilirubin level is elevated in these patients (treated with right ventricular assist device/inotropes), their long-term survival is not affected. Future studies should assess recipients' optimization before organ acceptance to improve long-term survival.

Clinical characteristics and prognosis of cardiac amyloidosis defined by mass spectrometry-based proteomics in an Australian cohort.

Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival. Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis. We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry. A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis. AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

What is the Role of the Preoperative Blood-Based Inflammation Biomarkers in the Prognosis of Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy? A Single-Centre Retrospective Study.

Objective: To assess the prognostic value of preoperative blood-based inflammation biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), on the survival outcomes of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). Methods: We retrospectively studied the data of 172 patients who were diagnosed with UTUC after RNU during 2008 to 2018. We determined the cut-off value by using X-tile software. The area under the curve (AUC) and concordance index (C-index) were utilized to compare the predictive accuracy between subgroups. We also performed decision curve analysis (DCA) to evaluate the clinical net benefit of prognostic models. The Kaplan–Meier method and Cox proportional hazards regression models were performed to evaluate the association between these inflammation biomarkers and survival outcomes. Results: The median follow-up period was 45.5 (range: 1-143; interquartile range, IQR: 27-77) months. Kaplan–Meier analyses showed that a high NLR or PLR significantly reduced overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and metastasis-free survival (MFS), and a low LMR markedly decreased RFS and MFS. The multivariate Cox proportional hazards model revealed that the NLR plus PLR was an independent predictor of worse survival (all P < .05). Additionally, the AUC and C-index of the new prognostic models were the largest for the 1- to 5-year OS, CSS, RFS, and MFS were the largest. Conclusion: Our study confirms that the combination of preoperative NLR and PLR could be an independent risk factor for UTUC patients who have undergone RNU. The addition of NLR and PLR may improve the accuracy of current prognostic models and help guide clinical strategies in the treatment of UTUC.

Extracellular vesicles miR-210 as a potential biomarker for diagnosis and survival prediction of oral squamous cell carcinoma patients.

BackgroundThe identification of early diagnostic and prognostic biomarkers in oral squamous cell carcinoma (OSCC) is an unmet clinical need. We hypothesized that extracellular vesicles miR‐210 expression (EV‐miR‐210) could be a potential biomarker for OSCC diagnosis and follow‐up.MethodsThe expression of EV‐miR‐210 was measured in the plasma of OSCC patients (n = 30) and compared to that of controls (n = 14).ResultsThe median EV‐miR‐210 expression was significantly higher in OSCC patients compared to controls who had often, undetectable levels (p < 0.0001). We performed receiver operating characteristic (ROC) analysis for discriminating OSCC cases from controls. EV‐miR‐210 yielded an area under the curve (AUC) of 0.9513 with sensitivity 92.3% and specificity 86.6%. Kaplan‐Meier curves indicated that high EV‐miR‐210 expression was associated with worse 3 years’ survival (p < 0.05). Cox regression hazard model indicated that high EV‐miR‐210, G2, and G3 grading and pathological nodal status (pN)>1 were independent predictors of worse survival in OSCC patients.ConclusionThese preliminary data suggest that EV‐mir‐210 may be a novel diagnostic and prognostic biomarker in OSCC.

The impact of left ventricular size on outcomes after centrifugal-flow left ventricular assist device implantation.

The influence of preoperative left ventricular size in outcomes following centrifugal-flow left ventricular assist device (LVAD) implantation has not been well characterized. A cohort of 313 patients who received a centrifugal-flow LVAD at a single institution was analysed. Using a maximally selected log-rank statistic, we investigated whether a left ventricular end-diastolic dimension (LVEDD) cut-off point was associated with worse outcomes. The cohort was then divided in 2 groups based on the LVEDD cut-off point. An LVEDD cut-off point of 59 mm was found to predict worse survival. Smaller LVEDD patients (≤59 mm, N = 52) were older and more likely to have a history of coronary artery disease compared those with a larger LVEDD (>59 mm, N = 261). Smaller LVEDD patients had lower survival compared to larger LVEDD patients (71% vs 85% at 1 year and 58% vs 80% at 2 years, P = 0.003). The need for temporary right ventricular mechanical support was significantly higher in the smaller LVEDD cohort (11.5% vs 1.9%, P = 0.002). Pump flows at time of discharge were lower in the smaller LVEDD group (3.8 vs 4.2 l/min, P = 0.005), who also had a higher incidence of late right ventricular failure (23% vs 12%, P = 0.02), higher rates of gastrointestinal bleeding (0.416 vs 0.256 events per patient-year, P = 0.025) and higher readmissions secondary to low flow alarms (0.429 vs 0.240 events per patient-year, P = 0.007). Multivariable analysis demonstrated that smaller LVEDD, older age, high BUN and high bilirubin levels were independent predictors of worse survival. In patients receiving a centrifugal-flow LVAD, smaller preoperative LVEDD (≤59 mm) was associated with lower survival and higher incidence of adverse outcomes.

Mucoepidermoid carcinoma: Evaluating the prognostic impact of primary tumor site

Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients with MEC. Material and MethodsThis cohort identified 308 patients with MEC who underwent primary surgery between 1985 and 2015. Survival outcomes were determined using the Kaplan–Meier method. Hazard ratios for primary site were determined using the Cox proportional-hazards model. ResultsOne hundred eighty (58%) patients were diagnosed with minor and 128 (42%) with major salivary gland cancer. Primary site in the minor salivary gland group included 137 (44%) oral cavity, 38 (12%) pharynx, 3 (0.9%) nasal cavity, and 2 (0.6%) trachea and larynx. The major salivary gland group included 118 (38%) parotid, 8 (3%) submandibular, and 2 (0.6%) sublingual. With a median follow-up of 73 months, 5-year overall survival and disease-specific survival were 84% and 91%, respectively. Patients with tumors located in the hard palate and retromolar trigone had the best survival, while patients with tumors located in the paranasal sinuses and submandibular gland had the poorest survival. After controlling for tumor grade and stage, MEC primary site was not predictive of survival or recurrence. On multivariate analysis, worse DSS was associated with stage III–IV tumors (HR: 7,11; 95% CI: 1.19–26.43; p = 0.0034) and high-grade tumors (HR: 19.12; 95% CI: 2.26–162.77; p = 0.0068). ConclusionsWhile high grade and advanced overall stage were found to be independent predictors of worse survival, primary tumor site was not predictive of poor outcome.

Myocardial injury in patients hospitalized for SARS-CoV19: a maker or a marker of prognosis?

Abstract Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, literature data are progressively accumulating, attesting to the possible prognostic role of cardiac troponins in patients who need hospitalization because of COVID-19 infection. Purpose To assess whether myocardial injury (measured by high sensitivity troponins) is an independent cause of disease severity and prognosis. Methods We performed a patient-level metanalysis (PROSPERO ID: CRD42020213209) in unselected patients hospitalized because of COVID-19 infection in whom the severity of respiratory failure was also evaluated at admission. To allow for comparison, troponin values were normalized to their threshold levels to obtain a normalized troponin (nTn) value which was used as a continuous variable in all analysis. Results A total of 722 patients were included in the analysis. Of note, patients who had elevated troponins at hospital admission had a significantly lower oxygenation status than those with normal nTn (PaO2/FiO2 232±215 vs. 276±124 mmHg/%; p&amp;lt;0.001). On the contrary, those with cardiovascular comorbidities had similar PaO2/FiO2 but higher nTn than those without (5.6817 vs. 2.1110 ng/mL; p=0.002). After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age, male sex, moderate-severe renal dysfunction (eGFR &amp;lt;30 mL/min/m2) and lower PaO2/FiO2, were independent predictor of death (igure 1). The restricted cubic spline curves in Figure 2A and 2B show the hazard ratios (HRs) and 95% confidence interval for death according to nTn and PaO2/FiO2 levels as continuous variables. A linear increase in the HR is observed with lower PaO2/FiO2 values below the normal value of 300. On the contrary, the nTn spline curve is near-flat with large confidence interval for values above the normality thresholds. Conclusion In patients hospitalized for COVID-19, mortality is mainly driven by gender, age and respiratory failure while myocardial damage is not an independent predictor of worse survival when respiratory function is accounted for. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

High troponin levels in patients hospitalized for coronavirus disease 2019: a maker or a marker of prognosis?

Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P < 0.0001], male sex (HR 2.049, 95% CI 1.319-3.184, P = 0.0014), moderate-severe renal dysfunction (estimated glomerular filtration rate < 30 mL/min/m2) (HR 2.108, 95% CI 1.237-3.594, P = 0.0061) and lower PaO2/FiO2 (HR 0.901, 95% CI 0.829-0.978, P = 0.0133) were the independent predictors of death. A linear increase in the HR was associated with decreasing values of PaO2/FiO2 below the normality threshold. On the contrary, the HR curve for troponin plasma levels was near-flat with large CI for values above the normality thresholds. In unselected patients hospitalized for COVID-19, mortality is mainly driven by male gender, older age and respiratory failure. Elevated plasma levels of high-sensitivity troponins are not an independent predictor of worse survival when respiratory function is accounted for.