Limited Prognostic Value Research Articles

Immune Checkpoint Espression Associates with Rejection in Lung Transplant Recipients

Purpose The outcome of lung transplantion (LuTx) suffers from a high rejection rate, and there are still huge gaps of knowledge about immune-mediated rejection mechanisms. Acute rejection (AR) can lead to chronic lung allograft dysfunction (CLAD), the main cause of poor survival and low quality of life. The standardized morphologic evaluation of rejection is based on histopathologic diagnostic criteria at a given time-point, but it has a limited prognostic value towards clinical outcome and the likelihood to develop CLAD. We analyzed immune-check point proteins in lung tissues of patients who received a LuTx and who were or were not undergoing rejection in the attempt to define novel immunological markers that could predict rejection. Methods We conducted an observational retrospective study on eight consecutive explanted grafts for chronic rejection and on transbronchial cryobiopsies (TCB) obtained from 24 consecutive patients during the first year LuTx follow-up. A broad spectrum of immunohistochemical analysis was carried out (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein). Of those TCB-patients we recorded at least 1 year follow up of survival, infections and rejections (acute and chronic) rate. Results Exhausted (PD1+/TOX+) as well as Treg (PD1+/FOXP3+) lymphocytes were significantly reduced in restrictive allograft syndrome (RAS)-compared to bronchiolitis-obliterans-syndrome (BOS)-rejected lungs. PD1-expressing T-lymphocytes in TCBs correlated (sensitivity 0.69; specificity 1) with the presence of AR and were highly suggestive of CLAD development (sensitivity 0.86; specificity 0.82; overall 10 times higher risk of developing CLAD) at one-year follow-up. Conclusion Results herein for the first time show the importance of immunological checkpoints in the setting of LuTx rejection and indicate that the evaluation of the expression of such proteins could offer a distinct prognostic advantage in monitoring the onset of AR in patients who underwent LuTx. Longitudinal analyses in ampler cohorts will be needed to confirm these data.

Mismatch Repair Deficiency and Microsatellite Instability in Triple-Negative Breast Cancer: A Retrospective Study of 440 Patients.

PurposeTo investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.MethodsWe retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.ResultsThe median age of the cohort was 49 years (range: 24–90 years) with a median follow-up period of 68 months (range: 1–170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible EPCAM deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.ConclusionsThe incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.

A prognostic model for colorectal cancer based on CEA and a 48-multiplex serum biomarker panel

Mortality in colorectal cancer (CRC) remains high, resulting in 860,000 deaths annually. Carcinoembryonic antigen is widely used in clinics for CRC patient follow-up, despite carrying a limited prognostic value. Thus, an obvious need exists for multivariate prognostic models. We analyzed 48 biomarkers using a multiplex immunoassay panel in preoperative serum samples from 328 CRC patients who underwent surgery at Helsinki University Hospital between 1998 and 2003. We performed a multivariate prognostic forward-stepping background model based on basic clinicopathological data, and a multivariate machine-learned prognostic model based on clinicopathological data and biomarker variables, calculating the disease-free survival using the value of importance score. From the 48 analyzed biomarkers, only IL-8 emerged as a significant prognostic factor for CRC patients in univariate analysis (HR 4.88; 95% CI 2.00–11.92; p = 0.024) after correcting for multiple comparisons. We also developed a multivariate model based on all 48 biomarkers using a random survival forest analysis. Variable selection based on a minimal depth and the value of importance yielded two tentative candidate CRC prognostic markers: IL-2Ra and IL-8. A multivariate prognostic model using machine-learning technologies improves the prognostic assessment of survival among surgically treated CRC patients.

Examining the utility of extended laboratory panel testing in the emergency department for risk stratification of patients with COVID-19: a single-centre retrospective service evaluation

BackgroundThe role of specific blood tests to predict poor prognosis in patients admitted with infection from SARS-CoV-2 remains uncertain. During the first wave of the global pandemic, an extended laboratory...

Stereology in Grading and Prognosis of Canine Cutaneous Mast Cell Tumors.

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume (), a stereological estimation that provides information about nuclear size and its variability. of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in were found between grade II (= 115 ± 29 µm3) and grade III ccMCTs (= 197 ± 63 µm3), as well as between low-grade (= 113 ± 28 µm3) and high-grade ccMCTs (= 184 ± 63 µm3). An optimal cutoff value of ≥ 150 µm3 and ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, was not able to predict the clinical outcome in 42% of the cases; however, cases with <125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, is highly reproducible and is associated with histological grade as well as with benign behavior.

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia.

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.

Ultrasound examination predicts 6-month progression in carpal tunnel syndrome patients.

Carpal tunnel syndrome (CTS) is a peripheral neuropathy resulting from chronic median nerve compression. Chronic compression leads to neurological changes that are quantified through nerve conduction studies (NCS). Although NCS represents the gold standard in CTS assessment, they provide limited prognostic value. Several studies have identified ultrasound as a tool in diagnosing and potentially predicting the progression of CTS in patients. The purpose of this study was to evaluate the predictive value of ultrasound examination in CTS patients. Twenty patients recruited at their first visit with the neurologist completed two NCS and ultrasound examinations approximately 6 months apart. Ultrasound examination consisted of B-mode, pulse-wave Doppler and colour Doppler ultrasound videos and images to quantify median nerve cross-sectional area, intraneural blood flow velocity in three wrist postures (15° flexion, neutral, and 30° extension), and displacement of the flexor digitorum superficialis (FDS) tendon and the adjacent subsynovial connective tissue (SSCT) of the middle finger during repetitive finger flexion-extension cycles. A questionnaire was administered to assess the work-relatedness of CTS. Linear regression analyses revealed that intraneural blood flow velocity (R2 = 0.36, p = .03), assessed in wrist flexion, and relative FDS-SSCT displacement (R2 = 0.27, p = .04) and shear strain index (R2 = 0.28, p = .04) were significant predictors of nerve sensory and motor changes at 6 months. Results suggest the possibility of using a battery of ultrasound measures as viable markers to predict median nerve functional changes within 6 months.

Low rate of life-threatening events and limitations in predicting invasive and noninvasive markers of symptoms in a cohort of type 1 Brugada syndrome patients: Data and insights from the GenBra registry.

Brugada syndrome (BrS) has diagnostic challenges and controversial risk assessment. We aimed to investigate invasive and noninvasive parameters in symptomatic and asymptomatic patients from a Brazilian cohort of type-1 BrS. Patients with spontaneous and drug-induced type-1 BrS were classified into two groups, asymptomatic (n = 116, 84.1%) and symptomatic (n = 22, 15.9%; 13 with arrhythmogenic syncope, 9 with aborted sudden cardiac death). Genetic testing, EPS parameters, and electrocardiogram (ECG) parameters were analyzed. A total of 138 consecutive patients were eligible, 101 men (73.2%), mean 41.4 years, mostly probands (79%). Spontaneous pattern, observed in 77.5% of the patients, was associated with symptoms only if expressed in V1 and V2 standard position (not high precordial leads;p = .014). All symptomatic patients were probands. The presence of right ventricularoutflow tract conduction delay (RVOTcd) signs, positive EPS, and SCN5A status was similar between symptomatic and asymptomatic subjects. During the mean 75-month follow-up, eight patients had appropriate therapies. All had spontaneous type-1 ECG pattern and 2/8 (25%) were asymptomatic, with positive EPS. The overall LAE incidence of 1.1% per year dropped to 0.27% in asymptomatic patients. RVOTcd occurred more frequently in SCN5A carriers (QRS-f 33.3% vs. 7.7%; p = .005, AVR sign 58.3% vs. 13.6%; p < .001; deep S in lead I 75% vs. 48.5%, p = .025%), as well as longer HV interval (66vs. 49 ms; p < .001). Spontaneous type-1 Brugada pattern in standard leads and proband status were more frequent in symptomatic subjects. RVOTcd, more common in SCN5A carriers, did not predict symptoms in BrS patients. EPS exhibited limited prognostic value for this low-risk population.

Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder.

Simple SummaryThere is substantial heterogeneity in the prognosis and responsiveness to registered therapies in bladder cancer. Biomarkers that can accurately predict prognosis and treatment outcome are urgently needed. Bladder cancer is considered an immunogenic tumor. In this review, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells and immune checkpoint expression. Several immunological markers have been associated with prognosis and treatment outcome. These markers have not yet been implemented in the clinic, likely due to the limited prognostic or predictive value of the individual markers. Future studies should, therefore, focus on combinations of biomarkers to accurately predict survival and response to treatment. The extensive overview provided here can be used to guide further biomarker research in bladder cancer. The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8+ T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as a biomarker for the response to checkpoint inhibitors, there are some indications that high CD8+ T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment.

Cribriform pattern does not have a significant impact in Gleason Score ≥7/ISUP Grade ≥2 prostate cancers submitted to radical prostatectomy

Introduction:The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP).Methods:This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients.Results:At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = −0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ2 0.906; P = .341; Rp = χ2 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ2 = 3.617; P = .057) in cases without CP.Conclusions:In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.

Doppler indices of the equine fetal carotid artery throughout gestation

Assessment of pregnancy viability in the equine patient is currently based on gestational profiles of limited prognostic value. In recent years Doppler technology has been applied to uterine and umbilical arteries of pregnant mares to monitor fetal responsive haemodynamics, suggestive of compromise. To date, uterine artery Doppler indices failed to provide sufficient evidence of pregnancy viability and the umbilical cord of the equine fetus is inconsistently visualized past 250 days gestation.The objectives of this study were to: i) evaluate intracranial blood flow impedance by Doppler examination of the fetal carotid artery and ii) establish reference values for healthy, uncomplicated pregnancies. The middle cerebral artery (MCA), a branch of the carotid artery, is commonly employed to assess intracranial hemodynamics in the human fetus, exhibiting high resistance to circulation to the fetal brain in uncomplicated pregnancies. For the purpose of this study, 12 pregnant mares were examined at 2–3 weeks interval by B mode and Doppler ultrasonography until delivery and a novel technique was developed for Doppler evaluation of the carotid artery in the equine fetus, in order to provide objective evidence of the hemodynamic status of the equine fetus. Additional biophysical and biochemical parameters were collected to demonstrate appropriate pregnancy development. In this study Doppler waveform analysis of fetal intracranial vasculature demonstrated an elevated blood flow impedance, showing a significant correlation of carotid Doppler indices with gestational age. Results were comparable to human fetal trends for the middle cerebral artery (MCA) from mid gestation to term. Biochemical data showed expected patterns of uncomplicated pregnancies.

Plasma Neprilysin Displays No Relevant Association With Neurohumoral Activation in Chronic HFrEF.

BackgroundNeprilysin is a transmembrane endopeptidase involved in the breakdown of a variety of vasoactive peptides and serves as a therapeutic target in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the relationship of circulating neprilysin with neurohumoral activation and the impact of plasma neprilysin activity on prognosis in HFrEF.Methods and ResultsA total of 369 chronic HFrEF patients were enrolled prospectively. Plasma neprilysin concentration and activity were determined by a specific ELISA and a fluorometric method. The association between plasma neprilysin and heart failure (HF) severity, neurohumoral activation, ie norepinephrine and absolute renin concentration, as well as all‐cause mortality was assessed. Median plasma neprilysin concentrations and activity levels were 413 pg/mL (interquartile range 0–4111) and 2.36 nmol/mL per minute (interquartile range 1.16–4.59). No correlation could be shown between plasma neprilysin concentrations and activity (r s=0.09, P=0.088). Plasma neprilysin activity correlated with HF severity reflected by New York Heart Association stage (P=0.003) and tertiles of N‐terminal pro‐B‐type natriuretic peptide (P<0.001), whereas neprilysin concentrations did not (P=0.220; P=0.849). There was no relevant relationship between plasma neprilysin concentrations and activity, with neurohumoral activation reflected by absolute renin concentration (r s=−0.02, P=0.648; r s=0.03, P=0.574) or norepinephrine levels (r s=−0.06, P=0.248; r s=0.20, P<0.001). Neither circulating neprilysin concentrations nor activity were associated with outcome.ConclusionsPlasma neprilysin concentrations and activity are not directly related to neurohumoral activation, indicating that neprilysin regulation is either more complex or not correctly mirrored by circulating neprilysin as a biomarker. Circulating neprilysin concentrations and activity were not associated with overall survival, implicating limited prognostic value of plasma neprilysin measurements in HFrEF patients.

Cardiac Biomarkers in the Setting of Asthma Exacerbations: a Review of Clinical Implications and Practical Considerations.

The present paper aims to highlight clinical implications of elevated cardiac biomarkers and associated myocardial dysfunction in a variety of cardiac and non-cardiac scenarios in patients with an asthma exacerbation, and to propose a basic algorithm for cardiovascular evaluation and triage (and hence, for further management) of these patients primarily based on evaluation of cardiac biomarkers along with basic diagnostic modalities and specific cardiac symptoms in the hospital setting. Elevation of cardiac biomarkers in the setting of an asthma exacerbation mostly signifies a new-onset subclinical myocardial dysfunction/injury generally associated with certain asthma-related factors including acute hypoxemia and bronchodilator therapy, and usually has a limited prognostic value in these patients. On the other hand, elevation of these biomarkers in patients with an asthma exacerbation might also denote a variety of certain life-threatening cardiac or non-cardiac conditions associated with significant myocardial dysfunction (acute coronary syndromes (ACSs), sepsis, etc.) that might be masked by the rampant course of the asthma exacerbation, and hence, might possibly go undetected potentially aggravating the prognosis in a portion of these patients. In patients with an asthma exacerbation, it seems imperative to timely diagnose and manage emerging diverse clinical conditions particularly through the guidance of cardiac biomarkers and associated myocardial dysfunction patterns in an effort to improve overall prognosis in these patients.

Current Progress on Assessing the Prognosis for Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antineuronal antibody encephalitis in autoimmune encephalitis found at present. It has complex clinical manifestations such as psychiatric and behavioral abnormalities, seizures, movement disorders, consciousness, and autonomic dysfunction. The relationship between those manifestations and prognosis is unclear. Electroencephalography (EEG) is gradually becoming useful in the evaluation of the prognosis of anti-NMDAR encephalitis patients, while imaging and antibody testing have a limited prognostic value. Starting the patients on adequate treatments (such as immunotherapy) in a timely fashion has a positive impact on their prognosis. Nevertheless, research on the prognosis of anti-NMDAR encephalitis remains scarce. Here, we review the current advances of prognosis-related research from the clinical manifestations of the disease and auxiliary examinations such as EEG, magnetic resonance imaging (MRI), 18F fluorodeoxyglucose positron emission tomography (FDG-PET), and antibody measurement. In addition, we also discuss the impact of different treatment options on prognosis. In-depth research on the prognosis of patients with anti-NMDAR encephalitis will contribute to a better understanding of this disease, leading to better treatments options and, ultimately, a better prognosis.

A modified predilation, sizing, and postdilation scoring system for patients undergoing metallic drug-eluting stent implantations.

This study sought to assess whether the predilation, scaffold/stent sizing, and postdilation (PSP) score for bioresorbable scaffold (BRS) implantation was associated with outcomes following metallic drug-eluting stent (DES) implantation. The PSP score is associated with patients' prognoses after BRS implantation. This study involved 2,348 patients who underwent biodegradable polymer DES implantations during the PANDA III trial. The optimal PSP technique was defined according to previous studies of BRS implantations. The main outcome was target lesion failure (TLF) that comprised cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization. Twenty-five (1.1%) patients fulfilled all the PSP criteria. The BRS-derived PSP score was of limited prognostic value for 2-year TLF after metallic DES implantation; optimal sizing was a protective factor, but optimal predilation was a risk factor. We built a new PSP model for DESs by identifying the following risk factors: predilation performed with a residual stenosis ≥70% or a balloon-to-quantitative coronary angiography (QCA)-determined reference vessel diameter (RVD) ratio >1:1, sizing performed with an RVD <2.25 mm or a stent diameter >0.25 mm wider than the QCA-RVD, a postprocedural stenosis diameter ≥30%, age, and the baseline SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score. The new PSP scoring system predicted 2-year TLF (area under the curve, 0.69; 95% confidence interval, 0.65-0.73); a cutoff value of 19.2 points identified high-risk patients. The new PSP scoring system, based on redefined PSP criteria, age, and the SYNTAX score, could help optimize metallic DES implantations.

Short-Term Prognostic Impact of Arterial Stiffness in Older Adults Without Prevalent Cardiovascular Disease.

Arterial stiffness, represented as carotid-femoral pulse wave velocity (cfPWV), predicts cardiovascular disease (CVD). In older populations, however, this association seems attenuated. Moreover, the prognostic values of pulse wave velocity at different arterial segments and newer parameters like cardio-ankle vascular index (CAVI) remain unclear, especially in US older adults. In 3034 Atherosclerosis Risk in Communities (ARIC) study participants (66-90 years) without CVD, we examined the associations of 4 pulse wave velocity measures (cfPWV, heart-femoral, brachial-ankle, heart-ankle) and 2 new measures of arterial stiffness (CAVI and cardio-femoral vascular index derived from heart-ankle and heart-femoral, respectively) with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality. Over a median follow-up of 4.4 years, there were 168 incident CVD events and 244 deaths. Overall, stiffness measures did not show strong associations with CVD, except cfPWV, which demonstrated a J-shaped association even after adjusting for potential confounders (hazard ratio, 1.83 [95% CI, 1.08-3.09] in top quartile and 1.97 [1.14-3.39] in bottom quartile versus second bottom quartile). When each CVD was examined separately, heart failure was most robustly associated with higher cfPWV, and stroke was strongly associated with lower cfPWV. There were no significant associations with all-cause mortality. Among different measures of pulse wave velocity, cfPWV showed the strongest associations with CVD, especially heart failure, in older adults without CVD. Other pulse wave velocity measures had no strong associations. Our findings further support cfPWV as the index measure of arterial stiffness and the link of arterial stiffness to heart failure development but also suggest somewhat limited prognostic value of arterial stiffness in older adults overall.

Eating expectancies before bariatric surgery: assessment and associations with weight loss trajectories

BackgroundWhile presurgical eating behaviors have demonstrated limited prognostic value, cognitions regarding the effects of eating may serve as important predictors of weight loss outcomes after bariatric surgery. The Eating Expectancies Inventory (EEI) is a commonly used, self-report measure of expected consequences of eating; however, its psychometric and predictive properties have not yet been evaluated among bariatric surgery patients. ObjectivesThis study sought to examine the factor structure and internal consistency of the EEI among bariatric surgery candidates, to examine relationships between EEI factors and measures of eating psychopathology, and to explore the effects of eating expectancies on postsurgical weight loss. SettingData originated from an interdisciplinary bariatric surgery center in the Midwest United States. MethodsTwo hundred sixty-two women completed self-report questionnaires before bariatric surgery. Presurgical data and available postsurgical weights (at 6, 12, and 18 mo) were obtained from medical records. ResultsAnalyses indicated that the original 5-factor model was a good-to-excellent fit for the EEI data. All EEI factors demonstrated good reliability and were significantly associated with eating disorder symptoms and behaviors at baseline. Higher scores on EEI Factor 1 (negative affect) and Factor 5 (alleviates boredom) predicted poorer weight loss at 18 months postsurgery (n = 132). ConclusionsFindings support the reliability and validity of the EEI among female bariatric candidates. Presurgical eating expectancies were linked to pathologic eating patterns and also predicted postsurgical weight loss trajectories, suggesting that eating expectancies may have prognostic value as predictors of bariatric surgery outcomes.

D-dimer level and long-term outcome in patients with end-stage heart failure secondary to idiopathic dilated cardiomyopathy.

BackgroundPrevious studies had demonstrated hemostatic abnormalities in patients with heart failure (HF) and several studies have shown that abnormal coagulation indices, represented by elevated D-dimer, had prognostic significance in patients with compatible or acute decompensated HF. However, the impact of D-dimer on the outcome in patients with end-stage HF remains unclear.MethodsA total of 244 consecutive patients with end-stage HF due to idiopathic dilated cardiomyopathy (DCM) were prospectively enrolled from February 2011 to September 2014. D-dimer levels were measured and its prognostic value was assessed. Primary endpoint was all-cause mortality during the follow-up period. Secondary endpoints were stroke, bleeding, occurrence of sustained ventricular tachycardia or ventricular fibrillation, and major adverse cardiovascular events (MACE).ResultsD-dimer was significantly elevated in the non-survivors (median: 0.8 vs. 1.1 mg/L, P < 0.001). Traditional markers including B-type natriuretic peptide, troponin I, left ventricular ejection fraction, and left ventricular end-diastolic dimension provided limited prognostic value; but the addition of D-dimer refined the risk stratification. The optimal cut-off value of D-dimer to predict all-cause mortality was 0.84 mg/L by receiver operator characteristic analysis. Elevated D-dimer level was independently associated with increased risk of long-term all-cause mortality (HR = 2.315, 95% CI: 1.570–3.414, P < 0.001) and MACE (HR = 1.256, 95% CI: 1.058–1.490, P = 0.009), and the predictive value was independent of age, sex, atrial fibrillation and anticoagulation status.ConclusionsElevated D-dimer level was independently associated with poor long-term outcome in patients with end-stage HF secondary to idiopathic DCM, and the predictive value was superior to that of traditional prognostic markers.

Diagnostic and Prognostic Value of Plasma Factor V Activity and Parameters in Thrombin Generation for Disseminated Intravascular Coagulation in Patients with Hematological Malignancies.

In this study, we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies. A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology, Union Hospital, between Apr. 2014 and Dec. 2014 were enrolled in this study. There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC. The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System, and they were divided into four subgroups [score ≤3 (n=35), score=4 (n=37), score=5 (n=47), and score ≥6 (n=12)] according to ISTH scores. Using 28-day mortality as the endpoint, the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20). The results showed that the plasma factor V activity was significantly weaker, and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01). The factor V activity, peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01). Among factor V activity, lag time, peak, ETP, and ttPeak, only the factor V activity was significantly decreased in the non-survival subgroup compared with the survival subgroup (P<0.01). With the increase in ISTH score, the ETP and peak decreased gradually. The binary logistic regression analysis revealed that PLT, D-dimer, factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System. Using DIC diagnosed by ISTH Integral System as the endpoint, the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT). In conclusion, factor V activity, ETP and peak had diagnostic value for DIC in patients with hematological malignancies, and only factor V activity had limited prognostic value.

Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma

Pancreatic cancer is an aggressive disease with a poor prognosis for which current standard chemotherapeutic treatments offer little survival benefit. Receptor tyrosine kinases (RTK)s have garnered interest as therapeutic targets to augment or replace standard chemotherapeutic treatments because of their ability to promote cell growth, migration, and survival in various cancers. Met and Ron, which are homologous RTKs activated by the ligands hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), respectively, are over-activated and display synergistic malignant effects in several cancers. Despite the homology between Met and Ron, studies that have directly compared the functional outcomes of these systems in any context are limited. To address this, we sought to determine if the HGF/Met and MSP/Ron systems produce overlapping or divergent contributions towards a malignant phenotype by performing a characterization of MSP and HGF driven signaling, behavioral, and transcriptomic responses in a primary pancreatic adenocarcinoma (PAAD) cell line in vitro. The impact of dual Met and Ron expression signatures on the overall survival of PAAD patients was also assessed. We found HGF and MSP both encouraged PAAD cell migration, but only HGF increased proliferation. RNA sequencing revealed that the transcriptomic effects of MSP mimicked a narrow subset of the responses induced by HGF. Analysis of clinical data indicated that the strong prognostic value of Met expression in primary PAAD does not appear to be modulated by Ron expression. The relatively reduced magnitude of MSP-dependent effects on primary PAAD cells are consistent with the limited prognostic value of Ron expression in this cancer when compared to Met. Although HGF and MSP produced a differing breadth of responses in vitro, overlapping pro-cancer signaling, behavioral, and transcriptional effects still point to a potential role for the MSP/Ron system in pancreatic cancer.