Surrogate Marker Research Articles

The effectiveness of case method in developing intrapreneurship among business students

Intrapreneurship skill has considered as the alternative learning outcomes of entrepreneurship education. However, entrepreneurship teachers need a complex learning program to develop intrapreneurship among business students. At the same time, The Ministry of Education and Culture of The Republic of Indonesia recommends university teachers implement case methods to deliver complex learning environments and build critical skills among students.  Therefore, this study aims to i) examine the effect of micro small medium enterprise (MSME) cases on the intrapreneurship of business students, ii) investigate the influence of MSME cases on flow experience in entrepreneurship education and iii) investigate the effect of flow experience during entrepreneurship education on intrapreneurship skill.  We used field experiments on entrepreneurship and digital business student in business development courses.  The result indicates that the case method effectively developed student intrapreneurship skill and flow experience during the course positively impacting student intrapreneurship skill.

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Prevalence of Anti- Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study.

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients' quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae , and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease. This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals. Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M). Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups ( P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M. Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.

Neutrophil to lymphocyte ratio (NLR) as a surrogate marker of diabetic nephropathy

Background and objectives: Diabetic nephropathy and retinopathy are microvascular complications of diabetes. Nephropathy is clinically manifested as an increase in urine albumin excretion. Total white blood cell count is a crude but sensitive indicator of inflammation and studied in many cardiac and non-cardiac diseases as an inflammatory marker such as acute myocardial infarction, stroke, and heart failure. In this study, the association of neutrophil to lymphocyte ratio (NLR) with diabetic nephropathy and retinopathy. Methods: This was a prospective observational study performed on patients with diabetic nephropathy +/- retinopathy. A total of v104 subjects diagnosed with 3type 2 diabetes mellitus registered in this study. NLR was calculated by analyzing differential leukocyte count in complete blood picture. Spot Albuminuria was tested by immune turbidimetry method. Urine creatinine was tested by jaffe’s kinetic method by which spot urine microalbumin to creatinine ratio is calculated. ANOVA, Independent t-test, chi-square test, Karl Pearson correlation were applied to find significance. P&lt;0.05 was considered as statistically significant. Results: Totally 104 diabetic subjects were registered, 52 subjects had DN and 52 had normal urine albumin. Mean±SD NLR for a normal group is 2.5±1.1 and in DN group is 3.4±1.4 which was highly significant (P =0.001). Conclusion: Our study showed that there was a significant relation between NLR and DN; and positive correlation between NLR and urine microalbumin to creatinine ratio. Therefore, NLR may be considered as a novel surrogate marker of DN.

Antecedents of memorable heritage tourism experiences: an application of stimuli–organism–response theory

Purpose Based on stimulus-organism-response theory, this study aims to develop and tests a model of memorable heritage tourism experience (MHTE). The model proposes that experiencescape, experience co-creation, education and photography are important antecedents of MHTE, which is then a driver of place attachment. Design/methodology/approach Data for this study were collected using a Web-based questionnaire of people aged 18 years and over who had a heritage tourism experience during the previous three months (February–April 2023). The survey was distributed in May 2023 using Amazon Mechanical Turk (MTurk). A survey link was posted on MTurk, which remained active for the first week of May 2023. Out of the 283 responses received, 272 were valid responses from individuals who met the participation criteria. Findings Experiencescape, experience co-creation, education and photography were found to be positive drivers of the MHTE, with a positive relationship between MHTE and place attachment. Originality/value Many studies linked to memorable tourism experience (MTE) mainly replicate Kim, Ritchie, &amp; McCormick’s (2012) MTE scale, regardless of the specific study context. This study offers an alternative framework through which alternative antecedents and outcomes of tourists’ MTE can be identified.

Social Determinants of Health and Patient-reported Outcomes Following Autologous Breast Reconstruction, Using Insurance as a Proxy.

Insurance type can serve as a surrogate marker for social determinants of health and can influence many aspects of the breast reconstruction experience. We aimed to examine the impact of insurance coverage on patients reported outcomes with the BREAST-Q (patient reported outcome measure for breast reconstruction patients, in patients receiving) in patients receiving deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. We retrospectively examined patients who received DIEP flaps at our institution from 2010 to 2019. Patients were divided into categories by insurance: commercial, Medicaid, or Medicare. Demographic factors, surgical factors, and complication data were recorded. Descriptive statistics, Fisher's exact, Kruskal-Wallis rank sum tests, and generalized estimating equations were performed to identify associations between insurance status and five domains of the BREAST-Q Reconstructive module. A total of 1,285 patients were included, of which 1,011 (78.7%) had commercial, 89 (6.9%) had Medicaid, and 185 (14.4%) had Medicare insurances. Total flap loss rates were significantly higher in the Medicare and Medicaid patients as compared to commercial patients; however, commercial patients had a higher rate of wound dehiscence as compared to Medicare patients. With all other factors controlled for, patients with Medicare had lower Physical Well-being of the Chest (PWBC) than patients with commercial insurance (β = - 3.1, 95% confidence interval (CI): -5.0, -1.2, p = 0.002). There were no significant associations between insurance classification and other domains of the BREAST-Q. Patients with government-issued insurance had lower success rates of autologous breast reconstruction. Further, patients with Medicare had lower PWBC than patients with commercial insurance regardless of other factors, while other BREAST-Q metrics did not differ. Further investigation as to the causes of such variation is warranted in larger, more diverse cohorts.

What Clinicians Should Know About Surrogate Endpoints in Hematologic Malignancies.

Use of surrogates as primary endpoints is commonplace in hematology/oncology clinical trials. As opposed to prognostic markers, surrogates are endpoints that can be measured early and yet can still capture the full effect of treatment, as it would be captured by the true outcome (e.g., overall survival). We discuss the level of evidence of the most commonly used endpoints in hematology and share recommendations on how to apply and evaluate surrogate endpoints in research and clinical practice. Based on the statistical literature, this clinician-friendly review intends to build a bridge between clinicians and surrogacy specialists.

Relationship between METS-IR and thyroid cancer incidence in Korea: a nationwide population-based study

BackgroundSeveral previous studies found a positive relationship between metabolic syndrome (MetS) and thyroid cancer (TC) risk. However, there is no research that has studied the relationship between the metabolic score for insulin resistance (METS-IR), a novel surrogate marker for IR, and TC incidence. Thus, we designed this retrospective cohort study to evaluate the relationship between the incidence of TC and METS-IR.MethodWe analyzed a cohort of 314,321 Korean adults aged over 40 years who participated in the National Health Screening Program from 2009 to 2010. The individuals were divided into four groups based on METS-IR quartiles. Follow-up was until the diagnosis of TC or death, or until December 31, 2019, if neither. The relationship between METS-IR and TC incidence was analyzed using the Cox proportional-hazards model with multi-variable adjustments.ResultsA total of 4,137 participants (1.3%) were diagnosed with TC during a mean follow-up of 9.5 ± 1.5 years. The population with Q1 METS-IR scores showed higher disease-free probabilities than those with Q4 METS-IR scores (p &amp;lt;0.001). The hazard ratio (95% confidential interval) for TC incidence in Q2, Q3, and Q4 METS-IR value were 1.14 (1.05 to 1.25), 1.21 (1.11 to 1.33), and 1.30 (1.18 to 1.42) compared with Q1 of METS-IR, respectively. The incidence of TC tended to increase with increasing METS-IR values in the total population, especially the male population in the restricted cubic spline. In subgroup analysis, the TC risk was more pronounced in the subgroups under 65 and with a BMI &amp;lt; 25 kg/m2.ConclusionMETS-IR was positively correlated with TC incidence in Korea.

Multicomponent Amorphous Solid Forms of Telmisartan: Insights into Mechanochemical Activation and Physicochemical Attributes.

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy

ObjectivesThis study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy.MethodsThis study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results.ResultsThe median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was −0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p&amp;lt; 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR.ConclusionsBRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Author Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Editors' Note: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Reader Response: Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Therapeutic Drug Monitoring as a Tool for the Clinical Outcome Prediction in Vedolizumab-Treated Patients: An Italian Pilot Study

Over the years, vedolizumab (VDZ) has emerged as a more effective target therapy for inflammatory bowel disease. The aim of this work was to analyze a cohort of inflammatory bowel disease patients, evaluating the association between VDZ serum concentrations at 6 months from starting therapy and their clinical and biochemical indexes within one year of treatment, correlating drug levels with response and clinical remission. Forty patients treated with VDZ were enrolled. Drug concentrations were quantified through ELISA methods. VDZ levels correlated with hemoglobin levels at twelve months of therapy (p = 0.03) and with clinical remission at twelve months of therapy (p = 0.03); patients who reached clinical remission showed higher VDZ concentrations. A VDZ cut-off value of 43.1 μg/mL was suggested, predicting clinical remission at twelve months of therapy. A statistically significant association between VDZ levels at T6 and calprotectin &lt;250 μg/g at T12 was found (p = 0.04). Furthermore, the optimal threshold value of VDZ levels at T6 associated with calprotectin &lt;250 μg/g at T12 was identified: through levels higher than 45.2 µg/mL, we were able to predict remission one year after therapy. In the final regression multivariate model, no factor was retained as a predictor of clinical remission at one year of treatment. In conclusion, this is the first pilot study reporting a possible VDZ serum cut-off value able to predict not only the clinical remission at twelve months of therapy but also the calprotectin level, which is very important, as it is a surrogate marker of mucosal healing.

Classification of postoperative complications in plastic and reconstructive surgery: a systematic review

"Introduction: Postoperative complications are an integral aspect of the surgical audit, being a surrogate marker of surgical quality. Despite demonstrated efficacy in most specialties, there is scarce validation of current systems in plastic and reconstructive surgery, let alone a system unique to the specialty. This review aims to establish the efficacy of current systems in plastic and reconstructive surgery and formulate a classification unique to our specialty. Methods: A PUBMED literature search was performed in January 2023 encompassing all available literature. Search terms included ‘classification’, ‘grading’, ‘postoperative complications’ and ‘adverse events’. Further additions through bibliographic linkage generated a total of 363 articles. Results: Twenty-four papers were related to PRS. Sixteen used current systems to describe postoperative complications, whereas eight papers used a system designed uniquely for PRS. The downfall of conventional systems is the simplicity of return to the operating theatre, constituting a single grade in the Clavien-Dindo Classification. Return to theatre has a broad scope for heterogeneity in plastic and reconstructive surgery, particularly in reconstructive patients. A modification of the Clavien-Dindo Classification is proposed. Conclusion: There is limited efficacy of current classification systems for postoperative complications in plastic and reconstructive surgery nor a well-validated system unique to the specialty. A modified system with a detailed emphasis on return to the theatre will be of value to plastic and reconstructive surgery and ideally correlate with important outcomes. This will be validated in a retrospective review of the complication audit from the developing institution."

P16 overexpression identifies oncogenic high-risk HPV infection in non-oropharyngeal squamous cell carcinoma of the head and neck.

Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle-related proteins, to identify HPV-driven non-OPSCC is less well understood. We stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV-status was assessed by HPV DNA PCR. In 119 non-OPSCC, RNA in situ hybridization was additionally performed. HPV-status was correlated with staining patterns, p53 and clinical data. The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV-testing was performed in 57%, and 53% were positive for HPV DNA. HPV-association correlated with absence of pRb and cyclin D1 and favorable outcome. In non-OPSCC, 18% showed p16-blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost pRb and cyclin D1. Compared to HPV-negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV-positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common. We conclude that HPV-positive non-OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV-negativity.

Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation.

Patients with first-diagnosed atrial fibrillation (FDAF) exhibit major adverse cardiovascular events (MACEs) during follow-up. Preclinical models have demonstrated that thrombo-inflammation mediates adverse cardiac remodeling and atherothrombotic events. We have hypothesized that thrombin activity (FIIa) links coagulation with inflammation and cardiac fibrosis/dysfunction. Surrogate markers of the thrombo-inflammatory response in plasma have not been characterized in FDAF. In this prospective longitudinal study, patients presenting with FDAF (n = 80), and 20 matched controls, were included. FIIa generation and activity in plasma were increased in the patients with early AF compared to the patients with chronic cardiovascular disease without AF (controls; p < 0.0001). This increase was accompanied by elevated biomarkers (ELISA) of platelet and endothelial activation in plasma. Pro-inflammatory peripheral immune cells (TNF-α+ or IL-6+) that expressed FIIa-activated protease-activated receptor 1 (PAR1) (flow cytometry) circulated more frequently in patients with FDAF compared to the controls (p < 0.0001). FIIa activity correlated with cardiac fibrosis (collagen turnover) and cardiac dysfunction (NT-pro ANP/NT-pro BNP) surrogate markers. FIIa activity in plasma was higher in patients with FDAF who experienced MACE. Signaling via FIIa might be a presumed link between the coagulation system (tissue factor-FXa/FIIa-PAR1 axis), inflammation, and pro-fibrotic pathways (thrombo-inflammation) in FDAF.

The asymmetric impact of decision-making confidence on regret and relief

When individuals make uncertain decisions, they often evaluate the correctness of their choices in what is referred to as decision-making confidence. The outcomes of such decision-making can lead to counterfactual thinking wherein alternative possible outcomes are contemplated. This, in turn, can elicit counterfactual emotions including upward and downward counterfactual thinking, which, respectively, refer to regret and relief. Decision-making confidence and counterfactual emotions have key effects on how individuals learn from the past and prepare for the future. However, there has been little understanding of how these experiences are related. For this study, 98 total adults were recruited with the goal of assessing the connections between decision-making confidence and sensations of regret and relief when completing a card-based gambling task. The results of this study suggest that decision-making confidence may reduce the intensity of relief while increasing the degree of regret experienced. These findings thus emphasize the important effect that decision confidence has on emotional processing.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Response assessment of GBM during immunotherapy by delayed contrast treatment response assessment maps

IntroductionAssessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting.MethodsWe recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS &amp;gt; 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored).ResultsUsing receiver operating characteristic (ROC) curves, a threshold of −0.066 in VBlue/VCE (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median “blue” volumes.DiscussionIn conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.