Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients

BackgroundAlthough gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome.MethodsPeripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters.ResultsChanges in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient’s outcome.ConclusionsThis work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use.

A Diagnostic Model for Kawasaki Disease Based on Immune Cell Characterization From Blood Samples

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. However, distinguishing KD from febrile infections early in the disease course remains difficult. Our goal was to estimate the immune cell composition in KD patients and febrile controls (FC), and to develop a tool for KD diagnosis.Methods: We used a machine-learning algorithm, CIBERSORT, to estimate the proportions of 22 immune cell types based on blood samples from children with KD and FC. Using these immune cell compositions, a diagnostic score for predicting KD was then constructed based on LASSO regression for binary outcomes.Results: In the training set (n = 496), a model was fit which consisted of eight types of immune cells. The area under the curve (AUC) values for diagnosing KD in a held-out test set (n = 212) and an external validation set (n = 36) were 0.80 and 0.77, respectively. The most common cell types in KD blood samples were monocytes, neutrophils, CD4+-naïve and CD8+ T cells, and M0 macrophages. The diagnostic score was highly correlated to genes that had been previously reported as associated with KD, such as interleukins and chemokine receptors, and enriched in reported pathways, such as IL-6/JAK/STAT3 and TNFα signaling pathways.Conclusion: Altogether, the diagnostic score for predicting KD could potentially serve as a biomarker. Prospective studies could evaluate how incorporating the diagnostic score into a clinical algorithm would improve diagnostic accuracy further.

Synovial calprotectin for the diagnosis of periprosthetic joint infection: a diagnostic meta-analysis

Background Periprosthetic joint infections (PJI) are a rare but severe complication of total joint arthroplasty (TJA). However, the diagnosis of PJI remains difficult. It is one of the research that focuses about diagnosis for PJI for majority researchers to discover a novel biomarker. This meta-analysis tried to evaluate diagnostic value of synovial calprotectin for PJI. Methods This meta-analysis search of the literature was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. Literature quality was appraised using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) based on RevMan (version 5.3). The diagnostic value of calprotectin for PJI was evaluated by calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), diagnostic score and area under SROC (AUC) based on the Stata version 14.0 software. We conduct subgroup analysis according to the study design, cutoff values, the country of study, and gold standard. Results Seven studies were included in this meta-analysis. The pooled sensitivity of synovial calprotectin for the diagnosis of PJI was 0.94 (95% CI, 0.87–0.98), and the specificity was 0.93 (95% CI, 0.87–0.96). The pooled AUC, PLR, and NLR for synovial calprotectin were 0.98 (95% CI, 0.96–0.99), 13.65 (95% CI, 6.89–27.07), and 0.06 (95% CI, 0.02–0.15), respectively. The pooled diagnostic score and DOR were 5.4 (95% CI, 3.96–6.85) and 222.32 (95% CI, 52.52–941.12), respectively. Conclusion In summary, this meta-analysis indicates that synovial calprotectin is a promising biomarker of assistant diagnosis for PJI, as well as recommended test for excluding diagnostic tool.

Case Report: Successful Treatment of Acute Generalized Exanthematous Pustulosis With Secukinumab

Acute generalized exanthematous pustulosis is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base. Most cases of acute generalized exanthematous pustulosis (AGEP) clear quickly with a systemic corticosteroid, but severe or recalcitrant cases may need other systemic therapies. In this case, a man in his 40 s with a history of psoriasis consulted a physician about widespread erythema, pustules, target lesions, and fever after the administration of a quadruple antituberculosis drug. Routine laboratory testing revealed elevated white blood cell count and C-reactive protein. The histopathology showed subcorneal pustules, spongiosis as well as lymphocyte and eosinophils infiltration in the dermis. The patient was diagnosed with definitive AGEP according to the diagnostic score from the EuroSCAR study. Cutaneous lesions especially pustules and erythema multiforme-like lesions on the upper arms and palms are crucial for distinguishing AGEP from Generalized pustular psoriasis. The patient was treated with secukinumab as a result of his failure to respond to topical corticosteroids and constrain of systemic steroids. Remission with secukinumab therapy was safe without increased risks of infections. This case indicates that secukinumab is a potential therapy that can rapidly improve the clinical symptoms of AGEP.

Usefulness of the modified hemophagocytic syndrome diagnostic score as a prognostic factor in lung transplantation patients

Background: Lung transplantation (LTX) is an established treatment for end-stage lung disease; however, the post-LTX mortality rate remains high. This study aimed to evaluate the prognostic value of the modified reactive hemophagocytic syndrome diagnostic score (mHScore) and its individual components on mortality after LTX.Methods: We retrospectively analyzed 294 patients who underwent LTX at Severance Hospital, Yonsei University, Korea, from January 2012 and December 2020, and classified them into high (n=114, mHScore > 104.0) and low mHScore (n=180, mHScore ≤ 104.0) groups. Triglyceride, ferritin, serum glutamic oxaloacetic transaminase, fibrinogen, and cytopenia were used to calculate the mHScore. We compared baseline characteristics and mortality rates as LTX prognostic factors.Results: The high mHScore group had significantly more cytopenia and higher ferritin, triglyceride, lactate dehydrogenase, and C-reactive protein levels than the low mHScore group. The mortality rate was significantly higher in the high than in the low mHScore group (hazard ratio, 4.429, p < 0.001). Multivariate regression analysis revealed that a high mHScore was significantly associated with postoperative mortality, even after adjusting for other confounding factors. A high mHScore was also associated with postoperative complications.Conclusions: The mHScore can be used to estimate post-LTX prognosis and predict postoperative mortality.

A Novel Clinical Score Predicting the Presence of Fatty Pancreas

Background: Fatty pancreas (FP) has become an increasingly encountered entity in recent years. Several studies have shown an association with several disease states. Aims: we aimed to generate a simple non-invasive scoring model to predict the presence of FP. Method: We performed a retrospective cross-sectional analysis at Galilee Medical Center. Inclusion criteria included patients who underwent endoscopic ultrasound (EUS) for hepatobiliary indications and who had either hyperechogenic pancreas consistent with FP or no sonographic evidence of fatty pancreas. Results: We included 569 patients. Among them, 78 patients had FP by EUS and 491 patients did not have FP. On univariate analysis, obesity (odds ratio (OR) 5.11, p < 0.0001), hyperlipidemia (OR 2.86, p = 0.0005), smoking (OR 2.02, p = 0.04), hypertension (OR 2.58, p = 0.0001) and fatty liver (OR 5.94, p < 0.0001) were predictive of FP. On multivariate analysis, obesity (OR 4.02, p < 0.0001), hyperlipidemia (OR 2.22, p = 0.01) and fatty liver (OR 4.80, p < 0.0001) remained significantly associated with FP. We developed a diagnostic score which included three parameters that were significant on multivariate regression analysis, with assignment of weights for each variable according to the OR estimate. A low cut-off score of ≤1 was associated with a negative predictive value (NPV) of 98.1% for FP, whereas a high cut-off score of ≥2 was associated with a positive predictive value (PPV) of 35–56%. Conclusion: We recommend incorporating this simple score as an aid to identify individuals with FP.

FAT score: an Indian insight to a novel diagnostic score to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis

Background The aim of this study was to propose a simple predictive score to differentiate NASH from simple steatosis. Results This study included 64 patients who had biopsy-proven NAFLD, of which 34 patients had steatohepatitis and 30 had simple steatosis. Clinical, anthropometric, and biochemical variables of the study population were analyzed. Univariate analysis showed platelet count, ferritin, and transaminases (ALT&AST) were predictors of NASH. This led to the proposal of a new diagnostic tool, FAT score (F signifies Ferritin, A indicates AST&ALT, T denotes t in Platelet) with AUROC of 0.95. The ROC curves for the significant variables were plotted and cutoff values were identified. Each component is awarded a score of 0 or 1, based on this cutoff value. The component is awarded a score of 1 if the component score is above the cutoff value and 0, if the score is below cutoff. The maximum score which can be obtained is 4. A score of ≥ 3 was able to predict NASH from simple steatosis with a sensitivity of 76.5% and a specificity of 100%. The score was validated with a cohort of 84 liver biopsy patients wherein a cutoff ≥ 3 was found to give a specificity of 100% in the validation cohort. Conclusions FAT score is a simple predictive model to differentiate NASH from simple steatosis (cutoff of more than or equal to 3) without performing a liver biopsy. A FAT score less than 3 rules out the need for biopsy.

417 Multi-chamber speckle tracking imaging and diagnostic value of left atrial strain in cardiac amyloidosis

Aims Amyloid deposits in all cardiac chambers, impairing their function. We investigated for the first time if a speckle-tracking echocardiography (STE) analysis extended to all four chambers might hold additive diagnostic value for CA and its subtypes [amyloid transthyretin (ATTR-) and light-chain (AL)-CA]. Methods and results We evaluated 423 consecutive patients undergoing a diagnostic workup for CA in two referral centres from 2015 to 2020. CA was diagnosed in 261 patients (62%; ATTR-CA, n = 144, 34%; AL-CA, n = 117, 28%). Patients with CA had an impaired function of all cardiac chambers, particularly those with ATTR-CA. Peak left atrial longitudinal strain (LA-PALS) was the only STE parameter that predicted CA and ATTR-CA independent of laboratory and standard echocardiographic variables (Model 1). It also predicted ATTR-CA among patients with unexplained hypertrophy regardless of a diagnostic score (IWT score). Patients with either LA-PALS or LA-peak atrial contraction strain (PACS) in the first quartile (LA-PALS &lt;6.65% or LA-PACS &lt;3.62%) had an almost 4-fold higher likelihood of CA and ATTR-CA regardless of Model 1. Among patients with unexplained hypertrophy, those with LA-PALS or LA-PACS in the first quartile had an almost 9-fold higher likelihood of ATTR-CA irrespective of Model 1, and a 2-fold higher likelihood of ATTR-CA beyond the IWT score. Conclusions STE measures of all two chambers are abnormal in patients with CA, particularly in those with ATTR-CA. LA strain holds independent diagnostic significance. Among patients screened for CA, those with LA-PALS &lt;6.65% and/or LA-PACS &lt;3.62% have a high likelihood of CA and ATTR-CA.

Distinguishing Between Multisystem Inflammatory Syndrome, Associated With COVID-19 in Children and the Kawasaki Disease: Development of Preliminary Criteria Based on the Data of the Retrospective Multicenter Cohort Study

Objectives: Diagnostic between multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) and Kawasaki disease (KD) can make difficulties due to many similarities. Our study aimed to create a Kawasaki/MIS-C differentiation score (KMDscore) allowing discrimination of MIS-C and KD.Study design: The retrospective multicenter cohort study included clinical, laboratory, and instrumental information about MIS-C (n = 72) and KD (n = 147). The variables allowed to discriminate both conditions used to construct and validate the diagnostic score called the KMDscore.Results: Patients with MIS-C were older, had earlier admission to the hospital, had a shorter time before fever resolution, two times frequently had signs of GI and CNS involvement observed, and had more impressive thrombocytopenia, higher level of CRP, ferritin, ALT, AST, LDH, creatinine, triglycerides, troponin, and D-dimer compared to KD patients. Respiratory signs in MIS-C were presented with pleuritis, acute respiratory distress syndrome, oxygen dependency, lung infiltration, and ground-glass opacities in CT. The heart involvement with fast progression of myocarditis provided the severity of MIS-C and ICU admission due to 12 times higher arterial hypotension or shock and required cardiotonic. No differences in the frequency of CA lesions were seen in the majority of cases. Five criteria, CRP &gt;11 mg/dl (18 points), D-dimer &gt;607 ng/ml (27 points), age &gt;5 years (30 points), thrombocytopenia (25 points), and GI involvement (28 points), were included in the KMDscore. The summa &gt;55 points allowed to discriminate MIS-C from KD with a sensitivity of 87.5% and specificity of 89.1%.Conclusion: The KMDscore can be used to differentiate the diagnostic of MIS-C from KD.

Identification of Patients Requiring Adrenalectomy for Unilateral Adrenal Tumors Through a Dual Approach: ceCT and [18F]FDG-PET

PurposeHormonal assessment (HA) and contrast-enhanced CT (ceCT) show insufficient sensitivity and specificity when staging unilateral adrenal lesions (ALs). We aimed at: 1) developing an imaging-based, i.e. ceCT and FDG-PET, diagnostic score able to discriminate adrenal tumors entailing adrenalectomy from those who need clinical monitoring, and 2) identifying a diagnostic flow-chart that allows clinicians to avoid unneeded diagnostic procedures and to address patients to the optimal management.MethodsRetrospective single-center study assessing patients with unilateral AL and the following inclusion criteria: a) a four-phase ceCT; b) FDG-PET within one month of the ceCT; c) histopathology or a clinical follow-up of at least 24 months. Firstly, multivariate logistic regression analysis was employed to identify the predictors of adrenal tumors to treat surgically (AL-to-treat) and regression-based coefficients were used to develop a diagnostic score. Secondly, using cut-offs of predictor variables, a diagnostic flow-chart was defined.ResultsForty-eight patients were enrolled (mean age 61 years), of whom 21/48 (44%) had AL-to-treat. The remaining 27/48 (56%) presented with AL to follow-up only (i.e. benign). Maximum and minimum lesion diameter, Hounsfield units (HU) before contrast media injection and HU at the delayed phase (HUdelayed), relative and absolute washout, AL SUVmax, AL SUVmean, ratio SUVmax AL/SUVmax liver (adrenal-liver ratio) were associated with the presence of AL-to-treat (all p<0.05). In multiple logistic regression analysis, SUVmax and HUdelayed showed to be significant predictors of AL-to-treat and were used to create a diagnostic score. ceCT parameters’ cut-offs discriminating AL-to-treat surgically from AL-to-follow-up with 100% PPV and NPV were first identified, finding 4/48 AL-to-treat and 15/48 ALs to follow-up. Applying the adrenal-liver ratio cut-off of 1.7 to the 29/48 remaining patients with uncertain AL management, for adrenal tumors we found an overall accuracy, sensitivity and specificity of 83%, 76% and 89%, respectively, and a diagnostic flow-chart based on these results was proposed. ConclusionWe developed a two-parameter imaging-based score that may be applied to predict adrenal tumors requiring adrenalectomy. Furthermore, a diagnostic flow-chart to stratify patients on the basis of the optimal management was proposed, thus guiding undefined unilateral adrenal lesions to FDG-PET imaging.