Noninvasive Diagnostic Criteria Research Articles

Noninvasive prediction of BRAF V600E mutation status of pleomorphic xanthoastrocytomas with MRI morphologic features and diffusion-weighted imaging

ObjectivesSeeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters.MethodsThe clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value.ResultsA comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADCratio) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984.ConclusionThe BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics.Critical relevance statementThe noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future.

Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience.

Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods. We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022). Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier ( P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005]. This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA.

Reappraising imaging features of pancreatic acinar cystic transformation: be aware of differential diagnoses.

Imaging features of pancreatic acinar cystic transformation (ACT) have been published. We aimed to describe the clinical and radiological characteristics of patients with a presumed pancreatic ACT diagnosis, reappraising the value of these published imaging criteria. Single-center retrospective study (2003-2021) of consecutive patients with a presumed diagnosis of ACT as suggested by the local expert multidisciplinary case review board. Patients without available imaging (CT or MRI) for review were excluded. Patients were classified into "certain" ACT (if ≥ 2 imaging criteria and no differential diagnosis) or "uncertain" ACT (if ≥ 1 imaging criteria and suggested differential diagnoses). Sixty-four patients (35 males, [55%]) were included. ACT was considered "certain" for 34 patients (53%) and "uncertain" for 30 patients (47%). The number of ACT criteria did not differ between groups, with 91.2% of patients with ≥ 3 ACT imaging criteria in the "certain" group vs 93.3% in the "uncertain" group (p = 0.88). In the "uncertain" group, the main suggested differentials were branch-duct intraductal papillary mucinous neoplasm (18/30 patients, 60%), calcifying chronic pancreatitis (8/30 patients, 27%), both (three patients, 10%) and serous cystadenoma (one patient, 3%). Calcifications were significantly more frequent in the "uncertain" group (89% vs 63% in the "certain" group, p = 0.02). Published ACT imaging criteria are frequently associated with features suggesting differential diagnoses. They appear insufficient to reach a final diagnosis in a subset of patients. ACT displays a heterogeneous morphological imaging presentation challenging the non-invasive diagnostic work-up. Physicians' and radiologists' awareness of this entity is important to better understand its natural history and improve non-invasive diagnostic criteria. The criteria to help diagnose ACT are frequently associated with features suggestive of differentials. The main alternatives suggested when ACT diagnosis was "uncertain" were branch-duct intraductal papillary mucinous neoplasm and calcifying chronic pancreatitis. Published ACT diagnostic imaging criteria can be insufficient for a definite non-invasive diagnosis.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

Management of Patients With Unexplained Syncope: Derivation and Validation of a Simplified 2-Step Diagnostic Approach.

The aim of this study was to develop a structured 2-step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2-step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study-based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter-defibrillator. The primary end point was the time until the event of recurrent syncope (syncope-free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow-up of ≈4 years. After the structured 2-step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter-defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow-up of ≈2.5 years (29.29±12.58 months, P=0.03). The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2-step electrophysiology-inclusive algorithm as a potentially low-cost, 1-day, structured tool for these patients.

Radiomics: A radiological evidence-based artificial intelligence technique to facilitate personalized precision medicine in hepatocellular carcinoma.

The high postoperative recurrence rates in hepatocellular carcinoma (HCC) remain a major hurdle in its management. Appropriate staging and treatment selection may alleviate the extent of fatal recurrence. However, effective methods to preoperatively evaluate pathophysiologic and molecular characteristics of HCC are lacking. Imaging plays a central role in HCC diagnosis and stratification due to the non-invasive diagnostic criteria. Vast and crucial information is hidden within image data. Other than providing a morphological sketch for lesion diagnosis, imaging could provide new insights to describe the pathophysiological and genetic landscape of HCC. Radiomics aims to facilitate diagnosis and prognosis of HCC using artificial intelligence techniques to harness the immense information contained in medical images. Radiomics produces a set of archetypal and robust imaging features that are correlated to key pathological or molecular biomarkers to preoperatively risk-stratify HCC patients. Inferred with outcome data, comprehensive combination of radiomic, clinical and/or multi-omics data could also improve direct prediction of response to treatment and prognosis. The evolution of radiomics is changing our understanding of personalized precision medicine in HCC management. Herein, we review the key techniques and clinical applications in HCC radiomics and discuss current limitations and future opportunities to improve clinical decision making.

Hippocampal spindles and barques are normal intracranial electroencephalographic entities

ObjectiveTo assess whether hippocampal spindles and barques are markers of epileptogenicity. MethodsFocal epilepsy patients that underwent stereo-electroencephalography implantation with at least one electrode in their hippocampus were selected (n = 75). The occurrence of spindles and barques in the hippocampus was evaluated in each patient. We created pairs of pathologic and pathology-free groups according to two sets of criteria: 1. Non-invasive diagnostic criteria (patients grouped according to focal epilepsy classification). 2. Intracranial neurophysiological criteria (patient’s hippocampi grouped according to their seizure onset involvement). ResultsHippocampal spindles and barques appear equally often in both pathologic and pathology-free groups, both for non-invasive (Pspindles = 0.73; Pbarques = 0.46) and intracranial criteria (Pspindles = 0.08; Pbarques = 0.26). In Engel Class I patients, spindles occurred with similar incidence both within the non-invasive (P = 0.67) and the intracranial criteria group (P = 0.20). Barques were significantly more frequent in extra-temporal lobe epilepsy defined by either non-invasive (P = 0.01) or intracranial (P = 0.01) criteria. ConclusionsBoth spindles and barques are normal entities of the hippocampal intracranial electroencephalogram. The presence of barques may also signify lack of epileptogenic properties in the hippocampus. SignificanceUnderstanding that hippocampal spindles and barques do not reflect epileptogenicity is critical for correct interpretation of epilepsy surgery evaluations and appropriate surgical treatment selection.

Subcentimeter hepatocellular carcinoma in treatment-naïve patients: noninvasive diagnostic criteria and tumor staging on gadoxetic acid-enhanced MRI.

It is controversial to adopt non-invasive diagnostic criteria of hepatocellular carcinoma (HCC) in subcentimeter lesions. This study was aimed to define the optimal noninvasive diagnostic criteria of subcentimeter HCC and to evaluate the effect on tumor staging. We included 110 treatment-naïve patients at risk of HCC and eligible for curative treatment who had subcentimeter lesions (n = 136) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) performed between January 2013 and December 2013. Modified diagnostic criteria for subcentimeter HCC were developed using logistic regression analysis. Accuracies of MR staging with and without using the modified criteria were compared by generalized estimating equation test using pathologic staging as reference standards. Subgroup analysis was performed for patients with co-existing HCC ≥ 1 cm (co-HCC). The modified criteria (presence of co-HCC, arterial phase hyperenhancement, and hypointensity on transitional phase [TP]) showed 61.5% (95% CI, 41.6-78.2) of sensitivity and 98.2% (95% CI, 93.0-99.5) of specificity. Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001). Fifty percent of subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). In the subgroup with co-HCCs, the accuracy of MR staging with subcentimeter HCCs was improved from 69.0% to 92.8% (p = 0.001). Including subcentimeter HCCs based on the modified diagnostic criteria (co-existing HCC ≥ 1 cm, arterial phase hyperenhancement, and hypointensity on TP) improved MR staging accuracy. • Fifty percent of non-benign appearing subcentimeter lesions found in patients with co-HCCs were HCC, whereas 5.9% of them without co-HCCs were HCC (p = 0.001). • Including subcentimeter HCCs improved the accuracy of MR staging from 84.5 to 94.5% (p = 0.001).

Evaluation of Primary Liver Cancers Using Hepatocyte-Specific Contrast-Enhanced MRI: Pitfalls and Potential Tips.

When radiologists interpret hepatic focal lesions seen on dynamic magnetic resonance imaging (MRI) scans, it is important not only to distinguish malignant lesions from benign ones but also to distinguish nonhepatocellular carcinoma (HCC) malignancies from HCCs. In addition, most major guidelines, including those of the American Association for the Study of Liver Disease, European Association for the Study of the Liver, and Korean Liver Cancer Association and National Cancer Center, allow for the noninvasive imaging diagnosis of HCC in at-risk patients. However, ~40% of HCC cases show atypical imaging features mimicking non-HCC malignancies. Furthermore, several benign and malignant lesions, such as flash-filling hemangioma and intrahepatic mass-forming cholangiocarcinoma, frequently look like HCC. In contrast, although multiparametric MRI options, including hepatobiliary phase and diffusion-weighted imaging, provide useful information that could help address these challenges, there remain several unresolved issues with regard to the noninvasive diagnostic criteria characterizing HCC. In this article, we discuss the typical imaging features and challenging situations related to primary liver cancers in MRI, while considering how to make a correct diagnosis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

P897Diagnostic utility of tissue biopsy in transthyretin cardiac amyloidosis diagnosed by non-invasive diagnostic criteria

Abstract Background In the recent past, transthyretin cardiac amyloidosis (TTR-CA) is recognized as an important cause of heart failure with preserved ejection fraction, and diagnostic utility of 99mTc-pyrophosphate (99mTc-PYP) scintigraphy in TTR-CA has been established. However, pathological evaluation is still the basis to confirm diagnosis. Subcutaneous tissue and gastrointestinal tract biopsy are useful examinations alternative to endomyocardial biopsy. Nevertheless, the positive ratio of amyloid deposition in these organs is not fully evaluated based on recent non-invasive diagnostic criteria. Purpose Our aim was to evaluate the diagnostic sensitivity of tissue biopsy in TTR-CA patients diagnosed by 99mTc-PYP scintigraphy. Methods We retrospectively evaluated 124 consecutive TTR-CA patients [wild-type (ATTRwt): 90, hereditary (hATTR): 34] who were diagnosed by positive findings of 99mTc-PYP scintigraphy (visual score 2 or 3) between June 2002 and January 2019 at our institute. Results A total of 114 patients underwent tissue biopsy at least one organ. Amyloid was detected on Congo red staining of subcutaneous tissue (43/97: 44%), gastrointestinal tract (52/78: 67%) and heart (78/79: 99%), respectively. Among 70 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsy, amyloid was detected at least one specimen in 57/70 (81%). Compared to hATTR CA patients, ATTRwt CA patients had lower positive ratio of subcutaneous tissue (81% vs. 27%) and gastrointestinal tract (73% vs. 63%) biopsy. Conclusion Non-invasive diagnostic criteria of TTR-CA had excellent sensitivity of amyloid deposition in heart. The diagnostic sensitivity of subcutaneous tissue and gastrointestinal tract biopsy was lower in ATTRwt CA compared to hATTR CA. Combination of subcutaneous tissue and gastrointestinal tract biopsy was useful for pathological confirmation of amyloid deposition without endomyocardial biopsy.

Early Ultrasound Signs of Splenomegaly in Neonates

The purpose of the study is to determine early non-invasive (ultrasound) diagnostic criteria of splenomegaly in neonates with a high risk of congenital or postnatal infection.Materials and methods. In the prospective study, 163 newborn infants of the first week of live were included. All neonates included in the study were classified as possessing a high risk of an intra-uterine infection (IUI). Depending on the birth weight, the infants were split into two groups: group «А» — 80 full-term newborns with normal birth weight, and group «В» — 83 full-term newborns with fetal growth restriction (FGR). A comprehensive examination of newborns including spleen ultrasound was carried out.Results. An increased spleen weight coefficient (Km) was found in newborns with high risk of infection development that included congenital oromaxillofacial and gastrointestinal defects, perinatal contacts with various microorganism. The increased spleen weight and Km reflected conditions of the immune system organ of the newborn in response to an adverse exposure including infection.Conclusion. Ultrasound examination of morphometrical characteristics of the spleen in newborns with various medical conditions represents a convenient and simple method of early diagnosis of splenomegaly. The most sensitive index is the spleen weight coefficient (Km), which reflects the immune system organ response to an adverse perinatal exposure including contact with an infectious agent. The mean spleen weight coefficient is within the range of 1.1 to 3.0. When the index exceeds 4, the risk of development of an infectious disease increases. This method can be used as a screening approach for newborns of different gestation age who have been included in the high-risk group based on a congenital or early postnatal infection.

From the Editor’s desk…: June 2019

From the Editor’s desk…: June 2019

Noninvasive diagnostic criteria for nonalcoholic steatohepatitis based on gene expression levels in peripheral blood mononuclear cells.

Nonalcoholic fatty liver disease (NAFLD) consists of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); the latter progresses to liver cirrhosis and hepatocellular carcinoma. Discriminating NASH from NAFL typically involves liver biopsy. The mechanism of NASH progression is unclear but may involve immunological pathways. In this study, we examined expression levels of cytokine- and chemokine-encoding genes in peripheral blood mononuclear cells (PBMCs) from NAFLD patients and established immunological criteria for discriminating NASH from NAFL. PBMCs were obtained from 54 patients diagnosed histologically with NAFLD (NAFL, 18; NASH, 36). mRNA was extracted from PBMCs, and expression levels of cytokine- and chemokine-encoding genes were determined by quantitative real-time PCR. Statistical analysis was performed by nonparametric test. Expression levels of interferon (IFN)γ, interleukin (IL)2, IL15, C-C-motif chemokine ligand (CCL)2, IL10, and C-X-C-motif chemokine ligand (CXCL)11 were significantly upregulated in NASH patients compared with NAFL patients. Moreover, their expression levels were positively correlated with the degree of ballooning of hepatocytes but not of steatosis or lobular inflammation. We focused on those encoding IL10, IFNγ, and CCL2, and developed a scoring system to discriminate NASH from NAFL. The discriminatory power of the criteria was validated in an independent cohort. Expression levels of the cytokine- and chemokine-encoding genes in PBMCs were positively correlated with ballooning, suggesting their utility for the diagnosis of NASH. The data indicate that peripheral as well as intrahepatic immunity is involved in the progression of NASH. Our findings afford new insight into immunological mechanisms of NASH and will facilitate its noninvasive diagnosis.

Design and validation of a noninvasive diagnostic criteria for biliary atresia in infants based on the STROBE compliant

It is difficult for clinicians to distinguish biliary atresia (BA) from other causes of neonatal cholestasis (NC) at an early stage. The aim of this study was to design and validate noninvasive diagnostic criterion for early diagnosis of BA in infants.In this retrospective cohort study, a total of 482 medical records of patients with NC were recruited to design diagnostic criteria. Parameters showing a significant difference between BA (n = 166) and non-BA (n = 316) patients were analyzed by logistic regression to predict the occurrence of BA, and then a nomogram scoring system was designed and validated in another cohort that included 190 cases of NC.A prediction diagnostic criterion with parameters including direct bilirubin, total bilirubin, globulin, albumin, gamma glutamyl transpeptidase, cholesterol, total bile acid, hepatobiliary scintigraphy, birth weight, and stool color was established; the sensitivity and specificity of this diagnostic criterion was 89% and 84%, respectively. The accuracy was 86% and the AUC was 0.91 [95% CI (0.88-0.97)]. The total score ranged from 0 to 402, with a cut-off value of ≥254 discriminating BA from other causes of NC. By applying this score in the validation set with age <60 days, the accuracy was 95.3%, the sensitivity was 93.8% and the specificity was 96.0%, respectively.This prediction diagnostic criterion could facilitate clinicians to distinguish infants with and without BA based on a particular series of parameters, reducing treatment burden and enhancing therapeutic efficiency.

Low specificity of washout to diagnose hepatocellular carcinoma in nodules showing arterial hyperenhancement in patients with Budd-Chiari syndrome

It remains unclear whether the classic imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be applied to chronic vascular liver diseases, such as Budd-Chiari syndrome (BCS). Herein, we aimed to evaluate the diagnostic value of washout for the discrimination between benign and malignant lesions in patients with BCS. This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal lesions on MRI from 2000 to 2016. MRI images were reviewed by 2 radiologists blinded to the nature of the lesions. Patient and lesion characteristics were recorded, with a focus on washout on portal venous and/or delayed phases. Lesions were compared using Chi-square, Fisher's, Student's t or Mann-Whitney U tests. A total of 49 patients (mean age 35 ± 12 years; 34 women [69%] and 15 men [31%]) with 241 benign lesions and 12 HCC lesions were analyzed. Patients with HCC were significantly older (mean age 44 ± 16 vs. 33 ± 9 years, p = 0.005), with higher alpha-fetoprotein (AFP) levels (median 16 vs. 3 ng/ml, p = 0.007). Washout was depicted in 9/12 (75%) HCC, and 69/241 (29%) benign lesions (p <0.001). A total of 52/143 (36%) lesions ≥1 cm with arterial hyperenhancement showed washout (9 HCC and 43 benign lesions). In this subgroup, the specificity of washout for the diagnosis of HCC was 67%. Adding T1-w hypointensity raised the specificity to 100%. A serum AFP >15 ng/ml was associated with 95% specificity. Washout was observed in close to one-third of benign lesions, leading to an unacceptably low specificity for the diagnosis of HCC. The non-invasive diagnostic criteria proposed for cirrhotic patients cannot be extrapolated to patients with BCS. Washout on MRI is depicted in a significant proportion of benign nodules in patients with Budd-Chiari syndrome (BCS), limiting its value for the differentiation between benign and malignant lesions. Criteria proposed for the non-invasive diagnosis of hepatocellular carcinoma in patients with cirrhosis cannot be extrapolated to patients with BCS. Additional imaging findings and patient characteristics, including alpha-fetoprotein serum level, can help determine the probability of a nodule being HCC in patients with BCS.

Haptoglobin degradation product as a novel serum biomarker for hematopoietic stem cell transplant-associated thrombotic microangiopathy.

Hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a well-known complication of HSCT and carries high risk of morbidity and mortality. A lack of consistent non-invasive diagnostic criteria can delay diagnosis and lead to irreversible organ damage. Serum samples of 100 patients that underwent HSCT at Cincinnati Children's Hospital were serially collected. Unbiased proteomic profiling by SELDI-TOF-MS was performed on serum from TA-TMA patients at baseline (pre-HSCT), 2weeks before TMA diagnosis (pre-TMA), and at clinical TMA diagnosis. Two proteins with mass to charge ratios of 12-13kDa were consistently elevated at the 2week pre-TMA time point by SELDI-TOF, compared to control samples. Potential peptides were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the Linear Trap Quadropole (LTQ). A MASCOT search identified haptoglobin fragments in the 12-17-kDa range. Western blot was performed to validate haptoglobin fragments as a potential biomarker. Western blot of TA-TMA patients showed haptoglobin fragments at 12, 14, and 17kDa that varied between baseline, pre-TMA, and TMA time points for each patient. By densitometric analysis, the 17-kDa fragment in the pre-TMA samples differed significantly from TMA diagnosis (p < 0.0001). There was no significant difference in the concentrations of the 12-kDa and 14-kDa fragments. The 17-kDa haptoglobin degradation product may represent a novel early serum biomarker for TA-TMA that could potentially allow for earlier diagnosis and intervention.

Non-invasive diagnosis of cardiac amyloidosis due to transthyretin. Case report

Amyloidosis due to deposits of transthyretin (ATTR) is currently considered the most frequent form of cardiac amyloidosis and its incidence is increasing thanks to the advances in diagnostic imaging techniques. Some non-invasive diagnostic criteria have recently been published on this entity that due to the development of new drugs for the specific treatment of cardiac ATTR, have prognostic and therapeutic implications. That is why cardiac ATTR could cease to be a rare disease and become a frequent one, and become potentially treatable instead of incurable. We present the case of an 80-year-old male diagnosed with non-hereditary cardiac ATTR by means of gammagraphy with 99mTc diphosfonate scintigraphy (99mTc-DPD) following the new criteria of non-invasive diagnosis.

A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing. Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or noncardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. The derivation cohort included 414 consecutive patients (267 cases with HFpEF and 147 controls; HFpEF prevalence, 64%). The test cohort included 100 consecutive patients (61 with HFpEF; prevalence, 61%). Obesity, atrial fibrillation, age >60 years, treatment with ≥2 antihypertensives, echocardiographic E/e' ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mm Hg were selected as the final set of predictive variables. A weighted score based on these 6 variables was used to create a composite score (H2FPEF score) ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI, 1.74-2.30; P<0.0001), with an area under the curve of 0.841 ( P<0.0001). The H2FPEF score was superior to a currently used algorithm based on expert consensus (increase in area under the curve of 0.169; 95% CI, 0.120-0.217; P<0.0001). Performance in the independent test cohort was maintained (area under the curve, 0.886; P<0.0001). The H2FPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.

Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines

One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96–100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions.