Semiquantitative Scoring Systems Research Articles

Correlation and Comparison of Somatostatin Receptor Type 2 Immunohistochemical Scoring Systems with 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms

Introduction: The overexpression of somatostatin receptor type 2 (SSTR2) is a unique characteristic of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), which establishes the basis for both diagnosis and therapy. The SSTR status can be evaluated by immunohistochemical staining (IHC) and 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) imaging. This study attempted to determine the relationship between IHC and 68Ga-DOTATATE PET/CT imaging and to explore the optimal cutoff value for SSTR IHC reading. Patients and Methods: A total of 100 GEP-NENs with SSTR PET/CT and pathological data were retrospectively analyzed, which consisted of neuroendocrine tumor (NET) G1 (n = 9), NET G2 (n = 64), NET G3 (n = 13), neuroendocrine carcinoma ( n = 10), and mixed neuroendocrine-non-NENs ( n = 4). SSTR2-IHC results were interpreted by 4 well-established semiquantitative scoring systems, including human epidermal growth factor receptor 2 (HER2) score, Volante score, H score, and immunoreactive score. Results: In the homogeneous SSTR2 expression group (accounting for 57% of all cases), the 4 scoring systems were highly concordant with each other (Kendall’s Tau-b coefficient range: 0.80–0.96, p < 0.001) and also highly correlated with the 68Ga-DOTATATE PET/CT imaging results (Spearman’s rank correlation coefficients: 0.71, 0.86, 0.80, and 0.71, p < 0.001). In the heterogeneous group (43%), the 4 scoring systems revealed a lower level of concordance (the Kendall Tau-b coefficient range: 0.40–0.75, p < 0.01), and the correlation with 68Ga-DOTATATE PET/CT imaging was also lower, albeit statistically significant (Spearman’s rank correlation coefficients: 0.53, 0.38, 0.36, and 0.33, p < 0.05). Heterogeneous SSTR2 expression was mainly observed in the HER2 2+ cases, for which the combination with H score could help identify positive cases with increased sensitivity and specificity. The highest sensitivity and specificity of H scores in predicting the imaging results were achieved at 86.10 and 89.30% when defining the cutoff value as 160, indicating that 80% of the tumor cells were moderately positive or 55% were strongly positive. Conclusions: SSTR2 IHC was found to predict 68Ga-DOTATATE PET/CT imaging accurately, especially in the homogeneous expression group. According to the positive 68Ga-DOTATATE PET/CT outcomes, 80% of the tumor cells moderately positive or 55% strongly positive was the cutoff values for SSTR2-IHC reading.

The contribution of the histopathological examination to the diagnosis of adverse local tissue reactions in arthroplasty.

The histopathological examination of the periprosthetic soft tissue and bone has contributed to the identification and description of the morphological features of adverse local tissue reactions (ALTR)/adverse reactions to metallic debris (ARMD). The need of a uniform vocabulary for all disciplines involved in the diagnosis and management of ALTR/ARMD and of clarification of the parameters used in the semi-quantitative scoring systems for their classification has been considered a pre-requisite for a meaningful interdisciplinary evaluation.This review of key terms used for ALTR/ARMD has resulted in the following outcomes: (a) pseudotumor is a descriptive term for ALTR/ARMD, classifiable in two main types according to its cellular composition defining its clinical course; (b) the substitution of the term metallosis with presence of metallic wear debris, since it cannot be used as a category of implant failure or histological diagnosis; (c) the term aseptic lymphocytic-dominated vasculitis- associated lesion (ALVAL) should be replaced due to the absence of a vasculitis with ALLTR/ALRMD for lymphocytic-predominant and AMLTR/AMRMD for macrophage-predominant reaction.This review of the histopathological classifications of ALTR/ARMD has resulted in the following outcomes: (a) distinction between cell death and tissue necrosis; (b) the association of corrosion metallic debris with adverse local lymphocytic reaction and tissue necrosis; (c) the importance of cell and particle debris for the viscosity and density of the lubricating synovial fluid; (d) a consensus classification of lymphocytic infiltrate in soft tissue and bone marrow; (e) evaluation of the macrophage infiltrate in soft tissues and bone marrow; (f) classification of macrophage induced osteolysis/aseptic loosening as a delayed type of ALTR/ARMD; (g) macrophage motility and migration as possible driving factor for osteolysis; (h) usefulness of the histopathological examination for the natural history of the adverse reactions, radiological correlation, post-marketing surveillance, and implant registries.The review of key terms used for the description and histopathological classification of ALTR/ARMD has resulted in a comprehensive, new standard for all disciplines involved in their diagnosis, clinical management, and long-term clinical follow-up.Cite this article: EFORT Open Rev 2021;6:399-419. DOI: 10.1302/2058-5241.6.210013

Whole-Body MRI and Whole Body [123I]-I-mIBG Scintigraphy: a Comparison in Intermediate and High Risk Neuroblastoma and validation of SIOPEN Scoring System in WB-MRI

Purpose: To assess the agreement between 123I-metaiodobenzylguanidine or [123I]-I-mIBG and Whole Body Magnetic Resonance Imaging with diffusion-weighted whole-body imaging with background body signal suppression (WB MRI-DWIBS) in High and Intermediate risk Neuroblastoma, a retrospective review was performed on [123I]-I-mIBG and DWIBS paired scans acquired at diagnosis, response-to-therapy, after-surgery, off therapy and after relapse with systemic involvement, and osteo-bone marrow metastatic load was evaluated for each of them. Methods: 80 paired [123I]-I-mIBG and DWIBS scans were acquired for 31 patients between June 2009 and June 2019 within 30 days and without intercurrent therapy. SIOPEN Semi-quantitative Scoring Systems for NB with 12 body sections was applied at whole body MIBG and WB MRI-DWIBS acquired to evaluate the skeletal disease extent. In each case thoracic-abdominal SPECT was used to confirm or exclude doubtful scintigraphic alterations. We evaluated specificity, sensitivity, overall accuracy, positive predictive value (PPV) and negative predictive value (NPV) of WB MRI-DWIBS respect [123I]-I-mIBG scintigraphy considered as gold standard. The inverse theoretical statistic exercise was performed for [123I]-I-mIBG respect DWIBS results. Results: DWIBS and [123I]-I-mIBG images were concordant in 890 out of the 960 analyzed segments, with high agreement between the two techniques (Kendal=0.85 P < 0.0001 and Chi 536.5975 P < 0.0001). Considering [123I]-I-mIBG as gold standard, WB MRI-DWIBS overall accuracy was 93%, sensitivity 78%, specificity 95%, PPV 77% and NPV 96%. Otherwise, on the theoretical statistic exercise, [123I]-I-mIBG overall accuracy was 93%; sensitivity 77%; specificity 97%; VPP 78%; VPN 95%, respect DWIBS. [123I]-I-mIBG and WB MRI-DWIBS SIOPEN scoring resulted superimposable (Rho Spearman=0.88, P < 0.0001). Conclusion: DWIBS and [123I]-I-mIBG images showed a very high concordance: a first validation of SIOPEN Scoring System seems possible on the basis of these data. WB MRI may represent an alternative in weak-avid MIBG tumors and for follow up assessment. A multimodal imaging protocol is proposed for High and Intermediate Risk protocols.

Liver biopsy evaluation in chronic hepatitis b infection: ‘Back to basics’ - re-visiting semi-quantitative scoring systems

Context: Despite advances in understanding into the pathophysiology of chronic hepatitis B, liver biopsy evaluation on H&E stained sections has stood the test of time. There is therefore, a need to re-visit the most commonly used scoring systems with an aim to look for an ideal semi-quantitative system which is objective, simple to apply and versatile enough to incorporate newer advances. Aims: To compare various semi-quantitative scoring systems with a view to (a) look for consistency in reporting, (b) assess usefulness in follow-up and (c) recommend a scoring system that is practical and easy to apply. Settings and Design: Chronic hepatitis B was defined as HBsAg positive status for at least six months. All liver biopsies were evaluated using semi-quantitative scoring systems viz the Knodell, Ishak’s modified HAI and Scheuer systems. Materials and Methods: Baseline biopsies were assessed for intra- and inter-observer variation in order to find the system best suited for routine use. The observer variation was also calculated separately for portal, peri-portal and lobular inflammation as well as for fibrosis. Statistical Analysis used: A Kappa analysis up to 95% confidence interval was done to look for statistical significance of inter- and intra-observer agreement between the three scoring systems. Results: On multivariate Kappa analysis, it was found that both inter- and intra-observer agreement were comparable in the Knodell and Ishak systems, and was significantly better with the Scheuer system. Further, agreement was better with fibrosis than with necro-inflammatory scores. Conclusions: The authors recommend Ishak’s modified system as it conveyed the most relevant and exhaustive information. Keywords: Chronic hepatitis B, Ishak’s system, Knodell’s system, Liver biopsy, Scheuer system, Semi-quantitative scoring systems.

Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: Histological perspective.

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis and cirrhosis. Accurate assessment of liver fibrosis is important for predicting disease outcomes and assessing therapeutic response in clinical practice and clinical trials. Although noninvasive tests such as transient elastography and magnetic resonance elastography are preferred where possible, histological assessment of liver fibrosis via semiquantitative scoring systems remains the current gold standard. Collagen proportionate area provides more granularity by measuring the percentage of fibrosis on a continuous scale, but is limited by the absence of architectural input. Although not yet used in routine clinical practice, advances in second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging show great promise in characterising architectural features of fibrosis at the individual collagen fiber level. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g., qFibrosis, q-FPs), which have been validated against fibrosis stage in NAFLD. Artificial intelligence is being explored to further refine and develop quantitative fibrosis scoring methods. SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis. This has reaffirmed the pivotal role of the liver biopsy in fibrosis assessment in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials; this approach may improve the outcomes of the trials evaluating therapeutic response to antifibrotic drugs.

Digital pathology: accurate technique for quantitative assessment of histological features in metabolic-associated fatty liver disease.

Histological evaluation of metabolic-associated fatty liver disease (MAFLD) biopsies is subjective, descriptive and with interobserver variability. To examine the relationship between different histological features (fibrosis, steatosis, inflammation and iron) measured with automated whole-slide quantitative digital pathology and corresponding semiquantitative scoring systems, and the distribution of digital pathology measurements across Fatty Liver Inhibition of Progression (FLIP) algorithm and Steatosis, Activity and Fibrosis (SAF) scoring system METHODS: We prospectively included 136 consecutive patients who underwent liver biopsy for MAFLD at three Spanish centres (January 2017-January 2020). Biopsies were scored by two blinded pathologists according to the Non-alcoholic Steatohepatitis (NASH) Clinical Research Network system for fibrosis staging, the FLIP/SAF classification for steatosis and inflammation grading and Deugnier score for iron grading. Proportionate areas of collagen, fat, inflammatory cells and iron deposits were measured with computer-assisted digital image analysis. A test-retest experiment was performed for precision repeatability evaluation. Digital pathology showed strong correlation with fibrosis (r=0.79; P<0.001), steatosis (r=0.85; P<0.001) and iron (r=0.70; P<0.001). Performance was lower when assessing the degree of inflammation (r=0.35; P<0.001). NASH cases had a higher proportion of collagen and fat compared to non-NASH cases (P<0.005), whereas inflammation and iron quantification did not show significant differences between categories. Repeatability evaluation showed that all the coefficients of variation were ≤1.1% and all intraclass correlation coefficient values were ≥0.99, except those of collagen. Digital pathology allows an automated, precise, objective and quantitative assessment of MAFLD histological features. Digital analysis measurements show good concordance with pathologists´ scores.

High-Throughput, Machine Learning–Based Quantification of Steatosis, Inflammation, Ballooning, and Fibrosis in Biopsies From Patients With Nonalcoholic Fatty Liver Disease

Background & AimsLiver biopsy is the reference standard for staging and grading nonalcoholic fatty liver disease (NAFLD), but histologic scoring systems are semiquantitative with marked interobserver and intraobserver variation. We used machine learning to develop fully automated software for quantification of steatosis, inflammation, ballooning, and fibrosis in biopsy specimens from patients with NAFLD and validated the technology in a separate group of patients.MethodsWe collected data from 246 consecutive patients with biopsy-proven NAFLD and followed up in London from January 2010 through December 2016. Biopsy specimens from the first 100 patients were used to derive the algorithm and biopsy specimens from the following 146 were used to validate it. Biopsy specimens were scored independently by pathologists using the Nonalcoholic Steatohepatitis Clinical Research Network criteria and digitalized. Areas of steatosis, inflammation, ballooning, and fibrosis were annotated on biopsy specimens by 2 hepatobiliary histopathologists to facilitate machine learning. Images of biopsies from the derivation and validation sets then were analyzed by the algorithm to compute percentages of fat, inflammation, ballooning, and fibrosis, as well as the collagen proportionate area, and compared with findings from pathologists’ manual annotations and conventional scoring systems.ResultsIn the derivation group, results from manual annotation and the software had an interclass correlation coefficient (ICC) of 0.97 for steatosis (95% CI, 0.95–0.99; P < .001); ICC of 0.96 for inflammation (95% CI, 0.9–0.98; P < .001); ICC of 0.94 for ballooning (95% CI, 0.87–0.98; P < .001); and ICC of 0.92 for fibrosis (95% CI, 0.88–0.96; P = .001). Percentages of fat, inflammation, ballooning, and the collagen proportionate area from the derivation group were confirmed in the validation cohort. The software identified histologic features of NAFLD with levels of interobserver and intraobserver agreement ranging from 0.95 to 0.99; this value was higher than that of semiquantitative scoring systems, which ranged from 0.58 to 0.88. In a subgroup of paired liver biopsy specimens, quantitative analysis was more sensitive in detecting differences compared with the nonalcoholic steatohepatitis Clinical Research Network scoring system.ConclusionsWe used machine learning to develop software to rapidly and objectively analyze liver biopsy specimens for histologic features of NAFLD. The results from the software correlate with those from histopathologists, with high levels of interobserver and intraobserver agreement. Findings were validated in a separate group of patients. This tool might be used for objective assessment of response to therapy for NAFLD in practice and clinical trials.

Application of ultrasonography scoring system in the assessment of IgG4-related sialadenitis

To assess the diagnostic value of salivary gland ultrasonography (SGUS) for IgG4-related sialadenitis. Ultrasonography examination of major salivary glands was conducted for 48 IgG4-related sialadenitis patients and 50 Sjögren's syndrome patients, whose ages and disease duration were matched. The imaging features were graded using two different scoring systems (0-16 and 0-48, respectively) obtained from the grades of bilateral parotid and submandibular glands. The scores were used to further evaluate the features of salivary gland ultrasonography in IgG4-related sialadenitis and to compare them with Sjögren's syndrome patients. The association of SGUS scores of IgG4-related sialadenitis group with serological tests was analyzed. The mean age of IgG4-related sialadenitis group and Sjögren's syndrome group was 49.23 years and 50.44 years, respectively. The serum IgG4 level of the patients in the IgG4-related sialadenitis group was increased, with an average (9.60±6.43) g/L. And the serum IgE level was at a median of 251.5 (123.4-543.6) IU/mL. In the 0-16 system, the scores of submandibular glands of the patients in IgG4-related sialadenitis and Sjögren's syndrome were 6.0 (6.0-8.0) and 4.0 (2.0-8.0), and the scores of the total four glands were 10.0 (8.0-14.0) and 8.0 (4.0-12.0) respectively. In the 0-48 system, the scores of submandibular glands with IgG4-related sialadenitis and Sjögren's syndrome were 18.0 (14.5-20.0) and 11.0 (7.0-14.0), and the scores of the total four glands were 26.0 (18.5-34.0) and 21.5 (15.0-26.3) respectively. It suggested that in the 0-16 system and the 0-48 system, scores of submandibular glands and the total of four glands of IgG4-related sialadenitis were higher than those of Sjögren's syndrome. Meanwhile, the association analysis of 0-48 system showed a positive correlation of SGUS scores with serum IgG4, which also showed a positive correlation of SGUS scores with serum IgE in 0-16 system. Semi-quantitative ultrasonography scoring systems can evaluate and quantify the lesions of salivary glands, which can be helpful in the diagnosis and differential diagnosis of IgG4-related sialadenitis combined with the clinical manifestations, serological indicators and/or histopathological manifestations. Ultrasonography can also assess the activity of IgG4-related sialadenitis preliminarily.

Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models.

Osteochondral lesions (OCs) are typically of traumatic origins but are also caused by degenerative conditions, in primis osteoarthritis (OA). On the other side, OC lesions themselves, getting worse over time, can lead to OA, indicating that chondral and OC defects represent a risk factor for the onset of the pathology. Many animal models have been set up for years for the study of OC regeneration, being successfully employed to test different treatment strategies, from biomaterials and cells to physical and biological adjuvant therapies. These studies rely on a plethora of post-explant investigations ranging from histological and histomorphometric analyses to biomechanical ones. The present review aims to analyze the methods employed for the evaluation of OC treatments in each animal model by screening literature data within the last 10 years. According to the selected research criteria performed in two databases, 60 works were included. Data revealed that lapine (50% of studies) and ovine (23% of studies) models are predominant, and knee joints are the most used anatomical locations for creating OC defects. Analyses are mostly conducted on paraffin-embedded samples in order to perform histological/histomorphometric analyses by applying semiquantitative scoring systems and on fresh samples in order to perform biomechanical investigations by indentation tests on articular cartilage. Instead, a great heterogeneity is pointed out in terms of OC defect dimensions and animal's age. The choice of experimental times is generally adequate for the animal models adopted, although few studies adopt very long experimental times. Improvements in data reporting and in standardization of protocols would be desirable for a better comparison of results and for ethical reasons related to appropriate and successful animal experimentation.

Evaluation of hepatobiliary ultrasound scores in healthy dogs and dogs with liver diseases.

Background and Aim:Ultrasonography is the first-line method for examining the canine liver. Hepatic ultrasound scoring systems are widely described in human medicine, yet there is no information on the use of semi-quantitative ultrasound scoring systems in canine liver diseases. This study aimed to evaluate the hepatobiliary ultrasound scores between physically healthy dogs and dogs with primary liver diseases confirmed by clinical, biochemical, and histological parameters. We also evaluated the putative correlations between ultrasound scores and ALT or ALP levels. Moreover, the severity of ultrasound scoring and fold changes in liver enzymes was also evaluated.Materials and Methods:A cross-sectional study design was conducted to compare the results of the six different parameters (liver surface, echogenicity of parenchyma, nodularity of parenchyma, gallbladder wall thickness, amount of gall sludge, and visibility of bile duct) of ultrasound scores between dogs with and without liver disease.Results:Our results showed that 17.4%, 88.2%, and 100% of dogs with liver diseases were identified according to the ultrasound severity classified as mild (total score 0-2), moderate (total score 3-5), and severe (total score 6-12). Approximately 30% of patients with chronic hepatitis, the most common canine liver disease, presented with normal or mild ultrasound score category, whereas most of the patients with vacuolar hepatopathy and steroid-induced hepatopathy due to secondary reactive changes had moderate-to-severe ultrasound score category. There were 75% of patients with tumor and 80% of patients with hepatic fibrosis that were identified with severe ultrasound score category. Dogs with moderate-to-severe ultrasound scores had significant liver enzyme elevation (both alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) compared to those of dogs with mild ultrasound scores. Ultrasound score was moderately associated with ALT and highly associated with ALP levels (p=0.553 and p=0.730, respectively).Conclusion:Our semi-quantitative, simplified ultrasonographic scoring system may have potential to be used as a screening tool to detect some groups of liver diseases.

The agreement between ultrasound-determined joint inflammation and clinical signs in patients with rheumatoid arthritis

BackgroundUltrasound (US) is sensitive for detecting joint and tendon inflammation in patients with rheumatoid arthritis (RA). So far, which grade of abnormalities on US corresponds to clinical manifestations is unclear. This study aimed to investigate the agreement between US-detected joint inflammation and clinical signs (joint swelling and tenderness).MethodsIn this cross-sectional study, 22 joints of the wrists and hands were, respectively, evaluated by physical examination (PE) and ultrasound in RA patients. Gray scale (GS) and power Doppler (PD) of synovitis, detected by ultrasound, were graded by semi-quantitative scoring systems (0–3). Tenosynovitis and peritendinitis were assessed qualitatively (0/1).ResultsA total of 258 consecutive RA patients were included, with median disease duration of 57 months and mean Disease Activity Score based on 28 joints (DAS28)-ESR/DAS28-CRP of 4.47/3.99. In a total of 5676 joints assessed, the overall concordance rate between positive clinical signs and ultrasound-determined joint inflammation was fair (κ = 0.365, p < 0.01). In wrists, joint tenderness showed higher κ coefficient (κ = 0.329, p < 0.01) with ultrasound-determined joint inflammation than swelling (κ = 0.263, p < 0.01); however, swelling showed higher κ coefficient (κ = 0.156–0.536, p < 0.01) with ultrasound-determined joint inflammation than tenderness (κ = 0.061–0.355, p < 0.01) in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. Synovitis had consistently higher agreement with tenderness and swelling than tenosynovitis/peritendinitis. Tenderness and swelling had the highest κ coefficient with GS ≥ 1 synovial hyperplasia in most MCP and PIP joints, while with GS ≥ 2 synovial hyperplasia in wrists. For all 22 joints, PD ≥ 1 synovitis had the highest κ coefficient with clinical tenderness and swelling.ConclusionsSynovitis had better agreement with clinical signs than tenosynovitis/peritendinitis. Joint swelling showed better agreement with US-determined inflammation than tenderness for MCP and PIP joints, while the opposite for wrists. Both tenderness and swelling are more likely to correspond to GS ≥ 2 for wrists, GS ≥ 1 for MCP and PIP joints, and PD ≥ 1 for any joint.

MRI-based multi-task deep learning for cartilage lesion severity staging in knee osteoarthritis

MRI-based multi-task deep learning for cartilage lesion severity staging in knee osteoarthritis

Semi-automated quantification of cartilage volume in knee osteoarthritis: responsiveness and concurrent validity

Purpose: Cartilage change on Magnetic Resonance Imaging (MRI) is a potential surrogate endpoint in osteoarthritis (OA) research. Semi-quantitative scoring systems are based on qualitative and subjective assessments that require expensive and time-intensive radiology expertise; ordinal scores also have limited sensitivity to change. Quantitative measurement of cartilage that involves manual segmentation of cartilage is also time-intensive and costly. To overcome these limitations, semi-automated software systems have been developed to measure cartilage - providing a rapid, inexpensive, quantitative and objective method of evaluating disease status and progression. A novel and semi-automated Local-Area Cartilage Segmentation (LACS) software for knee OA has previously been demonstrated to be fast, responsive, and associated with radiographic and pain progression. However, LACS was initially developed to segment medial femur cartilage only. We aimed to update and extend LACS to the lateral femur, medial tibia, and lateral tibia - and evaluate responsiveness to change, as well as correlation with existing cartilage measurements using an established independent manual segmentation method from publicly available Osteoarthritis Initiative (OAI) data. Methods: 115 participants with symptomatic knee OA were selected from the OAI progression sub-cohort, defined by definite osteophytes and frequent knee symptoms. Cartilage volume in fixed weight-bearing areas was measured with LACS on unilateral knee MRIs at the baseline and 24 month visit, paired and blinded to image date, using the sagittal 3D double-echo steady-state (DESS) sequence (3 Tesla, 0.365mm x 0.365mm, 0.7mm slice thickness, repetition time 16.5 msec, echo time 4.7 msec). Briefly, a non-expert reader identified a set of consistent anatomical landmarks for each compartment on the femur and tibia, which were used to generate consistent cartilage measurement areas. Automated edge detection algorithms then outlined cartilage in regions defined by the landmarks (Figure). The expert reader corrected the cartilage margins in areas of misidentified cartilage margins when necessary. Change in cartilage volume was calculated between the baseline and the 24-month visit. Responsiveness was quantified by standardized response mean (SRM = mean (ΔVol)/SD (ΔVol)). Concurrent validity was evaluated by estimating the correlation between LACS volume measurements and Chondrometrics measurements of cartilage thickness based on manual segmentation in the four corresponding sub-regions. Results: Baseline Kellgren-Lawrence grade distribution was KL1 4.3%, KL2 32.2%, KL3 61.7%, and KL4 1.7% in knees of the 115 participants (53% females, mean (SD) age 62.6 (±8.8) years, mean (SD) and BMI 30.1 (±5.3) kg/m2). The Figure shows a rendered 3D-model of segmented cartilage, with red areas indicating selected regions of measurement. The SRM was -0.54 for the medial femoral region and lower in the other sub-regions (Table 1). Correlation with Chondrometrics measures of cartilage thickness ranged between 0.67 and 0.88 (Table 2). The expert reader time was under 5 minutes and total reader time less than 10 minutes total per compartment. Conclusions: We updated the semi-automated LACS software method for knee cartilage segmentation to not only include the medial femur, but also medial tibia, lateral tibia, and lateral femur. The automated steps increase efficiency compared to manual segmentation, and limit the need and cost of an expert reader. We found favorable SRMs for cartilage volume change over two years with default regions of interest. The flexible nature of this software enables further adjustment of sub-regions to potentially improve responsiveness. The software correlated well against established measurements of cartilage thickness based on manual segmentation. Although a comparison between thickness and volume is not ideal, the current results are encouraging. In summary, the updated LACS software represents a powerful tool for fast segmentation of knee cartilage in larger cohorts and could facilitate clinical evaluation of potential structure modifying OA interventions.

Harmonization of MRI-based semi-quantitative knee osteoarthritis scoring systems

Harmonization of MRI-based semi-quantitative knee osteoarthritis scoring systems

ERAMRS: a new MR scoring system for early rheumatoid arthritis of the wrist.

To (i) devise a new semi-quantitative scoring system known as Early Rheumatoid Arthritis Magnetic Resonance Score (ERAMRS) to assess inflammation of the wrist on magnetic resonance imaging in early rheumatoid arthritis and to (ii) test ERAMRS and other MR scoring systems against everyday used clinical scorings. One hundred six treatment-naïve patients (81 females, 25 males, mean age 53 ± 12years) with early rheumatoid arthritis (ERA) underwent clinical/serological testing as well as 3-T MRI examination of the most symptomatic wrist. Clinical assessment included Disease Activity Score-28 and Health Assessment Questionnaire; erythrocyte sedimentation rate and C-reactive protein were measured. MR imaging data was scored in all patients using three devised MR semi-quantitative scoring systems, namely, the (a) ERAMRS system, (b) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) system, and the (c) McQueen Score system. Synovitis was present in 106 (100%), tenosynovitis in 98 (92%), and bone marrow edema in 84 (79%) of 106 ERA wrists. ERAMRS had the highest correlation with clinical disease activity scores (r = 0.476, p < 0.001) and serological parameters (r = 0.562, p < 0.001). RAMRIS system had the lowest correlation (r = 0.369, p < 0.001 for clinical disease activity; r = 0.436, p < 0.001 for serological parameters). RAMRIS synovitis subscore had a lower correlation than ERAMRS for clinical disease activity (r = 0.410, p < 0.001) and for serological parameters (r = 0.456, p < 0.001). The ERAMRS system, designed to grade inflammation on wrist MRI in ERA, provided the best correlation with all clinical scoring systems and serological parameters, indicating its improved clinical relevance over other MR scoring systems. • We devised a clinically relevant, easy-to-use semi-quantitative scoring system for scoring inflammation on MRI of the wrist in patients with early rheumatoid arthritis. • ERAMRS system showed better correlation with all clinical and serological assessment of inflammation in patients with early rheumatoid arthritis indicating its improved clinical relevance over other MR scoring systems.

Application of color Superb microvascular imaging and high-frequency ultrasonography in juvenile idiopathic arthritis

Objective To explore the application of color Super Microvascular Imaging (cSMI) and high-frequency ultrasonography (US) in evaluating the knee joint diseases of juvenile idiopathic arthritis (JIA) in the active period. Methods 90 patients diagnosed JIA clinically with knees pain and swelling were collected, the ultrasound diagnostic apparatus was used to examine knee joints. the main US signs were observed, the numbers of thickening of suprapatellar bursa synovial joints were recorded. The thickness of synovial membrane and the thickness of suprapatellar bursa effusion were also recorded, the blood flow signals of the thickening of synovial joints was checked by the cSMI and power doppler ultrasound (PDUS) separately. Color flow signals were graded by the semi-quantitative scoring systems. At the same period, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. The differences of cSMI and PDUS in thickened synovial blood flow were compared. The correlations between the parameters were analyzed. Results 110 suprapatellar bursa synovial joints showed synovial thickening, synovial thickened joints are associated with varying degrees of suprapatellar bursa effusion. The thickness of synovial membrane and the thickness of suprapatellar bursa effusion were (6.01±3.08) mm, (7.45±3.91) mm, respectively. The proportion of blood flow signals detected by cSMI in thickened synovial membranes of Wri was 86.36%, while that of PDUS was 59.09%. The differences of blood flow signals rate were statistically significant (P=0.000). The differences of grading of PDUS and cSMI were statistically significant (P=0.000), Compared with PDUS, cSMI can raise the blood flow classification level. PDUS and cSMI blood flow signals grading were positively correlated with CRP, ESR, synovial membrane and suprapatellar bursa effusion (P=0.000). CRP was positively correlated with ESR, synovial membrane and suprapatellar bursa effusion (P=0.000). Synovial membrane was positively correlated with suprapatellar bursa effusion (P=0.000). Conclusion The application of cSMI and High-frequency US is helpful in the early diagnosis of knee joint lesions in active JIA children. Key words: Juvenile idiopathic arthritis; Knee joint; Color super microvascular imaging; High-frequency ultrasonography

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.

Qualitative analysis and identification of pattern of errors in Clock Drawing Tests of community-dwelling older adults.

The Clock Drawing Test (CDT) is a frequently employed screening tool with different scoring systems. Quantitative and semi-quantitative scoring systems, such as Sunderland’s et al. (1989), do not discriminate different error patterns. Thus, the same score can represent a number of different neuropsychological profiles. Therefore, the use of a scoring method that emphasizes qualitative aspects to determine specific error patterns is fundamental.Objective:To use a qualitative scale to analyze error patterns in the CDTs of older adults who scored 5 in a previous study.Methods:49 CDTs with score of 5 were analyzed using the qualitative scale. Linear regression and hierarchical and non-hierarchical cluster analyses were performed.Results:The linear regression showed a significant association between the total score and all the error patterns of the qualitative scale. The hierarchical cluster yielded three groups. However, due to the heterogeneity observed among the groups, a non-hierarchical cluster analysis was performed to better understand the results. Three groups were determined with different neuropsychological profiles and patterns of errors.Conclusion:The qualitative scoring of the CDT is important when examining and analyzing specific neuropsychological domains in older adults, especially executive functions.

Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.

Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.

A simplified and validated ultrasound scoring system to evaluate synovitis of bilateral wrists and hands in patients with rheumatoid arthritis.

The objective of this study was to develop and validate an optimal simplified combination of joints for ultrasonographic assessment of synovitis in wrists and hands in patients with rheumatoid arthritis (RA). Twenty-two joints, including bilateral wrists, all proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints, were evaluated by grey-scale (GS) and power Doppler (PD) ultrasound using semi-quantitative scoring systems in 705 RA patients. Candidate joint sets were then selected by multiple linear regression analysis and the optimal candidate set was eventually validated in 235 RA patients. Through multiple linear regression analysis, the standard coefficient (β) of MCP2, MCP3, and MCP5 joints in terms of GS was higher than other joints. The adjusted R 2 of the model composed of wrist, MCP2, MCP3, and MCP5 joints was greater than 0.9. Among the sum GS and PD scores of various selected joint combinations, total score-8, including bilateral wrist, MCP2, MCP3, and MCP5 joints, not only showed highest sensitivity and negative predictive value (93.86 and 92.90% for GS; 97.20 and 97.21% for PD, respectively) but also the best correlation with the total score-22 (r=0.955 and 0.972 for GS and PD). The score-8 was further validated in 235 RA patients. The sensitivity for detecting synovitis by GS and PD was 94.35 and 94.12%, and the negative predictive values were 94.07 and 95.68%, respectively. Total score-8 system, including bilateral wrist, MCP2, MCP3, and MCP5 joints, is simple and efficient to pick up active synovitis of wrists and hands in patients with RA in daily practice.