Macrophage membrane-modified targeted phase-change nanoparticles for multimodal imaging of experimental autoimmune myocarditis.

Myocarditis is an important public health issue due to the high prevalence of sudden death in adolescents and young adults. Nevertheless, the early identification of myocarditis remains a serious problem for clinicians. There is no single non-invasive method to diagnose myocarditis in the currently available clinical guidelines and consensus. Molecular imaging is an effective approach for accurate diagnosis. Poly(lactic acid-glycolic acid) (PLGA) is considered to be the preferred carrier for molecular imaging because of its biosafety and modifiability. Macrophage membrane-modified biomimetic nanoprobes (MM-NPs) possess low immunogenicity and inflammation-directed chemotaxis capabilities and are repeatedly chosen as materials for targeted diagnosis and treatment of inflammatory diseases. In this study, experimental autoimmune myocarditis (EAM) was used as an animal model of inflammation. Previous studies have confirmed that this model is similar to pathological injury caused by acute myocarditis in humans. In multimodal imaging (US/PA/MRI), a phase-change material (PFH) and superparamagnetic iron oxide (SPIO) are used as imaging substances. Early identification of myocardial inflammatory sites was achieved by the tail vein injection of MM/NPs loaded with PFH and SPIO. This probe is expected to be a powerful tool for clinicians to diagnose myocarditis.

Differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma using CT characteristics: a systematic review and meta-analysis.

OBJECTIVES: To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy. METHODS: A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model. RESULTS: A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7). CONCLUSION: Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate. CLINICAL RELEVANCE STATEMENT: This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement. KEY POINTS: • Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.

Differential Diagnosis of IgG4-related Pancreatitis and Pancreatic Cancer by MRI Features and Its Correlation with Serum IgG4 Level.

It was to analyze the diagnostic value of MRI in immunoglobulin G (IgG4)-related autoimmune pancreatitis (AIP) and pancreatic cancer (PC) and its relationship with serum IgG4 level. 35 patients with IgG4-related AIP (group A1) and 50 patients with PC (group A2) were enrolled. MRI was performed to determine serum IgG4 levels. Spearsman was used to analyze the relationship between MRI characteristics and serum IgG4 level. It was found that patients in group A1 showed double duct sign (DDS), pancreatic duct (PD) perforation sign, the proportion of main PD truncation, and main PD diameter/pancreatic parenchymal width ratio, which were different from those of patients in group A2 (P < 0.05). MRI had a sensitivity (Sen) of 88%, specificity (Spe) of 91.43%, accuracy (Acc) of 89.41%, positive predictive value (PPV) of 0.936, and negative predictive value(NPV) of 0.842 for the diagnosis of IgG4-related AIP and PC. Serum IgG4 levels were significantly negatively correlated with DDS and main PD truncation, significantly positively correlated with PD penetration sign, and extremely significantly negatively correlated with main PD diameter/pancreatic parenchymal width (P < 0.001). The results showed that MRI had high sensitivity and specificity for differentiating IgG4-related AIP from PC, and the diagnostic effect was good, which had a high correlation with serum IgG4 levels in patients.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

Concomitant Pancreatic Ductal Adenocarcinoma and Type 1 Autoimmune Pancreatitis: A Potential Issue in the Diagnosis of Carcinoma by Endoscopic Ultrasound-guided Fine-needle Biopsy.

We herein report a 64-year-old man with concomitant pancreatic ductal adenocarcinoma (PDAC) and type 1 autoimmune pancreatitis (AIP). An endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from the pancreatic head mass revealed level 2 histology of AIP and atypical glands. We diagnosed definitive focal AIP using the clinical diagnostic criteria. Computed tomography revealed that the pancreatic mass had not been reduced by steroid therapy. Surgery was performed after a histological PDAC diagnosis was made via a transpapillary biliary biopsy. The resected specimen revealed PDAC associated with AIP. It is important to consider the cooccurrence of PDAC and AIP even if the histological diagnosis via an EUS-FNB is AIP.

Autoimmune Pancreatitis with Massive Ascites and Multiple Pancreatic Cysts Successfully Treated with Prednisolone.

A 64-year-old man with a history of diabetes and gallstones was admitted to our institution with suspected pancreatic malignancy. Computed tomography (CT) revealed multiple pancreatic cysts and massive ascites, and endoscopic ultrasonography (EUS) revealed a 28×27-mm hypoechoic mass in the pancreatic head. An EUS-guided fine-needle aspiration biopsy was performed, and there were no malignant findings. Based on the test results and imaging findings, type 1 autoimmune pancreatitis was suspected. The patient was administered 30 mg of prednisolone daily. After 11 days, CT revealed that the pancreatic cysts and ascites had reduced in size.

Analysis of Clinical, Serological, and Imaging Features of Autoimmune Pancreatitis and a Case-Control Study on Prognostic Factors in Response to Hormone Therapy.

Objective: The paper aimed to analyze the clinical, serological, and imaging features of autoimmune pancreatitis (AIP) and the prognostic factors affecting hormone therapy. Methods: A total of 106 patients with AIP enrolled in our hospital from March 2016 to August 2018 were treated with the hormone. The curative effect and recurrence were followed up. The patients were divided into relapse group (n = 42) and nonrelapse group (n = 64) according to the recurrence within 3 years after initial hormone therapy. The symptoms and signs, laboratory examination, and treatment were compared, and binary logistic regression was employed to explore the risk factors of AIP recurrence. Results: Among the 106 patients included in this study, there were 78 males and 28 females, with a male-to-female ratio of 3:1. The average age of onset was 56.25 ± 8.87 years; the minimum age was 39 years; and the maximum age was 7 years. The main clinical symptoms were jaundice (67.92%), abdominal pain (48.11%), and abdominal distension (33.96%). In addition, there were symptoms of weight loss, nausea, vomiting, itching, and gray stool. Previous complications included 27.35% diabetes (29/106), 22.64% hypertension (24/106), 35.84% smoking (38/106), and 28.30% alcohol consumption (30/106). The serological characteristics were mainly the increase in serum IgG4 level; 92.45% (98/106) level was higher compared to the upper limit of normal value; the median level was 11.65 g/L; and the highest level was 35.79 g/L. A total of 88.67% (94/106) had an abnormal liver function. The results of imaging examination indicated that 58.49% (62/106) of extrapancreatic organs were involved, of which 46.22% (49/106) were the most common bile duct involvement. All the patients in the group reached a state of remission after hormone treatment. After the disease was relieved, the patients were followed up for 3 years. The recurrence rate was 39.62% (42/106), and the median time of recurrence (month) was 9 (range 2-36). The recurrence rates within 1, 2, and 3 years were 20.75%, 31.13%, and 39.62%, respectively. Among the recurrent patients, 52.38% (22/42) relapsed within 1 year, 78.57% (33/42) within 2 years, and 100.00% (42/42) within 3 years. Multivariate analysis showed that the short duration of glucocorticoid therapy and involvement of extrapancreatic organs were risk factors for relapse after glucocorticoid therapy in patients with type I AIP. Conclusion: Type 1 AIP is more common in middle-aged and elderly men. The clinical symptoms of jaundice, abdominal pain, and abdominal distension are common, often accompanied by involvement of extrapancreatic organs, of which bile duct involvement is the most common. Type 1 AIP glucocorticoid treatment acceptance and disease remission are better, but the recurrence rate is higher after glucocorticoid treatment. Patients with a short time of glucocorticoid treatment and involvement of extrapancreatic organs may have a higher risk of recurrence.

The role of [18F]FDG PET/CT in paraneoplastic autoimmune disorders: an umbrella review.

Paraneoplastic autoimmune disorders (PAD) are a group of autoimmune diseases associated with neoplasms. Several evidence-based articles (systematic reviews and meta-analyses) have reported data about the role of positron emission tomography (PET) and related hybrid modalities (e.g., PET/CT) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in patients with PAD. We performed an umbrella review of published systematic reviews and meta-analyses in this setting to provide an evidence-based summary and suggestions for further studies. Several databases were searched to find systematic reviews and meta-analysis on [18F]FDG PET/CT in PAD. Evidence-based data support the use of [18F]FDG PET/CT in patients with suspected PAD for investigating an underlying malignancy even if it is still unclear whether [18F]FDG PET/CT should be performed after negative/inconclusive conventional imaging or as part of the initial workup of PAD.

The role of PET/CT in thyroid autoimmune diseases.

Autoimmune thyroid diseases (AITD) are a heterogeneous group of disorders. They include, in particular, Graves' disease and Hashimoto's thyroiditis with a wide range of different functional status ranging from subclinical biochemical abnormalities to severe hyperthyroidism or severe hypothyroidism respectively. Furthermore, other conditions more frequently infectious or drug related can cause an immune reaction in the thyroid tissue. In AITDs, positron emission tomography/computed tomography (PET/CT) does not play a primary role for disease diagnosis or management, but accidental findings can occur in both symptomatic and asymptomatic patients, and they should be recognized and well interpreted. A comprehensive literature search of the PubMed databases was conducted to identify papers (systematic review, prospective and retrospective study, case report) evaluating the role of PET/CT in thyroid autoimmune diseases. Thyroid diffuse uptake of 18F-fluoro-2-deoxy-2-d-glucose ([18F]FDG) has been shown to be frequently associated with AITDs, but also with immune-induced thyroid disorders related to SARS-CoV-2 or immunotherapy, while malignant lesions more often have a focal aspect. Other radiopharmaceuticals as [68Ga]-DOTA-peptides, [68Ga]-fibroblast activation protein inhibitors (FAPIs) and [68Ga]-prostate specific membrane antigen ([68Ga]-PSMA) showed similar findings. In conclusion, PET/CT scan in AITDs does not play a primary role in the diagnosis, but the occasional finding of a thyroid uptake must always be described in the report and possibly investigated for a better patient's management.

Autoimmune disease of head and neck, imaging, and clinical review.

Autoimmune disease of the head and neck (H&N) could be primary or secondary to systemic diseases, medications, or malignancies. Immune-mediated diseases of the H&N are not common in daily practice of radiologists; the diagnosis is frequently delayed because of the non-specific initial presentation and lack of familiarity with some of the specific imaging and clinical features. In this review, we aim to provide a practical diagnostic approach based on the specific radiological findings for each disease. We hope that our review will help radiologists expand their understanding of the spectrum of the discussed disease entities, help them narrow the differential diagnosis, and avoid unnecessary tissue biopsy when appropriate based on the specific clinical scenarios.

IgG4-Related Disease: A Constellation of Abdominal Manifestations.

IgG4-related disease is an autoimmune condition that results in inflammation and fibrosis throughout multiple organ systems. This disease is rare; however, it can mimic many more prevalent conditions clinically and thus should be included in their differential diagnoses. Although autoimmune pancreatitis is the most common abdominal manifestation, the disease can afflict the hepatobiliary, vascular and renal systems as well. We present a case of a 78-year-old male with symptoms of chronic fatigue and weight loss. Imaging was performed with the expectation of revealing a malignancy, although the features of IgG4-related disease involving multiple organs were detected instead. Serology confirmed the diagnosis. It is imperative to diagnose IgG4-related disease early as it has a different treatment and favorable prognosis compared to many malignancies.

Systematic review and meta-analysis of MRI features for differentiating autoimmune pancreatitis from pancreatic adenocarcinoma.

OBJECTIVES: To identify reliable MRI features for differentiating autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to summarize their diagnostic accuracy. METHODS: We conducted a systematic literature review and meta-analysis using PubMed, EMBASE, and the Cochrane Library to identify original articles published between January 2006 and July 2021. The pooled diagnostic accuracy, including the diagnostic odds ratios (DORs) with 95% confidence intervals (CIs) of the identified features, was calculated using a bivariate random effects model. RESULTS: Twelve studies were included, and 92 overlapping descriptors were subsumed under 16 MRI features. Ten features favoring AIP were diffuse enlargement (DOR, 75; 95% CI, 9-594), capsule-like rim (DOR, 52; 95% CI, 20-131), multiple main pancreatic duct (MPD) strictures (DOR, 47; 95% CI, 17-129), homogeneous delayed enhancement (DOR, 46; 95% CI, 21-104), low apparent diffusion coefficient value (DOR, 30), speckled enhancement (DOR, 30), multiple pancreatic masses (DOR, 29), tapered narrowing of MPD (DOR, 15), penetrating duct sign (DOR, 14), and delayed enhancement (DOR, 13). Six features favoring PDAC were target type enhancement (DOR, 41; 95% CI, 11-158), discrete pancreatic mass (DOR, 35; 95% CI, 15-80), upstream MPD dilatation (DOR, 13), peripancreatic fat infiltration (DOR, 10), upstream parenchymal atrophy (DOR, 5), and vascular involvement (DOR, 3). CONCLUSION: This study identified 16 informative MRI features to differentiate AIP from PDAC. Among them, diffuse enlargement, capsule-like rim, multiple MPD strictures, and homogeneous delayed enhancement favored AIP with the highest DORs, whereas discrete mass and target type enhancement favored PDAC. KEY POINTS: • The MRI features with the highest pooled diagnostic odds ratios (DORs) for autoimmune pancreatitis were diffuse enlargement of the pancreas (75), capsule-like rim (52), multiple strictures of the main pancreatic duct (47), and homogeneous delayed enhancement (46). • The MRI features with the highest pooled DORs for pancreatic ductal adenocarcinoma were target type enhancement (41) and discrete pancreatic mass (35).

Cancer and immune-mediated necrotizing myopathy: a longitudinal referral case-controlled outcomes evaluation.

OBJECTIVES: To investigate immune-mediated necrotizing myopathy (IMNM) association with cancer and its clinical implications. METHODS: IMNM cases were identified 1 January 2000 to 31 December 2020 matching sex and age controls (4:1). RESULTS: A total of 152 patients with IMNM were identified and among serologically tested, 60% (83/140) were HMGCR-IgG+, 14% (20/140) were SRP-IgG+ and 26% (37/140) were seronegative. Cancer rates were not significantly different between serological subgroups; 18.1% (15/83) HMGCR-IgG+, 25% (5/20) SRP-IgG+ and 30% (11/37) seronegative (P = 0.34). Cancer screening was performed within 12 months from IMNM diagnosis in 88% (134/152) (whole-body CT plus FDG-PET CT in 53, CT alone in 72 and FDG-PET alone in 9). FDG-PET/CT was positive in 73% (25/34) of cancers. Increasing age was the only risk associated with cancer (P = 0.02). The odds of developing cancer at ±3 or ±5 years from IMNM diagnosis was not higher than controls (OR = 0.49; CI: 0.325-0.76). Lifetime IMNM diagnosis of cancer was less compared with controls (OR = 0.5 CI: 0.33-0.78, P = 0.002). Most patients responded to treatment (137/147, P < 0.001). Death and treatment response did not significantly differ between cancer [23% (8/34); 88% (29/33)] and non-cancer patients [19% (23/118); 92% (108/118)]. In total, 13% (20/152) of patients died during follow-up compared with 14% (41/290) of medicine and 16% (46/290) of neurology controls (P = 0.8). Seropositives had greater life expectancy than seronegatives (P = 0.01). CONCLUSIONS: Greater cancer risk is not observed in IMNM vs controls. Cancer screening in IMNM should be individualized based on age-personal and family history, including consideration of FDG-PET/CT. Immune-treatment response did not differ with cancer.

"Usual" interstitial pneumonia with autoimmune features: a prospective study on a cohort of idiopathic pulmonary fibrosis patients.

OBJECTIVES: The classification interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease (ILD) associated with autoimmune characteristics insufficient to reach classification criteria for a specific autoimmune disease (SAD). These criteria are divided into three domains: clinical, serological and morphological. The latter domain does not include the usual interstitial pneumonia (UIP) pattern, which is deemed not to be significantly associated with SAD. Therefore, the enrolment of these patients is more difficult, requiring at least one item from both of the other domains. The objective of this study is to evaluate the rate of progression towards SAD of a cohort of UIP patients satisfying only one IPAF domain (we called this group "UIPAF") compared with classic idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively enrolled IPF patients with radiologic and/or histologic UIP pattern, followed jointly by rheumatologists and pulmonologists from January 2017 to January 2021, with a minimum follow-up of 12 months. RESULTS: We enrolled 190 IPF patients, 38 (20%) of whom were classified as UIPAF. IPF and UIPAF patients were similar for general characteristics, severity and prognosis, at presentation and at annual check-up. However, 28.9% of UIPAF patients progressed towards SAD, compared with 2% of IPF patients (χ2=30.4, p≤0.0001). CONCLUSIONS: The association between a single clinical or serological domain of IPAF and UIP pattern is predictive for the development of a SAD if compared with isolated UIP. ILD can be the first manifestation of SAD, even with a UIP pattern, therefore, the morphological domain of IPAF criteria could be removed.

Diffuse Involvement of Pancreas is not Always Autoimmune Pancreatitis.

RATIONALE AND OBJECTIVES: To determine the prevalence of diffuse involvement of pancreas and to identify the findings of malignancies using enhancement computed tomography (CT). MATERIALS AND METHODS: A total of 1,0249 patients performed enhancement CT in our hospital over 62 months were investigated and the final study cohort includes 245 patients (170 males, 75 females; mean age, 56.94 ± 12.17 years). The reference standard is the final clinical/pathological diagnosis. The lesion-to-aorta enhancement ratio (LAR) on the pancreatic arterial phase, portal phase and delayed phase (DP) and the traditional CT findings were evaluated. Intergroup comparisons between malignancies and non-malignancies lesions were performed. Univariate and multivariate analyses were conducted to identify findings predicting malignancies. RESULTS: The prevalence of malignancy was 45.3% (111/245) of diffuse enlargement of pancreas. All benign lesions were autoimmune pancreatitis 54.7% (n = 134). The most common malignant lesion was pancreatic ductal adenocarcinoma (n = 88, 35.9%). Other rare lesions with malignant potential included pancreatic neuroendocrine tumor (n = 11, 4.5%), lymphoma (n = 4, 1.6%), metastasis (n = 4, 1.6%), solid pseudopapillary neoplasm (n = 3, 1.2%) and acinar cell carcinoma (n = 1, 0.4%). Residual normal pancreas parenchyma, heterogeneity, short axis (cut-off value, 3.15 cm) and LARDP (cut-off value, 0.75) were independent predictors of malignancies. When the above predictors were combined, a sensitivity of 94.2%, a specificity of 90.8% were attained. CONCLUSION: Diffuse involvement of the pancreas is rare and is not a specific sign of autoimmune pancreatitis, and it is associated with a wide spectrum of malignant conditions. Dynamic enhancement CT is helpful to identifying malignancies.

[Contrast-enhanced ultrasound manifestations of IgG4 related autoimmune pancreatitis].

To analyze and summarize the contrast-enhanced ultrasound (CEUS) characteristics in patients with IgG4 related autoimmune pancreatitis (IgG4-AIP). A total of 54 patients (aged 26 to 76 years old) with IgG4-AIP were collected and retrospectively analyzed. The results demonstrated that there is a variety of enhanced performance on CEUS in patients with IgG4-AIP in the early stage, for some them, especially for those with mass-type pancreatitis, their sonographic appearance and the CEUS characteristics are similar when compared with the patients with pancreatic carcinoma, with varying degrees of low enhancement in the arterial phase, venous phase and delayed stage. Therefore, it is not advisable to make a differential diagnosis based on CEUS alone, and comprehensive evaluation is warranted.

Chest high-resolution computed tomography in patients with connective tissue disease: pulmonary conditions beyond "the usual suspects".

The term "connective tissue diseases" (CTDs) refers to a heterogeneous group of autoimmune disorders, including systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, polymyositis, dermatomyositis, antisynthetase syndrome, and mixed connective tissue disease. Chest high-resolution computed tomography (HRCT) is the imaging method of choice for evaluating patients with known or suspected CTD-related interstitial lung disease (CTD-ILD), a complication accounting for substantial morbidity and mortality. While specific HRCT patterns and signs of CTD-ILD have been extensively described (hence the designation "the usual suspects"), the knowledge of various, less frequent conditions involving the lungs in patients with CTD would help the radiologist produce a clinically valuable report, thus potentially influencing patient management. This paper aims to provide an up-to-date review of various unusual pulmonary CTD-related conditions the radiologist should be aware of; namely, acute exacerbation of CTD-ILD, CTD-related interstitial lung abnormalities, lung amyloidosis, MALT lymphoma, antisynthetase syndrome, pleuroparenchymal fibroelastosis-like lesion, drug-induced ILD, combined pulmonary fibrosis and emphysema, and pulmonary hypertension. For each condition, the chest HRCT appearance and the key histopathological and clinical features are resumed, helping the radiologist participate actively in the multidisciplinary discussion of complex clinical cases.