Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.

Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development.

Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein-Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE.

Dual-Energy CT Evaluation of Gastrointestinal Bleeding.

Gastrointestinal (GI) bleeding is a potentially life-threatening condition accounting for more than 300 000 annual hospitalizations. Multidetector abdominopelvic CT angiography is commonly used in the evaluation of patients with GI bleeding. Given that many patients with severe overt GI bleeding are unlikely to tolerate bowel preparation, and inpatient colonoscopy is frequently limited by suboptimal preparation obscuring mucosal visibility, CT angiography is recommended as a first-line diagnostic test in patients with severe hematochezia to localize a source of bleeding. Assessment of these patients with conventional single-energy CT systems typically requires the performance of a noncontrast series followed by imaging during multiple postcontrast phases. Dual-energy CT (DECT) offers several potential advantages for performing these examinations. DECT may eliminate the need for a noncontrast acquisition by allowing the creation of virtual noncontrast (VNC) images from contrast-enhanced data, affording significant radiation dose reduction while maintaining diagnostic accuracy. VNC images can help radiologists to differentiate active bleeding, hyperattenuating enteric contents, hematomas, and enhancing masses. Additional postprocessing techniques such as low-kiloelectron voltage virtual monoenergetic images, iodine maps, and iodine overlay images can increase the conspicuity of contrast material extravasation and improve the visibility of subtle causes of GI bleeding, thereby increasing diagnostic confidence and assisting with problem solving. GI bleeding can also be diagnosed with routine single-phase DECT scans by constructing VNC images and iodine maps. Radiologists should also be aware of the potential pitfalls and limitations of DECT. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Involvement of trained immunity during autoimmune responses.

Recently, it has been described that innate immune cells such as monocytes, macrophages, and natural killer cells can develop a non-specific immune response induced by different stimuli, including lipopolysaccharides, Mycobacterium bovis Bacillus Calmette-Guérin, and oxidized low-density lipoprotein. This non-specific immune response has been named "trained immunity," whose mechanism is essential for host defense and vaccine response, promoting better infection control. However, limited information about trained immunity in other non-infectious diseases, such as autoimmune illness, has been reported. The complexity of autoimmune pathology arises from dysfunctions in the innate and adaptive immune systems, triggering different clinical outcomes depending on the disease. Nevertheless, T and B cell function dysregulation is the most common characteristic associated with autoimmunity by promoting the escape from central and peripheral tolerance. Despite the importance of adaptative immunity to autoimmune diseases, the innate immune system also plays a prominent and understudied role in these pathologies. Accordingly, epigenetic and metabolic changes associated with innate immune cells that undergo a trained process are possible new therapeutic targets for autoimmune diseases. Even so, trained immunity can be beneficial or harmful in autoimmune diseases depending on several factors associated with the stimuli. Here, we reviewed the role of trained immunity over the innate immune system and the possible role of these changes in common autoimmune diseases, including Systemic Lupus Erythematosus, Rheumatoid Arthritis, Multiple Sclerosis, and Type 1 Diabetes.

Management of gastrointestinal bleeding: Society of Abdominal Radiology (SAR) Institutional Survey.

Despite guidelines developed to standardize the diagnosis and management of gastrointestinal (GI) bleeding, significant variability remains in recommendations and practice. The purpose of this survey was to obtain information on practice patterns for the evaluation of overt lower GI bleeding (LGIB) and suspected small bowel bleeding. A 34-question electronic survey was sent to all Society of Abdominal Radiology (SAR) members. Responses were received from 52 unique institutions (40 from the United States). Only 26 (50%) utilize LGIB management guidelines. 32 (62%) use CT angiography (CTA) for initial evaluation in unstable patients. In stable patients with suspected LGIB, CTA is the preferred initial exam at 21 (40%) versus colonoscopy at 24 (46%) institutions. CTA use increases after hours for both unstable (n = 32 vs. 35, 62% vs. 67%) and stable patients (n = 21 vs. 27, 40% vs 52%). CTA is required before conventional angiography for stable (n = 36, 69%) and unstable (n = 15, 29%) patients. 38 (73%) institutions obtain two post-contrast phases for CTA. 49 (94%) institutions perform CT enterography (CTE) for occult small bowel bleeding with capsule endoscopy (n = 26, 50%) and CTE (n = 21, 40%) being the initial test performed. 35 (67%) institutions perform multiphase CTE for occult small bowel bleeding. In summary, stable and unstable patients with overt lower GI are frequently imaged with CTA, while CTE is frequently performed for suspected occult small bowel bleeding.

Gastrointestinal Bleeding at CT Angiography and CT Enterography: Imaging Atlas and Glossary of Terms.

Gastrointestinal (GI) bleeding is a common potentially life-threatening medical condition frequently requiring multidisciplinary collaboration to reach the proper diagnosis and guide management. GI bleeding can be overt (eg, visible hemorrhage such as hematemesis, hematochezia, or melena) or occult (eg, positive fecal occult blood test or iron deficiency anemia). Upper GI bleeding, which originates proximal to the ligament of Treitz, is more common than lower GI bleeding, which arises distal to the ligament of Treitz. Small bowel bleeding accounts for 5-10% of GI bleeding cases commonly manifesting as obscure GI bleeding, where the source remains unknown after complete GI tract endoscopic and imaging evaluation. CT can aid in identifying the location and cause of bleeding and is an important complementary tool to endoscopy, nuclear medicine, and angiography in evaluating patients with GI bleeding. For radiologists, interpreting CT scans in patients with GI bleeding can be challenging owing to the large number of images and the diverse potential causes of bleeding. The purpose of this pictorial review by the Society of Abdominal Radiology GI Bleeding Disease-Focused Panel is to provide a practical resource for radiologists interpreting GI bleeding CT studies that reviews the proper GI bleeding terminology, the most common causes of GI bleeding, key patient history and risk factors, the optimal CT imaging technique, and guidelines for case interpretation and illustrates many common causes of GI bleeding. A CT reporting template is included to help generate radiology reports that can add value to patient care. An invited commentary by Al Hawary is available online. Online supplemental material is available for this article. ©RSNA, 2021.

MR Enterography of Complicated Crohn Disease: Stricturing and Penetrating Disease.

ABSTRACT: Stricturing and penetrating disease are complications of Crohn disease (CD) that significantly affect patient outcomes. Careful evaluation for such complications is critical to the interpretation of magnetic resonance enterography. This manuscript outlines the key findings related to stricturing and penetrating CD and discusses current understanding of the pathophysiology and prognosis of complicated CD based on the literature.

Pancreatic Trauma: Imaging Review and Management Update.

Traumatic injuries of the pancreas are uncommon and often difficult to diagnose owing to subtle imaging findings, confounding multiorgan injuries, and nonspecific clinical signs. Nonetheless, early diagnosis and treatment are critical, as delays increase morbidity and mortality. Imaging has a vital role in diagnosis and management. A high index of suspicion, as well as knowledge of the anatomy, mechanism of injury, injury grade, and role of available imaging modalities, is required for prompt accurate diagnosis. CT is the initial imaging modality of choice, although the severity of injury can be underestimated and assessment of the pancreatic duct is limited with this modality. The time from injury to definitive diagnosis and the treatment of potential pancreatic duct injury are the primary factors that determine outcome following pancreatic trauma. Disruption of the main pancreatic duct (MPD) is associated with higher rates of complications, such as abscess, fistula, and pseudoaneurysm, and is the primary cause of pancreatic injury-related mortality. Although CT findings can suggest pancreatic duct disruption according to the depth of parenchymal injury, MR cholangiopancreatography and endoscopic retrograde cholangiopancreatography facilitate direct assessment of the MPD. Management of traumatic pancreatic injury depends on multiple factors, including mechanism of injury, injury grade, presence (or absence) of vascular injury, hemodynamic status of the patient, and associated organ damage. ©RSNA, 2020 See discussion on this article by Patlas.

Peripheral Blood Classical Monocytes and Plasma Interleukin 10 Are Associated to Neoadjuvant Chemotherapy Response in Breast Cancer Patients.

Worldwide, breast cancer (BC) is the leading cause of cancer death among women. For many patients the most effective treatment is a resection surgery that removes the tumor. Within this subset, patients sometimes receive chemotherapy treatment (CT) prior to surgery aiming to reduce tumor size in order to preserve healthy breast tissue. This strategy is commonly called neoadjuvant chemotherapy (NAC). This approach also offers an opportunity to determine treatment sensitivity, especially in aggressive tumors. Post NAC absence of residual disease is associated to long term survival in BC patients and is used to define the need of adjuvant therapy options. Studies suggest that NAC allows the recognition of tumor antigens by immune cells potentiating the eradication of the tumor. However, the dynamic changes in patients' immune cells under NAC remain unclear. Here, we assessed changes in leucocyte and cytokine profiles in order to determine its association to NAC response in BC patients. Peripheral blood patient samples were taken prior to each NAC cycle to assess the abundance of leukocyte subsets and serum cytokines in 20 patients. These immunological features were associated with clinical outcomes including pathological response. We found a positive correlation between plasma Interleukin 10 (IL-10) and classical monocytes in HER2+ BC patients under NAC. We also observed a trend between increased IL-10 and classical monocytes levels and lower rates of pathologic complete response at the end of NAC. These data support the notion that monocyte subsets and IL-10 could be applied as a novel indicator of NAC efficacy in HER2+ BC patients. Finally, we confirm a key role of the immune system in cancer progression and CT response.

Small Bowel Crohn Disease at CT and MR Enterography: Imaging Atlas and Glossary of Terms.

Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society for Pediatric Radiology, the American Gastroenterological Association, and other international experts recently reported consensus recommendations for standardized nomenclature for the interpretation and reporting of CT enterography and MR enterography findings of small bowel Crohn disease. The consensus recommendations included CT enterography and MR enterography bowel wall findings that are associated with Crohn disease, findings that occur with penetrating Crohn disease, and changes that occur in the mesentery related to Crohn disease. Also included were recommended radiology report impression statements that summarize the findings of small bowel Crohn disease at CT enterography and MR enterography. This article, authored by the Society of Abdominal Radiology Crohn's Disease-Focused Panel, illustrates the imaging findings and recommended radiology report impression statements described in the consensus recommendations with examples of CT enterography and MR enterography images. Additional interpretation guidelines for reporting CT enterography and MR enterography examinations are also presented. The recommended standardized nomenclature can be used to generate radiology report dictations that will help guide medical and surgical management for patients with small bowel Crohn disease. Online supplemental material is available for this article. ©RSNA, 2020See discussion on this article by Heverhagen.

Recombinant BCG Vaccines Reduce Pneumovirus-Caused Airway Pathology by Inducing Protective Humoral Immunity.

The Human Respiratory Syncytial Virus (hRSV) and the Human Metapneumovirus (hMPV) are two pneumoviruses that are leading agents causing acute lower respiratory tract infections (ALRTIs) affecting young infants, the elderly, and immunocompromised patients worldwide. Since these pathogens were first discovered, many approaches for the licensing of safe and effective vaccines have been explored being unsuccessful to date. We have previously described that immunization with recombinant strains of Mycobacterium bovis Bacillus Calmette-Guérin (rBCG) expressing the hRSV nucleoprotein (rBCG-N) or the hMPV phosphoprotein (rBCG-P) induced immune protection against each respective virus. These vaccines efficiently promoted viral clearance without significant lung damage, mainly through the induction of a T helper 1 cellular immunity. Here we show that upon viral challenge, rBCG-immunized mice developed a protective humoral immunity, characterized by production of antibodies specific for most hRSV and hMPV proteins. Further, isotype switching from IgG1 to IgG2a was observed in mice immunized with rBCG vaccines and correlated with an increased viral clearance, as compared to unimmunized animals. Finally, sera obtained from animals immunized with rBCG vaccines and infected with their respective viruses exhibited virus neutralizing capacity and protected naïve mice from viral replication and pulmonary disease. These results support the notion that the use of rBCG strains could be considered as an effective vaccination approach against other respiratory viruses with similar biology as hRSV and hMPV.

Texture analysis as a radiomic marker for differentiating renal tumors.

PURPOSE: To evaluate the utility of texture analysis for the differentiation of renal tumors, including the various renal cell carcinoma subtypes and oncocytoma. MATERIALS AND METHODS: Following IRB approval, a retrospective analysis was performed, including all patients with pathology-proven renal tumors and an abdominal computed tomography (CT) examination. CT images of the tumors were manually segmented, and texture analysis of the segmented tumors was performed. A support vector machine (SVM) method was also applied to classify tumor types. Texture analysis results were compared to the various tumors and areas under the curve (AUC) were calculated. Similar calculations were performed with the SVM data. RESULTS: One hundred nineteen patients were included. Excellent discriminators of tumors were identified among the histogram-based features noting features skewness and kurtosis, which demonstrated AUCs of 0.91 and 0.93 (p < 0.0001), respectively, for differentiating clear cell subtype from oncocytoma. Histogram feature median demonstrated an AUC of 0.99 (p < 0.0001) for differentiating papillary subtype from oncocytoma and an AUC of 0.92 for differentiating oncocytoma from other tumors. Machine learning further improved the results achieving very good to excellent discrimination of tumor subtypes. The ability of machine learning to distinguish clear cell subtype from other tumors and papillary subtype from other tumors was excellent with AUCs of 0.91 and 0.92, respectively. CONCLUSION: Texture analysis is a promising non-invasive tool for distinguishing renal tumors on CT images. These results were further improved upon application of machine learning, and support the further development of texture analysis as a quantitative biomarker for distinguishing various renal tumors.

Iatrogenic, blunt, and penetrating trauma to the biliary tract.

Iatrogenic and traumatic bile leaks are uncommon. However, given the overall increase in number of hepatobiliary surgeries and the paradigm shift toward nonoperative management of patients with liver trauma, they have become more prevalent in recent years. Imaging is essential to establishing early diagnosis and guiding treatment as the clinical signs and symptoms of bile leaks are nonspecific, and a delay in recognition of bile leaks portends a high morbidity and mortality rate. Findings suspicious for a bile leak at computed tomography or ultrasonography include free or contained peri- or intrahepatic low density fluid in the setting of recent trauma or hepatobiliary surgery. Hepatobiliary scintigraphy and magnetic resonance cholangiopancreatography (MRCP) with hepatobiliary contrast agents can be used to detect active or contained bile leak. MRCP with hepatobiliary contrast agents has the unique ability to reveal the exact location of bile leak, which often governs whether endoscopic management or surgical management is warranted. Percutaneous transhepatic cholangiography and fluoroscopy via an indwelling catheter that is placed either percutaneously or surgically are useful modalities to guide percutaneous transhepatic biliary drain placement which can provide biliary drainage and/or diversion in the setting of traumatic biliary injury. Surgical treatment of a bile duct injury with Roux-en-Y hepaticojejunostomy is warranted if definitive treatment cannot be accomplished through percutaneous or endoscopic means.

Utility of MDCT findings in predicting patient management outcomes in renal trauma.

PURPOSE: The purpose of this study is to assess the utility of computed tomography (CT) in predicting clinical outcomes in renal trauma. MATERIALS/METHODS: This retrospective study was IRB approved and HIPAA compliant; informed consent was waived. One-hundred-sixty-two, trauma-related renal injuries (157 adults) from January 01, 2006 to December 31, 2013 were included in this retrospective study. CT findings of vascular and collecting system (CS) injuries were recorded, and American Association for the Surgery of Trauma (AAST) renal injury grades were assigned. Fisher's exact test evaluated correlations between AAST grade and active hemorrhage, AAST grade and surgical/endovascular therapy, active hemorrhage and surgical/endovascular therapy, and size of perinephric hematomas and CS injuries. The unpaired t test correlated to the size of perinephric hematomas in CS injuries diagnosed on initial versus repeat imaging. RESULTS: AAST grades were as follows: 120 grades I-III and 42 grade IV/V. Active hemorrhage was diagnosed in 25 (15%) patients and CS injury in 22 (14%) patients. Seven (8%) patients received surgical/endovascular therapy. There were statistically significant correlations between AAST grade and active hemorrhage (p = 0.003), active hemorrhage and surgical/endovascular therapy (p < 0.0001), and large perinephric hematomas (>2 cm) and CS injuries (p < 0.0001). There was no significant correlation between AAST grade and surgical/endovascular therapy (p = 0.08). Of the CS injuries (50%), 11/22 had no evidence of CS injury on initial imaging, being detected on follow-up CT. These "masked cases" demonstrated significant differences in perinephric hematoma size when compared to CS injuries diagnosed on initial imaging (p = 0.01). CONCLUSION: Active hemorrhage in renal trauma is a significant predictor of surgical/endovascular therapy, in contradistinction to the AAST grade. In collecting system injuries, a large fraction was not detectable on initial CT, supporting the need for repeat imaging in cases with large perinephric hematomas.

Damage control surgery: use of diagnostic CT after life-saving laparotomy.

Damage control surgery (DCS) is a limited exploratory laparotomy that is performed in unstable trauma patients who, without immediate intervention, would acutely decompensate. Patients usually present with shock physiology and metabolic derangements including acidosis, hypothermia, and coagulopathy. Delayed medical correction of these metabolic derangements leads to an irreversible state of coagulopathic hemorrhagic shock and inevitable patient demise. Therefore, once a patient meets DCS criteria, a limited exploratory laparotomy is performed to stabilize life-threatening injury and expedite initiation of medical resuscitation in the intensive care unit (ICU). The surgeon plans to return to the operating room for definitive surgical treatment once the patient is hemodynamically stabilized and the metabolic derangements have been corrected. DCS patients are frequently sent to the ICU with an open abdomen and purposefully retained surgical equipment. The lack of response to resuscitation efforts, persistent hypotension, tachycardia, and/or the development of sepsis are common indications for this patient population to undergo CT imaging. The indications and findings of multi-detector CT (MDCT) in patients post-DCS have not been thoroughly evaluated in the radiology literature. A radiologist's knowledge of the DCS protocol and pre-imaging surgical interventions helps optimize the MDCT protocol. This enhances the radiologist's ability to evaluate for failure of surgical interventions performed prior to imaging and to search for injuries in areas that were not explored or that were missed during the initial surgical exploration.

Using texture analyses of contrast enhanced CT to assess hepatic fibrosis.

PURPOSE: To determine the ability of texture analyses of contrast-enhanced CT images for distinguishing between varying degrees of hepatic fibrosis in patients with chronic liver disease using histopathology as the reference standard. MATERIALS AND METHODS: Following IRB approval, 83 patients who underwent contrast enhanced 64-MDCT of the abdomen and pelvis in the portal venous phase between 12/2005 and 01/2013 and who had a liver biopsy within 6 months of the CT were included. An in-house developed, MATLAB-based texture analysis program was employed to extract 41 texture features from each of 5 axial segmented volumes of liver. Using the Ishak fibrosis staging scale, histopathologic grades of hepatic fibrosis were correlated with texture parameters after stratifying patients into three analysis groups, comparing Ishak scales 0-2 with 3-6, 0-3 with 4-6, and 0-4 with 5-6. To assess the utility of texture features, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was used to determine the performance of each feature in distinguishing between normal/low and higher grades of hepatic fibrosis. RESULTS: A total of 19 different texture features with 7 histogram features, one grey level co-occurrence matrix, 6 gray level run length, 1 Laws feature, and 4 gray level gradient matrix demonstrated statistically significant differences for discriminating between fibrosis groupings. The highest AUC values fell in the range of fair performance for distinguishing between different fibrosis groupings. CONCLUSION: These findings suggest that texture-based analyses of contrast-enhanced CT images offer a potential avenue toward the non-invasive assessment of liver fibrosis.

Traumatic and non-traumatic adrenal emergencies.

Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.