The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK ؉ ) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor on lymphocytes, we generated transgenic mice that express IL-22R1 on lymphocytes. The health of these animals progressively deteriorated at 8 to 12 weeks of age, as they displayed respiratory distress, rough coat and sluggish movement, and subsequent lethality due to multiorgan inflammation. The IL-22R1 transgenic animals developed neutrophilia that correlated with increased levels of circulating IL-17 and granulocyte colony-stimulating factor. In addition, these mice had increased serum
BackgroundThere have been conflicting reports of the role of Type I interferons (IFN) in inflammatory bowel disease (IBD). Clinical trials have shown potent efficacy of systemic interferon-beta (IFN-β) in inducing remission of ulcerative colitis. Likewise, IFNAR1−/− mice display an increased sensitivity to dextran sulfate sodium (DSS)-induced colitis, suggesting Type I IFN play a protective role during inflammation of the gut. Curiously, however, there have also been reports detailing the spontaneous development of IBD in patients receiving systemic IFN-β therapy for multiple sclerosis or hepatitis.Methodology/Principal FindingsTo investigate the effects of local administration of IFN-β on a murine model of colitis, we developed a transgenic Lactobacillus acidophilus strain that constitutively expresses IFN-β (La-IFN-β). While pretreatment of mice with control Lactobacillus (La-EV) provided slight protective benefits, La-IFN-β increased sensitivity to DSS. Analysis showed colitic mice pretreated with La-IFN-β had increased production of TNF-α, IFN-γ, IL-17A and IL-13 by intestinal tissues and decreased regulatory T cells (Tregs) in their small intestine. Examination of CD103+ dendritic cells (DCs) in the Peyer's patches revealed that IFNAR1 expression was dramatically reduced by La-IFN-β. Similarly, bone marrow-derived DCs matured with La-IFN-β experienced a 3-fold reduction of IFNAR1 and were impaired in their ability to induce Tregs.Conclusions/SignificanceOur IFNAR1 expression data identifies a correlation between the loss/downregulation of IFNAR1 on DCs and exacerbation of colitis. Our data show that Lactobacillus secreting IFN-β has an immunological effect that in our model results in the exacerbation of colitis. This study underscores that the selection of therapeutics delivered by a bacterial vehicle must take into consideration the simultaneous effects of the vehicle itself.
Localization of parathyroid adenomas for treatment of primary hyperparathyroidism can be challenging. This retrospective study compared single-photon emission computed tomography/computed tomography (SPECT/CT), 4D-CT, and US studies in detection of adenomas prior to surgery. A retrospective chart review was performed on all consecutive patients with parathyroid adenoma presenting to an urban tertiary care medical center. A total of 58 patients (45 female, 13 male) underwent surgery for parathyroid adenoma. Patients aged 28 to 80 years (mean: 58.8) with parathyroid hormone levels ranging from 42 to 424 pg/mL (mean: 168). All patients underwent preoperative SPECT/CT with 20 mCi technetium-99m MIBI (99m Tc-MIBI). Fifty-three patients had additional US imaging and 14 patients had 4D-CT scans. Additionally, 34 patients had injection of 20 mCi 99m Tc-MIBI on the day of surgery. Pathological correlation was performed. Comparing SPECT/CT versus 4D-CT resulted in sensitivity (77% vs 80%), specificity (71% vs 75%), and accuracy (77% vs 79%). Ultrasound was less sensitive with similar specificity (44%, 86%, respectively). Combination of SPECT/CT and 4D-CT increased sensitivity to 88%, specificity to 100%, and accuracy to 89%. Combining SPECT/ CT with US resulted in sensitivity of 85%, specificity of 83%, and accuracy of 85%. Intraoperative localization substantially improved in patients who received preoperative injections. The SPECT/CT remains the best imaging modality for preoperative localization of parathyroid adenomas with high sensitivity. Combining SPECT/CT with US resulted in increased sensitivity and accuracy. For suspicion of ectopic cases or suspicion of unidentifiable adenoma with negative scintigraphy, addition of 4D-CT is recommended. Intraoperative localization and adjunctive imaging may improve surgical management of patients with hyperparathyroidism.
The COVID-19 pandemic has created unprecedented challenges in healthcare including pressure to provide efficient and timely patient care while maintaining a safe environment for physicians and staff. Radiology plays a vital role as part of a multidisciplinary team in the care of these patients. We address the experiences of our radiology residency at a large urban US academic institution with an underserved population in our fight against COVID-19. The unprecedented challenges faced during this pandemic has created monumental impacts on our training and allowed for development of skills and resources in order to better handle future situations.
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