Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo

Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the “two-signal” model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2–like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid–binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid “missing self”–responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance

Novel grading system of sigmoid sinus dehiscence for radiologic evaluation of pulsatile tinnitus.

BackgroundSigmoid sinus dehiscence (SSD) is an important etiology of pulsatile tinnitus (PT) though there is currently no consensus on the prevalence of SSD in non-PT populations. This study establishes a grading system of SSD and analyzes a non-PT cohort for prevalence of SSD.MethodsIn this retrospective study temporal bone CT scans of 91 patients without PT were analyzed for SSD. The dehiscence was divided into three grades: Grade 1 indicating a micro dehiscence of <3.5 mm with an opening to the mastoid air cells, Grade 2 indicating a major dehiscence of >3.5 mm with an opening to the mastoid air cells, and Grade 3 indicating a sigmoid sinus wall dehiscence opening directly to the underlying tissue.ResultsIn patients without PT, SSD occurred in 34% of the cohort. Of these, 75% were Grade 1 and 25% were Grade 2. The range of dehiscence measurements for Grade 1 dehiscences was 0.9-3.4 mm. The range of dehiscence measurements for Grade 2 was 4-7.5 mm. There were no cases of Grade 3 dehiscence among this cohort.ConclusionsSSD occurred in over a third of our non-symptomatic cohort. While all grades of SSD may currently be treated surgically, a large portion of non-PT patients may have these sigmoid sinus anomalies asymptomatically. This grading system allows for the standardization of SSD definition and severity in future studies. Grade 3 dehiscences were completely absent in this cohort of non-PT patients

Novel grading system of sigmoid sinus dehiscence for radiologic evaluation of pulsatile tinnitus.

BackgroundSigmoid sinus dehiscence (SSD) is an important etiology of pulsatile tinnitus (PT) though there is currently no consensus on the prevalence of SSD in non-PT populations. This study establishes a grading system of SSD and analyzes a non-PT cohort for prevalence of SSD.MethodsIn this retrospective study temporal bone CT scans of 91 patients without PT were analyzed for SSD. The dehiscence was divided into three grades: Grade 1 indicating a micro dehiscence of <3.5 mm with an opening to the mastoid air cells, Grade 2 indicating a major dehiscence of >3.5 mm with an opening to the mastoid air cells, and Grade 3 indicating a sigmoid sinus wall dehiscence opening directly to the underlying tissue.ResultsIn patients without PT, SSD occurred in 34% of the cohort. Of these, 75% were Grade 1 and 25% were Grade 2. The range of dehiscence measurements for Grade 1 dehiscences was 0.9-3.4 mm. The range of dehiscence measurements for Grade 2 was 4-7.5 mm. There were no cases of Grade 3 dehiscence among this cohort.ConclusionsSSD occurred in over a third of our non-symptomatic cohort. While all grades of SSD may currently be treated surgically, a large portion of non-PT patients may have these sigmoid sinus anomalies asymptomatically. This grading system allows for the standardization of SSD definition and severity in future studies. Grade 3 dehiscences were completely absent in this cohort of non-PT patients

Superior semicircular canal dehiscence postoperative outcomes: a case series of 350 repairs.

BACKGROUND: Superior Semicircular Canal Dehiscence (SSCD) is a dehiscence of the otic capsule which normally lies over the superior semicircular canal. This database constitutes the largest series of SSCD patients to date. OBJECTIVE: To determine what preoperative factors, if any, contribute to postoperative outcomes and evaluate symptom resolution in a large SSCD patient cohort. METHODS: A single-institution, retrospective chart review collected patient demographics, intraoperative findings, and pre-and postoperative symptoms. Fishers exact t-test was performed for unpaired categorical variables, with a significance level of p < 0.05. RESULTS: 350 SSCD repairs were performed. The median age was 52 years (range: 17-86 years, ± 6.4 years), and the median follow-up duration was 4.6 months (range: 0.03-59.5 months, ± 6.8 months). Preoperative hearing loss was significantly associated with female sex (p = 0.0028). The most reported preoperative symptoms were tinnitus (77.4%), dizziness (74.0%), autophony (66.3%), amplification (63.7%), and disequilibrium (62.6%). Between patients who received unilateral versus bilateral SSCD repair, the greatest postoperative symptomatic resolution was seen in autophony (74.9%, p < 0.001), amplification (77.3%, p = 0.00027), hyperacusis (77.4%, p = 0.023), hearing (62.9%, p = 0.0063), and dizziness (54.6%, p < 0.001) for patients with unilateral SSCD repair. CONCLUSION: Surgical repair via the middle cranial fossa approach can significantly resolve auditory, vestibular, and neurological symptoms of patients with SSCD. Although this is one of the largest single-institution SSCD studies to date, future multi-institutional, prospective studies would be beneficial to validate these results

Racial Differences in Hospital Stays among Patients Undergoing Craniotomy for Tumour Resection at a Single Academic Hospital.

BACKGROUND:Racial differences in American patients undergoing brain tumour surgery remain poorly characterized within urban medical centres. Our objective was to assess racial differences in operative brain tumour patients at a single academic hospital in Los Angeles, California. METHODS:We reviewed medical records of adult patients undergoing craniotomy for tumour resection from March 2013 to January 2017 at UCLA Medical Centre. Patients were categorized as Asian, Hispanic, Black, or White. Racial cohorts were matched on demographic variables for comparisons. Our primary outcome was post-operative length of stay (LOS). Secondary outcomes included hospital mortality and discharge disposition. RESULTS:In this study, 462 patients identified as Asian (15.1%), Hispanic (8.7%), Black (3.9%), or White (72.3%). After cohort matching, non-White patients had elevated risk of prolonged LOS [odds ratio (OR)=2.62 (1.44, 4.76)]. No differences were observed in hospital mortality or non-routine discharge. Longer LOS was positively correlated with non-routine discharge [rpb (458)=0.41, p<0.001]. Black patients with government insurance had average LOS 2.84 days shorter than Black patients with private insurance (p=0.04). Among Hispanics, government insurance was associated with non-routine discharge [OR=4.93 (1.03, 24.00)]. CONCLUSION:Racial differences manifested as extended LOS for non-White patients, with comparable rates of hospital mortality and non-routine discharge across races. Prolonged LOS loosely reflected complicated clinical course with greater risk of adverse discharge disposition. Private insurance coverage predicted markedly lower risk of non-routine discharge for Hispanic patients, and LOS of three additional days among Black patients. Further research is needed to elucidate the basis of these differences

Association of Shadowing Program for Undergraduate Premedical Students with Improvements in Understanding Medical Education and Training.

OBJECTIVE:Physician shadowing has become ubiquitous to the premedical experience. However, students without connections to a medical professional are oftentimes forced to reach out to physicians independently from a program. Subsequently, these inquiries may go unanswered as they oftentimes appear unsolicited. The primary goals in the design and development of our program were to increase access to a clinical observership experience at our academic institution utilizing resident physicians as primary supervisors. METHODS:In January 2017, the Educational Shadowing Program (ESP) was established at our institution wherein undergraduate students could shadow within the Pediatric Continuity Clinic (PCC) staffed by pediatric resident physicians. ESP undergraduates shadowed the residents as they performed their history taking and physical exams and as they presented their patients to the attending physicians. Between patient encounters, the students assisted the residents in their administrative work which was completed as needed. ESP students were surveyed at their first orientation meeting and during the final case conference. RESULTS:The pre-participation survey showed that none of the student participants strongly agreed to having a good understanding of what the job of a resident physician entails. By the end of their 30 weeks, the proportion of participants with a strongly perceived understanding increased significantly. The proportion of student respondents that strongly agreed with their understanding of the physician-patient interaction also improved significantly over the study period, from 33% to 78%. Seventy-two percent of the residents surveyed agreed or strongly agreed that they enjoyed having the undergraduates in the clinic, affirming the positive effects of the program on the resident physicians. Forty-five percent of residents agreed or strongly agreed that the undergraduates improved their workflow in the clinic. CONCLUSION:This study demonstrates that establishing an undergraduate shadowing program in a busy academic pediatric clinic that involves resident physicians can be an overall positive experience for all participants. Fostering premedical student interest in pediatric care and primary care can possibly lead to more physician commitment to these fields, potentially helping to alleviate impending physicians in these specialties

Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian Patients of Los Angeles: A Single Institution Analysis.

BackgroundWorldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood.MethodsA retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS).ResultsA total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18-90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian patients was 55.9 years (SD: 14.6 range: 26-89). Asian-only cohort tumor pathologies included glioblastoma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (p=0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048, respectively), or OS (p=0.3711 and p=0.8183, respectively).ConclusionStudies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consideration when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results