Pediatric Patients with Osteomyelitis and/or Septic Joint Undergoing Surgical Debridement Have Equivalent Short-Term Outcomes with or without Preoperative MRI.

The purpose of this study was to determine if short-term outcomes differed for pediatric patients with suspected musculoskeletal infection with or without a preoperative MRI. This was a multicenter, retrospective review of patients aged 0-16 years who presented with atraumatic extremity pain, underwent irrigation and debridement (I&D), and received at least one preoperative or postoperative MRI over a 10-year period. Primary outcomes were time to OR, total I&Ds, readmission rate, time from OR to discharge, and total number of MRIs. Secondary outcomes entailed the rate at which concurrent osteomyelitis was identified in patients with septic arthritis and the extent of the resulting surgical debridement. Of the 104 patients, 72.1% had a preoperative MRI. Patients with a preoperative MRI were significantly less likely to have surgery on the day of admission. No difference was found between groups regarding total I&Ds, readmission rate, time from OR to discharge, and total number of MRIs. Of the 57 patients diagnosed with septic arthritis, those with a preoperative MRI were significantly more likely to have concurrent osteomyelitis identified and to undergo bony debridement in addition to arthrotomy of the joint. In conclusion, patient outcomes are not adversely affected by obtaining a preoperative MRI despite the delay in time to OR. Although preoperative MRI can be beneficial in ruling out other pathologies and identifying the extent of concurrent osteomyelitis, the decision to obtain a preoperative MRI and timing of surgery should be left to the discretion of the treating surgeon.

Development and Validation of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

PURPOSE: To develop and validate a novel patient-reported outcome (PRO) measure to assess vision-related functioning in individuals with severe peripheral field loss (PFL). DESIGN: Prospective outcome measure development/validation study. METHODS: A 127-item questionnaire was developed based on a prior qualitative interview study. A total of 116 participants with severe PFL due to retinitis pigmentosa (RP) or glaucoma were recruited at the Kellogg Eye Center and completed the Likert-scaled telephone-administered questionnaire. Included participants had a horizontal extent of their visual field <20 degrees (RP) or a mixed or generalized stage 4 to 5 defect using the Enhanced Glaucoma Staging System (glaucoma) in the better seeing eye (or in 1 eye if the fellow eye visual acuity was <20/200). Response data were analyzed using exploratory factor analysis and Rasch modeling. Poorly functioning items were eliminated, confirmatory factor analysis was used to ensure scale unidimensionality, and the model was refit to produce the final instrument. RESULTS: The final Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire contains 53 items across 6 domains: mobility, object localization, object recognition, reading, social functioning, and technology. There were 74 items removed because of high missingness, poor factor loadings, low internal consistency, high local dependency, low item information, item redundancy, or differential item functioning. Using Rasch item calibrations, person ability scores could be calculated for each of the 6 unidimensional LV-SCOPE domains with good test-retest stability. CONCLUSIONS: The LV-SCOPE Questionnaire provides a valid and reliable measure of vision-related functioning across 6 key domains relevant to individuals with severe PFL. Findings support the clinical utility of this psychometrically valid instrument.

T-bet+ B cells accumulate in adipose tissue and exacerbate metabolic disorder during obesity.

Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet+ B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet+ cells exacerbates metabolic disorder in obesity, while ablation of Tbx21 specifically in B cells reduces serum IgG2c levels, inflammatory cytokines, and inflammatory macrophages in adipose tissue, ameliorating metabolic symptoms. Furthermore, transfer of serum or purified IgG from HFD mice restores metabolic disease in T-bet+ B cell-deficient mice, confirming T-bet+ B cell-derived IgG as a key mediator of inflammation during obesity. Together, these findings reveal an important pathological role for T-bet+ B cells that should inform future immunotherapy design in type 2 diabetes and other inflammatory conditions.

Receptor Interacting Protein Kinase Pathways Regulate Innate B Cell Developmental Checkpoints But Not Effector Function in Mice.

Mutations in the scaffolding domain of Receptor Interacting Protein kinases (RIP) underlie the recently described human autoimmune syndrome, CRIA, characterized by lymphadenopathy, splenomegaly, and autoantibody production. While disease mechanisms for CRIA remain undescribed, RIP kinases work together with caspase-8 to regulate cell death, which is critical for normal differentiation of many cell types. Here, we describe a key role for RIP1 in facilitating innate B cell differentiation and subsequent activation. By comparing RIP1, RIP3, and caspase-8 triple deficient and RIP3, caspase-8 double deficient mice, we identified selective contributions of RIP1 to an accumulation of murine splenic Marginal Zone (MZ) B cells and B1-b cells. We used mixed bone-marrow chimeras to determine that innate B cell commitment required B cell-intrinsic RIP1, RIP3, and caspase-8 sufficiency. RIP1 regulated MZ B cell development rather than differentiation and RIP1 mediates its innate immune effects independent of the RIP1 kinase domain. NP-KLH/alum and NP-Ficoll vaccination of mice doubly deficient in both caspase-8 and RIP3 or deficient in all three proteins (RIP3, caspase-8, and RIP1) revealed uniquely delayed T-dependent and T-independent IgG responses, abnormal splenic germinal center architecture, and reduced extrafollicular plasmablast formation compared to WT mice. Thus, RIP kinases and caspase-8 jointly orchestrate B cell fate and delayed effector function through a B cell-intrinsic mechanism.

Vision-related quality of life in adults with severe peripheral vision loss: a qualitative interview study.

BACKGROUND: Existing patient-reported outcome (PRO) measures may not be relevant to the full range of functional and vision-related quality of life (VR-QOL) concerns of individuals with vision impairment due to severe peripheral field loss (PFL). Measurement of VR-QOL in severe PFL is important in order to determine the effectiveness of vision rehabilitation interventions for this population. The purpose of this study was to characterize the impact of severe PFL due to retinitis pigmentosa (RP) and glaucoma on VR-QOL as the initial phase in the development of a novel PRO measure. METHODS: Individuals with severe PFL due to RP or glaucoma were recruited from the Kellogg Eye Center and the Association for the Blind and Visually Impaired. Participants completed semi-structured qualitative interviews, the Impact of Vision Impairment (IVI) questionnaire and the RAND 36-Item Health Survey. Interviews were analyzed by two coders using thematic analysis. A matrix analysis was conducted to compare VR-QOL by cause of severe PFL. Sample size was determined by thematic saturation. RESULTS: The study included 37 participants (19 RP, 18 glaucoma). Median best-corrected visual acuity for those with RP and glaucoma was 20/40 and 20/27.5, while Pelli-Robson contrast sensitivity was 1.2 log contrast sensitivity (logCS) and 1.1 logCS, respectively. Median domain scores on the IVI (reading, mobility, well-being) ranged from a low of - 0.2 to a high of 0.7 logits in those with RP and from 0.5 to 1.2 logits in those with glaucoma. Qualitative interviews identified six VR-QOL themes relevant across participants with both RP and glaucoma, including activity limitations, driving, emotional well-being, reading, mobility, and social function. VR-QOL concerns were largely consistent among those with severe PFL due to RP and glaucoma. These overarching themes contained content relevant to specific challenges related to severe PFL. CONCLUSIONS: There are commonly occurring VR-QOL concerns among individuals with severe PFL due to RP and glaucoma. The outlined themes will serve as the basis for development of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

Vision Impairment and Receipt of Eye Care Among Older Adults in Low- and Middle-Income Countries.

Importance: Vision impairment (VI), including blindness, affects hundreds of millions globally, and 90% of those with VI live in low- and middle-income countries. Cross-national comparisons are important to elucidate the unique and shared factors associated with VI and receipt of eye care in different countries and to target those most in need. Objective: To identify the characteristics associated with VI and receipt of eye care in a sample of low- and middle-income countries. Design, Setting, and Participants: In this study of cross-sectional survey data from wave 1 of the World Health Organization Study on Global Aging and Adult Health, data on sociodemographic characteristics and health were collected from nationally representative samples in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010. Probability sampling with multistage, stratified, random-cluster samples was used to identify households and participants. The survey was completed by 34 159 adults 50 years and older. Data were analyzed from December 2017 to February 2018. Main Outcomes and Measures: We analyzed associations of individual-level and household-level covariates with 3 primary outcomes: distance VI (visual acuity worse than 6/18 in the better-seeing eye), near VI (visual acuity worse than 6/18 in the better-seeing eye), and receipt of an eye examination within the previous 2 years. Results: The study sample in China consisted of 13 350 participants (50.2% female; mean [SD] age, 62.6 [9.0] years); in Ghana, 4725 participants (50.4% female; mean [SD] age, 64.2 [10.8] years); in India, 7150 participants (48.9% female; mean [SD] age, 61.5 [9.0] years); in Mexico, 2103 participants (52.3% female; mean [SD] age, 69.2 [9.2] years); in Russia, 3763 participants (61.1% female; mean [SD] age, 63.9 [10.4] years); and in South Africa, 3838 participants (55.9% female; mean [SD] age 61.6 [9.5]) (all demographic characteristics weighted to reflect respective populations). The weighted proportion of the study sample with distance VI ranged from 9.9% (95% CI, 9.3-10.5) in China to 25.4% (95% CI, 22.0-29.2) in Russia; near VI, from 28.5% (95% CI, 26.9-30.1) in Ghana to 43.1% (95% CI, 41.1-45.1) in India; and receipt of a recent eye examination, from 15.0% (95% CI, 13.8-16.2) in Ghana to 53.1% (95% CI, 49.3-56.8) in Russia. Educational attainment, medical comorbidities, and memory were significantly associated with all outcomes across most low- and middle-income countries. Female sex, low household wealth, food insecurity, no health insurance, rurality, disability, being unmarried, and low social participation were significantly associated with adverse vision-related outcomes, though less consistently. Conclusions and Relevance: There are both common and unique characteristics associated with VI and receipt of eye care across low- and middle-income countries. Our findings suggest that recognizing these factors is important to identify those most at risk and allocate resources optimally. Additional local epidemiological studies are needed.