Evaluation of a Human Trafficking Educational Intervention for Nursing Professionals.

BACKGROUND: Human trafficking (HT) is a serious public health issue. Survivors of HT seek medical care. Health care professionals may be inadequately trained to identify and support survivors. This study evaluated improvements in nurses' knowledge after a professional development workshop on HT. METHOD: Pre- and postevaluation surveys assessed nurses' self-reported changes in perceived knowledge of HT and its vulnerability factors, the health impact of HT, strategies for identification and assessment of HT, and response to and follow-up of HT. RESULTS: After the workshop, participants showed significant improvement in perceived knowledge of all measures, regardless of hours of previous training and years of practice. CONCLUSION: Perceived knowledge of HT identification and response can be improved through training of nurses, regardless of hours of previous training and years of practice. [J Contin Educ Nurs. 2024;55(1):26-32.].

Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study.

OBJECTIVES: 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia. METHODS: Serum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models. RESULTS: No compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not. CONCLUSIONS: No longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA.

EUS-guided versus percutaneous liver biopsy: A comprehensive review and meta-analysis of outcomes.

EUS-guided liver biopsy (EUS-LB) has gained momentum in recent years, especially with availability of newer needle designs. Given the emerging comparative data on EUS-LB with second-generation needles and percutaneous LB (PC-LB), we conducted a systematic review and meta-analysis to compare the safety and efficacy of the two techniques. We searched multiple databases from inception through November 2021 to identify studies comparing outcomes of EUS-LB and PC-LB. Pooled estimates were calculated using a random-effects model, and the results were expressed in terms of pooled proportions and odds ratio (OR) along with relevant 95% confidence intervals (CIs). Five studies with 748 patients were included in the final analysis. EUS-LB was performed in 276 patients and PC-LB in 472 patients. Across all studies, PC-LB had an overall higher diagnostic accuracy than EUS-LB, 98.6% confidence interval (CI: 94.7-99.7) versus 88.3% (49.6-98.3), OR: 1.65, P = 0.04. On assessing data from randomized controlled trials, there was no difference between the two. While pooled diagnostic adequacy and overall adverse events were not significantly different between PC-LB and EUS-LB, the former was superior in terms of the mean number of complete portal tracts (CPT) and total specimen length. PC-LB and EUS-LB produce similar results. PC-LB allows obtaining longer samples and more CPT. Further studies are needed to see if these trends hold up as more providers begin to perform EUS-LB.

Liver resection after Y-90 radioembolization: a systematic review and meta-analysis of perioperative morbidity and mortality.

BACKGROUND: Data on morbidity and mortality following liver resection after radioembolization (Y90) are limited and controversial. Therefore, the perioperative morbidity and mortality of liver resections after Y90 treatment were investigated with systematic review and meta-analysis. METHODS: A PubMed search was conducted to identify studies of liver resection after previous Y90 treatment. Systematic review and meta-analysis for perioperative morbidity and mortality were perfomed using the 2009 PRISMA guidelines and STATA 16.1 software. RESULTS: A total of 16 studies reporting on 276 patients who underwent liver resection after Y90 met the inclusion criteria and were included in the meta-analysis. Meta-analysis of 30-day mortality rates yielded pooled mortality of 0.5% (95% CI 0.0-3.2%). Six studies (155 patients) reported a pooled 90-day mortality of 3.0% (95% CI 0.3-7.4%). The median time to resection after Y90 ranged from 2 to 12.5 months in various studies. In all studies where the median resection was undertaken eight or more months after Y90, zero 30-day mortality was reported. A meta-analysis of overall grade 3 or higher morbidity noted a rate of 26% (95% CI 16-37%). CONCLUSIONS: Liver resection after Y90 may be safe in very well selected patients. Delaying resection after Y90 may further decrease mortality.

Performance of a commercially available multiplex platform in the assessment of circulating cytokines and chemokines in patients with rheumatoid arthritis and osteoarthritis.

BACKGROUND/OBJECTIVE: Cytokines and chemokines (cytokines) are central to rheumatoid arthritis (RA) pathogenesis, with increasing use of multiplex immunoassays in clinical/research settings. Rheumatoid factor (RF) may interfere with assay outcomes by nonspecifically binding detection analytes. We evaluated the performance of a commercially available multiplex platform, including assessment of the impact of RF depletion. METHODS: Forty-five cytokines were tested using Meso Scale Discovery V-PLEX™ and samples from 40 RA and 40 osteoarthritis (OA) patients. Select samples were depleted of RF using a commercial binder. Performance was assessed using intra-assay coefficients of variation (CV), intraclass correlation coefficients (ICC), percent change following RF depletion, and disease discrimination. Values above or below quantification thresholds were imputed. RESULTS: Of the 45 cytokines analyzed, 31 yielded CVs <10%; none demonstrated CVs >30%. ICCs universally exceeded 0.85 with the exception of eight analytes. RF depletion altered cytokine values by <15% for 40 analytes with larger changes (>30%) only seen for one analyte. Twenty-three cytokines differed significantly based on measurement in plasma vs. serum. Three analytes were higher in the serum of RA vs. OA (IL-10, IP-10, TNFα), and none were significantly greater in OA vs. RA. Seventeen analytes required imputation for >50% of the samples tested, primarily related to concentrations below the lower limit of quantification threshold. CONCLUSION: The results from this commercially available multiplex assay were generally highly reproducible and interference induced by RF only meaningfully impacted the quantification of five of the analytes examined.

Investigating changes in disease activity as a mediator of cardiovascular risk reduction with methotrexate use in rheumatoid arthritis.

OBJECTIVE: Examine the association of methotrexate (MTX) use with cardiovascular disease (CVD) in rheumatoid arthritis (RA) using marginal structural models (MSM) and determine if CVD risk is mediated through modification of disease activity. METHODS: We identified incident CVD events (coronary artery disease (CAD), stroke, heart failure (HF) hospitalisation, CVD death) within a multicentre, prospective cohort of US Veterans with RA. A 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was collected at regular visits and medication exposures were determined by linking to pharmacy dispensing data. MSMs were used to estimate the treatment effect of MTX on risk of incident CVD, accounting for time-varying confounders between receiving MTX and CVD events. A mediation analysis was performed to estimate the indirect effects of methotrexate on CVD risk through modification of RA disease activity. RESULTS: Among 2044 RA patients (90% male, mean age 63.9 years, baseline DAS28-CRP 3.6), there were 378 incident CVD events. Using MSM, MTX use was associated with a 24% reduced risk of composite CVD events (HR 0.76, 95% CI 0.58 to 0.99) including a 57% reduction in HF hospitalisations (HR 0.43, 95% CI 0.24 to 0.77). Individual associations with CAD, stroke and CVD death were not statistically significant. In mediation analyses, there was no evidence of indirect effects of MTX on CVD risk through disease activity modification (HR 1.03, 95% CI 0.80 to 1.32). CONCLUSIONS: MTX use in RA was associated with a reduced risk of CVD events, particularly HF-related hospitalisations. These associations were not mediated through reductions in RA disease activity, suggesting alternative MTX-related mechanisms may modify CVD risk in this population.

Two-Stage Reimplantation of a Prosthetic Hip Infection: Systematic Review of Long-Term Reinfection and Pathogen Outcomes.

BACKGROUND: Although two-stage exchange for chronic periprosthetic hip infections remains an effective option for infection eradication, long-term outcome reporting remains scarce. Compiling outcomes data for this standard of care is necessary to characterize long-term reinfection risk and identify bacteria associated with reinfection. The purpose of our study was to perform a systematic review to determine the long-term risk of reinfection after two-stage reimplantation. The second purpose was to identify the proportion of reinfections caused by the same or different organism(s) relative to the index infection. METHODS: We performed a systematic review of two-stage reimplantation randomized control trials, cohort studies, and case series for the treatment of periprosthetic joint infections, yielding 320 unique citations for abstract review, of which 138 were reviewed in full. We collected reinfection data including the timing of reinfection after successful reimplantation and the bacteria identified at reinfection. Meeting inclusion criteria were 28 studies with 2047 patients and 2055 hips that completed both reimplantation stages with just seven studies having greater than 24 month follow-up. RESULTS: Studies with longer average follow-up reported significantly higher all-time reinfection rates (P = .042). Among studies with at least 5 years of follow-up, the risk of reinfection was 10.25% (8.21-12.47). Among studies with minimum follow-up of at least 24 months, the 24-month rate of reinfection was 4.58% (2.17-7.66), which increased to 7.34% (4.44-10.82) by final follow-up. Only 12 studies reported index and recurrent pathogen data. In those studies, 3.00% (1.19-5.38) of all hips which completed both reimplantation stages were reinfected by a new pathogen, and 1.70% (0.52-3.35) of patients became reinfected by recurrent pathogens. CONCLUSION: While the majority of two stage reimplantation literature follows patients for two years, there is significant risk of reinfection into the long term. Further studies with detailed outcomes and long-term follow-up are needed to identify factors associated with late infections.

Applying SLICC and ACR/EULAR systemic lupus erythematosus classification criteria in a cohort of patients with undifferentiated connective tissue disease.

BACKGROUND/OBJECTIVE: New classification criteria for SLE have recently been developed. How these criteria affect the classification of patients with the SLE-mimicking condition UCTD is poorly understood. This study investigated the reclassification of UCTD patients using newly derived SLE criteria. METHODS: Patients with UCTD were identified within a single academic medical center using ICD9/10 codes. Medical record review was performed to confirm UCTD diagnosis and identify disease features present at diagnosis. The SLICC and ACR/EULAR criteria were applied, after which we compared the proportion of patients reclassified as SLE and determined which disease features were associated with reclassification. RESULTS: A total of 129 patients were included in the study. When applying the SLICC and ACR/EULAR criteria, 18 (14.0%) and 26 patients (20.2%) were reclassified as SLE. Comparison with McNemar's test trended toward statistical significance (p = 0.057). Cohen's kappa coefficient was 0.62 (p < 0.001), indicating substantial agreement between these criteria. Disease features associated with reclassification as SLE were renal involvement, leukopenia, thrombocytopenia, anti- dsDNA antibody, hypocomplementemia, non-scarring alopecia (SLICC), and arthritis (ACR/EULAR). CONCLUSIONS: Both the SLICC and ACR/EULAR criteria exhibit increased SLE classification. These newer classification criteria could be used to increase the number of SLE patients in future clinical studies.

Incidental Findings on Brain MRI in People with HIV Infection.

BACKGROUND: Incidental findings are a well-known complication of imaging studies done for both diagnostic and research purposes. Little is known about the rates and types of incidental findings found on brain MRI in patients with HIV infection, who may be at risk for HIV-Associated Neurocognitive Disorders (HAND). METHODS: The parent study included 108 adults with HIV infection and 125 demographically-matched uninfected controls who completed MRI and neuropsychological testing. Incidental findings were classified by the study team as vascular, neoplastic, congenital, other neurologic, or non-neurologic. Categorical measures were compared using Pearson chi-square tests; continuous measures were compared using t-tests. RESULTS: Among participants with HIV infection, 36/108 (33%) had incidental findings compared to 33/125 (26%) controls (p = 0.248). Rates of incidental findings were significantly correlated with increasing age in both participants with HIV infection (p = 0.013) and controls (p = 0.022). We found no correlation between presence of incidental findings and sex or race/ethnicity among either cohort, and no correlation with CD4 count or HAND status for the HIV-infected cohort. CONCLUSIONS: Incidental findings were common in both participants with HIV infection and controls, at higher rates than previously reported in healthy populations. There was no significant difference in prevalence between the groups.

Step width variability as a discriminator of age-related gait changes.

BACKGROUND: There is scientific evidence that older adults aged 65 and over walk with increased step width variability which has been associated with risk of falling. However, there are presently no threshold levels that define the optimal reference range of step width variability. Thus, the purpose of our study was to estimate the optimal reference range for identifying older adults with normative and excessive step width variability. METHODS: We searched systematically the BMC, Cochrane Library, EBSCO, Frontiers, IEEE, PubMed, Scopus, SpringerLink, Web of Science, Wiley, and PROQUEST databases until September 2018, and included the studies that measured step width variability in both younger and older adults during walking at self-selected speed. Data were pooled in meta-analysis, and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. A single-decision threshold method based on the Youden index, and a two-decision threshold method based on the uncertain interval method were used to identify the optimal threshold levels (PROSPERO registration: CRD42018107079). RESULTS: Ten studies were retrieved (older adults = 304; younger adults = 219). Step width variability was higher in older than in younger adults (SMD = 1.15, 95% CI = 0.60; 1.70; t = 4.72, p = 0.001). The single-decision method set the threshold level for excessive step width variability at 2.14 cm. For the two-decision method, step width variability values above the upper threshold level of 2.50 cm were considered excessive, while step width variability values below the lower threshold level of 1.97 cm were considered within the optimal reference range. CONCLUSION: Step width variability is higher in older adults than in younger adults, with step width variability values above the upper threshold level of 2.50 cm to be considered as excessive. This information could potentially impact rehabilitation technology design for devices targeting lateral stability during walking.

The Likelihood of Self-reporting Balance Problems in Those With Advanced Chronic Kidney Disease, Slow Gait Speed, or Low Vitamin D.

OBJECTIVE: The purpose of this study was to determine the prevalence of vitamin D (25(OH)D) and balance deficits in persons with chronic kidney disease (CKD) and the likelihood of self-reporting balance and falling problems, measured gait speed in persons with kidney disease, and low levels of vitamin D and albumin. DESIGN: Analysis of the National Health and Nutrition Examination Survey 1999-2004 data set. SUBJECTS: The study included 8,554 subjects aged >40 years who were categorized into CKD stages based on the glomerular filtration rate (normal kidney function and stages 1 and 2 served as the control group, and stages 3 and 4/5 served as the CKD groups). MAIN OUTCOME MEASURES: Measured 25(OH)D levels, timed 20-feet walk, Romberg standing balance task, and self-reported balance and falling issues. RESULTS: The prevalence of balance deficits was found to be high in this CKD sample, with fail rates increasing with kidney disease severity. Similarly, when examining the relationship between CKD stage and the measurement of balance, fail rates (impaired balance) increased and gait speed decreased with kidney disease severity. In addition, the likelihood of self-reporting a balance and falling problem in the past year was higher in persons who had advanced CKD, were of older age, were of female sex, were with former or current smoking status, had lower 25(OH)D levels, and had lower albumin levels. Similarly, the likelihood of having a 20-feet walk time of more than 8 seconds was associated with those who were older, had higher body mass index, and had lower levels of 25(OH)D and albumin. CONCLUSION: The unique finding of this study is that increased reporting of balance and falling issues (both perceived and measured) and slower gait were found in persons with increased CKD severity and lower 25(OH)D status.

Midwest pharmacists' familiarity, experience, and willingness to provide pre-exposure prophylaxis (PrEP) for HIV.

INTRODUCTION: Pharmacist provision of pre-exposure prophylaxis (PrEP) through collaborative practice agreements with physicians could expand access to people at risk for HIV. We characterized pharmacists' familiarity with and willingness to provide PrEP services in Nebraska and Iowa. METHODS: An invitation to complete an 18-question survey was emailed to 1,140 pharmacists in Nebraska and Iowa in June and July of 2016. Descriptive analyses and Pearson chi-square tests were used to determine to what extent demographics, familiarity and experience were associated with respondent willingness to provide PrEP. Wilcoxon rank-sum tests compared ages and years of experience between groups of respondents. RESULTS: One hundred forty pharmacists (12.3%) responded. Less than half were familiar with the use of PrEP (42%) or the CDC guidelines for its use (25%). Respondents who were older (p = .015) and in practice longer (p = .005) were less likely to be familiar with PrEP. Overall, 54% indicated they were fairly or very likely to provide PrEP services as part of a collaborative practice agreement and after additional training. While familiarity with PrEP use or guidelines did not affect respondents' willingness to provide PrEP, respondents were more likely to provide PrEP with prior experience counseling HIV-infected patients on antiretroviral therapy (OR 2.43; p = 0.023) or PrEP (OR 4.67; p = 0.013), and with prior HIV-related continuing education (OR 2.77; p = 0.032). CONCLUSIONS: Pharmacist respondents in Nebraska and Iowa had limited familiarity and experience with PrEP, but most indicated willingness to provide PrEP through collaborative practice agreements after additional training. Provision of PrEP-focused continuing education may lead to increased willingness to participate in PrEP programs.

A pharmacist-led medication switch protocol in an academic HIV clinic: patient knowledge and satisfaction.

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored. METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with the switch process and knowledge about the new medication 4 to 8 weeks post-switch. RESULTS: Sixty five patients completed the switch and 57 (88%) completed a follow-up survey. Most (86%) reported understanding why the switch was made, while 91% correctly identified that TAF is associated with reduced renal toxicity, and 73% correctly identified that TAF is associated with reduced bone toxicity. No statistically significant difference was found in satisfaction with or understanding of why the medication switch was made when assessed by sex, age, race, or education, but there was a trend toward significance in the distribution of answers based on education level with those with a high school diploma, General Educational Development (GED) or less being more likely to be satisfied with the medication switch (p = 0.074). CONCLUSIONS: Education from an ambulatory clinic-based HIV pharmacist resulted in high rates of patient satisfaction and understanding of the switch from TDF to TAF-containing ART.

Effect of Clinical Variables on the Volume of Blood Collected for Blood Cultures in an Adult Patient Population.

OBJECTIVE To identify clinical variables that influence blood culture volume recovery DESIGN Retrospective chart review and linear model analysis SETTING A 621-bed Academic Medical Center with a Clinical Laboratory that processes 20,000+ blood cultures annually and dedicated phlebotomy staff for venipuncture PATIENTS Consecutive patients requiring blood culture METHODS Over a 6-day period, blood volume was determined in 568 culture bottles from 128 unique adult patients, and clinical data from the time of phlebotomy were extracted from hospital electronic medical records. Conditional hierarchical linear models with random effects for patient and phlebotomy occasion were utilized to analyze correlations between values collected from the same patient and during the same phlebotomy occasion. RESULTS Blood samples obtained from a central venous catheter yielded, on average, 2.53 mL more blood (95% CI, 1.63-3.44 mL; P<.001) than those from peripheral venipuncture, and aerobic bottles contained 0.38 mL more blood (95% CI, 0.1-0.67 mL; P=.009) than the anaerobic bottles. The remaining clinical variables (eg, hospital department, patient age, body mass index, gender, mean arterial pressure, concomitant systemic antibiotic use, and Charlson comorbidity index score) failed to reach statistical significance (P<.05) in relation to volume. CONCLUSIONS Blood cultures obtained from central venous catheters contain significantly greater volume than those obtained via peripheral venipuncture. These data highlight the clinically significant issue of low culture volume recovery, indicate that diagnostic and prognostic tools that rely on volume-dependent phenomena (ie, time to positivity) may require further validation under usual clinical practice circumstances, and suggest goals for future institutional performance improvement. Infect Control Hosp Epidemiol 2017;38:1493-1497.

Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.

OBJECTIVE: In addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrullinated peptide of cytokeratin 13 (CK-13) identified in gingival crevicular fluid (GCF), and comparing the response to 4 other citrullinated peptides in patients with RA who were well-characterized for PD and smoking. METHODS: The citrullinomes of GCF and periodontal tissue from patients with PD were mapped by mass spectrometry. ACPAs of CK13 (cCK13), tenascin-C (cTNC5), vimentin (cVIM), α-enolase (CEP-1), and fibrinogen ß (cFIBß) were examined by enzyme-linked immunosorbent assay in patients with RA (n = 287) and patients with osteoarthritis (n = 330), and cross-reactivity was assessed by inhibition assays. RESULTS: A novel citrullinated peptide cCK13-1 (444 TSNASGR-Cit-TSDV-Cit-RP458 ) identified in GCF exhibited elevated antibody responses in RA patients (24%). Anti-cCK13-1 antibody levels correlated with anti-cTNC5 antibody levels, and absorption experiments confirmed this was not due to cross-reactivity. Only anti-cCK13-1 and anti-cTNC5 were associated with antibodies to the periodontal pathogen Prevotella intermedia (P = 0.05 and P = 0.001, respectively), but not with antibodies to Porphyromonas gingivalis arginine gingipains. Levels of antibodies to CEP-1, cFIBß, and cVIM correlated with each other, and with smoking and shared epitope risk factors in RA. CONCLUSION: This study identifies 2 groups of ACPA fine specificities associated with different RA risk factors. One is predominantly linked to smoking and shared epitope, and the other links anti-cTNC5 and cCK13-1 to infection with the periodontal pathogen P intermedia.

Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint.

Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry. Results: Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01). Conclusion: Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.

Identification of an immunodominant peptide from citrullinated tenascin-C as a major target for autoantibodies in rheumatoid arthritis.

OBJECTIVES: We investigated whether citrullinated tenascin-C (cTNC), an extracellular matrix protein expressed at high levels in the joints of patients with rheumatoid arthritis (RA), is a target for the autoantibodies in RA. METHODS: Citrullinated sites were mapped by mass spectrometry in the fibrinogen-like globe (FBG) domain of tenascin-C treated with peptidylarginine deiminases (PAD) 2 and 4. Antibodies to cyclic peptides containing citrullinated sites were screened in sera from patients with RA by ELISA. Potential cross-reactivity with well-established anticitrullinated protein antibody (ACPA) epitopes was tested by inhibition assays. The autoantibody response to one immunodominant cTNC peptide was then analysed in 101 pre-RA sera (median 7 years before onset) and two large independent RA cohorts. RESULTS: Nine arginine residues within FBG were citrullinated by PAD2 and PAD4. Two immunodominant peptides cTNC1 (VFLRRKNG-cit-ENFYQNW) and cTNC5 (EHSIQFAEMKL-cit-PSNF-cit-NLEG-cit-cit-KR) were identified. Antibodies to both showed limited cross-reactivity with ACPA epitopes from α-enolase, vimentin and fibrinogen, and no reactivity with citrullinated fibrinogen peptides sharing sequence homology with FBG. cTNC5 antibodies were detected in 18% of pre-RA sera, and in 47% of 1985 Swedish patients with RA and 51% of 287 North American patients with RA. The specificity was 98% compared with 160 healthy controls and 330 patients with osteoarthritis. CONCLUSIONS: There are multiple citrullination sites in the FBG domain of tenascin-C. Among these, one epitope is recognised by autoantibodies that are detected years before disease onset, and which may serve as a useful biomarker to identify ACPA-positive patients with high sensitivity and specificity in established disease.

Does how much a resident teaches impact performance? A comparison of preclinical teaching hours to pathology residents' in-service examination scores.

BACKGROUND: While others have studied the effects of resident teaching on medical student performance, few have examined the benefits to the resident educator. Our study compared the quantity of pathology residents' didactic teaching with their performance on in-service examinations. METHODS: The academic records of anatomic/clinical pathology residents over 10 years were reviewed. Scores on step I of the United States Medical Licensing Examination (USMLE(®)), the annual percentile on the in-service examination, and preclinical teaching hours for each resident were obtained. RESULTS: Average annual teaching hours showed a weak positive correlation with mean in-service examination performance. Those below the 50th percentile had a lower number of teaching hours (average 7.8) than above the 50th percentile (mean 10.4, P=0.01). The incremental positive association between the two metrics increased by year in training and was strongest among senior residents, even controlling for USMLE performance (P<0.01). CONCLUSION: There is an association between the amount of pathology residents' preclinical educational activity and their mean performance on in-service examinations.