Pitfalls and pearls in diagnosing inflammatory arthritis in older patients.

Given current demographic shifts, the number of older adults continues to grow, with almost half of patients over 65 being diagnosed with some form of arthritis. Rheumatic diseases pose unique diagnostic challenges in older patients due to the convergence of physiologic changes of aging, confounding difficulties to care, and atypical disease manifestations. This review summarizes the current published evidence to guide clinicians in evaluating geriatric patients with rheumatologic concerns, focusing on inflammatory arthritis. Using the background of epidemiologic data on various musculoskeletal diseases, clinical presentations, current diagnostic tests, and known physiologic changes of aging, this review highlights five diagnostic pitfalls in inflammatory polyarthritis among older patients. The pitfalls include: 1) broader differential diagnosis; 2) atypical presentations; 3) communication, cognitive, and social impairments; 4) the role of chronological vs. biological age; and 5) anchoring bias by assuming older adults are simply "older young adults". These pitfalls are discussed in the context of geriatric principles such as the "hallmarks of aging" and the expected pathophysiologic changes of organ systems. Furthermore, the review discusses the strengths and weaknesses of diagnostic tests used in arthritis and introduces some of the geriatric assessment tools that systematically evaluate multimorbidity and geriatric syndromes. With familiarity of the potential diagnostic pitfalls, knowledge of both normal and pathologic aging processes, awareness of the difference between biological and chronological age, and the ability to use geriatric assessment tools to better characterize older patients, clinicians will be better able to diagnose and manage rheumatic conditions in this population.

Examining Implicit Racial Attitudes among College Students in Hawai'i, a Project of the Hawai'i Implicit Bias Initiative.

For the past 2 decades, investigations into implicit racial bias have increased, building evidence on the impact of bias on health and health care for many minority communities in the US. However, few studies examine the presence and impacts of implicit bias in Hawai'i, a context distinct in its history, racial/ethnic diversity, and contemporary inequities. The absence of measures for major racialized groups, such as Native Hawaiians, Pacific Islanders, and Filipinos, impedes researchers' ability to understand the contribution of implicit bias to the health and social disparities observed in Hawai'i. The purpose of this study was to measure bias toward these underrepresented groups to gain a preliminary understanding of the implicit racial bias within the distinctive context of this minority-majority state. This study measured implicit racial bias among college students in Hawai'i using 3 implicit association tests (IATs): (1) Native Hawaiian compared to White (N = 258), (2) Micronesian comparedto White (N =257), and (3) Filipino compared to Japanese (N = 236). Themean IAT D scores showed implicit biases that favored Native Hawaiiansover Whites, Whites over Micronesians, and Japanese over Filipinos. Multipleregression was conducted for each test with the mean IAT D score as theoutcome variable. The analysis revealed that race was a predictor in the vastmajority of tests. In-group preferences were also observed. This investigationadvances the understanding of racial/ethnic implicit biases in the uniquelydiverse state of Hawai'i and suggests that established social heirarchies mayinfluence implicit racial bias.

Predictors of overlapping autoimmune disease in Neuromyelitis Optica Spectrum disorder (NMOSD): A retrospective analysis in two inner-city hospitals.

BACKGROUND: The coexistence of Neuromyelitis Optica spectrum disorder (NMOSD) with other autoimmune diseases (AD-NMOSD) presents worse clinical outcomes and healthcare costs than NMOSD alone (NMOSD-only). NMOSD and other autoimmune diseases also have a higher prevalence and morbidity in Black. We aim to compare clinical features and treatment responses in NMOSD patients with and without overlapping autoimmunity in a predominantly Black cohort. We further identify predictors associated with each clinical subtype. METHODS: AD-NMOSD (n = 14) and NMOSD-only (n = 27) patients were identified retrospectively. Demographic, clinical, laboratory, imaging, and response to treatment data were examined. RESULTS: Our cohort was predominately Black (82.9%). The prevalence of grouped-comorbidities, history of infections, sensory symptoms, Expanded Disability Status Scale (EDSS) before treatment, double-stranded DNA, antinuclear, ribonucleoprotein, and antiphospholipid antibodies, spinal-cord edema, white matter occipital lesions, and the levels of C-reactive protein, urine protein/creatinine, white blood cell count in cerebrospinal fluid (CSF), were higher in AD-NMOSD patients (p < 0.05 and/or Cramer's V > 30, Cohen's d > 50), whereas the age of males, visual symptoms, serum albumin, platelet count, and optic nerve enhancement were lower. EDSS after treatment improved in both groups being more evident in NMOSD-only patients (p = 0.003, SE = 0.58 vs p = 0.075, SE = 0.51). Other variables had a close to moderate SE, and others did not differ between NMOSD subtypes. A higher frequency of grouped-comorbidities, lower serum albumin, and platelet count were independently associated with a higher risk for AD-NMOSD. CONCLUSIONS: Some clinical features between AD-NMOSD and NMOSD-only patients were similar, while others differed. Comorbidities, serum albumin, and platelet count may be independent predictors of AD-NMOSD.

Prevalence and Clinical Characteristics of Rheumatoid Arthritis in an Inner City Population with Sickle Cell Disease.

OBJECTIVES: Rheumatoid arthritis (RA) has been rarely reported in association with sickle cell disease (SCD). Our study aimed to estimate the prevalence of RA in SCD population and to describe the clinical characteristics of RA associated with SCD. METHODS: Retrospective chart review of SCD and RA patients followed at 2 large urban hospitals. Seven RA/SCD patients were identified and compared to age and sex matched cohort of SCD only and of RA only group. All patients were Black. RESULTS: There were 739 SCD cases, seven (0.94%) met ACR criteria for RA (SCD-RA), 411 cases were RA only group. Mean age was significantly higher in SCD-RA compared to the entire population of SCD and RA (41.7 ± 3.9 (± SEM) vs. 33.26 ± 0.47, vs. 61.39 ± 0.79, p<0.01). SCD-RA patients had lower hemoglobin (g/dl) when compared to the age and sex matched SCD or RA only patients (7.4 ± 0.49 vs. 8.3 ± 0.60 vs. 11 ± 0.59, p <0.01) respectively. There were no significant differences in laboratory and treatment approach between SCD-RA and RA only groups, except for the radiographic evidence of periarticular osteopenia and greater difficulty in the activities of daily living (ADL) among SCD-RA cohort, compared to the age and sex matched RA cohort (p=0.01). CONCLUSION: In contrast to older reports, the prevalence of RA among SCD patients in our study (0.94%) was similar to that reported in the general population (0.5-1%) and was to be associated with difficulty in ADL and periarticular osteopenia. Since RA manifests at an older age, our reported prevalence is likely explainable by improved survival of SCD patients due to enhanced medical care and the advent of hydroxyurea as a major therapeutic breakthrough for SCD.

Experimental Support for the Ecoimmunity Theory: Distinct Phenotypes of Nonlymphocytic Cells in SCID and Wild-Type Mice.

Immune tolerance toward "self" is critical in multiple immune disorders. While there are several mechanisms to describe the involvement of immune cells in the process, the role of peripheral tissue cells in that context is not yet clear. The theory of ecoimmunity postulates that interactions between immune and tissue cells represent a predator-prey relationship. A lifelong interaction, shaped mainly during early ontogeny, leads to selection of nonimmune cell phenotypes. Normally, therefore, nonimmune cells that evolve alongside an intact immune system would be phenotypically capable of evading immune responses, and cells whose phenotype falls short of satisfying this steady state would expire under hostile immune responses. This view was supported until recently by experimental evidence showing an inferior endurance of severe combined immunodeficiency (SCID)-derived pancreatic islets when engrafted into syngeneic immune-intact wild-type (WT) mice, relative to islets from WT. Here we extend the experimental exploration of ecoimmunity by searching for the presence of the phenotypic changes suggested by the theory. Immune-related phenotypes of islets, spleen, and bone marrow immune cells were determined, as well as SCID and WT nonlymphocytic cells. Islet submass grafting was performed to depict syngeneic graft functionality. Islet cultures were examined under both resting and inflamed conditions for expression of CD40 and major histocompatibility complex (MHC) class I/II and release of interleukin-1α (IL-1α), IL-1ß, IL-6, tumor necrosis factor-α (TNF-α), IL-10, and insulin. Results depict multiple pathways that appear to be related to the sculpting of nonimmune cells by immune cells; 59 SCID islet genes displayed relative expression changes compared with WT islets. SCID cells expressed lower tolerability to inflammation and higher levels of immune-related molecules, including MHC class I. Accordingly, islets exhibited a marked increase in insulin release upon immunocyte depletion, in effect resuming endocrine function that was otherwise suppressed by resident immunocytes. This work provides further support of the ecoimmunity theory and encourages subsequent studies to identify its role in the emergence and treatment of autoimmune pathologies, transplant rejection, and cancer.

Diminished activity of circulating α1-antitrypsin is associated with pre-gestational isolated obesity.

OBJECTIVE: To examine possible correlation between α1-antitrypsin (AAT) levels and activity in patients with and without obesity, after excluding complications such as gestational diabetes mellitus (GDM), during pregnancy. STUDY DESIGN: A prospective case-control study was conducted. AAT levels were determined by standard human AAT ELISA according to the manufacturer's instructions. Elastase inhibition was determined by kinetic assay according to manufacturer recommendations. Assays were performed in duplicates and repeated twice for each sample in separate sessions. Patients with diabetes mellitus were excluded from the study. The Mann-Whitney U-test was performed in order to determine statistical differences between the groups, and AAT concentration and activity. RESULTS: During the study period, 43 patients were recruited: 21 with isolated obesity and 22 non-obese parturients (control group). According to ELISA, AAT concentrations were mildly lower in obese women compared with non-obese women (8.31 ± 0.28 mg/ml versus 9.5 ± 0.37 mg/ml, p = 0.0155). However, the elastase inhibitory capacity was markedly lower in obese versus non-obese parturients (mean 27.33 ± 2.08 % versus 43.73 ± 3.1%, p < 0.001). CONCLUSIONS: Isolated obesity in pregnancy is associated with lower activity of AAT. These findings correlate with the reduced concentration and activity of AAT found in patients with GDM. Accordingly, it might suggest an inflammatory axis shared by obesity and the development of insulin resistance.

Innocent until primed: mock jurors' racially biased response to the presumption of innocence.

BACKGROUND: Research has shown that crime concepts can activate attentional bias to Black faces. This study investigates the possibility that some legal concepts hold similar implicit racial cues. Presumption of innocence instructions, a core legal principle specifically designed to eliminate bias, may instead serve as an implicit racial cue resulting in attentional bias. METHODOLOGY/PRINCIPAL FINDINGS: The experiment was conducted in a courtroom with participants seated in the jury box. Participants first watched a video of a federal judge reading jury instructions that contained presumption of innocence instructions, or matched length alternative instructions. Immediately following this video a dot-probe task was administered to assess the priming effect of the jury instructions. Presumption of innocence instructions, but not the alternative instructions, led to significantly faster response times to Black faces when compared with White faces. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the core principle designed to ensure fairness in the legal system actually primes attention for Black faces, indicating that this supposedly fundamental protection could trigger racial stereotypes.

Low levels of circulating alpha-1 antitrypsin are associated with spontaneous abortions.

OBJECTIVE: Alpha-1 antitrypsin (AAT), a circulating anti-inflammatory molecule, rises four- to sixfold during acute phase responses and during pregnancy. AAT deficiency is linked with various pregnancy complications. The aim of this study is to determine plasma concentrations and activity of AAT and serum cytokine levels in blood samples from women undergoing spontaneous abortions as compared with elective abortions. METHODS: A prospective case-control study consisted of patients with sporadic abortions (n = 15), recurrent spontaneous abortions (n = 14) and healthy pregnancies going through elective terminations (n = 11). Circulating AAT and cytokine levels were determined before dilatation and curettage. RESULTS: AAT levels were lower in both recurrent and sporadic spontaneous abortion groups compared with healthy pregnancies (1.421 ± 0.08, 1.569 ± 0.14 and 3.224 ± 0.45 mg/ml, respectively, p < 0.001). Reduced AAT levels correlated with elevated proinflammatory cytokines. CONCLUSIONS: AAT levels in patients with either sporadic or recurrent spontaneous abortions were lower than normal pregnancies, and were associated with an inflammatory profile. Future studies should examine larger cohort groups, effects of earlier time-points and the influence of antithrombotic therapy in such patients who are diagnosed with relatively low levels of circulating AAT, in an effort to improve pregnancy outcomes.