Flattening the Playing Field for Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) remains a major health care issue and is beset with significant racial and ethnic disparities in regard to its incidence, progression, and complication rate. An individual's health is influenced strongly by an array of societal-level factors commonly called the social determinants of health. Among these, DKD is influenced highly by structured resources and opportunities, as well as an individual's socioeconomic status, health insurance status, access to care, education, health literacy, nutrition, green space exposure, level of trust in the medical community, and more. Health equity is considered a state in which everyone has a fair and just opportunity to attain his or her highest level of health. Conversely, health inequities are a consequence of a structured discriminatory system of inequitable allocation of social determinants of health. When this discriminatory system is race-based it is referred to as structural racism, which eventually leads to racial and ethnic health disparities. The further downstream sequela of structural racism, consciously or unconsciously, impacts health systems, providers, and patients, and can lead to disparities in DKD development, progression, and complications. In this article, we explore potential interventions at the societal, health system, and provider levels that can help flatten the playing field and reduce racial and ethnic disparities in DKD.

The Autoantigen Repertoire and the Microbial RNP World.

Although autoimmunity and autoimmune disease (AID) are relatively common, the repertoire of autoantigens is paradoxically very limited. Highly enriched in this autoantigen repertoire are nucleic acids and their binding proteins, which together form large macromolecular structures. Most of these complexes are of ancient evolutionary origin, with homologs throughout multiple kingdoms of life. Why and if these nucleic acid-protein particles drive the development of autoimmunity remains unresolved. Recent advances in our understanding of the microbiome may provide clues about the origins of autoimmunity - and the particular puzzle of why the autoantigen repertoire is so particularly enriched in ribonucleoprotein particles (RNPs). We discuss the possibility that autoimmunity to some RNPs may arise from molecular mimicry to microbial orthologs.

Risk Factors for COVID-19 and Rheumatic Disease Flare in a US Cohort of Latino Patients.

OBJECTIVE: Latino patients are overrepresented among cases of coronavirus disease 2019 (COVID-19) and are at an increased risk of severe disease. Prevalence of COVID-19 in Latinos with rheumatic diseases is poorly reported. This study was undertaken to characterize COVID-19 clinical features and outcomes in Latino patients with rheumatic diseases. METHODS: We conducted a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1, 2020 and October 15, 2020 were analyzed in this study. We reviewed demographic characteristics, body mass index (BMI), comorbidities, and use of immunomodulatory therapies. An exploratory classification and regression tree (CART) analysis along with logistic regression analyses were performed to identify risk factors for COVID-19 and rheumatic disease flare. RESULTS: Of 178 Latino patients with rheumatic diseases, 32 (18%) were identified as having COVID-19, and the incidence rate of infection was found to be 3-fold higher than in the general Latino population. No patients required intensive care unit-level care. A CART analysis and multivariable logistic regression analysis identified a BMI of >30.35 as a risk factor for COVID-19 (odds ratio [OR] 3.37 [95% confidence interval (95% CI) 1.5-7.7]; P = 0.004). COVID-19 positivity was a risk factor for rheumatic disease flare (OR 4.57 [95% CI 1.2-17.4]; P = 0.02). CONCLUSION: Our findings indicate that Latino patients with rheumatic diseases have a higher rate of COVID-19 compared with the general Latino population. Obesity is a risk factor for COVID-19, and COVID-19 is a risk factor for rheumatic disease flare. Latino patients with risk factors should be closely followed up, especially post-COVID-19 in anticipation of disease flare.

Pulmonary fluid shifts occur as a result of scuba diving at NASA's Neutral Buoyancy Lab.

Introduction: Pulmonary fluid shifts can occur while scuba diving. Such shifts, generally thought to be rare, may result in a life-threatening phenomenon known as immersion pulmonary edema (IPE). This study aims to better classify the normal physiology of diving using ultrasound (US) to determine if these fluid shifts occur routinely during commercial diving work at the NASA Neutral Buoyancy Laboratory (NBL). Methods: Chest US was performed on commercial divers prospectively pre- and post-dive to evaluate the presence of B-lines in a total of 12 intercostal points on the anterior, posterior, and lateral chest wall. The number of B-lines at each anatomic site was recorded and scored by two independent reviewers. An increase in the number of B-lines post-dive was considered a positive result. Results: There were 67 exposures; 39 (58%) had an increase of one or more B-lines post dive; 64% of the female exposures and 57% of the male exposures were positive for B-lines post-dive, suggesting no difference across gender (Fisher's exact; p = 0.763). After the dive, all divers remained asymptomatic. Conclusion: From our results, fluid shifts can be viewed as a normal, transient, and physiologic process in commercial divers. This correlation can be compared to the formation of low-grade venous gas emboli (VGE) from decompression that does not result in decompression sickness. Further study of US B-lines in symptomatic divers may define the utility of field US in the diagnosis and management of IPE, and help identify associated risk factors.

Hansen's Disease and Complications among Marshallese Persons Residing in Northwest Arkansas, 2003-2017.

Persons from the Republic of the Marshall Islands have among the highest rates of Hansen's disease (HD) in the world; the largest Marshallese community in the continental United States is in northwest Arkansas. In 2017, the HD Ambulatory Care Clinic in Springdale, Arkansas, informed the Arkansas Department of Health (ADH) that Marshallese persons with HD had severe disease with frequent complications. To characterize their illness, we reviewed ADH surveillance reports of HD among Marshallese persons in Arkansas treated during 2003-2017 (n = 42). Hansen's Disease prevalence among Marshallese in Arkansas (11.7/10,000) was greater than that in the general U.S. population. Complications included arthritis (38%), erythema nodosum leprosum (21%), and prolonged treatment lasting > 2 years (40%). The majority (82%) of patients treated for > 2 years had documented intermittent therapy. Culturally appropriate support for therapy and adherence is needed in Arkansas.

Immune checkpoint inhibitor-induced inflammatory arthritis: identification and management.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune-related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant morbidity and limitation in anti-cancer therapy. AREAS COVERED: In this review, the authors focus on ICI-IIA. Relevant articles were identified through PubMed searches, spanning 2010 to the present. The authors detail the current understanding of its pathogenesis, diagnostic evaluation, and management strategies. EXPERT OPINION: ICI-IIA is a complex irAE that we are just beginning to understand mechanistically and pathologically. It often presents later in the disease course than other irAEs and, due to various reasons, is under-recognized. In some patients, ICI-IIA may become a chronic disease, which distinguishes it from most irAEs that resolve after ICI discontinuation. Multiple important questions still demand further research including which patients may develop ICI-IIA? What are possible diagnostic and prognostic markers? Do anti-arthritis therapies interfere with the anti-tumor response? and when should steroid-sparing agents be initiated? Close collaboration and shared decision-making between oncologists, rheumatologists, and the patient are essential when managing this particular irAE.

A Panoply of Rheumatological Manifestations in Patients with GATA2 Deficiency.

PURPOSE: To characterize rheumatological manifestations of GATA2 deficiency. METHODS: Single-center, retrospective review of 157 patients with GATA2 deficiency. Disease course, laboratory results, and imaging findings were extracted. In-person rheumatological assessments were performed on selected, available patients. A literature search of four databases was conducted to identify additional cases. RESULTS: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency. Notable rheumatological manifestations included: piezogenic pedal papules (PPP), joint hyperextensibility, early onset osteoarthritis, ankylosing spondylitis, and seronegative erosive rheumatoid arthritis. In peripheral blood of patients with rheumatological manifestations and GATA2 deficiency, CD4+ CD3+ helper T cells and naïve CD3+ CD4+ CD62L+ CD45RA+ helper T cell subpopulation fractions were significantly lower, while CD8+ cytotoxic T cell fractions were significantly higher, compared to those without rheumatological manifestations and with GATA2 deficiency. No changes in CD19, CD3, or NK populations were observed. CONCLUSION: GATA2 deficiency is associated with a broad spectrum of rheumatological disease manifestations. Low total helper T lymphocyte proportions and low naïve helper T cell proportions are associated with those most at risk of overt rheumatological manifestations. Further, PPP and joint hyperextensibility may explain some of the nonimmunologically-mediated joint problems encountered in patients with GATA2 deficiency. This catalogue suggests that rheumatological manifestations and immune dysregulation are relatively common in GATA2 deficiency.

Use of Magnetic Resonance Imaging to Identify Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis.

Importance: Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for an ever-increasing number of cancers. However, their use has also led to the emergence of immune-related adverse events, such as ICI-induced inflammatory arthritis. A reproducible, reliable, and accessible modality is needed to assess and distinguish early ICI-induced inflammatory arthritis and help in management. Magnetic resonance imaging (MRI) of joints may be helpful for early diagnosis, guiding therapeutic decision-making, and identifying patients at high risk for erosive disease. Objective: To assess the role of MRI of joints in patients with ICI-induced inflammatory arthritis. Design, Setting, and Participants: This retrospective case series included patients enrolled at the National Institutes of Health Clinical Center in Bethesda, Maryland. Patients were evaluated by the rheumatology consultation service between December 27, 2016, and May 28, 2019. A retrospective health record review was performed to determine demographic characteristics, clinical characteristics of inflammatory arthritis and malignant tumors, and imaging findings. Inclusion criteria were patients who were enrolled on various institutional review board-approved protocols of ICIs, developed joint-related symptoms, and had MRI data for at least 1 joint. Data were analyzed from June 1, 2019, to September 1, 2019. Exposures: Undergoing MRI of at least 1 joint. Main Outcomes and Measures: All MRIs were reviewed for synovitis, tenosynovitis, bone marrow edema, and soft tissue conditions. Results: A total of 8 patients (mean [SD] age, 58.8 [5.2] years; 6 women and 2 men) between the ages of 50 and 65 years who were undergoing ICI therapy for a variety of malignant tumors were included in this study. Only 1 patient was receiving combined ICI therapy. The results of 13 separate MRI examinations were reviewed. The most commonly performed MRIs were of the hands and wrists (9 MRIs), followed by knee examinations (3 MRIs). Tenosynovitis and synovitis were frequently seen in the hands and wrists. Bone marrow edema and erosions were also found in 3 patients, suggesting early damage. In larger joints (ie, knees and ankles), joint effusions and synovial thickening were characteristic. Most patients (5 patients) were treated with corticosteroids and had good responses. In patients with high-risk features on MRI imaging (eg, bone marrow edema, erosions), disease-modifying antirheumatic drug therapy was also discussed as a treatment option. Conclusions and Relevance: These findings suggest that advanced imaging may help to distinguish ICI-induced inflammatory arthritis from other causes of joint pain, aid in identifying patients at increased risk of joint damage, and provide utility in monitoring inflammatory arthritis treatment response in patients receiving ICI therapy.

Evidence for and Against ACC/AHA 2017 Guideline for Target Systolic Blood Pressure of < 130 mmHg in Persons with Type 2 Diabetes.

PURPOSE OF REVIEW: We summarize the evidence for and against a target systolic blood pressure (SBP) < 130 mmHg in individuals with type 2 diabetes mellitus (T2DM). RECENT FINDINGS: The primary ACCORD trial pooled data from patients with more- and less-intense glycemic control and found no benefit to lowering SBP < 140 mmHg, findings consistent with multiple meta-analyses. However, a re-analysis of the ACCORD trial found that participants randomized to less-intense glycemic control (HbA1c 7.0-7.9%) benefited from targeting SBP < 120 vs. 140 mmHg. The SPRINT trial also found benefit for targeting SBP < 120 vs. 140 mmHg in participants at risk for cardiovascular events but excluded persons with T2DM. There is no consensus as to the optimal SBP target for patients with T2DM, though data suggest a benefit to targeting SBP < 130 mmHg in patients with less-intensive glucose control. Further research is also needed on BP control in the setting of newer anti-diabetic agents.

Diagnostic accuracy and temporal impact of ultrasound in patients with dyspnea admitted to the emergency department.

OBJECTIVE: Few studies have prospectively evaluated the diagnostic accuracy and temporal impact of ultrasound in the emergency department (ED) in a randomized manner. In this study, we aimed to perform a randomized, standard therapy controlled evaluation of the diagnostic accuracy and temporal impact of a standardized ultrasound strategy, versus standard care, in patients presenting to the ED with acute dyspnea. METHODS: The patients underwent a standardized ultrasound examination that was blinded to the team caring for the patient. Ultrasound results remained blinded in patients randomized to the treating team but were unblinded in the interventional cohort. Scans were performed by trained emergency physicians. The gold standard diagnosis (GSDx) was determined by two physicians blinded to the ultrasound results. The same two physicians reviewed all data >30 days after the index visit. RESULTS: Fifty-nine randomized patients were enrolled. The mean±standard deviation age was 54.4±11 years, and 37 (62%) were male. The most common GSDx was acute heart failure with reduced ejection fraction in 13 (28.3%) patients and airway diseases such as acute exacerbation of asthma or chronic obstructive pulmonary disease in 10 (21.7%). ED diagnostic accuracy, as compared to the GSDx, was 76% in the ultrasound cohort and 79% in the standard care cohort (P=0.796). Compared with the standard care cohort, the final diagnosis was obtained much faster in the ultrasound cohort (mean±standard deviation: 12±3.2 minutes vs. 270 minutes, P<0.001). CONCLUSION: A standardized ultrasound approach is equally accurate, but enables faster ED diagnosis of acute dyspnea than standard care.

An evaluation of dehydrated human amnion/chorion membrane allografts for pressure ulcer treatment: a case series.

OBJECTIVE: Pressure ulcers (PU; also known as pressure injuries) affect about three million adults in the US and cost an estimated $11 billion dollars annually to treat. Prevention is most desirable, however, once a patient develops a PU, the focus shifts to effective treatment and rapid closure to improve health outcomes. We sought to evaluate outcomes in 10 patients with category II and III PUs treated with dehydrated human amnion/chorion membrane (dHACM) allografts. METHOD: All patients were treated with weekly application of dHACM plus standard wound care (SoC) and followed for eight weeks. RESULTS: Of the PUs, two were category II and eight were category III. The average PU size at dHACM initiation was 3.42±1.76cm2. After the first application of dHACM 7/10 (70%) of PUs responded to treatment with a reduction in wound size. Within two weeks of dHACM initiation into the plan of care, 4/10 (40%) of PUs had reduced in size by >50%. By week four, 60% of PUs (6/10) had reduced in size by >50%. Overall, during the eight week evaluation period, 9/10 PUs reduced in size, three of which healed completely. CONCLUSION: dHACM allografts appear to be a viable treatment option for category II and III PUs.

Comparing directed functional connectivity between groups with confirmatory subgrouping GIMME.

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group ("group-level edges") and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders.

Stressful life events and resilience among carers of Aboriginal children in urban New South Wales: cross-sectional findings from the Study of Environment on Aboriginal Resilience and Child Health (SEARCH).

OBJECTIVE: In caregivers of urban Aboriginal children, to determine the frequency of major stressful life events, the proportion who meet criteria for resilience, and factors that are associated with resilience. DESIGN: Cross-sectional survey. SETTING: Four Aboriginal Community Controlled Health Services located in urban or regional areas in New South Wales, Australia. PARTICIPANTS: 574 caregivers of Aboriginal children participating in the Study of Environment on Aboriginal Resilience and Child Health. PRIMARY OUTCOME MEASURE: Resilience, defined as having experienced three or more stressful life events in the last 12 months, and having scores of ≤21 on the Kessler 10 Psychological Distress scale. RESULTS: Over half (315, 55%) of the caregivers reported three or more stressful life events-the most common being a close family member who was hospitalised with a serious medical problem (259, 45%). Of the participants who experienced three or more stressful life events, almost three-quarters (227, 72%) met the criteria for resilience. Using multivariable analysis, two factors were independently associated with resilience: not having a physical health problem that limited normal activities (adjusted OR (aOR) 4.3; 95% CI 2.0 to 9.0), and not having problems caused by alcohol within the home (aOR 5.3; 95% CI 2.2 to 12.8). Having a child whose behaviour placed a great deal of burden on the family was associated with less resilience (aOR 0.25; 95% CI 0.09 to 0.68). CONCLUSIONS: Caregivers of urban Aboriginal children experienced a large number of stressful events, the most common being the poor health of close family members, but most exhibited resilience. Resilience was associated with stable family environments and good physical health. The high number of stressful life events that caregivers experience is reflective of broader inequalities that Aboriginal communities face. The availability of easily accessible and long-term health and support services may go some way to reducing this inequality and improving social and emotional well-being for Aboriginal families.

Hemodialysis Disparities in African Americans: The Deeply Integrated Concept of Race in the Social Fabric of Our Society.

End-stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non-Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre-ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.

Tuberculosis and leprosy infections in the Marshallese population of Arkansas, USA.

The cross-immunity between tuberculosis and leprosy is unknown. The aim of this pilot study was to evaluate the occurrence of Mycobacterium tuberculosis and M. leprae infection in Marshallese adult volunteers in Springdale, Arkansas, U.S.A., a population that experiences high rates of leprosy and tuberculosis. We used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic Mycobacterium leprae infection (22.2%). We found a negative association between presence of antibodies to Mycobacterium leprae and a positive interferon-γ release assay for Mycobacterium tuberculosis infection, prevalence odds ratio = 0.1 (95% CI = 0.0, 0.9). Although these findings require confirmation on a larger scale, they are supportive of the existence of cross-immunity.

SHOULD FNA BE PERFORMED IN PATIENTS WITH A MULTINODULAR GOITER AND COMPRESSIVE SYMPTOMS?

OBJECTIVE: In this study, we aimed to determine whether preoperative thyroid fine-needle aspiration (FNA) in patients with multinodular goiter (MNG) and compressive symptoms influences the type of thyroid surgery performed, the incidence of recurrent thyroid cancer, or the need for successive surgery. METHODS: We retrospectively reviewed the charts of 431 patients who underwent thyroidectomy at our institution from 2008 to 2011. Patients who presented with compressive symptoms and no prior FNA at initial presentation were included in this study. RESULTS: Eighty patients met the criteria for our study, of which 46 (57.5%) underwent FNA prior to surgery and 34 (42.5%) were referred to surgery without FNA. The prevalence rates of malignancy (>1 cm) on surgical pathology in the FNA and non-FNA groups were 41% (n = 19) and 38% (n = 13), respectively. There was no statistically significant difference between the rate of total/subtotal thyroidectomies (71.7% in FNA vs. 79.4% in non-FNA, P = .31), lobectomies/partial thyroidectomies (28.3% in FNA vs. 20.5% in non-FNA, P = .43), neck lymph node dissections (P = .89) or subsequent surgeries (P = .72) between the 2 groups. CONCLUSION: Our findings show that preoperative FNA in patients with an MNG and compressive symptoms does not influence the type of surgery performed, short-term outcomes, or the need for subsequent surgeries. Further studies are needed to validate the need for preoperative FNA in such patients. ABBREVIATIONS: FNA = fine-needle aspiration MNG = multinodular goiter WHO = World Health Organization.

Self-perceptions of pubertal timing and patterns of peer group activities and dating behavior among heterosexual adolescent girls.

This study identified patterns of past and concurrent peer group and dating behavior in a sample of adolescent girls (N = 511; aged 17-19 years; 49% White). Peer group activities and dating behaviors were classified as occurring in either early (ages 10-13 years), middle (ages 14-16 years), or late (ages 17-19 years) adolescence according to the age at which each participant indicated the activity/behavior was first experienced. Latent class analysis identified four latent classes: Early Interactions/Early Daters (15%), Early Interactions/Late Daters (17%), Early Interactions/Middle Daters (33%) and Middle Interactions/Middle Daters (35%). Class membership was associated with girl's perceived pubertal timing. Compared to Early Interactions/Early Daters, girls in the Early Interactions/Late Daters class reported higher levels of pubertal timing, indicating greater perception that their pubertal development was late relative to peers. Late perceived pubertal timing is potentially relevant for dating but not necessarily other mixed- and cross-sex peer interactions.