The role for endobronchial biopsy in the era of endobronchial ultrasound guided transbronchial needle aspiration for the diagnosis of sarcoidosis: a single center experience.

BACKGROUND AND AIM: Endobronchial biopsy (EBBX) has been reported to increase diagnostic yield for pulmonary sarcoidosis. The purpose of this study is to investigate the diagnostic yield for EBBX following endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). METHODS: We identified a cohort of patients in the University of Minnesota Sarcoidosis Registry who had EBBx and EBUS-TBNA as part of workup for abnormal chest imaging. Data regarding demographics, biopsy approach and technique were recorded. RESULTS: Our cohort included 37 patients (53.24±9.5, Male, 22±0.57; 3.8% were African American). In these patients who had EBBX, EBUS-TBNA was performed in 100% of patients and TBBX was performed in 2 patients (5%). EBBX was positive in 9 patients (24%) and EBUS-TBNA was positive in 34 patients (92%). TBBX was diagnostic in one of two patients. EBBX was the only diagnostic tissue in 3 of the 37 patients (8%).  Conclusion: The diagnostic yield of EBBX is lower than previously reported, with only 8% of EBBXs demonstrating granulomatous inflammation. However, instrumentation used for obtaining EBBX as well as the presence of visible lesions does influence the diagnostic yield. Studies with adequate power are needed before implementing changes in clinical practice.  When performed alongside EBUS-TBNA, EBBX did not significantly add to the diagnostic yield in sarcoidosis unless visible lesions were observed.

Gut microbial ß-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.

Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial ß-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities.

The active papillary muscle sign in 18F-FDG PET/CT cardiac sarcoidosis exams and its relationship with myocardial suppression.

OBJECTIVE: Papillary muscle (PM) activity may demonstrate true active cardiac sarcoidosis (CS) or mimic CS in 18FDG-PET/CT if adequate myocardial suppression (MS) is not achieved. We aim to examine whether PM uptake can be used as a marker of failed MS and measure the rate of PM activity presence in active CS with different dietary preparations. MATERIALS AND METHODS: We retrospectively reviewed PET/CTs obtained with three different dietary preparations. Diet-A: 24-h ketogenic diet with overnight fasting (n = 94); Diet-B: 18-h fasting (n = 44); and Diet-C: 72-h daytime ketogenic diet with 3-day overnight fasting (n = 98). Each case was evaluated regarding CS diagnosis (negative, positive, and indeterminant) and presence of PM activity. MaxSUV was measured from bloodpool, liver, and the most suppressed normal myocardium. Linear mixed-effects models were used to compare these factors between those with PM activity and those without. RESULTS: PM activity was markedly lower in the Diet-C group compared with others: Diet-C: 6 (6.1%), Diet-A: 36 (38.3%), and Diet-B: 26 (59.1%) (p < 0.001). MyocardiumMaxSUV was higher, and MyocardiummaxSUV/BloodpoolmaxSUV, MyocardiummaxSUV/LivermaxSUV ratios were significantly higher in the cases with PM activity (p < 0.001). Among cases that used Diet-C and had PM activity, 66.7% were positive and 16.7% were indeterminate. If Diet-A or Diet-B was used, those with PM activity had a higher proportion of indeterminate cases (Diet-A: 61.1%, Diet-B: 61.5%) than positive cases (Diet-A: 36.1%, Diet-B: 38.5%). CONCLUSION: Lack of PM activity can be a sign of appropriate MS. PM activity is less common with a specific dietary preparation (72-h daytime ketogenic diet with 3-day overnight fasting), and if it is present with this particular preparation, the likelihood that the case being true active CS might be higher than the other traditional dietary preparations.

Sociopolitical Diagnostic Tools to Understand National and Local Response Capabilities and Vulnerabilities to Epidemics and Guide Research into How to Improve the Global Response to Pathogens.

The AIDS and COVID-19 pandemics demonstrated that nations at similar economic development levels varied widely in their capacity to protect the health of their residents. For AIDS, Britain and Australia brought gay representatives into official counsels and adopted harm reduction far more rapidly than the United States or Spain, and East African countries responded more effectively than South Africa or the Democratic Republic of the Congo. National responses to COVID-19 varied widely, with New Zealand, China, and Vietnam more effective than Italy, Brazil, or the United States. Further, as phylogenetic research has demonstrated, these pandemics spread from one country to another, with those that responded poorly acting as sources for mutations and potentially sources of transmission to countries with more effective responses. Many observers expressed surprise at the poor responses of the United States to COVID-19, but in retrospect the cutbacks in public health funding at state and national levels made it clear that this was a predictable weakness even in addition to the political vacillations that crippled the US and Brazilian responses. In a time of global sociopolitical and climate instability, it is important to measure and conduct research into spatial and time variations in 1. public health and medical funding, 2. social influence networks, social cohesion and trust, and stigmatization, 3. income inequality, 4. social conflict, and 5. other factors that affect responsiveness to pandemics.

The urgent need to implement point-of-care RNA testing for hepatitis C virus to support elimination.

Hepatitis C virus (HCV) elimination is an important global public health goal. However, the United States (US) is not on track to meet the World Health Organization's 2030 targets for HCV elimination. Recently, the White House proposed an HCV elimination plan that includes point-of-care (POC) HCV RNA testing, which is currently in use in many countries, but is not approved in the US. POC HCV RNA testing is crucial for implementing community-based testing, and for enabling test-and-treat programs, assessing cure, and monitoring for reinfection.. In this commentary, we review the status of POC HCV RNA testing in the US, discuss factors that are needed for successful implementation, and issue specific public health and policy recommendations that would allow for the use of POC HCV RNA testing to support HCV elimination.

Upgrading on Per Protocol versus For Cause surveillance prostate biopsies: An opportunity to decreasing the burden of active surveillance.

BACKGROUND: Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx. METHODS: We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Surveillance prostate biopsies obtained 1 year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed FCSBx if any of these criteria were met: PSA velocity > 0.75 ng/mL/year; rise in PSA > 3 ng from baseline; surveillance magnetic resonance imaging (MRI) (sMRI) with a PIRADS ≥ 4; change in DRE. Biopsies were classified PPSBx if none of these criteria were met. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. The secondary objective was to assess for the association of reassuring (PIRADS ≤ 3) confirmatory or surveillance MRI findings and upgrading for patients undergoing PPSBx. Proportions were compared with the chi-squared test. RESULTS: We identified 1773 men with GG1 PC in MUSIC who underwent a surveillance biopsy. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared with those meeting criteria for PPSBx (26% and 4.9%, respectively, p < 0.001 and p < 0.001). Men with a reassuring confirmatory or surveillance MRI undergoing PPSBx had less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively) disease compared with men without an MRI (31% and 7.4%, respectively). CONCLUSIONS: Patients undergoing PPSBx had significantly less upgrading compared with men undergoing FCSBx. Confirmatory and surveillance MRI seem to be valuable tools to stratify the intensity of surveillance biopsies for men on AS. These data may help inform the development of a risk-stratified, data driven AS protocol.

Prioritized mass spectrometry increases the depth, sensitivity and data completeness of single-cell proteomics.

Major aims of single-cell proteomics include increasing the consistency, sensitivity and depth of protein quantification, especially for proteins and modifications of biological interest. Here, to simultaneously advance all these aims, we developed prioritized Single-Cell ProtEomics (pSCoPE). pSCoPE consistently analyzes thousands of prioritized peptides across all single cells (thus increasing data completeness) while maximizing instrument time spent analyzing identifiable peptides, thus increasing proteome depth. These strategies increased the sensitivity, data completeness and proteome coverage over twofold. The gains enabled quantifying protein variation in untreated and lipopolysaccharide-treated primary macrophages. Within each condition, proteins covaried within functional sets, including phagosome maturation and proton transport, similarly across both treatment conditions. This covariation is coupled to phenotypic variability in endocytic activity. pSCoPE also enabled quantifying proteolytic products, suggesting a gradient of cathepsin activities within a treatment condition. pSCoPE is freely available and widely applicable, especially for analyzing proteins of interest without sacrificing proteome coverage. Support for pSCoPE is available at http://scp.slavovlab.net/pSCoPE .

Initial recommendations for performing, benchmarking and reporting single-cell proteomics experiments.

Analyzing proteins from single cells by tandem mass spectrometry (MS) has recently become technically feasible. While such analysis has the potential to accurately quantify thousands of proteins across thousands of single cells, the accuracy and reproducibility of the results may be undermined by numerous factors affecting experimental design, sample preparation, data acquisition and data analysis. We expect that broadly accepted community guidelines and standardized metrics will enhance rigor, data quality and alignment between laboratories. Here we propose best practices, quality controls and data-reporting recommendations to assist in the broad adoption of reliable quantitative workflows for single-cell proteomics. Resources and discussion forums are available at https://single-cell.net/guidelines .

Association between follow-up blood cultures for gram-negative bacilli bacteremia and length of hospital stay and duration of antibiotic treatment: A propensity score-matched cohort study.

OBJECTIVE: It remains unclear whether a follow-up blood culture (FUBC) for gram-negative bacilli (GNB) bacteremia should be routinely or selectively performed. To evaluate the value of the practice, we analyzed the association between current FUBC practices and length of stay, antibiotic treatment duration, and in-hospital mortality. DESIGN: Retrospective cohort study. SETTING: The study was conducted in 4 acute-care hospitals in New York City. PATIENTS: The study included hospitalized adults with GNB bacteremia between 2017 and 2018. METHODS: An FUBC was defined as a blood culture performed between 24 hours and 7 days after an initial blood culture positive for GNB. Using propensity scores for FUBCs performed, patients were matched 1:1 for outcome comparison. RESULTS: In total, 376 hospitalized adults with GNB bacteremia met eligibility criteria. Among them, FUBCs were performed in 271 patients (72%). After propensity score matching, we analyzed 87 pairs of patients with and without an FUBC to compare outcomes. The median length of stay was longer among patients with FUBCs than patients without FUBCs (9 days vs 7 days; P = .017). The median duration of antibiotic treatment was also longer among patients with FUBCs than patients without FUBCs (8 vs 6 days; P = .007). No statistically significant difference was observed in in-hospital mortality between patients with and without an FUBC (odds ratio, 0.37; 95% confidence interval, 0.08-1.36). CONCLUSIONS: Current FUBC practices for GNB bacteremia were associated with prolonged length of stay and duration of antibiotic treatment. Further data to better inform selectivity criteria for FUBCs in GNB bacteremia are needed.

Syringe Service Program Perspectives on Barriers, Readiness, and Programmatic Needs to Support Rollout of the COVID-19 Vaccine.

BACKGROUND: We explored syringe service program (SSP) perspectives on barriers, readiness, and programmatic needs to support coronavirus disease 2019 (COVID-19) vaccine uptake among people who use drugs. METHODS: We conducted an exploratory qualitative study, leveraging an existing sample of SSPs in the United States. Semistructured, in-depth interviews were conducted with SSP staff between February and April 2021. Interviews were analyzed using a Rapid Assessment Process, an intensive, iterative process that allows for rapid analysis of time-sensitive qualitative data. RESULTS: Twenty-seven SSPs completed a qualitative interview. Many SSP respondents discussed that COVID-19 vaccination was not a priority for their participants because of competing survival priorities, and respondents shared concerns that COVID-19 had deepened participant mistrust of health care. Most SSPs wanted to participate in COVID-19 vaccination efforts; however, they identified needed resources, including adequate space, personnel, and training, to implement successful vaccine programs. CONCLUSIONS: Although SSPs are trusted resources for people who use drugs, many require additional structural and personnel support to address barriers to COVID-19 vaccination among their participants. Funding and supporting SSPs in the provision of COVID-19 prevention education and direct vaccine services should be a top public health priority.

Availability of and Obstacles to Providing COVID-19 Vaccinations at Syringe Services Programs in the United States, 2021.

Many syringe services programs (SSPs) have established trusting, long-term relationships with their clients and are well situated to provide COVID-19 vaccinations. We examined characteristics and practices of SSPs in the United States that reported providing COVID-19 vaccinations to their clients and obstacles to vaccinating people who inject drugs (PWID). We surveyed SSPs in September 2021 to examine COVID-19 vaccination practices through a supplement to the 2020 Dave Purchase Memorial survey. Of 153 SSPs surveyed, 73 (47.7%) responded to the supplement; 24 of 73 (32.9%) reported providing on-site COVID-19 vaccinations. Having provided hepatitis and influenza vaccinations was significantly associated with providing COVID-19 vaccinations (70.8% had provided them vs 28.6% had not; P = .002). Obstacles to providing vaccination included lack of appropriate facilities, lack of funding, lack of trained staff, and vaccine hesitancy among PWID. SSPs are underused as vaccination providers. Many SSPs are well situated to provide COVID-19 vaccinations to PWID, and greater use of SSPs as vaccination providers is needed.

Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Importance: In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients. Objective: To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up. Design, Setting, and Participants: This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data. Exposures: CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant. Main Outcomes and Measures: Composite of ventricular arrhythmic events and composite of heart failure events. Results: Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF. Conclusions and Relevance: This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

Barriers to engaging people who use drugs in harm reduction services during the COVID-19 pandemic: A mixed methods study of syringe services program perspectives.

BACKGROUND: Syringe services programs (SSPs) provide critical evidence-based public health services that decrease harms from drug use for people who use drugs (PWUD). Many SSPs have experienced significant and evolving COVID-19-related disruptions. We aimed to characterize the impacts of COVID-19 on SSP operations in the United States approximately one year into the pandemic. METHODS: Participating sites, selected from a national sample of SSPs, completed a semi-structured interview via teleconference and brief survey evaluating the impacts of COVID-19 on program operations. Data collection explored aspects of program financing, service delivery approaches, linkages to care, and perspectives on engaging PWUD in services one year into the pandemic. Interview data were analyzed qualitatively using Rapid Assessment Process. Survey data were analyzed using descriptive statistics and triangulated with qualitative findings. RESULTS: 27 SSPs completed study-related interviews and surveys between February 2021 - April 2021. One year into the pandemic, SSPs reported continuing to adapt approaches to syringe distribution in response to COVID-19, and identified multiple barriers that hindered their ability to engage program participants in services, including 1) isolation and decreased connectivity with participants, 2) resource restrictions that limit responsiveness to participant needs, 3) reduced capacity to provide on-site HIV/HCV testing and treatment linkages, and 4) changing OUD treatment modalities that were a "double-edged sword" for PWUD. Quantitative survey responses aligned with qualitative findings, highlighting increases in the number of syringes distributed, increases in mobile and home delivery services, and reductions in on-site HIV and HCV testing. CONCLUSION: These data illuminate persistent and cascading risks of isolation, reduced access to services, and limited engagement with program participants that resulted from COVID-19 and continue to create barriers to the delivery of critical harm reduction services. Findings emphasize the need to ensure SSPs have the resources and capacity to adapt to changing public health needs, particularly as the COVID-19 pandemic continues to evolve.

Neural Signatures of Pain Modulation in Short-Term and Long-Term Mindfulness Training: A Randomized Active-Control Trial.

OBJECTIVE: Mindfulness-based interventions are widely used to target pain, yet their neural mechanisms of action are insufficiently understood. The authors studied neural and subjective pain response in a randomized active-control trial of mindfulness-based stress reduction (MBSR) alongside long-term meditation practitioners. METHODS: Healthy participants (N=115) underwent functional neuroimaging during a thermal acute pain task before and after random assignment to MBSR (N=28), an active control condition (health enhancement program [HEP]) (N=32), or a waiting list control condition (N=31). Long-term meditators (N=30) completed the same neuroimaging paradigm. Pain response was measured via self-reported intensity and unpleasantness, and neurally via two multivoxel machine-learning-derived signatures: the neurologic pain signature (NPS), emphasizing nociceptive pain processing, and the stimulus intensity independent pain signature-1 (SIIPS1), emphasizing stimulus-independent neuromodulatory processes. RESULTS: The MBSR group showed a significant decrease in NPS response relative to the HEP group (Cohen's d=-0.43) and from pre- to postintervention assessment (d=-0.47). The MBSR group showed small, marginal decreases in NPS relative to the waiting list group (d=-0.36), and in SIIPS1 relative to both groups (HEP group, d=-0.37; waiting list group, d=-0.37). In subjective unpleasantness, the MBSR and HEP groups also showed modest significant reductions compared with the waiting list group (d=-0.45 and d=-0.55). Long-term meditators reported significantly lower pain than nonmeditators but did not differ in neural response. Within the long-term meditator group, cumulative practice during intensive retreat was significantly associated with reduced SIIPS1 (r=-0.65), whereas daily practice was not. CONCLUSIONS: Mindfulness training showed associations with pain reduction that implicate differing neural pathways depending on extent and context of practice. Use of neural pain signatures in randomized trials offers promise for guiding the application of mindfulness interventions to pain treatment.

Responding to a surge in overdose deaths: perspectives from US syringe services programs.

BACKGROUND: US overdose deaths have reached a record high. Syringe services programs (SSPs) play a critical role in addressing this crisis by providing multiple services to people who use drugs (PWUD) that help prevent overdose death. This study examined the perspectives of leadership and staff from a geographically diverse sample of US SSPs on factors contributing to the overdose surge, their organization's response, and ongoing barriers to preventing overdose death. METHODS: From 2/11/2021 to 4/23/2021, we conducted semi-structured interviews with leadership and staff from 27 SSPs sampled from the North American Syringe Exchange Network directory. Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process. RESULTS: Respondents reported that increased intentional and unintentional fentanyl use (both alone and combined with other substances) was a major driver of the overdose surge. They also described how the COVID-19 pandemic increased solitary drug use and led to abrupt increases in use due to life disruptions and worsened mental health among PWUD. In response to this surge, SSPs have increased naloxone distribution, including providing more doses per person and expanding distribution to people using non-opioid drugs. They are also adapting overdose prevention education to increase awareness of fentanyl risks, including for people using non-opioid drugs. Some are distributing fentanyl test strips, though a few respondents expressed doubts about strips' effectiveness in reducing overdose harms. Some SSPs are expanding education and naloxone training/distribution in the broader community, beyond PWUD and their friends/family. Respondents described several ongoing barriers to preventing overdose death, including not reaching certain groups at risk of overdose (PWUD who do not inject, PWUD experiencing homelessness, and PWUD of color), an inconsistent naloxone supply and lack of access to intranasal naloxone in particular, inadequate funding, underestimates of overdoses, legal/policy barriers, and community stigma. CONCLUSIONS: SSPs remain essential in preventing overdose deaths amid record numbers likely driven by increased fentanyl use and COVID-19-related impacts. These findings can inform efforts to support SSPs in this work. In the face of ongoing barriers, support for SSPs-including increased resources, political support, and community partnership-is urgently needed to address the worsening overdose crisis.

Detection of cell-cell interactions via photocatalytic cell tagging.

The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies leveraging therapeutic-based modalities to profile intercellular environments offer opportunities to study cell-cell interactions with molecular-level insight. We introduce photocatalytic cell tagging (PhoTag) for interrogating cell-cell interactions using single-domain antibodies (VHHs) conjugated to photoactivatable flavin-based cofactors. Following irradiation with visible light, the flavin photocatalyst generates phenoxy radical tags for targeted labeling. Using this technology, we demonstrate selective synaptic labeling across the PD-1/PD-L1 axis in antigen-presenting cell-T cell systems. In combination with multiomics single-cell sequencing, we monitored interactions between peripheral blood mononuclear cells and Raji PD-L1 B cells, revealing differences in transient interactions with specific T cell subtypes. The utility of PhoTag in capturing cell-cell interactions will enable detailed profiling of intercellular communication across different biological systems.

Toward a Theory of the Underpinnings and Vulnerabilities of Structural Racism: Looking Upstream from Disease Inequities among People Who Use Drugs.

Structural racism is increasingly recognized as a key driver of health inequities and other adverse outcomes. This paper focuses on structural racism as an "upstream" institutionalized process, how it creates health inequities and how structural racism persists in spite of generations of efforts to end it. So far, "downstream" efforts to reduce these health inequities have had little success in eliminating them. Here, we attempt to increase public health awareness of structural racism and its institutionalization and sociopolitical supports so that research and action can address them. This paper presents both a theoretic and an analytic approach to how structural racism contributes to disproportionate rates of HIV/AIDS and related diseases among oppressed populations. We first discuss differences in disease and health outcomes among people who use drugs (PWUD) and other groups at risk for HIV from different racial and ethnic populations. The paper then briefly analyzes the history of racism; how racial oppression, class, gender and other intersectional divisions interact to create health inequities; and how structural racism is institutionalized in ways that contribute to disease disparities among people who use drugs and other people. It examines the processes, institutions and other structures that reinforce structural racism, and how these, combined with processes that normalize racism, serve as barriers to efforts to counter and dismantle the structural racism that Black, indigenous and Latinx people have confronted for centuries. Finally, we discuss the implications of this analysis for public health research and action to undo racism and to enhance the health of populations who have suffered lifetimes of racial/ethnic oppression, with a focus on HIV/AIDS outcomes.