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Patients With Bw4 and Bw6 Antibodies Can Participate in Clinical Xenotransplantation Trials
No full textWith clinical xenotransplantation now underway, optimal patient selection is critical for achieving successful outcomes. Candidates with antibodies targeting Bw4 and Bw6 epitopes on HLA molecules often experience prolonged wait times for allotransplantation because of high calculated panel reactive antibody levels. We investigated whether these antibodies cross-react with class I swine leukocyte antigen (SLA) molecules and could therefore pose a barrier to xenotransplantation.
We performed sequence alignment and structural modeling to assess the presence of Bw4 and Bw6 epitopes in class I SLA proteins. Human sera containing anti-Bw4 or anti-Bw6 antibodies were tested for reactivity against SLA molecules encoded by 5 haplotypes from pigs we study in xenotransplantation. Genetically engineered pig renal endothelial cells and a prototype panel of SLA-coated beads served as antigenic targets in flow cytometry assays.
Structural analysis confirmed the absence of Bw4 and the presence of modified Bw6 motifs in SLA molecules. Despite the potential epitope conservation, anti-Bw6 sera showed no significant IgG binding to SLA, possibly because of residues adjacent to the canonical epitope. One anti-Bw4 patient showed IgG reactivity to SLA alleles lacking Bw4 or Bw6, implicating a distinct epitope. IgM reactivity was broadly observed across sera.
These findings indicate that the SLA of at least some pigs will not exhibit cross-reactivity with anti-Bw4 and anti-Bw6 antibodies. Incorporating detailed, epitope-level histocompatibility testing may allow these highly sensitized patients, access to xenotransplantation
Neonatal Mimicry of Caregivers at Home: Feasibility of an Asynchronous Online Paradigm
No full textWhile early life sets the stage for later learning, comparatively less is known about newborns' cognition than that of older infants. A striking example is the lack of consensus regarding the extent to which newborns spontaneously mimic gestures, and whether such behavior drives bonding and learning. Despite the theoretical importance of these questions, practical challenges limit researchers' ability to engage newborns in behavioral research. Webcam-based, asynchronous online studies have expanded developmental science's capacity to reach older infants. However, such scalable and replicable methods have yet to be deployed with younger infants. Taking a commonly-used neonatal mimicry paradigm as a test case, we assessed the feasibility of leveraging an open-source online platform (Children Helping Science) for asynchronous research with 0-6-week-olds and their caregivers. Caregivers modeled face movements to their 4-45 days-old infants (N = 29, N = 17 included) while webcams filmed their infants' responses; 13 dyads participated more than once (72 included test videos). Preliminary evidence suggested that infants do not mimic caregivers' tongue protrusions (Bayes Factor ∼ ⅓). Data on the mimicry of caregivers' mouth openings was inconclusive (⅓ < BF < 3). Additional analyses identified a target sample size for future studies. Finally, we asked whether caregivers perceived their newborns' behavior as imitative. Caregivers' perceptions of mimicry reflected infants' behaviors but did not align with an often-used metric of mimicry ("imitators"). These results demonstrate the feasibility of asynchronous online behavioral studies with newborns and provide a foundation for future research on neonatal mimicry of caregivers
Variations in Managing Acute Spinal Cord Injury in the North American Clinical Trials Network and Partner Institutes
No full textStudy DesignSurvey based study.ObjectivesTo evaluate current patterns for managing SCI among spine surgeons in North America.MethodsA survey of the North American Clinical Trials Network (NACTN) and other institutions collected institutional demographics and specific practices on acute SCI management. Variables included trauma level designation, annual case volumes (patient number, spine fracture and surgery performed), steroid usage, emergent cervical traction, magnetic resonance imaging (MRI) access, surgical decompression timing, intraoperative ultrasound and neuromonitoring use, mean arterial pressure (MAP) and spinal cord perfusion pressure (SCPP) targets, lumbar drain use, and the influence of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade on decision-making.ResultsThirty surgeons from 23 institutions responded (93.3% Level 1 trauma centers). Most centers (93.3%) had immediate MRI access; about 70% of physicians did not use steroids. Emergent cervical traction was used by 60%. An aim of surgical decompression within 24 h was reported by 90%, with 20% operating immediately upon arrival. MAP goals were used by 93.3%, most targeting 85-90 mmHg for ≥5 days. Lumbar drains for SCPP optimization were used in 30%, typically targeting intrathecal pressure (ITP) 60 mmHg. Management varied by AIS grade in 43.4%.ConclusionDespite agreement in the general scope of acute SCI care, significant implementation heterogeneity exists across North American spine centers. Variability was pronounced in steroid use, timing of decompression (90% within 24 h), cervical traction, and lumbar drain utilization. These findings call for evidence-based protocols to guide acute SCI management and reduce inter-institutional practice variation
Diabetic Retinopathy as a Risk Factor for Ocular Hypertension or Primary Open-Angle Glaucoma in a United States-based Cohort Study
No full textAssess the association between diabetic retinopathy (DR) and the risk of ocular hypertension (OHT) or primary open-angle glaucoma (POAG) in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM).
This retrospective cohort study utilized the TriNetX US Collaborative Network, including 166,471 patients with T1DM and 5,745,652 patients with T2DM, categorized by DR status, ages ≥ 18 years. International Classification of Diseases 10th Revision (ICD-10) codes identified T1DM, T2DM, and DR. Propensity score matching (PSM) adjusted for age, sex, race/ethnicity, body mass index (BMI), relevant medical history, blood markers, glycemic-controlling medications, intravitreal injections, and ophthalmic service visits. The primary outcome was the development of coded OHT or POAG over 10 years and lifetime, expressed as adjusted hazard ratios (aHR).
DM patients with DR exhibited a significantly heightened risk of developing coded OHT or POAG. T1DM patients showed a 4.966 fold increased lifetime risk of developing OHT (95% confidence interval (CI): 2.178-11.325) and 4.262 fold increased lifetime risk of developing POAG (95% CI: 1.435-13.255), while T2DM patients had a 2.651 fold increased lifetime risk of developing OHT (95% CI: 2.412-2.915) and 2.62 fold POAG (95% CI: 2.37-2.89). This risk remained high in our sub-analysis, and patients with PDR were at a higher risk compared to those with any stage of NPDR. Sensitivity analyses confirmed these findings across various demographic and clinical variables.
DR is significantly associated with OHT and POAG, particularly in T1DM. These findings emphasize the need for vigilant screening and comprehensive management of diabetic patients with coexisting DR.
Diabetic retinopathy in diabetic patients significantly increases the risk of ocular hypertension and primary open angle glaucoma, with the highest risk in type 1 diabetics as high as 5-fold compared to those without diabetic retinopathy
9 - Peripheral T-Cell Lymphomas
No full textPeripheral T-cell lymphoma (PTCL) remains one of the most challenging areas of hematopathology practice. This is partly due to the overall rarity of these neoplasms but also due to the complexity of the underlying biology as well as the marked heterogeneity of their clinical, phenotypic, and genetic features. Recent developments in classification of lymphoid neoplasms, outlined in the Preface to the Mature Lymphoid Proliferations, offer a blueprint for clinical practice and will be used as a template to address this complex area. For ease of use, this chapter is divided into six sections, each addressing distinct thematically related topics. These include (1) nodal follicular TCLs, (2) anaplastic large cell lymphoma, (3) PTCL, not otherwise specified, (4) intestinal and hepatosplenic TCL, (5) Epstein-Barr virus–associated natural killer (NK) and TCLs, and (6) cutaneous TCLs. Mature T-cell and NK-cell neoplasms with primarily leukemic presentation are discussed separately
Differential socioeconomic, psychosocial, and behavioral factors associated with psychological distress and uncontrolled blood pressure among women with and without HIV in the US
No full textIntroductionWomen with HIV (WWH) have a higher risk of hypertension compared to women without HIV (WWoH). Exposure to adverse socioeconomic (e.g., area level deprivation) and psychosocial factors (e.g., stigma, inadequate social support) may contribute to inequities in hypertension through their influence on health behaviors (e.g., substance use, diet, physical activity) and psychophysiological (e.g., stress) responses.MethodsWe examined the association between socioeconomic and psychosocial factors, psychological distress, and current uncontrolled blood pressure among WWH ( n =998) and WWoH ( n =353) enrolled in the Women’s Interagency HIV Study (WIHS) at a single visit between April and September 2019.ResultsSocioeconomic and psychosocial factors were similar among WWH and WWoH. Among WWH and WWOH, 50.2% had current uncontrolled blood pressure, defined as a systolic blood pressure ≥130 mmHg or diastolic pressure ≥ 80 mmHg at the time of the study visit. Among WWH, socioeconomic, psychosocial, and behavioral factors explained 3% of the variance in blood pressure with self-reported health risk behaviors ( r =0.15), and use of antihypertensive medication ( r =0.09) had weak to moderate impact. Among WWoH, socioeconomic, psychosocial, and behavioral factors explained 10% of the variance in blood pressure, with self-reported health risk behaviors ( r =0.19), use of antihypertensive medication ( r =0.19), area-level social vulnerability ( r =-0.17), and social support ( r =0.16) demonstrating weak to moderate impacts.DiscussionTailored interventions that address socioeconomic and psychosocial stressors at the individual and societal levels may improve outcomes and reduce disparities in uncontrolled blood pressure
P-293. A Qualitative Exploration of the Acceptability of Long-Acting PrEP among Haitians/Haitian Americans and Community Leaders
No full textBackground Pre-exposure prophylaxis (PrEP) to prevent HIV, is effective and widely available in oral form, and increasingly in long-acting injectable (LAI) form, but there are disparities in use. Haitians and Haitian Americans in South Florida are disproportionately affected by HIV and have low uptake of HIV prevention modalities due to factors like stigma, low education, and access. Despite LAI PrEP (Cabotegravir) being approved in 2021, the use is low, and little is known about how this form compares to other existing modalities. This study provides insights on barriers to LAI PrEP among Haitians and Haitian Americans. Methods We conducted semi-structured qualitative interviews in Miami, Florida, with 15 leaders in the Haitian community (e.g., nurse practitioners, pharmacists, psychologists, etc.) and 15 Haitian community members. Interviews occurred from August – November 2024 in partnership with the Community Health and Empowerment Network. Results We interviewed 21 women and 9 men with an average age of 39 years. About 93% of community members were aware of PrEP and most preferred the LAI form. Three primary themes emerged: 1) conflicting views among interviewees about the role of stigma. Community leaders believed that stigma would strongly limit individuals’ willingness to take LAI PrEP, however, community members expressed autonomy in health decisions and prioritized health over social judgment; 2) community members expressed a preference for LAI PrEP over the oral form; 3) community members expressed primary barriers were access and education rather than medical mistrust and/or stigma. Conclusion There are discrepancies in levels of stigma that may be influencing the use of LAI PrEP between community members and leaders in the Haitian community. Community members preferred the LAI PrEP and emphasized practical challenges over social concerns. To increase LAI PrEP uptake among Haitians, the approach should be multi-pronged and focused on addressing access and education gaps. Disclosures Maria L. Alcaide, MD, Gilead: Advisor/Consultan
Electronic Cigarette Use and Risk of Hypertension: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
No full textAcute increases in blood pressure (BP) after electronic cigarette (e-cigarette) use have been reported, but its long-term association with hypertension is unclear.The purpose of this study was to assess whether e-cigarette use is associated with prevalent and incident hypertension.We analyzed visit 2 (2014-2017) and visit 3 (2020-2024) data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a population-based cohort study including 11,623 individuals aged 18 to 74 years across 4 U.S. communities. The primary exposure was ever e-cigarette use at visit 2. We also explored current use and dual use with combustible cigarette use. Hypertension was defined as measured BP ≥ 140/90 mm Hg or self-reported antihypertensive medication use. Multivariable Poisson and Cox regression were used for prevalent and incident hypertension, respectively. Longitudinal BP change from visit 2 to 3 was assessed using mixed-effects models. All analyses accounted for the complex survey design.Of 11,593 participants with e-cigarette data (mean age 47 years; 52.2% female), 937 reported ever use (136 current users). Ever vs never e-cigarette use was not associated with prevalent hypertension. Over a median follow-up of 6.0 years, 1,409 participants developed hypertension. Ever vs never e-cigarette use was associated with incident hypertension (HR: 1.49; 95% CI: 1.14-1.95), as were current use (HR: 1.89; 95% CI: 1.12-3.18), former use (HR: 1.43; 95% CI: 1.07-1.93), and dual ever use (HR: 1.85; 95% CI: 1.37-2.49), compared to never use. Longitudinal BP change did not differ by e-cigarette use.Ever e-cigarette use was associated with increased risk of incident hypertension, suggesting potential long-term cardiovascular harm
P-859. Seeing Beyond the Culture: Smarter UTI Diagnosis in Spinal Cord Injury Patients
No full textBackground Diagnosing urinary tract infections (UTIs) in individuals with spinal cord injury (SCI) presents unique challenges due to atypical clinical presentations, which stem from altered sensation and varied bladder management strategies. This population also faces disproportionately high rates of asymptomatic bacteriuria (ASB) and multidrug-resistant organisms (MDROs), largely due to frequent bladder instrumentation, colonization, and repeated antimicrobial exposure. As a result, UTIs are often misdiagnosed or overtreated, leading to unnecessary antimicrobial use and increased risk of resistance. Improving diagnostic accuracy and antimicrobial stewardship is therefore crucial in the SCI population. Methods This quality improvement project was implemented in three phases starting July 2024: (1) baseline assessment of UC and antimicrobial prescribing practices, (2) introduction of a standardized UC order set in the electronic medical record (Figure 1) with provider education, and (3) post-intervention monitoring of diagnostic and prescribing patterns. Results Following the July 2024 intervention, adherence to the UC order set among SCI providers reached 93.8%. There was a notable reduction in the number of urine cultures ordered. Although a higher number of UTI cases were identified in newly admitted patients, there was also a significant increase in interventions to tailor antimicrobial therapy based on culture results, indicating improved alignment with diagnostic findings. Additionally, fewer ASB cases were treated with antimicrobials, suggesting improved clinician awareness and adherence to stewardship principles following the educational component. Please see Tables 1 and 2 to appreciate our results. Conclusion The implementation of a standardized urine culture order set, coupled with targeted provider training, led to improved diagnostic practices and more judicious antimicrobial use in the SCI unit at the Miami VAMC. These findings underscore the importance of combining system-level interventions with clinician education to enhance UTI diagnosis and treatment in complex patient populations. Disclosures All Authors: No reported disclosure
Dialysis modality and mortality of the Contemporary Infant and Neonatal Dialysis (COINED) Cohort: a Pediatric Nephrology Research Consortium (PNRC) study
No full textRecent technologic advances in neonatal dialysis have changed current dialysis practices. The goal of this study was to define demographics, diagnoses, initial dialysis modality, modality changes, and outcomes of neonates receiving dialysis.
Retrospective, multicenter cohort of neonates (≤ 30 days of age) from 26 U.S. centers, who received dialysis between 6/2017 and 5/2022. Measures of central tendency were calculated to describe the cohort stratified by the primary dialysis-related diagnosis including acute kidney injury requiring dialysis (AKI-D), stage 5 chronic kidney disease (CKD 5), hyperammonemia, and other causes. The primary outcome was death during the initial hospitalization.
For the 405 neonates in this cohort, AKI-D (57%) was the most common dialysis-related diagnosis, followed by CKD 5 (29%) and hyperammonemia (11%). Most neonates (58%) had a birth weight between 2500 and 3500 g. The most common initial neonatal dialysis modality was continuous kidney replacement therapy (CKRT) with (35%) or without extracorporeal membrane oxygenation (ECMO) (36%). Only 26% of neonates received peritoneal dialysis (PD) as their initial dialysis modality. Thirty percent of neonates received more than one dialysis modality. The overall mortality was 50% (59% in AKI-D and 41% in CKD 5). Withdrawal of care was reported as the most common reason for death. The odds of death were lower for neonates with AKI-D receiving PD as the initial modality when compared to CKRT (aOR 0.28, 95% CI 0.09-0.84) or CKRT with ECMO (aOR 0.24, 95% CI 0.10-0.58), but this association was not seen in neonates with CKD 5.
This multicenter, contemporary neonatal dialysis cohort shows increased use of CKRT as the initial dialysis modality but also shows that the mortality of neonates on dialysis remains high. Additional studies on modern neonatal dialysis are needed