Midkine is upregulated in the hippocampus following both spatial and olfactory reward association learning and enhances memory.

Hippocampal neuronal plasticity is a fundamental process underpinning learning and memory formation and requiring elaborate molecular mechanisms that result in the dynamic remodelling of synaptic connectivity. The neurotrophic properties of midkine (Mdk) have been implicated in the development and repair of the nervous system, while Mdk knockout resulted in deficits in the formation of certain types of memory. The role of Mdk in the process of memory-associated neuronal plasticity, however, remains poorly understood. We investigated the learning-induced regulation of Mdk in spatial navigation and association learning using the water maze and the odour reward association learning paradigms, characterising a temporal profile of Mdk protein expression post-learning. Both learning events revealed similar patterns of upregulation of expression of the protein in the rat hippocampal dentate gyrus, which were rapid and transient. Moreover, administration of recombinant Mdk during the endogenous Mdk upregulation following learning enhanced memory in the water maze task revealing a pro-cognitive action of Mdk. We further show that, within the adult hippocampus, Mdk mRNA is predominantly expressed in granular and pyramidal neurons and that hippocampal neuronal Mdk expression is regulated by the canonical plasticity-associated neurotransmitter glutamate. Finally, we confirm that the positive action of Mdk on neurite outgrowth previously noted in cortical and cerebellar neurons extends to hippocampal neurons. Together, our findings suggest a role for Mdk in glutamate-mediated hippocampal neuronal plasticity important for long-term memory consolidation.

Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression.

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.

Gender Minority Stress, Resilience, and Psychological Distress: The Role of Resilience Among Transgender and Gender Diverse Youth.

Purpose: Gender minority (GM) stress, resulting from distal (i.e., external) and proximal (i.e., internal) stigma-based stressors, is thought to drive mental health disparities among transgender and gender diverse (TGD) youth. We tested the gender minority stress and resilience (GMSR) model hypotheses that distal GM stress effects on mental health are partially mediated by proximal GM stress and moderated by GM-specific resilience (i.e., community connectedness, identity pride) among a U.S. national sample of TGD youth. Methods: As part of an HIV prevention study (NCT03185975), 159 TGD youth (ages 15-24) completed an online survey that included the GMSR measure, assessing distal and proximal GM stress and GM resilience, and the 18-item Brief Symptom Inventory, assessing past-7-day psychological distress. Three models linking GMSR constructs to psychological distress were tested using PROCESS v4.0: (1) simple partial mediation, (2) moderated partial mediation, and (3) serial partial mediation. Results: A direct effect of distal GM stress was observed in all models. An indirect effect through proximal GM stress alone was observed in model 1, but not models 2 or 3. In model 2, resilience did not moderate the effects of distal or proximal GM stress. In model 3, indirect effects were observed through proximal GM stress and GM resilience serially as well as GM resilience alone. Conclusion: Larger prospective studies are needed to confirm the role of GM resilience as a mediator, rather than moderator, of GM stress effects on mental health and a critical, rather than supplementary, target for mental health intervention among TGD youth.

Factors associated with favourable pathological tumour response after neoadjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma.

INTRODUCTION: Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) has been associated with oncological outcome. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatic resection for PDAC. METHODS: Patients who received NAT before undergoing PDAC resection at two institutions were reviewed. Tumour regression grading (TRG) was scored according to the College of American Pathologists (CAP) system. Interactions between chemotherapy, tumour and surgical factors with TRG were explored. RESULTS: 54 patients were identified, with 12 (22%) displaying a favourable response to NAT. The type of chemotherapy agent received, the number of cycles or a dose reduction during NAT course was not significantly different between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. A favourable TRG was associated with greater disease-free survival median 33.2 months vs. 10.3 months; p = 0.0) but not overall survival (median 43.8 months vs. 32.3 months; p = 0.200), which may be due to small sample size. CONCLUSIONS: Chemotherapy factors were not significantly related to a favourable response to NAT. Future studies should seek to identify modifiable factors associated with a favourable TRG.

Assessing the association between necrotizing enterocolitis and the type of initial central venous access in preterm infants.

AIM: Umbilical venous catheters (UVC) have been associated with an increased risk of necrotizing enterocolitis (NEC). We aimed to assess the relationship between the type of initial central venous access in preterm infants and NEC. METHODS: Using the Canadian Neonatal Network database, we identified preterm infants <30 weeks gestation born between 2014 and 2021 in one of 32 participating centres who had a peripherally inserted central catheter (PICC) as initial vascular access. These infants were matched in a 1:1 ratio based on gestational age, sex and birth weight to infants in two other groups: (i) those who initially had an UVC and (ii) those who had an UVC followed by a PICC. RESULTS: A total of 497 infants were included in this study: 165 in the PICC group, 164 in the UVC group and 165 in the UVC + PICC group. There was no association between the type of initial central venous access and NEC. CONCLUSION: Although this retrospective study did not find an association between the type of initial central venous access and NEC, larger prospective studies are required to evaluate this association.

A Web-Based Antiretroviral Therapy Adherence Intervention (Thrive With Me) in a Community-Recruited Sample of Sexual Minority Men Living With HIV: Results of a Randomized Controlled Study.

BACKGROUND: Most new HIV infections are attributed to male-to-male sexual contact in the United States. However, only two-thirds of sexual minority men living with HIV achieve an undetectable viral load (UVL). We tested a web-based antiretroviral therapy adherence intervention called Thrive with Me (TWM) with core features that included medication self-monitoring and feedback, HIV and antiretroviral therapy information, and a peer-to-peer exchange. OBJECTIVE: We assessed the efficacy of TWM on HIV UVL among adult (aged ≥18 years) sexual minority men. Moreover, we assessed the impact of overall engagement and engagement with specific intervention features on HIV UVL. METHODS: In total, 401 sexual minority men (mean age 39.1, SD 10.8 y; 230/384, 59.9% African American) in New York City were recruited between October 2016 and December 2019 and randomized to receive TWM (intervention) or a weekly email newsletter (control) for 5 months. Computerized assessments occurred at baseline and months 5, 11, and 17. The primary outcome was a dichotomous measure of HIV UVL (≤20 copies/µL). Generalized estimating equations with robust SEs were used to assess the effect of the TWM intervention on HIV UVL over the follow-up period in an unadjusted model and a model adjusted for baseline differences and then stratified by baseline recent drug use urinalysis. In secondary analyses, generalized linear models were used to estimate risk differences in the association of overall engagement with TWM (the sum of the number of days participants accessed ≥1 screen of the TWM intervention out of a possible 150 days) and engagement with specific TWM components on HIV UVL throughout the 17-month intervention period. RESULTS: Participant retention was 88.5% (355/401; month 5), 81.8% (328/401; month 11), and 80.3% (322/401; month 17). No consistent differences in HIV UVL were found between those randomized to receive TWM or the control at the 5- (difference-in-differences [DD]=-7.8, 95% CI -21.1 to 5.5), 11- (DD=-13.9, 95% CI -27.7 to 0.04), or 17-month (DD=-8.2, 95% CI -22.0 to 5.7) time points, or when stratified by baseline recent drug use. However, those TWM-assigned participants with high overall levels of engagement (in the upper 25th percentile) were more likely to have an HIV UVL at the end of the 5-month active intervention period compared to those with low engagement (below the 75th percentile; risk difference=17.8, 95% CI 2.5-33.0) or no engagement (risk difference=19.4, 95% CI 3.3-35.5) in the intervention. Moreover, high engagement with the peer-to-peer exchange was associated with HIV UVL over time in unadjusted models. CONCLUSIONS: TWM did not have overall impacts on HIV UVL; however, it may assist some sexual minority men who are highly engaged with this web-based intervention in achieving HIV viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT02704208; https://clinicaltrials.gov/study/NCT02704208.

Transperineal vs Transrectal Prostate Biopsy-The PREVENT Randomized Clinical Trial.

This randomized clinical trial compares the effect of transperineal vs transrectal prostate biopsy on infection rates after biopsy.

Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy.

BACKGROUND: The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse. AIM: To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement. METHODS: A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected. RESULTS: Twelve studies were included. The definition of "unresectable" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively. CONCLUSION: Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network® criteria for pancreatic ductal adenocarcinoma.

A Possible Nocebo Effect in Children Following the Flint Water Crisis: Evidence From Schoolteacher Perceptions and Neuropsychological Evaluations.

OBJECTIVE: Special education enrollment increased in Flint following the 2014-2015 Flint Water Crisis, but lead exposure is not plausibly responsible. Labeling Flint children as lead poisoned and/or brain damaged may have contributed to rising special education needs (ie, nocebo effect). To better document this possibility, we surveyed schoolteachers and reviewed neuropsychological assessments of children for indications of negative labeling. METHODS: A survey of Flint and Detroit (control) public schoolteachers using a modified Illness Perception Questionnaire was conducted 5 years post-crisis. We also examined neuropsychological assessments from a recently settled class lawsuit. RESULTS: Relative to Detroit (n = 24), Flint teachers (n = 11) believed that a higher proportion of their students had harmful lead exposure (91.8% Flint vs 46% Detroit; P = 0.00034), were lead poisoned (51.3% vs 24.3%; P = 0.018), or brain damaged (28.8% vs 12.9%; P = 0.1), even though blood lead of Flint children was always less than half of that of Detroit children. Neuropsychological assessments diagnosed lead poisoning and/or brain damage from water lead exposure in all tested children (n = 8), even though none had evidence of elevated blood lead and a majority had prior learning disability diagnoses. CONCLUSION: Teachers' responses and neuropsychological assessments suggest Flint children were harmed by a nocebo effect.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM: This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS: A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS: 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION: SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

Integrating Emotional Health Assessments into Pediatric Care: Initial Learnings from an MOC Part 4 Activity.

Introduction: Living with a chronic condition often impacts the emotional health of children. Pediatricians frequently feel unprepared to address these concerns. The American Board of Pediatrics Roadmap Project aims to support these clinicians. We describe the results from the initial cohort of pediatricians who completed the American Board of Pediatrics Maintenance of Certification (MOC) Roadmap Part 4 activity. Methods: The Roadmap MOC activity uses a standardized improvement template with accompanying resources to guide participants. Physicians self-assess their ability to provide emotional health support by completing a Roadmap Readiness Checklist and creating a personal project relevant to their practice. They collect data at three time points: baseline, midpoint, and completion for two measures (the Readiness Checklist and a participant-selected measure). Physicians also reflect on their experience. Results: Of the initial cohort of 29 physicians, 22 submitted three sequential checklist assessments. Scores increased for "developing a family resource list" (by 90%), "confidence to address emotional health" (79%), "having a family crisis plan" (78%), and "staff awareness" (34%). Twenty-four physicians who measured whether clinical encounters addressed emotional health documented an increase from 21% to 77%. Physician feedback was positive, for example, "This project has had a profound impact on our care of children." Conclusions: This initial cohort of participants improved on the Readiness Checklist and emotional health assessment. Both generalist and subspecialty pediatricians found the activity useful and relevant, suggesting that this MOC Part 4 activity is a feasible resource for supporting physicians in addressing emotional health.

The potential clinical utility of an artificial intelligence model for identification of vertebral compression fractures in chest radiographs.

PURPOSE: To assess the ability of the Annalise Enterprise CXR Triage Trauma artificial intelligence model to identify vertebral compression fractures on chest radiographs and its potential to address undiagnosed osteoporosis and its treatment. MATERIALS AND METHODS: This retrospective study used a consecutive cohort of 596 chest radiographs from four U.S. hospitals between 2015 and 2021. Each radiograph included both frontal (anteroposterior or posteroanterior) and lateral projections. These radiographs were assessed for the presence of vertebral compression fracture in a consensus manner by up to three thoracic radiologists. The model then performed inference on the cases. A chart review was also performed for the presence of osteoporosis-related ICD-10 diagnostic codes and medication use for the study period and an additional year of follow up. RESULTS: The model successfully completed inference on 595 cases (99.8%); these cases included 272 positive cases and 323 negative cases. The model performed with area under the receiver operating characteristic curve of 0.955 (95% CI: 0.939 to 0.968), sensitivity 89.3% (95% CI: 85.7 to 92.7%) and specificity 89.2% (95% CI: 85.4 to 92.3%). Out of the 236 true-positive cases (i.e., correctly identified vertebral compression fractures by the model) with available chart information, only 86 (36.4%) had a diagnosis of vertebral compression fracture and 140 (59.3%) had a diagnosis of either osteoporosis or osteopenia; only 78 (33.1%) were receiving a disease modifying medication for osteoporosis. CONCLUSION: The model identified vertebral compression fracture accurately with a sensitivity 89.3% (95% CI: 85.7 to 92.7%) and specificity of 89.2% (95% CI: 85.4 to 92.3%). Its automated use could help identify patients who have undiagnosed osteoporosis and who may benefit from taking disease modifying medications.

Technology-Based Interventions, with a Stepped Care Approach, for Reducing Sexual Risk Behaviors and Increasing PrEP Initiation Among Transgender and Gender Expansive Youth and Young Adults.

TechStep was a technology-based trial, with a stepped care approach, to reduce sexual risks and increase PrEP uptake among transgender and gender expansive youth and young adults (15-24 years old). From October 2019 to September 2021, 254 participants were randomized into: 1) Text (n = 82), or 2) Webapp (n = 87), or 3) Control (n = 85). At the 3-month follow-up assessment, those randomized to Text and Webapp and did not demonstrate improvement on primary outcomes were re-randomized to receive virtual eCoaching (Text + or Webapp +), or to remain in their initial condition without eCoaching. Results showed no effect on condomless encounters at 6-month, the primary endpoint, when comparing the Webapp + (0.33 decrease; 95%CI: -0.01, 0.67, p-value = 0.057) or the Text + (0.27 decrease; 95%CI: -0.13, 0.68, p-value = 0.181) conditions to the Control condition. However, in secondary analyses, condomless encounters were significantly reduced for Text compared to Control. The rate of PrEP uptake was low for all study arms.Trial registration: Clinical Trials # NCT04000724 (registered June 26, 2019).

Outcome of Minimally Invasive and Open Pancreatoduodenectomy in Patients with Intestinal- and Pancreatobiliary Subtype Ampullary Cancer: An International Multicenter Cohort Study.

OBJECTIVE: To compare minimally invasive and open pancreatoduodenectomy in different subtypes of ampullary adenocarcinoma. SUMMARY BACKGROUND DATA: Ampullary adenocarcinoma (AAC) is widely seen as the best indication for minimally invasive pancreatoduodenectomy (MIPD) due to the lack of vascular involvement and dilated bile and pancreatic duct. However, it is unknown whether outcomes of MIPD for AAC differ between the pancreatobiliary (AAC-PB) and intestinal (AAC-IT) subtypes as large studies are lacking. METHODS: This is an international cohort study, encompassing 27 centers from 12 countries. Outcome of MIPD and open pancreatoduodenectomy (OPD) were compared in patients with AAC-IT and AAC-PB. Primary end points were R1 rate, lymph node yield, and 5-year overall survival (5yOS). RESULTS: Overall, 1187 patients after MIPD for AAC were included, of whom 572 with AAC-IT (62 MIPD, 510 OPD) and 615 with AAC-PB (41 MIPD and 574 OPD). The rate of R1 resection was not significantly different between MIPD and OPD for both AAC-IT (3.4% vs 6.9%, P=0,425) and AAC-PB (9.8% vs 14.9%, P=0,625). AAC-IT, more lymph nodes were resected with MIPD group (19 vs 16, P=0.007), compared to OPD. The 5y-OS did not differ after MIPD and OPD for both AAC-IT (56.8% vs 59.5%, P=0.827 and AAC-PB (52.5% vs 44.4%, P=0.357). The rates of surgical complication between MIPD and OPD did not differ between AmpIT and AmpPB. DISCUSSION: This international multicenter study found no differences in outcomes between MIPD and OPD for AAC-IT and AAC-PB. MIPD and OPD demonstrated comparable outcomes in oncological resection, survival and surgical outcomes for both subtypes of AAC.

Perspectives and Factors Related to Pre-exposure Prophylaxis Use Among Young Men Who Have Sex With Men in the United States: A Mixed-Methods Study on the Role of History of PrEP Use.

ABSTRACT: This study quantitatively examined factors related to young men who have sex with men (YMSM)'s decisions to use pre-exposure prophylaxis (PrEP) by their history of PrEP use and qualitatively elicited their perspectives on PrEP options. Higher proportions of YMSM who had never used (vs. ever used) PrEP considered the following factors as important in their decisions to use PrEP: (a) Returning to PrEP follow-up visits (p = .02), (b) having to talk about sex/PrEP with providers (p = .013), (c) people assuming they are infected with HIV (p = .021), (d) family finding out about their PrEP use (p = .001), and (e) friends finding out about their PrEP use (p = .008). Through inductive content analysis, qualitative data showed that a higher proportion of YMSM who had never used PrEP (vs. ever used) expressed concerns about HIV stigma from nonaffirming health care providers and the potential risk of inadvertently revealing their LGBTQ+ identity to others, which were described as potential barriers to PrEP use. Overall, our findings suggest that future interventions may consider tailoring PrEP messaging to YMSM's history of PrEP use, which may ultimately increase PrEP uptake and adherence.

Analysis of Gout Remission Definitions in a Randomized Controlled Trial of Colchicine Prophylaxis for People With Gout Initiating Allopurinol.

OBJECTIVE: To investigate (1) the effect of colchicine prophylaxis on gout remission when commencing urate-lowering therapy (ULT), and (2) illness perceptions of people in remission using 2 definitions of gout remission. METHODS: Data from a 12-month double-blind placebo-controlled trial of 200 people with gout commencing allopurinol were analyzed. Participants were randomly assigned to prophylaxis with 0.5 mg daily colchicine or placebo for 6 months, followed by 6 months of additional follow-up. Gout remission was assessed using the 2016 preliminary definition or simplified definition without patient-reported outcomes. Illness perceptions were assessed using a gout-specific version of the Brief Illness Perception Questionnaire. RESULTS: In the first 6 months, few participants were in remission according to either the 2016 preliminary definition (3% for colchicine and 4% for placebo) or the simplified definition (7% for colchicine and 12% for placebo). In the second 6 months, after study drug (colchicine or placebo) discontinuation, fewer participants in the colchicine group than in the placebo group were in remission according to the 2016 preliminary definition (4% vs 14%, P = 0.03), and the simplified definition (14% vs 28%, P = 0.02). Participants fulfilling remission using either definition had more favorable perceptions about their gout symptoms and illness concerns, as well as consequences, when using the simplified definition. CONCLUSION: Using either definition, 6 months of colchicine prophylaxis when initiating ULT does not provide an advantage in the fulfillment of gout remission. People fulfilling either definition report fewer symptoms, less concern about their gout, and, when using the simplified definition, are less affected by gout.

Hif-2α programs oxygen chemosensitivity in chromaffin cells.

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia-inducible transcription factor (HIF), HIF-2α, as having a nonredundant role in the development and function of that organ. Here, we show that activation of HIF-2α, including isolated overexpression of HIF-2α but not HIF-1α, is sufficient to induce oxygen chemosensitivity in adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues resembling the fetal organ of Zuckerkandl, which also manifests oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of gene classes that are ordinarily characteristic of the carotid body, including G protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2α acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking 2 major oxygen-sensing systems.

Early Detection of Heart Failure with Autonomous AI-Based Model Using Chest Radiographs: A Multicenter Study.

The opportunistic use of radiological examinations for disease detection can potentially enable timely management. We assessed if an index created by an AI software to quantify chest radiography (CXR) findings associated with heart failure (HF) could distinguish between patients who would develop HF or not within a year of the examination. Our multicenter retrospective study included patients who underwent CXR without an HF diagnosis. We included 1117 patients (age 67.6 ± 13 years; m:f 487:630) that underwent CXR. A total of 413 patients had the CXR image taken within one year of their HF diagnosis. The rest (n = 704) were patients without an HF diagnosis after the examination date. All CXR images were processed with the model (qXR-HF, Qure.AI) to obtain information on cardiac silhouette, pleural effusion, and the index. We calculated the accuracy, sensitivity, specificity, and area under the curve (AUC) of the index to distinguish patients who developed HF within a year of the CXR and those who did not. We report an AUC of 0.798 (95%CI 0.77-0.82), accuracy of 0.73, sensitivity of 0.81, and specificity of 0.68 for the overall AI performance. AI AUCs by lead time to diagnosis (<3 months: 0.85; 4-6 months: 0.82; 7-9 months: 0.75; 10-12 months: 0.71), accuracy (0.68-0.72), and specificity (0.68) remained stable. Our results support the ongoing investigation efforts for opportunistic screening in radiology.

Challenges and Opportunities with at-Home Blood Collection for HIV-1 Viral Load Monitoring among Sexual Minoritized Men who use Stimulants.

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10-71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume.