Prior Pilot Study Research Articles

P1201 Pre- and postnatal metal exposures impact Crohn’s Disease risk and intestinal inflammation in an analysis of deciduous teeth

Abstract Background Early-life exposures influence long-term health, including the risk of IBD, however measuring these exposures is challenging. A prior pilot study showed that deciduous teeth could quantify environmental exposures. Here we analyzed essential and toxic metals in baby teeth to explore their impact on Crohn’s Disease (CD) risk during pre- and early postnatal periods. Methods We obtained deciduous teeth from 2 cohorts:1) individuals with CD and controls who had their baby teeth stored (IBD Tooth Fairy Study), and 2) offspring of women with and without IBD, followed since birth (MECONIUM Study). Essential [magnesium, calcium, chromium, manganese, cobalt, nickel, copper, zinc, molybdenum] and non-essential [lithium, aluminum, arsenic, strontium, cadmium, tin, lead, bismuth] metals were measured using laser ablation-inductively coupled plasma mass spectrometry. Teeth neonatal line was used as a reference to differentiate pre- and postnatal exposures. Data were analyzed using metal-to-calcium ratios to evaluate metal content variations over time. Weighted quantile regression analyses determined the relationship between metal mixtures (essential and non-essential) pre- and postnatally with incident CD (IBD Tooth Fairy Study) and with fecal calprotectin (Fcal) level at 2 years of age (MECONIUM Study). Results Sixty teeth were analyzed from the IBD Tooth Fairy cohort (27 CD, mean age at diagnosis 17y (range 5-32); 33 controls; mean age at recruitment 21.6y (range 7-48). Pre- and postnatal mixture of essential metals was associated with lower adjusted odds ratio (aOR) of CD, with manganese as the primary contributor (aOR [95%CI]: 0.51 [0.28, 0.91] and 0.69 [0.43, 1.12], respectively). Conversely, a mixture of non-essential metals was linked to increased odds of CD, with cadmium as the main contributor (aOR [95%CI]: 3.23 [1.11, 9.41] and 2.46 [1.24, 4.88], respectively) (Figure 1A). From the MECONIUM Study, 29 teeth were analyzed (6, 6, and 17 from offspring of women with CD, UC, and controls, respectively). Median Fcal (mcg/gm) at age 2 years was 243.5 in offspring of women with IBD and 111 in offspring of women without IBD. A mixture of essential metals (pre- and postnatal) was associated with lower Fcal levels at age 2 years, with manganese being the highest contributor in both periods (Figure 1B). Conclusion Pre- and postnatal exposures to essential and non-essential metals, measured in baby teeth, were associated with the risk of developing CD and higher Fcal levels in babies at risk for IBD, with manganese being the top contributor in both cohorts. Future research should expand these findings and explore the mechanistic pathways through which these exposures affect IBD risk.

The effect of mindfulness-based cognitive therapy on PTSD and depression symptoms in trauma-exposed black adults: Pilot randomized controlled trial results

Low-income, urban-dwelling Black adults are disproportionately affected by traumatic experiences, posttraumatic stress disorder (PTSD), and depression and encounter inequities in treatment access. In addition to the benefits Mindfulness-Based Cognitive Therapy (MBCT) for depression, there is preliminary evidence of successful symptom reduction in PTSD via MBCT across two prior pilot studies in veterans. Studies examining the effects of MBCT among trauma-exposed Black adults remains limited, and examination of effects across specific PTSD clusters is almost nonexistent. We examined the preliminary efficacy of adapted MBCT versus waitlist control (WLC) on PTSD and depression symptoms in a pilot randomized controlled trial (RCT). Black adults (N = 80; 86.10 % women) with repeated trauma exposure, who screened positive for PTSD and depression, were recruited from an urban public hospital and randomized to 8-week adapted MBCT or WLC. Symptoms were measured pretreatment and posttreatment with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Beck Depression Inventory-II (BDI-II). Mixed model analyses were conducted with an intent-to-treat approach, examining change in PTSD and depression scores between MBCT and WLC over time. There was no significant difference in total PTSD and depression symptom change between MBCT and WLC. CAPS-5 avoidance symptoms showed a nominally significant decrease in the MBCT group (F[1, 68.10] = 5.98, p = .017; t[71.60] = 3.61, p < .001). Findings suggest MBCT might be helpful for addressing avoidance symptoms among Black adults with comorbid PTSD and depression. Although lacking power to draw final conclusions about treatment efficacy, this study provides preliminary data suggesting the importance of future fully powered trials.

Relationship Marketing and Customer Loyalty among Deposit-Taking SACCOS in Western Kenya

Deposit-taking Savings and Credit Cooperative Societies (SACCOS) in Kenya have faced significant challenges due to intense competition and declining customer numbers, which underscores the need for further investigation into relationship marketing strategies. A key research gap is the role of digital platforms in moderating the effectiveness of these strategies and their impact on customer loyalty. This study aimed to evaluate how digital platforms influence the relationship between relationship marketing (RM) and customer loyalty among SACCOs in Western Kenya. Using Relationship Commitment, Social Exchange, and Commitment Trust theories, the research focused on 23 SACCOs with 37,137 customers and surveyed 396 respondents, including prior pilot study. Descriptive and correlational research designs were used, with data collected via self-administered questionnaires and systematic sampling. Analysis with SPSS assessed validity and reliability, employing descriptive statistics and inferential methods such as Pearson’s Correlation, Simple Linear Regression, and Hierarchical Regression Analysis. Assumption tests confirmed that the research data met normality, linearity, homoscedasticity, and multicollinearity criteria, with a response rate of 87.63% and significant correlations (p&lt;0.05) among variables. Digital Platforms were found to contribute significant moderating role on the link between Relationship Management and Customer Loyalty (p&lt;0.05), emphasizing features like interactivity, personalization, and trustworthiness. The results suggest that in order to enhance customer experience, SACCOs should allocate resources towards the development of user-friendly digital platforms, utilize data analytics in targeted marketing efforts, so as to enhance engagement with the community via online channels. Moreover, it is crucial for SACCOs to prioritize personalized service, establish trust, and strive for continuous improvement, while taking into account regulatory revisions, in order to maximize the effectiveness of digital platforms within the financial sector.

Gulf War Illness Is Associated with Host Gut Microbiome Dysbiosis and Is Linked to Altered Species Abundance in Veterans from the BBRAIN Cohort.

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron, Bacteroides fragilis, and Lachnospiraceae genera and increase in Blautia, Streptococcus, Klebsiella, and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.

(145) TRANSDERMAL APPLICATION OF H100™ GEL TO THE PENILE SHAFT IN PATIENTS WITH PEYRONIE’S DISEASE INFILTRATES THE TUNICA ALBUGINEA

Abstract Introduction Noninvasive treatment options for Peyronie’s disease (PD) remain limited. Topical H100™ gel (Hybrid Medical, Edina, USA) which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind, placebo- controlled pilot study. Objective The present study evaluates if topically applied H100™ gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100™ and serves as a surrogate marker. Methods 3 men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100™ gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid- chromatograph-mass spectrometry (LCMS). Results All 3 patients tolerated H100™ gel application without side effects. All 3 tunica albuginea specimens showed detectable nicardipine in the tunica tissue. Conclusions Transdermal application of commercially available H100™ gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100™ pilot study. Disclosure Yes, this is sponsored by industry/sponsor: Hybrid Medical. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Hybrid Medical.

Learning about science topics of social relevance using lower and higher autonomy-supportive scaffolds

Evaluation of plausible alternative explanations of scientific phenomena is an authentic scientific activity. Instructional scaffolding can facilitate students’ engagement in such evaluations by facilitating their reflections on how well various lines of scientific evidence support alternative explanations. In the present study, we examined two forms of such scaffolding, with one form providing more autonomy support than the other, to determine whether any differential effects existed between the two. Nearly 300 adolescent students in middle school, high school, and university courses completed two activities on scientific topics of social relevance (e.g., the climate crisis, fossils and fossil fuel use, water resources, and astronomical origins), with the less autonomy-supportive form being completed prior to the more autonomy-supportive form. In line with prior pilot studies, both scaffold types demonstrated significant pre- to post-instructional shifts in plausibility judgments toward the scientific model and gains in knowledge with small to medium effect sizes. A mediation model provided a robust replication of previous findings showing that the indirect path meaningfully linked greater levels of evaluation to more scientific plausibility judgments and topic knowledge, above and beyond the direct relational path linking greater levels of evaluation to topic knowledge. However, we found no difference in relations between the two scaffold types, counter to our hypothesis that the more autonomy-supportive version would lead to better outcomes. This suggests that the implementation of more autonomy-supportive learning environments may be conditional, opening up a promising avenue for additional research, such as looking at specific contexts and how activities could be sequenced to optimize learning.

A novel MRI-based tumor-targeting theragnostic agent: Magnetoelectric nanoparticles in an in vivo murine KRAS/P53 pancreatic flank tumor model.

3075 Background: Magnetoelectric nanoparticles (MENPs) are a novel material with a magnetoelectric (ME) property that allows for conversion of an external magnetic field to a local electric field (EF) that can be exploited to generate a Coulomb force to target and electroporate the relatively non-polarized tumor cell walls. We hypothesized that their local EF and superparamagnetic cores can be exploited as an MRI-based anti-cancer theragnostic agent for solid tumors. Methods: 35 immunocompetent C57BL/6 mice were inoculated with KPC961 pancreatic adenocarcinoma cells in their flank. The 27 mice with the largest tumors at 4 weeks were randomized into 5 cohorts based on treatment: 300 µg of MENP (300; n=6), 600 µg of MENP (600; n=6), 300 µg of low-ME coefficient MENP (LM; n=5), 300 µg of MENP without M1 MRI (NM; MRI field control, n=5), and normal saline (NS; MENP causal effect control; n=5). The 300, 600, LM, and NS cohorts had T2 MRI maps (M0) on a 7T MRI. NM had T2 weighted MRIs at M0. All mice had a neodymium magnet placed over their tumors for 12 hours after tail vein injections (300 µl for all mice) for targeting. The 300, 600, LM, and NS cohorts then underwent MRI mapping (M1) after magnet removal (No M1 MRI for NM). MRI mapping was repeated 5 days after (M2). NM had a T2 weighted MRIs at M2. M1 and M2 data were used to assess relaxation time (contrast effect) and tumor volume from M0, respectively. Student t and ANOVA tests were used to compare differences for tumor volume and relaxation time data and one-sided Fisher’s exact test was used for complete response (CR) data. Results: The median M0 tumor volume was 109.6 mm3 for all mice, and there were no differences between any cohort ( p = 0.978; Table). The 300 and 600 MENP cohorts demonstrated a 102.7% reduction in volume (M2/M0; 56.7% vs. 159.4% for NS and NM controls, p = &lt;0.001) and a 7.2% T2 negative contrast effect (M1/M0; 94.2% vs. 101.3% for NS, p = 0.046) compared to controls. Six mice in 300, 600, and LM (2 each) achieved a clinical CR (between 1 to 2 weeks after M1) vs. none in the NS and NM control cohorts ( p = 0.0418), without any recurrences until end of study (6 weeks after M2). Conclusions: This is the first report demonstrating the theragnostic effects of MENPs having both T2 contrast and locally ablative therapy properties as an in vivo tumor targeting agent. These results confirm prior pilot study and point towards irreversible electroporation as the likely mechanism of action (MOA) since the antitumor effect is not seen within the NM cohort. Additional studies characterizing the MOA, dose-response relationships, and immunomodulatory effects are needed to better understand their full clinical potential.[Table: see text]

Human Fc gamma receptor IIIA blockade inhibits platelet destruction in a humanized murine model of ITP

AbstractFc gamma receptor (FcγR) IIIA is an important receptor for immunoglobulin G (IgG) and is involved in immune defense mechanisms as well as tissue destruction in some autoimmune diseases including immune thrombocytopenia (ITP). FcγRIIIA on macrophages can trigger phagocytosis of IgG-sensitized platelets, and prior pilot studies observed blockade of FcγRIIIA increased platelet counts in patients with ITP. Unfortunately, although blockade of FcγRIIIA in patients with ITP increased platelet counts, its engagement by the blocking antibody drove serious adverse inflammatory reactions. These adverse events were postulated to originate from the antibody’s Fc and/or bivalent nature. The blockade of human FcγRIIIA in vivo with a monovalent construct lacking an active Fc region has not yet been achieved. To effectively block FcγRIIIA in vivo, we developed a high affinity monovalent single-chain variable fragment (scFv) that can bind and block human FcγRIIIA. This scFv (17C02) was expressed in 3 formats: a monovalent fusion protein with albumin, a 1-armed human IgG1 antibody, and a standard bivalent mouse (IgG2a) antibody. Both monovalent formats were effective in preventing phagocytosis of ITP serum–sensitized human platelets. In vivo studies using FcγR-humanized mice demonstrated that both monovalent therapeutics were also able to increase platelet counts. The monovalent albumin fusion protein did not have adverse event activity as assessed by changes in body temperature, whereas the 1-armed antibody induced some changes in body temperature even though the Fc region function was impaired by the Leu234Ala and Leu235Ala mutations. These data demonstrate that monovalent blockade of human FcγRIIIA in vivo can potentially be a therapeutic strategy for patients with ITP.

Transdermal application of H100 gel to the penile shaft in patients with Peyronie's disease infiltrates the tunica albuginea.

Treatment options for Peyronie's disease (PD) remain limited. Topical H100 gel, (Hybrid Medical, Edina, USA), which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind placebo-controlled pilot study. The present study evaluates if topically applied H100 gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100 and serves as a surrogate marker. Three men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100 gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid-chromatograph-mass spectrometry (LCMS). All three patients tolerated H100 gel application without side effects. All three tunica albuginea specimens showed detectable nicardipine in the tunical tissue. Transdermal application of commercially available H100 gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100 pilot study.

Community Informed Recruitment: A Promising Method to Enhance Clinical Trial Participation.

Low recruitment rates in palliative care clinical trials amongst Black and rural individuals have been attributed to lack of trust and procedural barriers. Community engagement strategies have increased clinical trial participation of under-represented populations. Describe a successful community-engaged recruitment strategy in an ongoing multi-site randomized clinical trial (RCT). Using community-based participatory research principles and input from a prior pilot study's community advisory group (CAG), we designed a novel recruitment strategy for Community Tele-Pal, a three-site, culturally based palliative care tele-consult RCT for Black and White seriously ill inpatients and their family caregivers. Local site CAGs helped design and implement a recruitment strategy in which a CAG member accompanied the study coordinators to introduce the study to eligible patients. Initially, CAG members could not accompany study coordinators in person due to pandemic restrictions. Hence, they created videos of themselves introducing the study, just as they would have done in person. We examined outcomes to date by the three recruitment methods and race. Of the 2879 patients screened, 228 were eligible and approached. Overall, the proportions of patients who consented 102 (44.7%) vs. not consented 126 (55.3%) were similar by race- White (consented= 75 [44.1%]) vs; Black (consented=27 [46.6%]). Proportionally, consent rates favored CAG-involved methods: coordinator only- 47 approached and 13 (12.7%) consented vs. coordinator/CAG video-105 approached and 60 (58.8%) consented. A novel community-enhanced recruitment strategy demonstrated the potential to increase clinical trial participation from historically under-represented populations.

Efficacy of combination lurbinectedin (LURBI) + doxorubicin (DOX) from the phase 1B soft-tissue sarcoma (STS) lead-in to a randomized phase 2 trial in leiomyosarcoma (LMS).

11507 Background: Single agent or combination chemotherapy, typically Dox- or gemcitabine-based, are standard 1st- and 2nd-line therapies in patients (pts) with metastatic LMS; however, objective response rates (ORR), progression-free, and overall survival (PFS/OS) remain inadequate. Lurbi (PharmaMar S.A. / Jazz Pharmaceuticals) binds to DNA inhibiting transcription and inducing double strand breaks leading to apoptosis and delaying S/G2 progression. In a prior pilot study, we showed Lurbi+Dox is well-tolerated, with signs of activity, particularly in LMS. We designed this phase 1b to optimize dosing to lead into a randomized (1:1) phase 2 trial of Dox+/-Lurbi in anthracycline-naïve LMS. Herein we provide updated efficacy and tolerability data for this Phase 1b cohort. Methods: Pts &gt; 18 yrs with locally advanced/metastatic, unresectable non-GIST STS (Phase 1b only) w/o prior anthracycline or Lurbi/trabectedin, ECOG PS &lt; 3, RECIST 1.1 measurable, and normal organ function were eligible. The phase 1b followed a 3+3 design. Dosing included fixed Lurbi (3.2 mg/m2 d1) with two Dox dose levels (DL; DL1: 25 mg/m2 d1; DL2 25 mg/m2 d1+8). All pts received GCSF prophylaxis. Tumor assessments were every 2 cycles. DL1 was chosen as RP2D and the phase 2 trial began accrual in Aug 2022 aiming to enroll 50 LMS pts randomized 1:1 (stratified by uterine LMS [uLMS]] v. other LMS) with PFS as primary endpoint. Pts progressing on Dox are allowed to cross to Lurbi monotherapy. Results: 10 patients were enrolled in Phase 1b. Histologies included 5 LMS (4 uLMS) and 1 each of myxofibrosarcoma (myxFS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), endometrial stromal sarcoma (ESS), and solitary fibrous tumor (SFT). With a median follow-up of 344 days, 5/10 pts remain on treatment with median PFS of 357 days (95%CI 175-ND). 6 pts demonstrated partial response (PR; 5 confirmed), 3 with stable disease (SD), and 1 with progressive disease (PD, Table). Median time to PR was 81 days (range 46-207). Duration of response was over 132 days in all responders with 3 still on treatment. Treatment-related AEs were typical for Dox/Lurbi, including nausea, fatigue, and reversible LFT elevations/cytopenias. Updated safety and response data will be provided at the time of the meeting. Conclusions: Lurbi+Dox is well-tolerated with efficacy in STS including 6/10 pts achieving PR, 9/10 pts staying on treatment for &gt;120d, and 6/10 pts &gt;200d. The randomized phase 2 study is currently enrolling. Clinical trial information: NCT05099666 . [Table: see text]

Excitation Transfer Between Sexual Arousal and Other Emotions: Study Protocol

Background: Sexual deviance is regarded as an important risk factor for sexual offending. However, little is known about the development of deviant sexual interests. The transfer of arousal between emotions, i.e., excitation transfer, could attribute sexual salience to stimuli that would otherwise not be sexual in nature. As such, excitation transfer could contribute to the very beginning of unusual or deviant sexual interests. The current protocol proposes a study to investigate to what extent excitation transfer occurs, i.e., to what extent genital and subjective sexual arousal to sexual stimuli is higher in an emotional state than in a neutral state. Following a prior pilot study, several adjustments were made to the study protocol, including a stronger emotional manipulation by using 360-degree film clips and the inclusion of a larger and more sexually diverse sample. Methods: We will recruit 50 adult male volunteers with diverse sexual interests. We will induce sexual arousal in four different emotional states (aggression/dominance, endearment, fear, disgust) and a neutral state. Sexual arousal will be measured genitally using penile plethysmography and subjectively via self-report. Using paired samples t-tests, sexual arousal in the emotional states will be compared with sexual arousal in the neutral state. Discussion: We aim to show that arousal in response to emotional stimuli that are initially nonsexual in nature, can enhance sexual arousal. These findings have potentially important implications for the development of unusual and/or deviant sexual interests and possibly for the treatment of such sexual deviant interests in people who have committed sexual offenses.

Microbial Changes in Response to a Plant-Based Diet and/or Supplements in SMM Patients: A National Multi-Arm Randomized Prospective Telehealth Study Via Healthtree: The Nutrition Prevention (NUTRIVENTION-2) Study

Background and Scientific Rationale: Multiple myeloma (MM) is often preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the current standard of care for MGUS and SMM is observation. Studies have found that patients with plasma cell disorders have gut dysbiosis. Plant-based diets, probiotics, omega 3, and curcumin supplements have previously been shown to alter the gut microbiome and increase stool butyrate. Butyrate is a short-chain fatty acid (SCFA) that inhibits histone deacetylases and NF-κB resulting in reduced formation of pro-inflammatory cytokines. It, therefore, has anti-cancer and anti-inflammatory properties. Therefore, a dietary/supplement intervention will be studied in patients with SMM. This is a two-week randomized study to evaluate the effects of a whole-food plant-based diet (WFPBD), probiotics, omega 3, and curcumin supplements on the gut microbiome and stool butyrate levels compared to baseline in SMM patients. This study builds on our prior NUTRIVENTION pilot study (NCT04920084). To our knowledge, this is the first telehealth national nutrition intervention study design with a microbiome endpoint. Study Design and Methods: This is a randomized, non-blinded, telehealth-based, remote, national pilot study with 100 patients in 4 arms (25 per arm) in partnership with HealthTree Foundation (Figure 1). Randomization will be stratified based on BMI (normal/elevated). Study Population: 100 SMM patients over the age of 18 years will be enrolled and randomized to one of four arms (25 patients per arm). Inclusion Criteria:ECOG performance status 0-3Willingness to comply with studyInterested in learning to cook plant-based recipesAccess to smart mobile phone or deviceBe residing within the United States for the study duration Exclusion Criteria:Supplement intake (other than those needed for a medical indication) must be reviewed by PI before enrollment. If patient is on a supplement (including curcumin, probiotic, omega 3) they must stop these for 2 weeks prior to enrollment on study.Legume allergySevere allergies such as anaphylactic shock to peanutsConcurrent participation in weight loss/dietary trials or defined programs (that require specified diets/supplements) Study Treatment: Patients will be randomized to one of four arms and will receive a whole-foods plant-based diet with nutrition counseling (via Plantable) or probiotics (via Vita Miracle) or omega-3 (via QWell pharmaceuticals) or curcumin (via Sabinsa pharmaceuticals) supplements twice daily for 2 weeks (Figure 1). The supplements will be provided through the WellRabbit platform. Data on dietary intake will be collected for all participants using a dietary monitoring app, Keenoa. Dietary adherence will be assessed by a research dietitian. Patients will participate in study visits remotely. Objectives: PrimaryEvaluate change in stool butyrate levels on a plant-based diet, curcumin, omega 3, and probiotic intervention at 2 weeks when compared to baseline. Secondary and Exploratory objectives include change in stool butyrate at 1 week, compliance at 2 weeks, baseline dietary patterns, other changes in the gut microbiome, and racial differences in the microbiome. Statistical Methods: The primary endpoint is change in stool butyrate levels at 2 weeks when compared to baseline (average of -1- and 0-week samples). Based on previous and internal studies, we expect the study to be adequately powered to detect a difference of ≥20% from baseline to the end of the intervention. We will call the intervention promising if we detect an increase in stool butyrate levels at 2 weeks (i.e., one-sided p-value <0.05) when compared with baseline. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Echocardiographic pattern of left ventricular function recovery in tachycardia-induced cardiomyopathy patients

Abstract Background Tachycardia-induced Cardiomyopathy (TIC) represents a reversible type of cardiomyopathy (CM) that is underdiagnosed. Prior pilot studies suggested a specific left ventricular (LV) function recovery pattern in TIC patients. Cardiac chamber remodeling in TIC, however, remains incompletely understood. Purpose We aimed to explore differences in LV dimensions and functional recovery in TIC patients when compared to a control group of patients with other forms of CM and functional recovery. Methods We identified patients with reduced left ventricular ejection fraction (≤50%) and/or atrial fibrillation or flutter treated between 2015 and 2022. Patients had at least two serial transthoracic echocardiographies (TTE). The minimal interval between the TTEs had to be at least 3 months, and the left ventricular ejection fraction (LVEF) had to either improve (≥15% in absolute value) or normalize (LVEF at follow-up ≥50%). Patients were then divided into two groups: A) patients with atrial fibrillation or atrial flutter at baseline and sinus rhythm at follow-up. These patients were assumed to have TIC. B) Patients with sinus rhythm at both baseline and follow-up, consisting of patients with other forms of CM. The change in ventricular dimensions and function (indexed left ventricular end-systolic – LVESDI, end-diastolic diameters – LVEDDI – and volumes – LVEDVI, LVEF, and fractional shortening – FS) were compared within and across group A and B at baseline and at follow-up. The groups were compared using Kruskal (for independent data) and Wilcoxon (for paired data) tests. A p&amp;lt;0.05 was considered significant. Results A total of 261 patients were included (34% female, median age 68 years). The median time between TTEs was 25 months. 104 (39.8%) patients were considered to suffer from TIC and 157 (60.2%) patients were considered to suffer from other forms of CM. The changes in ventricular dimensions and function in both groups are shown in Figure 1 and Table 1. The TIC group showed no improvement in LVEDVI from baseline to the follow-up examination, while the control group showed significant improvement in LVEDVI (1.7% [−24.7, 22.8] vs. 12.4% [−7.1, 29.3], p=0.008). There was no difference in LVEDDI recovery between TIC and control patients (1.7% [−7.3, 10.3] versus 3.1% [−5.4, 10.2], p=0.578). Conclusions TIC patients have a specific pattern of functional recovery with similar improvements in systolic function and diameters compared with patients with other CMs, while diastolic parameters remained impaired. Funding Acknowledgement Type of funding sources: None.

789O Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study

CSCC is highly immune-responsive; a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC.

A phase 1b lead-in to a randomized phase 2 trial of lurbinectedin plus doxorubicin in leiomyosarcoma (LMS).

TPS11592 Background: Single agent or combination chemotherapy regimens, typically including doxorubicin or gemcitabine, represent standard of care options for first- and second-line therapy in patients (pts) with metastatic LMS. However, response rates (ORR) and progression-free (PFS)/overall survival (OS) remain poor. Lurbinectedin (PharmaMar S.A. and Jazz Pharmaceuticals) uniquely binds DNA, inducing DNA double strand breaks leading to apoptosis and delaying progression through phase S/G2 of the cell cycle. Lurbinectedin is a novel structural analog of trabectedin with improved toxicity profile, potency, and pharmacokinetics. In a prior pilot study, we showed that the combination of lurbinectedin and doxorubicin (L+D) was safe, with early signs of clinical activity, particularly in LMS. Thus, we designed this investigator-initiated/investigator-sponsored phase 1b lead-in to optimize doses of L+D, to be followed by a randomized (1:1) phase 2 study of L+D versus doxorubicin monotherapy in anthracycline-naïve LMS. Methods: Pts age &gt; 18 years with locally advanced or metastatic, unresectable LMS (non-GIST soft-tissue sarcoma histologies allowed in Phase 1b), without prior anthracycline or lurbinectedin/trabectedin, ECOG PS &lt; 3, measurable disease by RECIST 1.1, and normal organ function, are eligible. Phase 1b dosing will include a fixed dose of lurbinectedin and two dose levels of doxorubicin. The Phase 1b lead-in follows a standard 3+3 design where dose escalation will occur if 0/3 or 1/6 patients experience a dose-limiting toxicity (DLT). Tumor assessments are conducted every two cycles. Once the recommended phase 2 dose (RP2D) is confirmed, Phase 2 will be initiated. Fifty pts will be randomized 1:1 including doxorubicin +/- lurbinectedin. Randomization will be stratified by uterine v. non-uterine origin of LMS. Pts progressing on single agent doxorubicin will be allowed to cross over to lurbinectedin monotherapy. The Phase 2 primary endpoint is PFS. Secondary endpoints include disease control rate, ORR, OS, PFS2 (for doxorubicin monotherapy patients who cross to lurbinectedin monotherapy). Archival tumor, germline DNA, and ctDNA will be collected for correlative studies exploring genomic markers of sensitivity/resistance. We will provide respective point estimate along with 90% confidence interval for each of the arms. Log-rank test will be performed to test the difference in survival (both PFS and OS) between groups. Regression analyses of survival data will be based on the Cox proportional hazards model. The first pt in dose-level 1 of the Phase 1b lead-in was enrolled in February 2022. Clinical trial information: NCT05099666.

A Pilot Study of Brief, Stepped Behavioral Activation for Primary Care Patients with Depressive Symptoms.

In a prior pilot study with primary care patients experiencing depressive symptoms, we observed positive outcomes for a behavioral activation protocol involving one visit and three calls. We aimed to pilot test a stepped version with flexible numbers of contacts. Fifteen primary care patients scoring 5–14 on the Patient Health Questionnaire-9 engaged in the three-tiered telephone-based intervention: (1) two calls (15–20 min each); (2) one 30–60 min encounter followed by two calls; and (3) one to six calls. Participants completed assessments at pre-treatment, post-treatment, and three months later. Participants improved from baseline to post-treatment and three months later for depressive symptoms, anxiety symptoms, and disability. Most participants (9 of 15) engaged in the first tier only, averaging less than one hour of contact, and reported benefits and high satisfaction. This intervention showed preliminary evidence of feasibility, acceptability, satisfaction, and benefits, warranting further pilot testing with primary care personnel.

Nature Experiences in Science Education in School: Review Featuring Learning Gains, Investments, and Costs in View of Embodied Cognition

This review examines the didactic use of nature experiences in science education, in primary and secondary school (7–16 years) globally. From the perspective of embodied cognition the review explores the types of nature experiences used in science teaching. Focus is on returns when we invest in nature-based science learning, such as specific academic achievements in the form of long-term effects on learning and memory and how we maximize those returns. The review also addresses challenges and barriers, such as costs and labour involved when using nature experiences in science teaching. Initially, 3,659 articles were selected, with the initial screening leading to the inclusion of 159 studies. Of these articles, 34 studies forming the corpus in this review investigated the effect of using nature experiences as an intervention. These studies are divided into four themes: content understanding, environmental education, teaching scientific methods, and costs and challenges to teaching science outdoors. Informed by the perspective of embodied cognition, the review addresses the returns in terms of learning and academic achievements, the mode of action of the intervention, the investment, costs in the form of labour, challenges, and gaps in the theoretical underpinning of the field. Based on the review, using nature experiences in science education seems promising regarding increasing content knowledge, insight into science methodologies and pro-environmental behaviours. Interventions exploiting the schoolyard, school gardens, or nearby park areas are particularly promising due to the simultaneous strengthening of local engagement at low costs. However, using nature experiences as an alternative to traditional in-class teaching depends on profound didactic deliberations and preparations, which are difficult for the individual teacher to address single-handedly. The review also reveals an urgent need for research that thoroughly explores the connections between teaching practices and theoretical foundations to consolidate the field. To that end, it is noteworthy that a few studies also reported on prior pilot studies demonstrating the need for testing the entire design before conducting the actual research. Teachers seldom experience the opportunity to preview their teaching strategies before performing in front of their students.

Habitat and environmental risks of Chagas disease in low-income colonias and peri-urban subdivisions in South Texas

Both the planning and public health literature have discussed proximity to greenspaces as predominantly beneficial to health, based on studies mostly conducted in high-income regions. Understanding the health risks of proximity to greenspace and nature—where pathogens and wildlife coexist—is important, as nature-based solutions are increasingly called for to address complex urban challenges. This exploratory pilot study bridges planning and epidemiology approaches to develop a new method to analyze habitat and environmental factors associated with the risk of vector-borne Chagas disease in a low-income region, South Texas. Chagas disease is endemic in Latin America, where it affects between seven to eight million people and where environmental factors have been studied to limit the disease's spread. The disease is considered endemic in the southern United States, where little is known about environmental risks. In this pilot study, we developed a new methodology to analyze publicly available habitat and environmental secondary data, which could be used by planning departments. We applied the method to a prior pilot study, which determined a 19.6% prevalence level of T. cruzi (the agent of Chagas disease) among 209 domestic dogs. We geocoded the sample to 100 low-income residential locations, which yielded a 32% positivity rate, and collected secondary data surrounding each location. Logistical regression of factors yielded the following risks: adjacent unconstructed lots, and the presence of four or more dogs in a yard. Based on the results, we formulated vector control-based planning policy recommendations to prevent the spread of the disease.

The Kanyakla study: Randomized controlled trial of a microclinic social network intervention for promoting engagement and retention in HIV care in rural western Kenya

BackgroundExisting social relationships are a potential source of “social capital” that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based ‘microclinic’ intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.MethodsIn nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits (‘time-in-care’). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma.ResultsOf 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61–1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08–0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2–0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17).ConclusionsThe data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care.Trial registrationClinical trial number: NCT02474992.