Selection Of Optimal Candidates Research Articles

A reference framework for extremely metal-poor OB star studies: calibrations for stellar parameters and intrinsic colours

ABSTRACT We provide the first reference framework for extremely metal-poor (XMP) OB-type stars. We parsed a grid of 0.10 $Z_{\odot }$fastwind models, covering the parameter space of O stars and early-B supergiants, through contemporary spectral classification criteria to deliver a calibration of key stellar properties as a function of spectral type, and tabulated colours for the most common photometric systems. By using an extensive grid of models, we account for the different combinations of stellar parameters that result in the same spectral morphology and provide a range of parameters and colours compatible with each spectral subtype and luminosity class. We supply updated photometric criteria to optimize candidate selection of OB stars in XMP environments. We find 0.10 $Z_{\odot }$OB stars are 1–6 kK hotter and produce higher ionizing fluxes than their Galactic analogues. In addition, we find a bimodal distribution of the He ii-ionizing flux with spectral type; because of its known dependence on effective temperature and the wind, log $q_{\mathrm{He II}}$ for individual XMP late-O type stars could be underestimated by up to 4 orders of magnitude by other calibrations, some of them used by population synthesis codes. Finally, we used our calibrated colours to map the extinction of the 0.10 $Z_{\odot }$ galaxy Sextans A finding that reddening is non-negligible and uneven.

Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population-Based, Case-Control Study.

Gastric cancer with liver metastases (GCLM) is a challenging condition that significantly reduces long-term survival rates, but recent advancements in surgical techniques have shown promise. This study aims to comprehensively evaluate the impact of surgical resection on survival rates in GCLM patients. We conducted a population-based analysis utilizing the SEER database for patients diagnosed with GCLM between 2010 and 2015. Overall survival (OS) was compared between patients who underwent cancer-directed surgery (CDS) and those who did not. The overlap weighting method based on lasso regression with penalty factors was employed to minimize selection bias. Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models, with subgroup analyses to further explore the effects of surgery among patients. A total of 3694 patients with GCLM were identified. Of those, 354 (9.58%) patients underwent CDS. After propensity score adjustment, The median OS was significantly higher in the surgical resection group (12 months, 95% confidence interval (CI) 11-16) compared to the nonresection group (6 months, 95% CI: 5-6). Cox regression analysis revealed a substantial improvement in OS for the surgical resection group, with a hazard ratio (HR) of 0.562 (95% CI: 0.482-0.656), including patients with adverse conditions. The analysis demonstrated a clear association between surgical resection and enhanced OS in GCLM patients. Nevertheless, further research endeavors should be undertaken to identify specific prognostic factors that aid in the selection of optimal candidates for surgical resection.

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum

A highly effective vaccine for malaria remains an elusive target, at least in part due to the under-appreciated natural parasite variation. This study aimed to investigate genetic and structural variation, and immune selection of leading malaria vaccine candidates across the Plasmodium falciparum's life cycle. We analysed 325P.falciparum whole genome sequences from Zambia, in addition to 791 genomes from five other African countries available in the MalariaGEN Pf3k Database. Ten vaccine antigens spanning three life-history stages were examined for genetic and structural variations, using population genetics measures, haplotype network analysis, and 3D structure selection analysis. Among the ten antigens analysed, only three in the transmission-blocking vaccine category display P. falciparum 3D7 as the dominant haplotype. The antigens AMA1, CSP, MSP119 and CelTOS, are much more diverse than the other antigens, and their epitope regions are under moderate to strong balancing selection. In contrast, Rh5, a blood stage antigen, displays low diversity yet slightly stronger immune selection in the merozoite-blocking epitope region. Except for CelTOS, the transmission-blocking antigens Pfs25, Pfs48/45, Pfs230, Pfs47, and Pfs28 exhibit minimal diversity and no immune selection in epitopes that induce strain-transcending antibodies, suggesting potential effectiveness of 3D7-based vaccines in blocking transmission. These findings offer valuable insights into the selection of optimal vaccine candidates against P.falciparum. Based on our results, we recommend prioritising conserved merozoite antigens and transmission-blocking antigens. Combining these antigens in multi-stage approaches may be particularly promising for malaria vaccine development initiatives. Purdue Department of Biological Sciences; Puskas Memorial Fellowship; National Institute of Allergy and Infectious Diseases (U19AI089680).

Fractures in Patients With Diabetes Mellitus: Findings From a 20-year Registry at a Single Level 1 Trauma Center.

Diabetes mellitus (DM) is a risk factor of infection. Although DM has been associated with worse functional outcomes after acetabular fracture, literature regarding the effect of DM on surgical site infection and other early complications is lacking. A 20-year registry from a level 1 trauma center was queried to identify 134 patients with DM and 345 nondiabetic patients with acetabular fractures. The diabetic patient population was older (57.2 versus 43.2; P < 0.001) and had higher average body mass index (33.6 versus 29.5; P < 0.001). Eighty-three patients with DM and 270 nondiabetics were treated surgically (62% versus 78%; P < 0.001). Diabetic patients who were younger (54.6 versus 61.4; P = 0.01) with fewer comorbidities (1.7 versus 2.2; P = 0.04) were more frequently managed surgically. On univariate analysis, patients with DM more commonly developed any early infection (28.4% versus 21%; P = 0.049) but were no more likely to develop surgical site infection, or other postoperative complications. Older patient age, length of stay, baseline pulmonary disease, and concurrent abdominal injury were independent predictors of postoperative infection other than surgical site infection. Diabetics that developed infection had more comorbidities (2.4 versus 1.5; P < 0.001) and higher Injury Severity Score (24.1 versus 15.8; P = 0.003), and were more frequently insulin-dependent (72.7% versus 41%; P = 0.01). Independent of management strategy, diabetic patients were more likely to develop an infection after acetabular fracture. Insulin dependence was associated with postoperative infection on univariate analysis. Optimal selection of surgical candidates among patients with DM may limit postoperative infections.

Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model

BackgroundIdentification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid...

MAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production

Vaccines are the main pharmaceutical intervention used against the global public health threat posed by influenza viruses. Timely selection of optimal seed viruses with matched antigenicity between vaccine antigen and circulating viruses and with high yield underscore vaccine efficacy and supply, respectively. Current methods for selecting influenza seed vaccines are labor intensive and time-consuming. Here, we report the Machine-learning Assisted Influenza VaccinE Strain Selection framework, MAIVeSS, that enables streamlined selection of naturally circulating, antigenically matched, and high-yield influenza vaccine strains directly from clinical samples by using molecular signatures of antigenicity and yield to support optimal candidate vaccine virus selection. We apply our framework on publicly available sequences to select A(H1N1)pdm09 vaccine candidates and experimentally confirm that these candidates have optimal antigenicity and growth in cells and eggs. Our framework can potentially reduce the optimal vaccine candidate selection time from months to days and thus facilitate timely supply of seasonal vaccines.

Impact of clinical variables on outcomes in refractory cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation.

In the past two decades, extracorporeal resuscitation (ECPR) has been increasingly used in the management of refractory cardiac arrest (CA) patients. Decision algorithms have been used to guide the care such patients, but the effectiveness of such decision-making tools is not well described. The aim of this study was to compare the rate of survival with a good neurologic outcome of patients treated with ECPR meeting all criteria of a clinical decision-making tool for the initiation of ECPR to those for whom ECPR was implemented outside of the algorithm. All patients who underwent E-CPR between January 2014 and December 2021 at the Montreal Heart Institute were included in this retrospective analysis. We dichotomized the cohort according to adherence or non-adherence with the ECPR decision-making tool, which included the following criteria: age ≤65 years, initial shockable rhythm, no-flow time <5 min, serum lactate <13 mmol/L. Patients were included in the "IN" group when they met all criteria of the decision-making tool and in the "OUT" group when at least one criterion was not met. The primary outcome was survival with intact neurological status at 30 days, defined by a Cerebral Performance Category (CPC) Scale 1 and 2. A total of 41 patients (IN group, n = 11; OUT group, n = 30) were included. A total of 4 (36%) patients met the primary outcome in the IN group and 7 (23%) in the OUT group [odds ratio (OR): 1.88 (95% CI, 0.42-8.34); P = 0.45]. However, survival with a favorable outcome decreased steadily with 2 or more deviations from the decision-making tool [2 deviations: 1 (11%); 3 deviations: 0 (0%)]. Most patients supported with ECPR fell outside of the criteria encompassed in a clinical decision-making tool, which highlights the challenge of optimal selection of ECPR candidates. Survival rate with a good neurologic outcome did not differ between the IN and OUT groups. However, survival with favorable outcome decreased steadily after one deviation from the decision-making tool. More studies are needed to help select proper candidates with refractory CA patients for ECPR.

On the signal combinations for a uniquely decodable coded MIMO-FSO communication system

Our previous works have clarified that exploiting uniquely decodable codes (UDC) can enhance the throughput of M-to-1 free space optical (FSO) systems due to the non-orthogonal property. Considering that multiple-input multiple-output (MIMO) technique can combat fading, this paper expands the original single-receiver case to the case of multiple receivers and establishes a UDC-MIMO-FSO system, aiming at combining the channel capacity gain of UDC with the diversity gain of MIMO. However, owing to the employed UDC codewords, it is discovered that the traditional maximal ratio combining (MRC) becomes no longer optimal. Two combination approaches are proposed in order to obtain better error performance, i.e. the suboptimal maximizing minimum distance combination (MMDC) and the optimal distance-based candidate selection (DBCS), which are verified to outperform traditional benchmarks by simulations. The complexities of the two proposed algorithms are also compared. In addition, we build a 2 × 2 equivalent experiment to further validate the feasibility of the UDC-MIMO-FSO architecture and the effectiveness of the proposed combination algorithms.

Postoperative subphenotypes modified the hepatoma arterial-embolization prognostic score: A novel smHAP-II nomogram.

Background: Three subphenotypes were identified for unresectable hepatocellular carcinoma (uHCC) after frontline transarterial chemoembolization (TACE). This study aimed to develop an individual smHAP-Ⅱ nomogram for uHCC patients after TACE. Methods: Between January 2007 to December 2016, 1517 uHCC patients undergoing TACE were included from four hospitals in China (derivation cohort: 597 cases; validation cohort: 920 cases). Multivariable Cox proportion regression analysis was used to develop a nomogram, incorporating postoperative subphenotypes (Phenotype 1, 2, 3) and HAP score (Score 0 to 4). The model was validated by a 1000-time bootstrap resampling procedure. The performance of the model was compared with existing ones by Harrell's C-index and Area Under Curve (AUC). Results: Postoperative subphenotypes modified the HAP score (smHAP-Ⅱ nomogram) was developed and validated, with the Harrell's C-index of the nomogram was 0.679 (SD: 0.029) for the derivation cohort and 0.727(SD:0.029) for the external cohort. The area under curves of the nomogram for 1-, 3-, and 5-year OS were 0.750, 0.710, and 0.732 for the derivation cohort, respectively (0.789, 0.762, and 0.715 for the external cohort). In the calibration curves stratified by treatment after TACE, the lines for re-TACE and stop-TACE cross at 0.23, indicating that patients with a 3-year predicted survival >23% would not benefit from TACE. Conclusions: The addition of postoperative subphenotypes significantly improved the prognostic performance. The smHAP-Ⅱ nomogram can be used for accurate prognostication and selection of optimal candidates for TACE, with the value to guide sequential treatment strategy.

Multivisceral Resection for Locally Advanced Gastric Cancer: A Systematic Review and Evidence Quality Assessment

Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75–69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99–12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85–12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23–10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection.

A critical appraisal of the four systematic reviews and meta-analysis on stereotactic body radiation therapy versus external beam radiotherapy for painful bone metastases and where we go from here.

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.

Query-based selection of optimal candidates under the Mallows model

We study the secretary problem in which rank-ordered lists are generated by the Mallows model and the goal is to identify the highest ranked candidate through a sequential interview process which does not allow rejected candidates to be revisited. The main difference between our formulation and existing models is that, during the selection process, we are given a fixed number of opportunities to query an infallible expert whether the current candidate is the highest-ranked or not. If the response is positive, the selection process terminates, otherwise, the search continues until a new potentially optimal candidate is identified. Our optimal interview strategy, as well as the expected number of candidates interviewed and expected number of queries used can be determined through the evaluation of well-defined recurrence relations. Specifically, if we are allowed to query s−1 times and to make a final selection without querying (thus, making s selections in total) then the optimum scheme is characterized by s thresholds that depend on the parameter θ of the Mallows distribution but are independent on the maximum number of queries.

Pulmonary Rehabilitation in Persons With COPD.

Pulmonary rehabilitation (PR) is a high-value intervention for persons with COPD and other chronic lung diseases. It is associated with improvement in exercise capacity, dyspnea, health-related quality of life, and depression as well as a reduction in hospitalization and improved survival when PR follows COPD-related hospitalizations. PR is underused in the United States and other countries despite strong evidence of both clinical effectiveness and cost-effectiveness. Additional challenges include a lack of equitable reimbursement and poor access, particularly in rural settings. Models, for example, virtual PR, may be an option for improving access but coverage in the United States by Medicare is tenuous. In addition, virtual PR models have considerable heterogeneity, which challenges uniform efficacy and selection of optimal candidates.

Global Longitudinal Strain Predicts Outcomes in Patients with Reduced Left Ventricular Function Undergoing Transcatheter Edge-to-Edge Mitral Repair.

The timing and selection of optimal candidates for mitral transcatheter edge-to-edge valve repair remains to be fully determined, especially in cases with severely depressed left ventricular ejection fraction (LVEF). The objective of this study is to evaluate the prognostic value of myocardial strain (LVGLS) in this setting. Retrospectively, 172 consecutive patients with LVEF ≤40% and severe MR treated with MitraClip were included. Four groups were generated according to the LVEF (<30% or ≥30%) and median LVGLS. The primary end-point was cardiovascular mortality. Procedural success was high (96.5%) and complications were rare. At one-year follow-up, 82.5% of patients maintained MR grade ≤2, 79.2% were at a NYHA class ≤II and a reduction of 80% in heart failure admissions was observed in all groups. Interestingly, among patients with a more depressed LVEF, LVGLS was found to be an independent predictor for cardiovascular mortality (HR: 3.3; 95% CI: 1.1-10, p = 0.023). Mitral valve repair with MitraClip is safe and it improves the mid-term functional class of patients regardless of LVEF. LVGLS can help in the selection of optimal candidates and timing for this procedure, as well as in the recognition of those patients with worse prognoses.

Molecular Imaging of Myocardial Fibroblast Activation in Patients with Advanced Aortic Stenosis Before Transcatheter Aortic Valve Replacement: A Pilot Study.

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity. Methods: Twenty-three AS patients underwent 68Ga-FAP inhibitor 46 (68Ga-FAPI) PET, cardiac MRI, and echocardiography within 1-3 d before TAVR. Imaging parameters were correlated and then were integrated with clinical and blood biomarkers. Control cohorts of subjects without a history of cardiac disease and with (n = 5) and without (n = 9) arterial hypertension were compared with matched AS subgroups. Results: Myocardial FAP volume varied significantly among AS subjects (range, 1.54-138 cm3, mean ± SD, 42.2 ± 35.6 cm3) and was significantly higher than in controls with (7.42 ± 8.56 cm3, P = 0.007) and without (2.90 ± 6.67 cm3; P < 0.001) hypertension. FAP volume correlated with N-terminal prohormone of brain natriuretic peptide (r = 0.58, P = 0.005), left ventricular ejection fraction (r = -0.58, P = 0.02), mass (r = 0.47, P = 0.03), and global longitudinal strain (r = 0.55, P = 0.01) but not with cardiac MRI T1 (spin-lattice relaxation time) and extracellular volume (P = not statistically significant). In-hospital improvement in left ventricular ejection fraction after TAVR correlated with pre-TAVR FAP volume (r = 0.440, P = 0.035), N-terminal prohormone of brain natriuretic peptide, and strain but not with other imaging parameters. Conclusion: FAP-targeted PET identifies varying degrees of left ventricular fibroblast activation in TAVR candidates with advanced AS. 68Ga-FAPI signal does not match other imaging parameters, generating the hypothesis that it may become useful as a tool for personalized selection of optimal TAVR candidates.

Relevance of Multiparametric Magnetic Resonance in the Evaluation of Patients with Prostate Cancer

The relevance of the use of mpMRI (multiparameter prostate magnetic resonance imaging) to evaluate the prostate in the context of PCa diagnosis lies in its ability to visualize primarily high-grade cancerous lesions that may be missed in routine diagnostic biopsies. standard. In several studies, mpMRI has shown improved performance compared to clinical models in identifying candidates who will benefit most from different therapies such as SA. Although data on mpMRI of the prostate during follow-up in men undergoing SA are sparse, there is potential to significantly improve AS programs through more accurate selection of optimal candidates which could achieve more accurate identification of progression of prostate cancer. disease and a reduction in the number of biopsies that would be needed to retest patients.

Abstract Number ‐ 244: Feasibility of Detecting Carotid Stenosis Microemboli Using Autonomous Robotic TCD at a Large Stroke Center

Introduction There is accumulating evidence that the presence of microembolic signals(MES) could be an independent risk factor and marker for future stroke or TIA. These signals detected by ultrasound represent small particles (platelets,plaque,fibrinogen) too small to cause a neurologic deficit, but can be a warning of a larger particle dislodging and blocking an intracranial artery. Transcranial doppler (TCD) studies are historically small. Few technicians have the specialized training to perform them and experienced users often have difficulty obtaining an adequate echogenic window. This study utilizes an autonomous robotic transcranial doppler (aTCD), driven by artificial intelligence to obtain and optimize the cerebral blood flow velocity signal. This tool makes data acquisition more efficient thus increasing analytical power through ease in obtaining larger sample sizes. This study focuses on the process of integrating such a tool. Complex vascular cases can utilize such a tool for patients on the borderline of needing a carotid stent or endarterectomy to help ensure the selection of optimal surgical candidates through better risk assessment methods. Methods NovaGuide™ 2 Intelligent Ultrasound (NovaSignal Corp. USA) was utilized to scan patients for microembolic signals that met our criteria. Our population consisted of male and female inpatients that were at least 18 years old at a single center with a CTA head and neck that revealed 50% or greater internal carotid artery stenosis for patients with neurological symptoms that could be associated with this artery. For patients that were asymptomatic with an incidental finding of internal carotid artery stenosis, we included 60% or greater stenosis. Stenosis was measured by NASCET criteria. If a patient received a stent or carotid endarterectomy during their hospitalization, a microembolic scan was obtained before and after their procedure if the initial scan was positive. Scans were performed for at least 30 minutes if the patient could tolerate this. Results Data collection is ongoing with a plan to scan 20 patients from July 2022 to October 2022, but the initial 12 patients revealed no MES which is contrary to the rate found in other studies. Potential confounders include antiplatelet and anticoagulation use as these were not delayed if clinically warranted. All cases were symptomatic and carotid stenosis ranged from 50% to 99%. A request for echo technician feedback is pending, but initial comments have revealed 30 minutes to be the maximum time feasible at our institution. Conclusions The aTCD has shown in a prospective study (NCT04604015) that data can be collected by non experts. Our study demonstrates that such a tool can be integrated into a large stroke center by echo technicians not formally trained in manual TCD. Utilization of technologies that allow for simplified data collection can help power larger TCD studies to explore its use as a risk utilization tool. This can help with selection of ideal surgical candidates for carotid stent and endarterectomy as an additional data point in their overall case. The significance of MES requires further investigation, but studies utilizing conventional TCD support MES being a risk factor for stroke and TIA.

Portal hypertension increases the risk of hepatic decompensation after 90Yttrium radioembolization in patients with hepatocellular carcinoma: a cohort study.

Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy. We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors. In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included. We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed. In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count. Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.

Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.

Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.

Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.