Antibodies to specific domains of Plasmodium falciparum erythrocyte membrane protein-1 and its relationship with protection from severe malarial anemia: A prospective study among Ghanaian children.

Background: Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is important in malaria pathogenicity as it mediates Pf-infected erythrocytes cytoadherence to host endothelial microvasculature receptors. Naturally acquired antibodies against specific PfEMP-1 antigens may be beneficial in clinical malaria protection. This study determined antibodies to DBLα2, CIDRα1, DBLß12, and DBLγ6 domains of PfEMP-1 in children with P. falciparum malaria in Tamale, Ghana. Methods: Sixty P. falciparum-infected children, and 30 controls, aged 1-12 years were recruited for this case-control study from April to July 2023 in Northern Ghana. Participants with uncomplicated malaria had asexual P. falciparum in peripheral blood and Hb ≥ 5.0 g/dL, and severe malaria was diagnosed when participants had Hb < 5.0 g/dL in addition to asexual P. falciparum in peripheral blood. Blood cell indices were measured using hematology analyzer, and IgG antibodies to DBLα2, CIDRα1, DBLß12, and DBLγ6 domains of PfEMP-1 and pro-inflammatory cytokines were detected using enzyme-linked immunosorbent assay. Data were analyzed using SPSS version 26.0. Results: The prevalence of PfEMP-1 IgG antibodies among P. falciparum-infected children and the uninfected group was 65.0% and 6.7%, respectively. PfEMP-1 IgG antibodies were present in 83.3% of uncomplicated malaria cases, and 46.7% in severe malaria subjects. Plasma levels of PfEMP-1 IgG antibodies were elevated in participants with uncomplicated malaria compared to those with severe malaria (p < 0.001). Hemoglobin, RBC, HCT, and platelet were significantly lower among P. falciparum-infected children without PfEMP-1 IgG antibodies than among those with the antibodies. Prevalence of anemia among children with PfEMP-1 IgG antibodies and those without the antibodies were 74.4% and 100%, respectively. Conclusion: The high prevalence of PfEMP-1 IgG antibodies to DBLα2, CIDRα1, DBLß12, and DBLγ6 domains observed in participants with uncomplicated malaria, and the relationship between PfEMP-1 IgG antibodies and blood cell parameters could indicate that the antibodies may be related to effective erythropoietic response in P. falciparum malaria. Immune antibodies against DBLα2, CIDRα1, DBLß12, and DBLγ6 domains of PfEMP-1 may suppress the deteriorating effects of PfEMP-1 antigens and provide immune protection against severe malarial anemia in children.

Pro- and anti-inflammatory cytokines mediate the progression of severe anemia in malaria-infected children: A prospective study.

BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: Malaria-infected children had higher tumor necrosis factor alpha (TNF-α) (p < .001), interferon-gamma (IFN-É£) (p < .001), interleukin (IL)-1ß (p < .001), IL-6 (p < .001), granulocyte macrophage-colony stimulating factor (GM-CSF) (p < .001), and IL-10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but reduced IL-3 (p < .001) and TGF-ß (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but lower IL-3 (p < .001) and TGF-ß (p < .001) than those with uncomplicated malaria. CONCLUSION: Parasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL-10, GM-CSF, IL-6, IL-1ß, IFN-É£, and TNF-α, but negatively associated with IL-3 and TGF-ß. Malaria is associated with enhanced secretion of pro- and anti-inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL-3 and TGF-ß may offer protection against severe malarial anemia.

The Utility of Prostate-Specific Membrane Antigen-11 PET in Detection and Management of Central Nervous System Neoplasms.

ABSTRACT: We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.2) who underwent PSMA PET imaging between March and September 2023. PET interpretation showed increased Ga-PSMA-11 accumulation in all patients with a mean SUV max of 3.11 ± 1.8. This series underscores PSMA PET's potential for CNS neoplasm detection.

Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study.

PURPOSE: To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression. METHODS: Patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUVmean from PET1 to PET2. Spearman's rank correlation coefficients and Fisher's exact test were used to evaluate the associations. RESULTS: Thirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539 days. Changes (%) in median PSA levels, WB-PSMA-SUVmean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUVmean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p < 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUVmean (Spearman ρ: 0.765 and 0.633, respectively; p < 0.001). CONCLUSION: Changes in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials.

Comparison of Low-Energy and Medium-Energy Collimators for Thyroid Scintigraphy with 123I.

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.123I thyroid scintigraphy can be performed with either a low-energy or a medium-energy (ME) collimator. The high-energy photon emissions from 123I cause septal penetration with scattered photons, which deteriorate image quality. The aim of this study was to evaluate the impact of collimator choice on 123I thyroid scintigraphy in clinical practice. Methods: Forty-seven patients who underwent thyroid planar scintigraphy with both a low-energy, high-resolution (LEHR) collimator and a ME collimator were prospectively recruited using the same imaging protocol. Image quality, collimator sensitivity, and estimation of thyroid size were assessed between LEHR and ME collimators and were compared with thyroid ultrasonography as the gold standard. Results: Images acquired with the ME collimator demonstrated reduced scattered background noise, improved thyroid-to-background contrast, and increased sensitivity in the thyroid gland compared with images acquired by the LEHR collimator. Manual measurement of the thyroid length is more accurate using the ME collimator. Automatic estimation of the thyroid area using the same thyroid threshold is larger in ME collimator images than in LEHR collimator images. Conclusion: Compared with the LEHR collimator, the ME collimator generates cleaner 123I thyroid scintigraphy images with less background noise and has higher collimator sensitivity for thyroid imaging. Different thyroid thresholds should be used to estimate the thyroid area and volume between low and ME collimators.