Metabolic impact of low dose IL-2 therapy for primary Sjögren's Syndrome in a double-blind, randomized clinical trial.

OBJECTIVES: Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS). METHOD: A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites. RESULTS: Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p < 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve. CONCLUSIONS: These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT02464319. Key Points • Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. • Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. • Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients.

QUALIPAED-A retrospective quality control study evaluating pediatric long axial field-of-view low-dose FDG-PET/CT.

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-of-variance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20-50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08-0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006-0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F]FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20 months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14 - p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

Diffusion probabilistic priors for zero-shot low-dose CT image denoising.

BACKGROUND: Denoising low-dose computed tomography (CT) images is a critical task in medical image computing. Supervised deep learning-based approaches have made significant advancements in this area in recent years. However, these methods typically require pairs of low-dose and normal-dose CT images for training, which are challenging to obtain in clinical settings. Existing unsupervised deep learning-based methods often require training with a large number of low-dose CT images or rely on specially designed data acquisition processes to obtain training data. PURPOSE: To address these limitations, we propose a novel unsupervised method that only utilizes normal-dose CT images during training, enabling zero-shot denoising of low-dose CT images. METHODS: Our method leverages the diffusion model, a powerful generative model. We begin by training a cascaded unconditional diffusion model capable of generating high-quality normal-dose CT images from low-resolution to high-resolution. The cascaded architecture makes the training of high-resolution diffusion models more feasible. Subsequently, we introduce low-dose CT images into the reverse process of the diffusion model as likelihood, combined with the priors provided by the diffusion model and iteratively solve multiple maximum a posteriori (MAP) problems to achieve denoising. Additionally, we propose methods to adaptively adjust the coefficients that balance the likelihood and prior in MAP estimations, allowing for adaptation to different noise levels in low-dose CT images. RESULTS: We test our method on low-dose CT datasets of different regions with varying dose levels. The results demonstrate that our method outperforms the state-of-the-art unsupervised method and surpasses several supervised deep learning-based methods. Our method achieves PSNR of 45.02 and 35.35 dB on the abdomen CT dataset and the chest CT dataset, respectively, surpassing the best unsupervised algorithm Noise2Sim in the comparative methods by 0.39 and 0.85 dB, respectively. CONCLUSIONS: We propose a novel low-dose CT image denoising method based on diffusion model. Our proposed method only requires normal-dose CT images as training data, greatly alleviating the data scarcity issue faced by most deep learning-based methods. At the same time, as an unsupervised algorithm, our method achieves very good qualitative and quantitative results. The Codes are available in https://github.com/DeepXuan/Dn-Dp.

Efficacy and safety of low-dose rituximab in the treatment of myasthenia gravis: a systemic review and meta-analysis.

Background: Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. Methods: This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. Results: A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84-96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of -1.69 (95% CI: -2.21 to -1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80-97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of -1.51 (95% CI: -0.80 to -2.21, Z = 4.50, P < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89-100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of -2.31 (95% CI: -2.99 to -1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Conclusion: Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. Systematic Review Registration: PROSPERO, identifier: CRD42024509951.

The Effect of COVID-19 on Lung Cancer Screening.

Background During the COVID-19 pandemic, many hospitals suspended non-essential medical procedures to reduce transmission and prioritize personal protective equipment (PPE) for COVID-19 patients. Hospitals that continued these procedures faced uncertainty about patient attendance. Multiple factors could explain a decline in patient attendance during the pandemic, including patients' reluctance to risk COVID-19 exposure in the hospital or their own illness requiring self-isolation. This study aimed to compare attendance rates of lung cancer screenings (LCS) before and during the pandemic. Unlike previous studies conducted on this research topic, the current study documents that the John B. Amos Cancer Center continued LCS throughout the pandemic. The alternative hypothesis was that there would be a decrease in the percentage of LCS performed during the pandemic period due to fear of nosocomial transmission. Materials and methods Data for 2,582 scheduled LCS were retrospectively analyzed on Microsoft Excel 2022 (Microsoft Corporation, Redmond, Washington) from 2018 to 2021. For analysis purposes, 2018 and 2019 were considered pre-COVID years, while 2020 and 2021 were considered COVID years. The average percentage attended was calculated for each year and the standard deviation of that year's percentage. The percentage of patients seen each month was averaged during pre-COVID and COVID years. The p-value was calculated by comparing the average attendance percentage for each month in the pre-COVID and COVID years. A p-value <0.05 was considered significant. Results From 2018 to 2021, over 300 more people were scheduled during the COVID years. Although the percentage seen remained consistent throughout the years, there was an increase in both patients scheduled and seen. The results revealed an insignificant difference in LCS attendance between pre-COVID and COVID years, confirming the importance of their continuation. Conclusion The alternative hypothesis was rejected due to no significant difference in attendance percentage between the pre-COVID and COVID years. Further direction of this study may include monitoring the trend of LCS attendance during post-pandemic years as the transmission rates continue to change.

Low-dose electron microscopy imaging for beam-sensitive metal-organic frameworks.

Metal-organic frameworks (MOFs) have garnered significant attention in recent years owing to their exceptional properties. Understanding the intricate relationship between the structure of a material and its properties is crucial for guiding the synthesis and application of these materials. (Scanning) Transmission electron microscopy (S)TEM imaging stands out as a powerful tool for structural characterization at the nanoscale, capable of detailing both periodic and aperiodic local structures. However, the high electron-beam sensitivity of MOFs presents substantial challenges in their structural characterization using (S)TEM. This paper summarizes the latest advancements in low-dose high-resolution (S)TEM imaging technology and its application in MOF material characterization. It covers aspects such as framework structure, defects, and surface and interface analysis, along with the distribution of guest molecules within MOFs. This review also discusses emerging technologies like electron ptychography and outlines several prospective research directions in this field.

The growth of screening-detected pure ground-glass nodules after 10 years of stability.

BACKGROUND: It remains uncertain how long pure ground-glass nodules (pGGNs) detected on low dose computed tomography (LDCT) should be followed. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. RESEARCH QUESTION: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? STUDY DESIGN AND METHODS: This was a retrospective cohort study originating from subjects with pGGNs detected on LDCT scans between 1997 and 2006, whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study subjects were followed by our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by 2 mm or more or the appearance of new solid portions within the nodules. RESULTS: A total of 89 patients with 135 pGGNs were followed for a median of 193 months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a size change was 71 months. Of the 23 growing pGGNs, 122 were detected on the first LDCT, and 13 were newly detected on the follow-up CT scan. An increase in size was observed within 5 years in 8 nodules (34.8%), between 5 and 10 years in 12 nodules (52.2%) and after 10 years in 3 nodules (13.0%). Fifteen nodules were histologically confirmed as adenocarcinoma by surgery. Among the 76 pGGNs stable for 10 years, 3 (3.9%) increased in size. INTERPRETATION: Among pGGNs that remained stable for 10 years, 3.9% eventually grew, indicating that some pGGNs can grow even after a long period of stability. We suggest that pGGNs may need to be followed for more than 10 years to confirm growth.

Efficacy and safety of a low-dose sulfamethoxazole/trimethoprim regimen in preventing pneumocystis pneumonia: A retrospective study using a large-scale electronic medical record database.

INTRODUCTION: Sulfamethoxazole/trimethoprim (ST) is a first-line drug for preventing pneumocystis pneumonia (PCP). Several small-scale studies have suggested the usefulness of the low-dose regimen of ST (200/40 mg/day) over the standard-dose one (400/80 mg/day). Thus, this study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in preventing PCP in patients with non human immunodeficiency virus infection using a large-scale electronic medical record database. METHODS: This retrospective study included patients who received ST prophylaxis for PCP registered in the RWD database between June 2007 and February 2023. Patients received either standard-dose (400/80 mg/day) or low-dose (200/40 mg/day) regimen groups. The incidence of cases initiated PCP therapeutic dose (ci-PCPTD) (ST ≥ 3600/720 mg/day) and adverse events (AEs) was evaluated, and risk factors for ci-PCPTD were investigated. RESULTS: A total of 11,384 patients received the standard-dose, whereas 7973 received the low-dose regimen groups. No significant difference in the cumulative incidence of ci-PCPTD was observed between the standard-dose (0.67%) and low-dose regimen group (0.47%). Lung disease was a significant risk factor for ci-PCPTD. The cumulative incidence of ci-PCPTD in patients with acute exacerbation of interstitial pneumonia was 1.3% in both groups, and no significant difference was observed between the two groups. The low-dose regimen group had a lower incidence of all AEs than the standard-dose regimen group. CONCLUSION: These results based on a large-scale electronic medical record database provide important evidence supporting the clinical significance of low-dose regimen of ST.

Trabecular Attenuation of L1 in Adult Patients with Multiple Myeloma: An Observational Study on Low-Dose CT Images.

BACKGROUND: The aim of this study was to evaluate the impact of trabecular attenuation of the L1 vertebral body in low-dose CT in adult patients with multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS). MATERIALS AND METHODS: The study population consisted of 22 patients with MGUS and 51 consecutive patients with newly diagnosed MM (SMM, n = 21; symptomatic MM, n = 36). CT scans were conducted using a 128-slice CT scanner (Somatom go.Top, Siemens, Munich, Germany). Low-dose whole-body CT scans were performed at a single time point for each patient. Trabecular bone density values were obtained by defining regions of interest on non-contrast images at the level of L1 vertebra. A threshold of p = 0.05 was applied to determine statistical significance. RESULTS: The median Hounsfield unit (HU) value in patients with MGUS, SMM, and MM was 148 HU (range 81-190), 130 HU (range 93-193), and 92 HU (range 26-190), respectively, with a statistically significant difference between the groups (p = 0.0015). Patients with HU values ≤ 92 had lower progression-free survival with statistically significant differences compared to the group with HU values > 92 (p < 0.0499). CONCLUSIONS: This is the earliest evidence of the importance of evaluating L1 attenuation values in low-dose CT images in patients with MGUS, SMM, and MM. Further prospective studies could contribute to reinforcing these results and exploring the clinical applicability and generalization of L1 attenuation values in low-dose whole-body CT scans in routine clinical practice.

Chronic Low-Dose-Rate Radiation-Induced Persistent DNA Damage and miRNA/mRNA Expression Changes in Mouse Hippocampus and Blood.

Our previous study demonstrated that the acute high-dose-rate (3.3 Gy/min) γ-ray irradiation (γ-irradiation) of postnatal day-3 (P3) mice with 5 Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of adult mice. The present study investigated the effects of chronic low-dose-rate (1.2 mGy/h) γ-irradiation from P3 to P180 with a cumulative dose of 5 Gy on animal behaviour, hippocampal cellular change, and miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal's body weight, and neuropsychiatric changes such as anxiety and depression were examined by neurobehavioural tests, including open field, light-dark box, elevated plus maze, tail suspension, and forced swim tests. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFRα). Nevertheless, γH2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low-dose-rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed the changed expression of some genes, including Fli1, Hs3st5, and Eif4ebp2. Database searching by miRDB and TargetScan predicted that Fli1 and Hs3st5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may be related to the chronic low-dose-rate radiation-induced persistent DNA damage.

Aspirin Hypersensitivity in Patients with Coronary Artery Disease: An Updated Review and Practical Recommendations.

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity.

A Comprehensive Review of Low-Dose Interleukin-2 (IL-2) Therapy for Systemic Lupus Erythematosus: Mechanisms, Efficacy, and Clinical Applications.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes extensive inflammation and tissue destruction across several organs. Conventional therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive drugs, can have serious adverse effects and are not always successful. This study looks at the possibility of low-dose interleukin-2 (IL-2) therapy as a new treatment for SLE, focusing on its mechanics, effectiveness, and clinical applicability. Low-dose IL-2 treatment selectively increases and activates regulatory T cells (Tregs), which are essential for immunological tolerance but are often lacking in SLE patients. Unlike standard medicines, which widely inhibit the immune system, low-dose IL-2 provides a more tailored approach with fewer side effects. We examined preclinical and clinical research and discovered that low-dose IL-2 dramatically enhances Treg numbers and function, lowers disease activity, and improves clinical outcomes. The primary molecular processes include the stimulation of the Janus kinase - signal transducer of activators of transcription (JAK-STAT), phosphatidylinositol 3-kinase - protein kinase B (PI3K-Akt), and mitogen­activated protein kinase (MAPK) pathways, which enhance Treg proliferation, survival, and activity. A thorough review of clinical studies finds that low-dose IL-2 treatment is well-tolerated and effective, with fewer side effects than biologics like belimumab and rituximab. Furthermore, IL-2 therapy provides prospects for combination therapies, which may improve therapeutic success by addressing numerous components of the immune response. Despite these encouraging findings, problems such as patient response variability and the need for long-term safety data persist. Future research should prioritize refining dose regimes, discovering biomarkers for patient selection, and investigating combination medicines. Addressing these issues might solidify low-dose IL-2 treatment as a cornerstone in SLE care, providing a more accurate and individualized approach to immune regulation while considerably improving patient outcomes.

Venetoclax with low-dose cytarabine, a forgotten combination in patients with acute myeloid leukemia ineligible for intensive chemotherapy: a systematic review.

BACKGROUND: Based on the VIALE-A and VIALE-C studies, the Food and Drug Administration approved venetoclax in 2020 in combination with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia ineligible for intensive chemotherapy. After the publication of these studies, venetoclax/azacitidine was assumed to be superior to venetoclax/low-dose cytarabine; however, these studies were not designed to demonstrate superiority between these combinations. Therefore, we conducted a systematic review to describe overall survival, complete remission rate, and composite complete remission rate to assess response of these two regimens in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. MATERIALS AND METHODS: The PubMed and Web of Science databases were searched for retrospective studies and complete remission, composite complete remission, and overall survival rates were recorded. RESULTS: Only 11 of the 815 publications identified were eligible to be included n this review, ten studies evaluated the venetoclax/azacitidine combination and one study evaluated the venetoclax/low-dose cytarabine combination. The median overall survival for venetoclax/azacitidine was 10.75 months, whereas for venetoclax/low-dose cytarabine the median overall survival had not been reached at the time of publication. Composite complete remission was 63.3 % for venetoclax/azacitidine and 90 % for venetoclax/low-dose cytarabine. Adverse events were similar for both combinations. CONCLUSIONS: A limited number of studies investigating the venetoclax/low-dose cytarabine combination exist. Based on the available data, the superiority of venetoclax/azacitidine over venetoclax/low-dose cytarabine cannot be assumed for all acute myeloid leukemia patients who are ineligible for intensive chemotherapy. Venetoclax/low-dose cytarabine can still be considered as an option for the drug combinations currently under investigation.

Low-Dose Aspirin and Risk of Anaemia in Older Adults: Insights from a Danish Register-based Cohort Study.

AIMS: To assess the risk of anaemia among low-dose aspirin (LDA) exposure in Danish older individuals in a real-world setting. METHODS: Population based-cohort study conducted using Danish registers. The study population included older individuals (≥65 years) exposed to LDA between 2008 and 2013 for primary or secondary prevention of cardiovascular events. Over a five-year follow-up, outcomes included anaemia incidence based on haemoglobin values and hematinic deficiency incidence based on antianemic prescriptions. RESULTS: Among the 313 508 individuals included in the study population, those exposed to LDA (n = 59 869, 19.1%) had an incidence of hematinic deficiency determined by the use of antianemic treatment of 9.6%, with an incidence rate ratio of 9.11 (95% Confidence Interval, CI: 8.81-9.41) when compared to non-users of LDA (n = 253 639, 80.9%), who had an incidence of 3.7%. Anaemia determined by haemoglobin value measurements was observed in 5.9% of those exposed to LDA, with an incidence rate ratio of 7.89 (95% CI: 7.58-8.21) when compared to non-users of LDA. Approximately one in five individuals (n = 2 422, 21.5%) who experienced anaemia also experienced bleeding. Severe anaemia was observed in 1.3% of those exposed to LDA compared to 0.6% of those not exposed. Among the exposed, the reduction in haemoglobin and ferritin levels was associated with the severity of anaemia. CONCLUSION: These findings indicate that in a real-world setting, anaemia with LDA can occur in 6 to 10 older individuals out of every 100 LDA users during the first 5 years of treatment.

Low-dose oral food challenges.

BACKGROUND: Infants aged <1 year with confirmed food allergies generally need to avoid causative foods completely for a certain period. Low-dose oral food challenges (LD-OFCs) may be an effective strategy for safely introducing small amounts of causative foods to individuals with food allergies. This study clarified the safety of LD-OFCs in infants aged <1 year with food allergies. METHODS: We retrospectively analyzed the clinical records of LD-OFCs performed in infants aged <1 year allergic to hen's egg, cow's milk, or wheat between April 2014 and October 2017. Approximately 1/25th-1/20th of the egg white from a heated whole hen's egg, 3 mL heated cow's milk, and 2 g wheat noodles (udon) were used as challenge foods. We examined the LD-OFC results, including the induced symptoms and treatment required for positive LD-OFC results. RESULTS: The LD-Egg, LD-Milk, and LD-Wheat OFC groups comprised 68, 42, and 13 participants, respectively. The positivity rates for the LD-Egg, LD-Milk, and LD-Wheat OFC groups were 7%, 24%, and 0%, respectively. Patients predominantly exhibited skin symptoms, and most were treated with oral antihistamines alone. None of the patients experienced anaphylaxis or required adrenaline injections. CONCLUSIONS: Infants aged <1 year with food allergies can safely undergo LD-OFCs by consuming low doses of causative foods. Avoiding the complete elimination of causative foods is an important strategy for managing infants with food allergies when initially introducing causative foods.

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-ß2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study.

Introduction: Anti-ß2-glycoprotein I (ß2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-ß2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies. Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-ß2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-ß2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-ß2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups. Results: The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-ß2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03). Discussion: This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aß2GPI/HLA-DR antibody positivity.

Real-world first round results from a charity lung cancer screening program in East Asia.

Background: Screening with low-dose computed tomography (LDCT) has been proven to potentially reduce the rate of mortality of lung cancer. Lack of real-world data outside of protocolized trials has been cited as an impediment to its more widespread implementation, especially in Asia. This report aims to provide such real-world data. Methods: A single round of LDCT was provided through a community-based charity program in Hong Kong, China to asymptomatic adults with a family history of lung cancer and/or smoking history. Anonymized data from this program were analyzed. Results: LDCT was performed for 99 participants, including 98 (99%) who had one or more family members with history of lung cancer, and 70 (71%) who were never-smokers. After a single round of screening, a positive LDCT was noted in 47 participants (47%). A sister with a history of lung cancer (28% vs. 8%, P=0.01) and a multiplex family (MF) (47% vs. 23%, P=0.02) were factors associated with a positive LDCT. After a median period of 10 months (range, 5-16 months) following LDCT, lung cancer (all adenocarcinoma) was diagnosed as a direct consequence of positive LDCT findings in six participants (6%), of whom four had stage I disease and five received surgery with curative intent. In the 47 participants with a positive LDCT, having a sister with a history of lung cancer was associated with an increased risk of lung cancer (relative risk =5.23; 95% confidence interval: 1.09-25.21). Detected lesions categorized as Lung Imaging Reporting and Data System (Lung-RADS) 3 or above (odds ratio =12.08; 95% confidence interval: 1.27-114.64) or deemed by an experienced specialist to be suspicious (odds ratio =63.33; 95% confidence interval: 5.48-732.29) were significantly more likely to turn out to be a lung cancer. Conclusions: This real-world data demonstrates that a single round of LDCT screening at a community level in East Asia can detect potentially curable lung cancer at a rate comparable to those reported by protocolized trials. When considering future LDCT screening programs in East Asia, a family history of lung cancer may be a key factor indicating a person for screening, and how features of a LDCT-detected lesion should trigger further intervention warrant further definition.

Enhanced tumor control and survival in preclinical models with adoptive cell therapy preceded by low-dose radiotherapy.

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone. Methods: We investigated this hypothesis using two NSG mouse models bearing GSU or CAPAN-2 solid tumors. The mice were treated with engineered CAR-T cells targeting guanyl cyclase-C (GCC) or mesothelin as monotherapy or in combination with LDRT. Additionally, we extended this approach to a C57BL/6 mouse model implanted with MC38-gp100+ cells, followed by adoptive transfer of pmel+ T cells before and after LDRT. Tumor growth and survival outcomes were monitored in all models. Furthermore, we employed atomic force microscopy (AFM) in a small cohort to assess the effects of radiotherapy on tumor stiffness and plasticity, exploring the role of tumor nanomechanics as a potential biomarker for treatment efficacy. Results: Our results demonstrated enhanced tumor control and prolonged survival in mice treated with LDRT followed by T-cell therapy across all models. The combination of LDRT with CAR-T or pmel+ T-cell therapy led to superior tumor suppression and survival compared to monotherapy, highlighting the synergistic impact of the combined approach. Additionally, AFM analysis revealed significant changes in tumor stiffness and plasticity in response to LDRT, suggesting that the nanomechanical properties of the tumor may be predictive of therapeutic response. Discussion: The findings of this study highlight the transformative potential of incorporating LDRT as a precursor to adoptive T-cell therapy in solid tumors. By promoting CAR-T and pmel+ T-cell infiltration into the tumor microenvironment, LDRT enhanced tumor control and improved survival outcomes, offering a promising strategy to overcome the challenges associated with CAR-T therapy in solid tumors. Additionally, the changes in tumor nanomechanics observed through AFM suggest that tumor stiffness and plasticity could be biomarkers for predicting treatment outcomes. These results support further investigation into the clinical application of this combined approach to improve the efficacy of cell-based therapies in patients with solid tumors.