Establishment and activity of the planning and acting network for low dose radiation research in Japan (PLANET): 2016-2023.

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection.

Low-dose tenecteplase during cardiopulmonary resuscitation in massive pulmonary embolism.

We report the case of an 18-year-old male who presented to the Emergency Department with sudden onset dyspnea. The patient was intubated on arrival, but suffered a cardiac arrest soon after. Point-of-care echocardiography during cardiopulmonary resuscitation revealed a grossly dilated right atrium and right ventricle, which alerted the Emergency physician to the possibility of massive pulmonary embolism leading to cardiac arrest. Due to no discernible history or risk factors in favour of pulmonary embolism, a decision was taken for thrombolysis with half dose Tenecteplase. Return of spontaneous circulation was achieved 14 min after thrombolysis, with massive pulmonary embolism subsequently being confirmed on CT Pulmonary Angiography.

Should we routinely assess hypothalamic-pituitary-adrenal axis in pediatric patients with Prader-Willi syndrome?

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.

Outcomes with low dose anti-thymocyte globulin based graft versus host disease prophylaxis after mismatched unrelated donor allogeneic hematopoietic cell transplantation.

BACKGROUND: Anti-thymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis is widely used for mismatched unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Although recent literature suggested improved outcomes with PTCy-based regimens when compared to ATG-based regimens these studies used doses of ATG ≥5 mg/kg. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower-dose ATG-based regimens at our center. METHODS: We retrospectively analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG-based regimens for all adults undergoing allogeneic HCT at The Ottawa Hospital from 2015 to 2022. Data regarding demographics, conditioning regimen, dose of ATG, rates of GVHD, duration of remission, and survival, were collected and analyzed. RESULTS: Seventy-seven (n = 77) patients (males 62.3%; median age 50 years) underwent allogeneic HCT from MMUD. Majority(81%; n = 63) received 2.5 mg/kg of rabbit ATG and remaining 18.2% (n = 14) received 4.5 mg/kg. Grade II-IV acute GVHD occurred in 24.7% (n = 19) while any chronic GVHD occurred in 32.5% (n = 25) patients. After a median follow-up of 21 months, relapse occurred in 28.6% of patients. Two-year OS, GRFS, CIR, and NRM were 60.6%, 45.3%, 16.9%, and 18.2% respectively. Dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses. CONCLUSIONS: When compared to published studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG may potentially lead to improved outcomes in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy-based regimens to determine ideal GVHD prophylaxis for these patients.

Low-dose atorvastatin calcium combined with evolocumab: effect on regulatory proteins, lipid profiles, and cardiac function in coronary heart disease patients.

OBJECTIVE: To assess the effects of combining low-dose atorvastatin calcium with evolocumab on complement regulatory protein levels, lipid profiles, and cardiac function in patients with coronary heart disease (CHD). METHODS: A prospective randomized controlled study was conducted, with 180 CHD patients enrolled from Guang'anmen Hospital, China Academy of Chinese Medical Sciences, and the Second Hospital of Shanxi Medical University between February 2022 and April 2023. These patients were randomly assigned to either the control group (n = 90), receiving low-dose atorvastatin calcium, or the research group (n = 90), receiving a combination of low-dose atorvastatin calcium and evolocumab. The changes in cardiac function indices, levels of blood lipids and complement proteins, incidence of side effects, and cardiovascular events were compared between the two groups. RESULTS: After treatment, both groups exhibited reductions in blood lipid levels. However, the research group demonstrated significantly lower levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) compared to the control group (all P < 0.001). Additionally, improvements in cardiac function indices were observed in both groups, with the research group displaying greater enhancements in cardiac output (CO), stroke volume (SV), and left ventricular ejection fraction (LVEF). Furthermore, the levels of complement regulatory proteins, including CD45, CD46, CD55, and CD59, increased in both groups after treatment, with the research group exhibiting significantly higher levels (all P < 0.001). Notably, the research group also exhibited a lower incidence of cardiovascular events. CONCLUSION: The combined use of low-dose atorvastatin calcium and evolocumab effectively modulates complement regulatory protein levels, optimizes blood lipid profiles, and enhances cardiac function in patients with CHD. This combination therapy represents a promising approach for management of CHD.

Diagnostic performance of coronary calcifications on CT to rule out acute coronary syndrome in the emergency department.

BACKGROUND: At present, the diagnosis of acute coronary syndrome (ACS) can be made by emergency physicians using the usual complementary tests, since the current troponin and electrocardiogram (ECG) protocols have been extensively tested for their safety. However, the detection of coronary calcifications on CT associated with coronary obstruction may be of interest for the diagnostic strategy in the emergency department (ED). The aim of this study was to evaluate a strategy combining a non-ischemic ECG with an initial normal troponin assay and the diagnostic accuracy of chest CT in detecting coronary calcifications to rule out the presence of an acute coronary event in patients presenting with chest pain in the ED. METHODS: This was a retrospective, single-center study carried out in an ED in France and included all patients over 18 years of age presenting with chest pain between 1 June 2021 and 31 December 2021 with a non-ischemic ECG and a negative first troponin assay. The primary endpoint was the diagnostic performance of the combing strategy in ruling out ACS. The secondary endpoints were the sensitivity and specificity of calcifications in acute coronary syndrome, comparison with the diagnostic performance of a second troponin assay and the rate of reconsultation, rehospitalisation and investigations within 2 months of the ED. RESULTS: Of the 280 patients included, 141 didn't have calcifications. A total of 14 events were found with a negative predictive value for the combining strategy of 99.8% [95%CI: 98.2 - 100]. Sensitivity and specificity were 98.4% [95%CI: 83.8 - 100] and 53% [95%CI: 47 - 58.9], respectively. Among patients with no calcification, 8.2% were admitted to hospital and none suffered an acute coronary event. A total of 36 patients (12.8%) consulted a doctor within 2 months, with 23 investigations, all of which were negative in the non-calcification group. CONCLUSIONS: A strategy combining the detection of coronary calcifications on chest CT in patients with a non-ischemic ECG and a single troponin assay is effective to rule out ACS in the ED, and may perform better then ECG and troponin alone.

Cost-Effectiveness of Low-Dose Computed Tomography Screenings for Lung Cancer in High-Risk Populations: A Markov Model.

Background: Domestic and foreign studies on lung cancer have been oriented to the medical efficacy of low-dose computed tomography (LDCT), but there is a lack of studies on the costs, value and cost-effectiveness of the treatment. There is a scarcity of conclusive evidence regarding the cost-effectiveness of LDCT within the specific context of Taiwan. This study is designed to address this gap by conducting a comprehensive analysis of the cost-effectiveness of LDCT and chest X-ray (CXR) as screening methods for lung cancer. Methods: Markov decision model simulation was used to estimate the cost-effectiveness of biennial screening with LDCT and CXR based on a health provider perspective. Inputs are based on probabilities, health status utility (quality-adjusted life years (QALYs)), costs of lung cancer screening, diagnosis, and treatment from the literatures, and expert opinion. A total of 1,000 simulations and five cycles of Markov bootstrapping simulations were performed to compare the incremental cost-utility ratio (ICUR) of these two screening strategies. Probability and one-way sensitivity analyses were also performed. Results: The ICUR of early lung cancer screening compared LDCT to CXR is $-24,757.65/QALYs, and 100% of the probability agree to adopt it under a willingness-to-pay (WTP) threshold of the Taiwan gross domestic product (GDP) per capita ($35,513). The one-way sensitivity analysis also showed that ICUR depends heavily on recall rate. Based on the prevalence rate of 39.7 lung cancer cases per 100,000 people in 2020, it could be estimated that LDCT screening for high-risk populations could save $17,154,115. Conclusion: LDCT can detect more early lung cancers, reduce mortality and is cost-saving than CXR in a long-term simulation of Taiwan's healthcare system. This study provides valuable insights for healthcare decision-makers and suggests analyzing cost-effectiveness for additional variables in future research.

Examining feature extraction and classification modules in machine learning for diagnosis of low-dose computed tomographic screening-detected in vivo lesions.

Purpose: Medical imaging-based machine learning (ML) for computer-aided diagnosis of in vivo lesions consists of two basic components or modules of (i) feature extraction from non-invasively acquired medical images and (ii) feature classification for prediction of malignancy of lesions detected or localized in the medical images. This study investigates their individual performances for diagnosis of low-dose computed tomography (CT) screening-detected lesions of pulmonary nodules and colorectal polyps. Approach: Three feature extraction methods were investigated. One uses the mathematical descriptor of gray-level co-occurrence image texture measure to extract the Haralick image texture features (HFs). One uses the convolutional neural network (CNN) architecture to extract deep learning (DL) image abstractive features (DFs). The third one uses the interactions between lesion tissues and X-ray energy of CT to extract tissue-energy specific characteristic features (TFs). All the above three categories of extracted features were classified by the random forest (RF) classifier with comparison to the DL-CNN method, which reads the images, extracts the DFs, and classifies the DFs in an end-to-end manner. The ML diagnosis of lesions or prediction of lesion malignancy was measured by the area under the receiver operating characteristic curve (AUC). Three lesion image datasets were used. The lesions' tissue pathological reports were used as the learning labels. Results: Experiments on the three datasets produced AUC values of 0.724 to 0.878 for the HFs, 0.652 to 0.965 for the DFs, and 0.985 to 0.996 for the TFs, compared to the DL-CNN of 0.694 to 0.964. These experimental outcomes indicate that the RF classifier performed comparably to the DL-CNN classification module and the extraction of tissue-energy specific characteristic features dramatically improved AUC value. Conclusions: The feature extraction module is more important than the feature classification module. Extraction of tissue-energy specific characteristic features is more important than extraction of image abstractive and characteristic features.

Low-dose radiation-induced SUMOylation of NICD1 negatively regulates osteogenic differentiation in BMSCs.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

Pulmonary nodule detection in low dose computed tomography using a medical-to-medical transfer learning approach.

Purpose: Lung cancer is the second most common cancer and the leading cause of cancer death globally. Low dose computed tomography (LDCT) is the recommended imaging screening tool for the early detection of lung cancer. A fully automated computer-aided detection method for LDCT will greatly improve the existing clinical workflow. Most of the existing methods for lung detection are designed for high-dose CTs (HDCTs), and those methods cannot be directly applied to LDCTs due to domain shifts and inferior quality of LDCT images. In this work, we describe a semi-automated transfer learning-based approach for the early detection of lung nodules using LDCTs. Approach: In this work, we developed an algorithm based on the object detection model, you only look once (YOLO) to detect lung nodules. The YOLO model was first trained on CTs, and the pre-trained weights were used as initial weights during the retraining of the model on LDCTs using a medical-to-medical transfer learning approach. The dataset for this study was from a screening trial consisting of LDCTs acquired from 50 biopsy-confirmed lung cancer patients obtained over 3 consecutive years (T1, T2, and T3). About 60 lung cancer patients' HDCTs were obtained from a public dataset. The developed model was evaluated using a hold-out test set comprising 15 patient cases (93 slices with cancerous nodules) using precision, specificity, recall, and F1-score. The evaluation metrics were reported patient-wise on a per-year basis and averaged for 3 years. For comparative analysis, the proposed detection model was trained using pre-trained weights from the COCO dataset as the initial weights. A paired t-test and chi-squared test with an alpha value of 0.05 were used for statistical significance testing. Results: The results were reported by comparing the proposed model developed using HDCT pre-trained weights with COCO pre-trained weights. The former approach versus the latter approach obtained a precision of 0.982 versus 0.93 in detecting cancerous nodules, specificity of 0.923 versus 0.849 in identifying slices with no cancerous nodules, recall of 0.87 versus 0.886, and F1-score of 0.924 versus 0.903. As the nodule progressed, the former approach achieved a precision of 1, specificity of 0.92, and sensitivity of 0.930. The statistical analysis performed in the comparative study resulted in a p -value of 0.0054 for precision and a p -value of 0.00034 for specificity. Conclusions: In this study, a semi-automated method was developed to detect lung nodules in LDCTs using HDCT pre-trained weights as the initial weights and retraining the model. Further, the results were compared by replacing HDCT pre-trained weights in the above approach with COCO pre-trained weights. The proposed method may identify early lung nodules during the screening program, reduce overdiagnosis and follow-ups due to misdiagnosis in LDCTs, start treatment options in the affected patients, and lower the mortality rate.

Treatment of Darier Disease with Radiation Therapy: Case Report and Literature Review.

Darier's disease (DD) is an autosomal dominant genodermatosis characterized by hyperkeratotic papules, often accompanied by scaling and crusting. Managing DD presents significant challenges due to the absence of an effective cure, with only symptom targeting treatments currently available. This study presents a case of refractory DD that showed poor response to established pharmacological treatments but demonstrated improvement with low-dose superficial X-ray radiotherapy (SRT). The radiation was delivered as a single 200 cGy treatment, which visibly improved the condition. Considering the different degrees of side effects, sequelae, and risk of developing radiation-induced cancer after exposure to moderate levels of radiation, it may be considered that we attempt to treat recalcitrant DD initially by applying a low dose of radiation in order to mitigate these undesired side effects. If larger doses or additional courses are necessary due to inadequate response, the risks and benefits must be carefully evaluated and discussed with patients.

An introduction to environmental neurotoxicology: Lessons from a clinical perspective.

In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: "all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure". Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.

Influence of loss function and electron dose on ptychography of 2D materials using the Wirtinger flow.

Iterative phase retrieval is based on minimising a loss function as a measure of the consistency of an initial guess and underlying experimental data. Under ideal experimental conditions, real data contains Poissonian noise due to counting statistics. In this work, we use the Wirtinger Flow concept in combination with four common loss functions, being the L1 loss, the mean-squared error (MSE), the amplitude loss and the Poisson loss. Since only the latter reflects the counting statistics as an asymmetric Poisson distribution correctly, our simulation study focuses on two main cases. Firstly, high-dose momentum-resolved scanning transmission electron microscopy (STEM) of an MoS2 monolayer is considered for phase retrieval. In this case, it is found that the four losses perform differently with respect to chemical sensitivity and frequency transfer, which we interprete in terms of the substantially different signal level in the bright and dark field part of diffraction patterns. Remedies are discussed using further simulations, addressing the use of virtual ring detectors for the dark field, or restricting loss calculation to the bright field. Secondly, a dose series is presented down to 100 electrons per diffraction pattern. It is found that all losses yield qualitatively reasonable structural data in the phase, whereas only MSE and Poisson loss range at the correct amplitude level. Chemical contrast is, in general, reliably obtained using the Poisson concept, which also provides the most continuous spatial frequency transfer as to the reconstructed object transmission function.

Performance of calcium quantifications on low-dose photon-counting detector CT with high-pitch: A phantom study.

Purpose: To evaluate the performance of calcium quantification on photon-counting detector CT (PCD-CT) with high-pitch at low radiation doses compared to third-generation dual-source energy-integrating detector CT (EID-CT). Materials and methods: The phantom with three calcium inserts (50, 100, and 300 mg of calcium per milliliter), with and without the elliptical outer layer, was evaluated using high-pitch (3.2) and standard pitch (0.8) on PCD-CT, and standard pitch on EID-CT. Scans were performed with different tube voltages (PCD-CT: 120 and 140 kilo-voltage peak [kVp]; EID-CT: 70/Sn150 and 100/Sn150 kVp) and four radiation doses (1, 3, 5, and, 10 milli-Gray [mGy]). Utilizing the true calcium concentrations (CCtrue) of the phantom as the gold standard references, regression equations for each kVp setting were formulated to convert CT attenuations (CaCT) into measured calcium concentrations (CCm). The correlation analysis between CaCT and CCtrue was performed. The percentage absolute bias (PAB) was calculated from the differences between CCm and CCtrue and used to analyze the effects of scanning parameters on calcium quantification accuracy. Results: A strong correlation was found between CaCT and CCtrue on PCD-CT (r > 0.99) and EID-CT (r > 0.98). For high- and standard-pitch scans on PCD-CT, the accuracy of calcium quantification is comparable (p = 0.615): the median (interquartile range [IQR]) of PAB was 5.59% (2.79%-8.31%) and 4.87 % (2.62%-8.01%), respectively. The PAB median (IQR) was 7.43% (3.77%-11.75%) for EID-CT. The calcium quantification accuracy of PCD-CT is superior to EID-CT at the large phantom (5.46% [2.68%-9.55%] versus 9.01% [6.22%-12.74%]), and at the radiation dose of 1 mGy (4.43% [2.08%-8.59%] versus 13.89% [8.93%-23.09%]) and 3 mGy (4.61% [2.75%-6.51%] versus 9.97% [5.17%-14.41%]), all p < 0.001. Conclusions: Calcium quantification using low-dose PCD-CT with high-pitch scanning is feasible and accurate, and superior to EID-CT.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Facing an un-met need in lung cancer screening: the never smokers.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide and the second most common cancer in both men and women. In addition to smoking, other risk factors, such as environmental tobacco smoke, air pollution, biomass combustion, radon gas, occupational exposure, lung disease, family history of cancer, geographic variability, and genetic factors, play an essential role in developing LC. Current screening guidelines and eligibility criteria have limited efficacy in identifying LC cases (50%), as most screening programs primarily target subjects with a smoking history as the leading risk factor. Implementing LC screening programs in people who have never smoked (PNS) can significantly impact cancer-specific survival and early disease detection. However, the available evidence regarding the feasibility and effectiveness of such programs is limited. Therefore, further research on LC screening in PNS is warranted to determine the necessary techniques for accurately identifying individuals who should be included in screening programs.

Utility of block-matching and 3D filter for reproducibility of lung density and denoising in low-dose chest CT: A pilot study.

PURPOSE: This study aimed to acquire an image quality consistent with that of full-dose chest computed tomography (CT) when obtaining low-dose chest CT images and to analyze the effects of block-matching and 3D (BM3D) filters on lung density measurements and noise reduction in lung parenchyma. METHODS: Using full-dose chest CT images, we evaluated lung density measurements and noise reduction in lung parenchyma images for low-dose chest CT. Three filters (median, Wiener, and the proposed BM3D) were applied to low-dose chest CT images for comparison and analysis with images from full-dose chest CT. To evaluate lung density measurements, we measured CT attenuation at the 15th percentile of the lung CT histogram. The coefficient of variation (COV) and contrast-to-noise ratio (CNR) were used to evaluate the noise level. RESULTS: The 15th percentile of the lung CT histogram showed the smallest difference between full- and low-dose CT when applying the BM3D filter, and the highest difference between full- and low-dose CT without filters (full-dose =  - 926.28 ± 0.32, BM3D =  - 926.65 ± 0.32, and low-dose =  - 959.43 ± 0.95) (p < 0.05). The COV was smallest when applying the BM3D filter, whereas the CNR was the highest (p < 0.05). CONCLUSIONS: The results of the study prove that the BM3D filter can reduce image noise while increasing the reproducibility of the lung density, even for low-dose chest CT.

Predicting High-Risk Esophageal Varices in Cirrhosis: A Multi-Parameter Splenic CT Study.

RATIONALE AND OBJECTIVES: To explore the value of splenic hemodynamic parameters from low-dose one-stop dual-energy and perfusion CT (LD-DE&PCT) in non-invasively predicting high-risk esophageal varices (HREV) in cirrhotic patients. METHODS: We retrospectively analyzed cirrhotic patients diagnosed with esophageal varices (EV) through clinical, laboratory, imaging, and endoscopic examinations from September 2021 to December 2023 in our hospital. All patients underwent LD-DE&PCT to acquire splenic iodine concentration and perfusion parameters. Radiation dose was recorded. Patients were classified into non-HREV and HREV groups based on endoscopy. Univariate and multivariate logistic regression analysis were performed, and the prediction model for HREV was constructed. P < 0.05 was considered statistically significant. RESULTS: Univariate analysis revealed that significant differences were found in portal iodine concentration (PIC), blood flow (BF), permeability surface (PS), spleen volume (V-S), total iodine concentration (TIC), and total blood volume of the spleen (BV-S) between groups. TIC demonstrated the highest predictive value with an area under the curve (AUC) value of 0.87. Multivariate analysis showed that PIC, PS, and BV-S were independent risk factors for HREV. The logistic regression model for predicting HREV had an AUC of 0.93. The total radiation dose was 20.66 ± 4.07 mSv. CONCLUSION: Splenic hemodynamic parameters obtained from LD-DE&PCT can non-invasively and accurately assess the hemodynamic status of the spleen in cirrhotic patients with EV and predict the occurrence of HREV. Despite the retrospective study design and limited sample size of this study, these findings deserve further validation through prospective studies with larger cohorts.

Low-Dose Prasugrel vs. Standard-Dose Clopidogrel for Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Low-dose prasugrel (3.75 mg) is used as maintenance therapy for percutaneous coronary intervention; however, data on long-term outcomes are scarce.Methods and Results: We analyzed 5,392 participants in the KiCS-PCI registry who were administered low-dose prasugrel or clopidogrel at discharge between 2008 and 2018 and for whom 2-year follow-up data were available. We adjusted for confounders using matching weight analyses and multiple imputations. Similarly, we used inverse probability- and propensity score-weighted analyses. We also performed instrumental variable analyses. The primary outcomes were acute coronary syndrome (ACS) and bleeding requiring readmission. Secondary outcomes were all-cause death and a composite outcome of ACS, bleeding, heart failure, stroke, coronary bypass requiring admission, and all-cause death. In this cohort, 12.2% of patients were discharged with low-dose prasugrel. Compared with clopidogrel, low-dose prasugrel was associated with a reduced risk of ACS (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.39-0.85), bleeding (HR 0.62; 95% CI 0.40-0.97), and the composite outcome (HR 0.71; 95% CI 0.59-0.86). Inverse probability-weighted analysis yielded similar results; however, matching weight analysis without multiple imputations and propensity score-matched analyses showed similar outcomes in both groups. Instrumental variable analyses showed reduced risks of ACS and composite outcome for those on low-dose prasugrel. All-cause mortality did not differ in all analyses. CONCLUSIONS: Low-dose prasugrel demonstrates comparable outcomes to clopidogrel in terms of ACS and bleeding.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.