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.

Long COVID management: a mini review of current recommendations and underutilized modalities.

Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.

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.

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.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

The effect of low-dose photodynamic therapy using the photosensitizer chloroaluminum phthalocyanine on a scratch wound model in skin fibroblasts.

Different approaches on wound healing have been developed over the years but they suffer from high costs and adverse effects for the patients. The current paper was designed to study low dose PDT, a novel healing approach, in an in vitro fibroblasts wound healing model. Chloroaluminum phthalocyanine (AlClPc) was used as photosensitizer and was activated by a red diode laser at 661 nm. After PDT optimization, wound closure rate and reactive oxygen species were quantified by image processing and analysis. Our results revealed that wound healing rates were significantly higher in PDT treated groups than in the control. Additionally, the study revealed that a prolonged ROS increase did not promote wound closure, while a small increase acted as a trigger, resulting in faster wound closure. Concluding, low dose PDT using AlClPc enhances wound healing in vitro in a ROS dependent manner, allowing the assumption of similar positive effects in vivo.

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.

Evaluation of low-dose pediatric chest CT examination using in-house developed various age-size pediatric chest phantoms.

PURPOSE: This study aims to develop Various Age-size Pediatric Chest Phantoms (VAPC) to evaluate low-dose protocol that approximates clinical conditions achieved by low organ-specific doses and optimal image quality among the challenges of pediatric size variations. METHODS: Three original pediatric data aged 1, 4, and 7 years were used as a reference for developing VAPC phantoms. Six protocols, namely standard dose (STD) and low dose (low mA and low kV) reconstructed using Filtered Back Projection (FBP) and iterative reconstruction (IR) algorithms, were investigated. This study directly measured the lungs, heart, and spinal cord dose using LD-V1 film. Linearity, Modulation Transfer Function (MTF), Contrast to Noise Ratio (CNR), and Noise Power Spectrum (NPS) were evaluated to assess the CT image quality of the VAPC phantom. RESULTS: This study found that the mean organ-specific dose was higher than CTDIvol. A Comparison of mean lung doses showed VAPC phantom 1 (y.o.) received 74.8% and 137.2% more doses than 4 (y.o.) and 7 (y.o.), respectively. Low kV produces a lower organ dose than low mA. The linearity of CT numbers is not biased at low doses. Differences in age measures significantly influenced organ-specific dose, MTF, CNR, and NPS. CONCLUSION: Smaller pediatrics are still exposed to higher doses at low-dose examinations, whereas larger pediatrics have lower contrast resolution and increased image noise. CT number linearity is unbiased. The combination of low kV with FBP produces higher spatial resolution, while low mA with IR effectively reduces noise to detect low-contrast objects better.

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.

Combined oral low-dose cyclophosphamide endocrine therapy may improve clinical response among patients with metastatic breast cancer via Tregs in TLSs.

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.

Navigating methotrexate toxicity: Examining the therapeutic roles of folinic acid and glucarpidase.

Methotrexate (MTX) toxicity varies depending on factors such as dosing frequency (acute or repeated), dosage (low or high) and the administration route (oral, parenteral or intrathecal). Renal impairment can trigger or exacerbate MTX toxicity. Acute oral low-dose MTX (LDMTX) overdoses seldom lead to toxicity due to the saturable maximal bioavailable dose, but toxicity risks increase with repeated low doses (>3 days), high-dose MTX (HDMTX) or intrathecal poisoning. Folinic acid shares MTX transporters in the gut and cells and bypasses the MTX-induced dihydrofolate reductase inhibition. The required folinic acid dosage differs for low-dose and high-dose MTX toxicities. Acute LDMTX poisoning rarely requires folinic acid, while chronic LDMTX poisoning needs low-dose folinic acid until cellular function is restored. In HDMTX toxicities, early intravenous folinic acid administration is recommended, with dose and duration being guided by MTX concentrations and clinical improvement. In intrathecal MTX poisoning, folinic acid should be administered intravenously. Glucarpidase, a recombinant bacterial enzyme, has a high affinity for MTX and folate analogues in the intravascular or intrathecal systems. It decreases serum MTX concentrations by 90%-95% within 15 min. Its primary indication is for intrathecal MTX poisoning. It is rarely indicated in HDMTX toxicity unless patients have renal injury. However, there is no literature evidence supporting its use in HDMTX poisoning. Its use is limited by its significant cost and lack of availability. Haemodialysis can be potentially useful for MTX removal in cases where glucarpidase is not available. Additionally, fluid hydration, renal support and urine alkalinization are important adjunctive therapies for managing MTX toxicities.

Successful maintenance of a sustained molecular response in CML patients receiving low-dose tyrosine kinase inhibitors.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8-98.7) and 90.5% (95% CI: 81.3-95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction (p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research.

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

Low-dose radiation decreases Lrrk2 levels in the striatum of large mammalian brains: New venues to treat Parkinson's disease?

INTRODUCTION: Among gene mutations and variants linked to an increased risk of PD, mutations of leucine-rich repeat kinase 2 gene (LRRK2) are among the most frequently associated with early- and late-onset PD. Clinical and neuropathological characteristics of idiopathic-PD (iPD) and LRRK2-PD are similar, and these similarities suggest that the pathomechanisms between these two conditions are shared. LRRK2 mutations determine a gain-of-function and yield higher levels of lrrk2 across body tissues, including brain. On another side, recent animal studies supported the potential use of low dose radiation (LDR) to modify the pathomechanisms of diseases such as Alzheimer's disease (AD). METHODS: We assessed if a single total-body LDR (sLDR) exposure in normal swine could alter expression levels of the following PD-associated molecules: alpha-synuclein (α-syn), phosphorylated-α-synuclein (pα-syn), parkin, tyrosine hydroxylase (th), lrrk2, phosphorylated-lrrk2 (pS935-lrrk2), and some LRRK2 substrates (Rab8a, Rab12) across different brain regions. These proteins were measured in frontal cortex, hippocampus, striatum, thalamus/hypothalamus, and cerebellum of 9 radiated (RAD) vs. 6 sham (SH) swine after 28 days from a sLDR of 1.79Gy exposure. RESULTS: Western Blot analyses showed lowered lrrk2 levels in the striatum of RAD vs. SH swine (p < 0.05), with no differences across the remaining brain regions. None of the other protein levels differed between RAD and SH swine in any examined brain regions. No lrrk2 and p-lrrk2 (S935) levels differed in the lungs of RAD vs. SH swine. CONCLUSIONS: These findings show a specific striatal lrrk2 lowering effect due to LDR and support the potential use of LDR to interfere with the pathomechanisms of PD.

Efficacy and Safety of 0.03% Atropine Eye Drops in Controlling Myopia Progression: A One-Year Prospective Clinical Study.

Objective: To investigate the efficacy and safety of one-year treatment with 0.03% atropine eye drops for slowing myopia progression among children aged 6-12 years. Methods: Healthy Caucasian children aged 6-12 years with cycloplegic spherical equivalent (SE) from -1.0 D to -5.0 D and astigmatism and anisometropia ≤1.5 D were included. Changes in mean axial length (AL) and objective SE as well as changes in intraocular pressure (IOP), central corneal thickness (CCT), anterior chamber depth (ACD) and lens thickness (LT) were assessed in the 0.03% atropine eye drops group and the control group from baseline through the 1-year follow-up. The proportion of participants showing myopia progression of <0.5 D from baseline in each group and any potential side effects in 0.03% atropine group were evaluated. Results: The study involved 31 patients in the 0.03% atropine eye drops group and 41 in the control group. Administration of 0.03% atropine for 1 year resulted in a mean change in SE of -0.34 (0.44) D/year, significantly lower than the -0.60 (0.50) D/year observed in the control group (p = 0.024). The change in AL was 0.19 (0.17) mm in the 0.03% atropine group, compared to 0.31 (0.20) mm in the control group (p = 0.015). There were no significant differences in changes of IOP, CCT and LT between the groups (all p ≥ 0.05). The 0.03% atropine group had a significantly greater increase in ACD compared to the control group (p = 0.015). In total, 64.5% of patients in the 0.03% atropine group showed progression <0.5 D/year, in contrast to 39.0% in the control group (p = 0.032). Adverse events were reported in 13 (35.0%) out of 37 patients in the treatment group, leading to discontinuation of the eye drops in six (16.0%) cases. None of the adverse events were severe. Conclusions: Despite a higher incidence of adverse events, 0.03% atropine eye drops effectively slowed the progression of myopia over 1-year.

Ultra-low-dose rituximab is effective for the treatment of patients with minimal change disease - A retrospective study.

BACKGROUND PURPOSE: Rituximab (RTX),an anti-CD20 monoclonal antibody can effectively treat minimal change disease (MCD),with low toxicity and a reduced steroid dosage. The optimal dosage of RTX for treating MCD remains unclear. This study aimed to investigate the efficacy of an ultra-low-dose regimen of RTX (100 mg per week for 4 weeks) for treating MCD. METHODS: We retrospectively analyzed clinical data from 31 patients with MCD who received RTX. Seventeen patients received ultra-low-dose RTX (ULD-RTX) therapy, and 14 patients received standard-dose RTX (SD-RTX) therapy (500 mg weekly for 4 weeks). All patients were followed up for at least 6 months. RESULTS: Both groups showed significant increases in the serum albumin levels and notable decreases in the urinary protein levels in the 1st and 6th months after RTX therapy. There were no significant differences in the plasma albumin or urinary protein levels between the groups (p > 0.05). B-cell depletion was observed in all patients after 1 month of RTX administration. At 6 months after RTX treatment, the remission rate was 93% in the SD-RTX group and 88% in the ULD-RTX group (p > 0.05). The ULD-RTX therapy incurred lower costs than did the SD-RTX therapy. One patient in the SD-RTX group developed community-acquired pneumonia. CONCLUSION: Ultra-low-dose RTX is effective at inducing remission in patients with MCD at a lower cost.

Low-dose-rate induces more severe cognitive impairment than high-dose-rate in rats exposed to chronic low-dose γ-radiation.

Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR). Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus. Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group. Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.

Deep learning-based low-dose CT simulator for non-linear reconstruction methods.

BACKGROUND: Computer algorithms that simulate lower-doses computed tomography (CT) images from clinical-dose images are widely available. However, most operate in the projection domain and assume access to the reconstruction method. Access to commercial reconstruction methods may often not be available in medical research, making image-domain noise simulation methods useful. However, the introduction of non-linear reconstruction methods, such as iterative and deep learning-based reconstruction, makes noise insertion in the image domain intractable, as it is not possible to determine the noise textures analytically. PURPOSE: To develop a deep learning-based image-domain method to generate low-dose CT images from clinical-dose CT (CDCT) images for non-linear reconstruction methods. METHODS: We propose a fully image domain-based method, utilizing a series of three convolutional neural networks (CNNs), which, respectively, denoise CDCT images, predict the standard deviation map of the low-dose image, and generate the noise power spectra (NPS) of local patches throughout the low-dose image. All three models have U-net-based architectures and are partly or fully three-dimensional. As a use case for this study and with no loss of generality, we use paired low-dose and clinical-dose brain CT scans. A dataset of 326 $\hskip.001pt 326$ paired scans was retrospectively obtained. All images were acquired with a wide-area detector clinical system and reconstructed using its standard clinical iterative algorithm. Each pair was registered using rigid registration to correct for motion between acquisitions. The data was randomly partitioned into training ( 251 $\hskip.001pt 251$ samples), validation ( 25 $\hskip.001pt 25$ samples), and test ( 50 $\hskip.001pt 50$ samples) sets. The performance of each of these three CNNs was validated separately. For the denoising CNN, the local standard deviation decrease, and bias were determined. For the standard deviation map CNN, the real and estimated standard deviations were compared locally. Finally, for the NPS CNN, the NPS of the synthetic and real low-dose noise were compared inside and outside the skull. Two proof-of-concept denoising studies were performed to determine if the performance of a CNN- or a gradient-based denoising filter on the synthetic low-dose data versus real data differed. RESULTS: The denoising network had a median decrease in noise in the cerebrospinal fluid by a factor of 1.71 $1.71$ and introduced a median bias of + 0.7 $ + 0.7$ HU. The network for standard deviation map estimation had a median error of + 0.1 $ + 0.1$ HU. The noise power spectrum estimation network was able to capture the anisotropic and shift-variant nature of the noise structure by showing good agreement between the synthetic and real low-dose noise and their corresponding power spectra. The two proof of concept denoising studies showed only minimal difference in standard deviation improvement ratio between the synthetic and real low-dose CT images with the median difference between the two being 0.0 and +0.05 for the CNN- and gradient-based filter, respectively. CONCLUSION: The proposed method demonstrated good performance in generating synthetic low-dose brain CT scans without access to the projection data or to the reconstruction method. This method can generate multiple low-dose image realizations from one clinical-dose image, so it is useful for validation, optimization, and repeatability studies of image-processing algorithms.