Prognostic Role of Pre-Treatment Body Composition Parameters in Patients Undergoing First-Line Immunotherapy for Metastatic Renal Cell Carcinoma.

Purpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan-Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes. Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively). Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways in which inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that mice in which IPMK knockout is deleted, specifically in the skeletal muscle, displayed an increased body weight, disrupted glucose tolerance, and reduced exercise tolerance under the normal diet. Moreover, these changes were associated with an increased accumulation of triglyceride in skeletal muscle. Furthermore, we have confirmed that a loss of IPMK led to reduced beta-oxidation, increased triglyceride accumulation, and impaired insulin response in IPMK-deficient muscle cells. Thus, our results suggest that IPMK mediates the whole-body metabolism via regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes.

High level of gamma-glutamyltransferase is a possible risk factor for psoriasis: A nationwide population-based cohort study.

Background Gamma-glutamyl transferase (GGT) has been associated with coronary heart disease, diabetes mellitus, and hypertension, but its association with psoriasis has not yet been elucidated. Aims We conducted this study to determine the association between the risk of psoriasis and the serum GGT. Methods We conducted a nationwide population-based study. A total of 9,939,350 people met the enrolment criteria. The study population was classified into four groups based on GGT levels and the risk of psoriasis was calculated for each group. Results The incidence rates of psoriasis per 1,000 person-years were 2.96105 and 3.68577 in the lowest and highest GGT groups, respectively. After adjusting for age, sex, income, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol intake, exercise, and body mass index, the highest GGT group showed a significantly increased risk of developing psoriasis (hazard ratio: 1.057, 95% confidence interval: 1.044-1.07). This risk of psoriasis was significantly higher among the old age group (hazard ratio: 1.162, 95% confidence interval: 1.128-1.197) and women (hazard ratio: 1.14, 95% confidence interval: 1.117-1.164). Limitations The limitations of this study included the retrospective design, International Classification of Diseases code-based diagnosis, small hazard ratio, and non-availability of data on covariates. Conclusion The GGT level was found to be an independent risk factor for developing psoriasis.

Epidemiologic relationship between alcohol flushing and smoking in the Korean population: the Korea National Health and Nutrition Examination Survey.

Although facial flushing after drinking alcohol (alcohol flushing response) is common in Asian populations, the epidemiological features in a large sample have been investigated in only a few studies. This study assessed the epidemiologic characteristics and associated factors for alcohol flushing in a Korean population. This study was based on data collected during the 2019 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5572 Korean adults was included in the general population group, and the alcohol flushing group consisted of 2257 participants. Smoking and physical activity were evaluated as possible associated factors for alcohol flushing. The overall prevalence of alcohol flushing was estimated at 40.56% of the general population (43.74% in males and 37.4% in females), and the prevalence was highest at 60-69 years of age and lowest in individuals older than 80 years. Occasional, frequent, and persistent alcohol flushing was reported by 11.9%, 3.7% and 15.0% of current flushers, among whom persistent flushers consumed the least amount of alcohol. Subjects who currently smoke had a higher propensity of alcohol flushing (adjusted OR 1.525, 95% CI 1.2-1.938), and subjects with smoking history of 20-29 pack-years (PYs) showed the highest association (adjusted OR 1.725, 95% CI 1.266-2.349) with alcohol flushing after adjustment for confounders. In contrast, significant association was not found between physical activity and alcohol flushing. The results demonstrated that current smoking status is shown to be significantly associated with alcohol flushing, and that current smokers with a history of smoking ≥ 20 PYs had a higher likelihood of alcohol flushing than non-smokers or ex-smokers.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

North American Cancer Center Clinical Research Capacity and Benchmarking in the Postpandemic Era.

PURPOSE: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here. METHODS: The 28 question 2023 survey was sent to directors of AACI's clinical member cancer centers. Survey participation was voluntary, no compensation was provided, and data requested covered operations during 2022. Definitions were consistent with National Cancer Institute (NCI) CCTO reporting requirements and AACI staff anonymously compiled results for descriptive statistical reporting. RESULTS: The survey response rate was 61% (60/99). The median annual CCTO budget was $11.5 million (M) US dollars (USD) versus $8.2M USD in 2018. These budgets support a median of 150 FTEs versus 104 previously, and a median total of 384 versus 280 interventional treatment trials and a median of 479 versus 531 interventional treatment accruals. Sources of support for CCTO annual budgets were primarily from industry revenue (45.3%) or institutional support (31.7%). Nearly 60% of centers reported activating NCI-sponsored studies within 90 days but only 9% reported meeting a 90-day activation timeline for industry sponsored studies. CONCLUSION: Contemporary benchmarks for CCTO operations through this survey demonstrate larger staff sizes, larger budgets, more trials supported, but fewer patients enrolled to interventional treatment trials in comparison with 2018. These data shine a critical light on the increasing complexity of cancer clinical trials, the importance of external funding sources, and necessary operational efficiency upgrades to provide cutting-edge cancer research and care.

A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia.

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed.This trial was registered at www.clinicaltrials.gov as #NCT02773732.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice.

Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.

Effects of goal-directed analgesia using the analgesia nociception index in children undergoing surgery for moyamoya disease: A randomised controlled trial.

BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µg kg -1  h -1 ) compared with the Standard group (0.30 ±â€Š0.12 and 0.39 ±â€Š0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P  = 0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24 h and maximum pain within 24 h (1 [0 to 2] vs. 3 [2 to 5]; P  = 0.004, 1 [0 to 2] vs. 3 [1 to 4]; P  = 0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P  = 0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P  = 0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24 h with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212.

Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia: A retrospective analysis.

BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10 µm or less and 2.5 µm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 µm or less in diameter (≥81 µg m -3 , 17/275, 6.2%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 µg m -3 , 472/12 900, 3.7%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P  = 0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 µm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.

Genetic polymorphisms linked to extreme postorthodontic external apical root resorption in Koreans.

BACKGROUND: External apical root resorption (EARR) is a common undesirable outcome of orthodontic treatment, this study aimed to identify genetic polymorphisms associated with the susceptibility to extreme orthodontic-induced EARR in a Korean population using extreme phenotype analysis sampling. METHODS: Genomic DNA was isolated from the saliva of 77 patients who underwent orthodontic treatment involving two maxillary premolar extractions. The patients were divided into two groups based on EARR values measured on periapical radiographs: The significant resorption group (SG, EARR ≥ 4 mm) and the normal group (NG, EARR < 2 mm). In the NG group, patients with EARR < 1 mm were named the non-resorption group (NonG). Targeted next-generation sequencing was performed using the screened single nucleotide polymorphisms (SNPs), and firth logistic regression analysis was used to determine genetic associations with EARR. Haplotype-based association analysis was performed for specific SNPs. RESULTS: SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 were found to be significantly associated with severe EARR (p < 0.05, pre-Bonferroni correction p-values). Additionally, the haplotype CCA of rs17525809, rs208294, and rs1718119 P2RX7 had a higher frequency in the SG group. CONCLUSION: Extreme phenotype analysis has identified eleven SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 that are associated with severe root resorption in the Korean population. These findings will contribute to the development of predictive diagnostic tools for identifying severe root resorption that may occur during orthodontic treatment.

Intravital Imaging of the Human Cornea Reveals the Differential Effects of Season on Innate and Adaptive Immune Cell Morphodynamics.

PURPOSE: Defining how the in vivo immune status of peripheral tissues is shaped by the external environment has remained a technical challenge. We recently developed Functional in vivo confocal microscopy (Fun-IVCM) for dynamic, longitudinal imaging of corneal immune cells in living humans. This study investigated the effect of seasonal-driven environmental factors on the morphodynamic features of human corneal immune cell subsets. DESIGN: Longitudinal, observational clinical study. PARTICIPANTS: Sixteen healthy participants (aged 18-40 years) attended 2 visits in distinct seasons in Melbourne, Australia (Visit 1, November-December 2021 [spring-summer]; Visit 2, April-June 2022 [autumn-winter]). METHODS: Environmental data were collected over each period. Participants underwent ocular surface examinations and corneal Fun-IVCM (Heidelberg Engineering). Corneal scans were acquired at 5.5 ± 1.5-minute intervals for up to 5 time points. Time-lapse Fun-IVCM videos were created to analyze corneal immune cells, comprising epithelial T cells and dendritic cells (DCs), and stromal macrophages. Tear cytokines were analyzed using a multiplex bead-based immunoassay. MAIN OUTCOME MEASURES: Difference in the density, morphology, and dynamic parameters of corneal immune cell subsets over the study periods. RESULTS: Visit 1 was characterized by higher temperature, lower humidity, and higher air particulate and pollen levels compared with Visit 2. Clinical ocular surface parameters and the density of immune cell subsets were similar across visits. At Visit 1 , corneal epithelial DCs were larger, with a lower dendrite probing speed (0.38 ± 0.21 vs. 0.68 ± 0.33 µm/min; P < 0.001) relative to Visit 2; stromal macrophages were more circular and had less dynamic activity (Visit 1, 7.2 ± 1.9 vs. Visit 2, 10.3 ± 3.7 dancing index; P < 0.001). Corneal T cell morphodynamics were unchanged across periods. Basal tear levels of interleukin 2 and CXCL10 were relatively lower during spring-summer. CONCLUSIONS: This study identifies that the in vivo morphodynamics of innate corneal immune cells (DCs, macrophages) are modified by environmental factors, but such effects are not evident for adaptive immune cells (T cells). The cornea is a potential in vivo window to investigate season-dependent environmental influences on the human immune system. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus.

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.

RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Determination of optimal positive end-expiratory pressure using electrical impedance tomography in infants under general anesthesia: Comparison between supine and prone positions.

AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.

Ultrasound and CT findings of subcutaneous metastases in trunk and pelvis: a comprehensive analysis.

OBJECTIVE: This study aimed to describe the ultrasound, CT findings, and clinical manifestations of pathologically confirmed metastases involving the subcutaneous fat layer of the trunk and pelvis. MATERIALS AND METHODS: We included 30 patients with subcutaneous metastases in the trunk and pelvis, verified by ultrasound-guided biopsy. We comprehensively reviewed ultrasound findings of all 30 patients and contrast-enhanced CT findings of 25 patients obtained before biopsy. Medical records were reviewed, including primary malignancy type, presence of coexisting distant metastasis, and detection method leading to biopsy referral. RESULTS: Most subcutaneous metastases were heterogeneously hypoechoic (86.7%) with well-defined margins (80.0%), lobulated (46.7%) or round-to-oval (40.0%) shape, and vascularity (96.7%). Metastases frequently exhibited no contact (53.3%) or focal contact with deep peripheral fascia, resulting in acute contact angle formation (30.0%). Common CT manifestations included central low attenuation with peripheral rim-like enhancement (60.0%) or well-circumscribed lesion with heterogeneous enhancement (32.0%). Lung cancer (46.7%) was the prevalent primary malignancy. CT was the predominant detection method (56.7%). Coexisting subcutaneous metastases were present in 50.0% of cases, and distant metastases (less subcutaneous metastases) were observed in 90.0% of patients. CONCLUSION: This study describes typical imaging findings of subcutaneous metastases involving the trunk and pelvis. CT may play a crucial role in their early detection, and our results may assist radiologists in their diagnosis.

Effects on Lung Tissue After Breast Cancer Radiation: Comparing Photon and Proton Therapies.

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.