Sex-Specific Disparities in Clinical Outcomes After Transcatheter Aortic Valve Replacement Among Different Racial Populations.

Background: Sex-related disparities in clinical outcomes following transcatheter aortic valve replacement (TAVR) and the impact of sex on clinical outcomes after TAVR among different racial groups are undetermined. Objectives: This study assessed whether sex-specific differences in baseline clinical and anatomical characteristics affect clinical outcomes after TAVR and investigated the impact of sex on clinical outcomes among different racial groups. Methods: The TP-TAVR (Trans-Pacific TAVR) registry is a multinational cohort study of patients with severe aortic stenosis who underwent TAVR at 2 major centers in the United States and 1 major center in South Korea. The primary outcome was a composite of death from any cause, stroke, or rehospitalization after 1 year. Results: The incidence of the primary composite outcome was not significantly different between sexes (27.9% in men vs 28% in women; adjusted HR: 0.97; 95% CI: 0.79-1.20). This pattern was consistent in Asian (23.5% vs 23.3%; adjusted HR: 0.99; 95% CI: 0.69-1.41) and non-Asian (30.8% vs 31.6%; adjusted HR: 0.95; 95% CI: 0.72-1.24) cohorts, without a significant interaction between sex and racial group (P for interaction = 0.74). The adjusted risk for all-cause mortality was similar between sexes, regardless of racial group. However, the adjusted risk of stroke was significantly lower in male patients than in female patients, which was more prominent in the non-Asian cohort. Conclusions: Despite significantly different baseline and procedural characteristics, there were no sex-specific differences in the adjusted 1-year rates of primary composite outcomes and all-cause mortality, regardless of different racial groups. (Transpacific TAVR registry [TP-TAVR]; NCT03826264).

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

BCG-booster vaccination with HSP90-ESAT-6-HspX-RipA multivalent subunit vaccine confers durable protection against hypervirulent Mtb in mice.

The quest for effective and enhanced multiantigenic tuberculosis (TB) subunit vaccine necessitates the induction of a protective pathogen-specific immune response while circumventing detrimental inflammation within the lung milieu. In line with this goal, we engineered a modified iteration of the quadrivalent vaccine, namely HSP90-ESAT-6-HspX-RipA (HEHR), which was coupled with the TLR4 adjuvant, CIA09A. The ensuing formulation was subjected to comprehensive assessment to gauge its protective efficacy against the hypervirulent Mycobacterium tuberculosis (Mtb) Haarlem clinical strain M2, following a BCG-prime boost regimen. Regardless of vaccination route, both intramuscular and subcutaneous administration with the HEHR vaccine exhibited remarkable protective efficacy in significantly reducing the Mtb bacterial burden and pulmonary inflammation. This underscores its notably superior protective potential compared to the BCG vaccine alone or a former prototype, the HSP90-E6 subunit vaccine. In addition, this superior protective efficacy was confirmed when testing a tag-free version of the HEHR vaccine. Furthermore, the protective immune determinant, represented by durable antigen-specific CD4+IFN-γ+IL-17A+ T-cells expressing a CXCR3+KLRG1- cell surface phenotype in the lung, was robustly induced in HEHR-boosted mice at 12 weeks post-challenge. Collectively, our data suggest that the BCG-prime HEHR boost vaccine regimen conferred improved and long-term protection against hypervirulent Mtb strain with robust antigen-specific Th1/Th17 responses.

Longitudinal immune kinetics of COVID-19 booster versus primary series vaccination: Insight into the annual vaccination strategy.

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9-12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9-12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

Evaluating the Clinical Utility of Brachial Plexus Block for Reducing Opioid Exposure in Pediatric Elbow Fracture Surgery: A Retrospective Cohort Study.

Background and Objectives: Reducing opioid exposure in common pediatric surgeries is of paramount importance. This study aimed to assess the efficacy of regional nerve blocks in reducing opioid exposure while preserving high success rates. Materials and Methods: We conducted a retrospective matched cohort study (1:1) including patients with elbow fractures < 12 years old who underwent treatment with percutaneous pinning. Patients were divided into general-anesthesia (GA) and GA-followed-by-supraclavicular-brachial-plexus-block (GA-SCB) groups. The primary outcome was the number of patients administered postoperative rescue opioids. The secondary outcomes included intraoperative and postoperative opioid administration, the time to first request for rescue analgesia, pain scores, block success rate, block performing time, and block-related complications. Results: In a total of 478 patients, 363 underwent percutaneous pinning, and 86 were cohort-matched (GA: n = 43, GA-SCB: n = 43). On the first postoperative day, 34 (79.0%) patients in the GA group were administered postoperative rescue opioids, compared with 12 (27.9%) in the GA-SCB group (p < 0.001). All the patients in the GA-SCB group were opioid-free during the intraoperative period. No SCB-associated complications were observed. Total opioid consumption was significantly lower in the GA-SCB group than in the GA group until the first postoperative day (GA vs. GA-SCB, 3.2 ± 3.0 mg vs. 0.9 ± 1.8 mg, p < 0.001). Conclusions: SCB application in pediatric patients who underwent elbow fracture surgery significantly reduced opioid exposure and had a high success rate when performed using ultrasound guidance by an expert. Furthermore, the complication risk and surgical delay were minimal.

Comparative Analysis of CT Findings and Clinical Outcomes in Adult Patients With Disseminated and Localized Pulmonary Nocardiosis.

BACKGROUND: Pulmonary nocardiosis is a rare opportunistic infection with occasional systemic dissemination. This study aimed to investigate the computed tomography (CT) findings and prognosis of pulmonary nocardiosis associated with dissemination. METHODS: We conducted a retrospective analysis of patients diagnosed with pulmonary nocardiosis between March 2001 and September 2023. We reviewed the chest CT findings and categorized them based on the dominant CT findings as consolidation, nodules and/or masses, consolidation with multiple nodules, and nodular bronchiectasis. We compared chest CT findings between localized and disseminated pulmonary nocardiosis and identified significant prognostic factors associated with 12-month mortality using multivariate Cox regression analysis. RESULTS: Pulmonary nocardiosis was diagnosed in 75 patients, of whom 14 (18.7%) had dissemination, including involvement of the brain in 9 (64.3%) cases, soft tissue in 3 (21.4%) cases and positive blood cultures in 3 (21.4%) cases. Disseminated pulmonary nocardiosis showed a higher frequency of cavitation (64.3% vs. 32.8%, P = 0.029) and pleural effusion (64.3% vs. 29.5%, P = 0.014) compared to localized infection. The 12-month mortality rate was 25.3%. The presence of dissemination was not a significant prognostic factor (hazard ratio [HR], 0.80; confidence interval [CI], 0.23-2.75; P = 0.724). Malignancy (HR, 9.73; CI, 2.32-40.72; P = 0.002), use of steroid medication (HR, 3.72; CI, 1.33-10.38; P = 0.012), and a CT pattern of consolidation with multiple nodules (HR, 4.99; CI, 1.41-17.70; P = 0.013) were associated with higher mortality rates. CONCLUSION: Pulmonary nocardiosis with dissemination showed more frequent cavitation and pleural effusion compared to cases without dissemination, but dissemination alone did not affect the mortality rate of pulmonary nocardiosis.

Immunogenicity and protective efficacy of RipA, a peptidoglycan hydrolase, against Mycobacterium tuberculosis Beijing outbreak strains.

Given that individuals with latent tuberculosis (TB) infection represent the major reservoir of TB infection, latency-associated antigens may be promising options for development of improved multi-antigenic TB subunit vaccine. Thus, we selected RipA, a peptidoglycan hydrolase required for efficient cell division of Mycobacterium tuberculosis (Mtb), as vaccine candidate. We found that RipA elicited activation of dendritic cells (DCs) by induction of phenotypic maturation, increased production of inflammatory cytokines, and prompt stimulation of MAPK and NF-κB signaling pathways. In addition, RipA-treated DCs promoted Th1-polarzied immune responses of naïve CD4+ T cells with increased proliferation and activated T cells from Mtb-infected mice, which conferred enhanced control of mycobacterial growth inside macrophages. Moreover, mice immunized with RipA formulated in GLA-SE adjuvant displayed remarkable generation of Ag-specific polyfunctional CD4+ T cells in both lung and spleen. Following an either conventional or ultra-low dose aerosol challenges with 2 Mtb Beijing clinical strains, RipA/GLA-SE-immunization was not inferior to BCG by mediating protection as single Ag. Collectively, our findings highlighted that RipA could be a novel candidate as a component of multi-antigenic TB subunit vaccines.

Effective remimazolam loading dose for adequate sedation in regional anesthesia.

PURPOSE: Remimazolam is a novel ultrashort-acting sedative considered appropriate for continuous infusion during surgical procedures. Nevertheless, information regarding its loading dose for sedation during surgery is limited. We aimed to determine the 90% effective dose (ED90) of the remimazolam loading dose for sedation in patients undergoing limb surgery under regional anesthesia. METHODS: We included 50 patients aged 19-80 yr undergoing limb surgery under regional anesthesia. After regional anesthesia, remimazolam besylate was administered at the assigned dose. For ten minutes after the initiation of loading, the level of sedation was evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the ED90 based on whether patients reached a MOAA/S score of ≤ 3 points (loss of response to verbal command) within ten minutes. The secondary outcomes were the ED50 and the estimated effect site and plasma concentration at the time of achieving successful sedation. RESULTS: In total, 49 patients were included in the final analysis, and adequate sedation with the assigned loading dose was successful in 42 patients. The log-logistic function showed that the ED90 and ED50 were 0.617 mg·kg-1·hr-1 (95% confidence interval [CI], 0.511 to 0.722; 98% CI, 0.492 to 0.741) and 0.438 mg·kg-1·hr-1 (95% CI, 0.335 to 0.541; 98% CI, 0.315 to 0.560), respectively. CONCLUSION: The ED90 of the remimazolam loading dose to achieve adequate sedation in patients undergoing limb surgery under regional anesthesia was 0.617 mg·kg-1·hr-1 (95% CI, 0.511 to 0.722; 98% CI, 0.492 to 0.741). STUDY REGISTRATION: ClinicalTrials.gov (NCT05340335); first posted 22 April 2022.

RéSUMé: OBJECTIF: Le remimazolam est un nouveau sédatif à action ultracourte considéré comme approprié pour la perfusion continue pendant les interventions chirurgicales. Néanmoins, les informations concernant sa dose de charge pour la sédation pendant la chirurgie sont limitées. Notre objectif était de déterminer la dose efficace à 90 % (DE90) de la dose de charge de remimazolam pour la sédation chez la patientèle bénéficiant d'une chirurgie d'un membre sous anesthésie régionale. MéTHODE: Cinquante personnes âgées de 19 à 80 ans bénéficiant d'une chirurgie des membres sous anesthésie régionale ont été incluses. Après l'anesthésie régionale, du bésylate de remimazolam a été administré à la dose assignée. Pendant dix minutes après le début de la charge, le niveau de sédation a été évalué à l'aide de l'échelle modifiée d'évaluation de la vigilance/sédation par l'observateur (MOAA/S). Le critère d'évaluation principal était la DE90 selon que les patient·es ont atteint un score MOAA/S de ≤ 3 points (perte de réponse à la commande verbale) dans les dix minutes. Les critères d'évaluation secondaires étaient la DE50 et l'estimation du site d'effet et de la concentration plasmatique au moment de l'obtention d'une sédation réussie. RéSULTATS: Au total, 49 personnes ont été incluses dans l'analyse finale, et une sédation adéquate avec la dose de charge assignée a été couronnée de succès chez 42 d'entre elles. La fonction log-logistique a montré que les DE90 et DE50 étaient de 0,617 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741) et 0,438 mg·kg−1·h−1 (IC 95 %, 0,335 à 0,541; IC 98 %, 0,315 à 0,560), respectivement. CONCLUSION: La DE90 de la dose de charge de remimazolam pour obtenir une sédation adéquate chez les personnes bénéficiant d'une chirurgie des membres sous anesthésie régionale était de 0,617 mg·kg−1·h−1 (IC 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741). ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05340335); première publication le 22 avril 2022.

Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: implications of immune imprinting and interference.

OBJECTIVES: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination. METHODS: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay. RESULTS: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups. DISCUSSION: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains.

Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data.

PURPOSE: We aimed to determine the current application and survival trends of hematopoietic stem cell transplantation (HSCT) among Korean children and adolescents with cancer. MATERIALS AND METHODS: Data of patients aged < 20 years with KCD-10 (Korean Classifications of Diseases, 10th revision) C codes and specific designation codes were collected from the National Health Insurance Service database. Thirty claim codes for HSCT were included, and data from 2009 to 2019 were analyzed. RESULTS: The operational definition of pediatric cancer yielded an annual average of 2,000, with annual cases decreasing. In 2019, 221 HSCTs were performed, a decrease from the ten-year average of 276. Allografts outnumbered autografts with a ratio of 1.5:1. The source of allograft was bone marrow in 15% of patients in 2009; however, it substantially decreased to 3.3% in 2019. Furthermore, 70.5% of allogeneic HSCT used peripheral blood stem cell (PBSC) grafts, which increased to 89.3% by 2015. Cord blood utilization markedly decreased to 2.7% in 2018. The 5-year overall survival (OS) rate of all patients was 85.1%. Overall mortality decreased among patients who underwent recent HSCT, and they exhibited a higher 5-year OS rate. CONCLUSION: In Korea, the number of pediatric patients with cancer is declining; however, the ratio of transplants to all patients remains constant. Patients who recently underwent transplantation showed better survival rates, possibly due to HSCT optimization. Korea showed a substantially greater PBSC utilization in pediatric HSCT. An in-depth examination encompassing donor relations and cause of death with a prospective registry is required in future studies.

Mechanical ventilation practices in Asian intensive care units: A multicenter cross-sectional study.

PURPOSE: This study investigated current practices of mechanical ventilation in Asian intensive care units, focusing on tidal volume, plateau pressure, and positive end-expiratory pressure (PEEP). MATERIALS AND METHODS: In this multicenter cross-sectional study, data on mechanical ventilation and clinical outcomes were collected. Predictors of mortality were analyzed by univariate and multivariable logistic regression. A scoring system was generated to predict 28-day mortality. RESULTS: A total of 1408 patients were enrolled. In 138 patients with acute respiratory distress syndrome (ARDS), 65.9% were on a tidal volume ≤ 8 ml/kg predicted body weight (PBW), and 71.3% were on sufficient PEEP. In 1270 patients without ARDS, 88.8% were on a tidal volume ≤ 10 ml/kg PBW. A plateau pressure < 30 cmH2O was measured in 92.2% of patients. Mortality rates increased from 13% to 74% as the generated predictive score increased from 5 to ≥8.5. Income classification, age, SOFA score, PaO2/FiO2 ratio, plateau pressure, number of vasopressors, and steroid use were associated with mortality. CONCLUSIONS: In Asia, low tidal volume ventilation and sufficient PEEP were underused in patients with ARDS. The majority of patients without ARDS were on intermediate tidal volumes. Country income, age, and severity of illness were associated with mortality.

Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Subclinical aortic valve complex (valvular and perivalvular) thrombus is not rare after transcatheter aortic valve replacement (TAVR). The risk factors and clinical implications of these findings remain uncertain. OBJECTIVES: This study sought to evaluate the frequency, predictors, and clinical outcome of aortic valve complex thrombus after TAVR. METHODS: In the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) trial comparing edoxaban vs dual antiplatelet therapy in TAVR patients without an indication for chronic anticoagulation, the frequency of valvular (subclinical leaflet thrombus) and perivalvular (supravalvular, subvalvular, and sinus of Valsalva) thrombus was evaluated by 4-dimensional computed tomography at 6 months. The association of these phenomena with new cerebral thromboembolism on brain magnetic resonance imaging, neurologic and neurocognitive dysfunction, and clinical outcomes was assessed. RESULTS: Among 211 patients with 6-month computed tomography evaluations, 91 patients (43.1%) had thrombus at any aortic valve complex, 30 (14.2%) patients had leaflet thrombus, and 78 (37.0%) patients had perivalvular thrombus. A small maximum diameter of the stent at the valve level and low body surface area were independent predictors of aortic valve complex and perivalvular thrombus, and decreased renal function was an independent predictor of leaflet thrombus. No significant differences were observed in new cerebral lesions, neurologic or neurocognitive functions, or clinical outcomes among patients with or without valvular or perivalvular thrombus. CONCLUSIONS: Subclinical aortic valve complex (valvular and perivalvular) thrombus was common in patients who had undergone successful TAVR. However, these imaging phenomena were not associated with new cerebral thromboembolism, neurologic or neurocognitive dysfunction, or adverse clinical outcomes. (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement [ADAPT-TAVR]; NCT03284827).

Differential Diagnosis of Thickened Gastric Wall between Hypertrophic Gastritis and Borrmann Type 4 Advanced Gastric Cancer.

Background/Aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them. Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness. Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4. Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study.

Purpose: The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few research examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. The aim of this sub-study was to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex. Materials and Methods: This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea. Results: A total of 1,170 patients with colorectal, gastric, or non-small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less post-operative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits. Conclusion: Our study found that females experienced a higher incidence of multiple any grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Hepatobiliary phase imaging in cirrhotic patients using compressed sensing and controlled aliasing in parallel imaging results in higher acceleration.

OBJECTIVE: We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15 s and 1.3 × 1.3 × 3 mm3 and 16 s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. RESULTS: CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CONCLUSIONS: CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. CLINICAL RELEVANCE STATEMENT: Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. KEY POINTS: • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.

Detecting residual soft tissue sarcoma after unplanned excision; model-free analysis of dynamic contrast-enhanced MRI at short-term follow-up.

OBJECTIVES: To evaluate diagnostic utility of additional DCE-MRI for detecting residual soft tissue sarcomas (STS) after unplanned excision (UPE). METHODS: We retrospectively evaluated 32 patients with UPE of STS, followed by conventional MRI with DCE-MRI and wide excision (WE), between November 2019 and January 2022. Residual tumors on conventional MRI were categorized into three groups: Lesion-type-0, no abnormal enhancement, Lesion-type-1, an indeterminate lesion, and Lesion-type-2, a definite enhancing nodule. On DCE-MRI, ROIs were manually placed on enhancing areas of suspected residual tumor. The mean and 95th percentile values of AUC of time-intensity curve were calculated at 60, 90, and 120 s of Enhancement-cycle-1 and -2. Optimal DCE parameters were identified by ROC analysis. Diagnostic performance of conventional MRI and DCE-MRI was compared using McNemar's test. RESULTS: On WE, residual tumor was present in 23 (71.9%) of 32 patients. On MRI, Lesion-type-1 was found in 16/32 (50%) patients and Lesion-type-2 in 16/32 (50%). The optimal DCE parameter was the 95th percentile value of AUC at 120s of Enhancement-cycle-2. The sensitivity, specificity, and AUC were as follows: 65.2% (95% CI, 45.8-85.7%), 88.9% (CI, 68.4-100%), and 0.77 (CI, 0.62-0.92) for conventional MRI, and 100%, 55.6% (CI, 23.1-88.0%), and 0.78 (CI, 0.61-0.95) for combined conventional and DCE-MRI. CONCLUSIONS: Additional DCE-MRI aided in detecting residual STS after UPE, particularly in cases without definite soft tissue nodular enhancement. ADVANCES IN KNOWLEDGE: Close follow up may be suggested for patients showing abnormality in DCE-MRI, with more suspicion of residual tumor.

Association of changes in body mass index and waist circumference with cardiovascular risk in non-alcoholic fatty liver disease: A nationwide study.

BACKGROUND: We investigated whether changes in body mass index (BMI) and waist circumference (WC) are associated with cardiovascular risk in patients with NAFLD using a nationwide dataset. METHODS: Using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in Korea, a total of 19,057 subjects who underwent two consecutive medical check-ups (2009-2010 and 2011-2012) and who had a fatty-liver index (FLI) value of ≥ 60 were included in the analysis. Cardiovascular events were defined as the occurrence of stroke or transient ischemic attack, coronary heart disease, and cardiovascular death. RESULTS: After multivariable adjustment, the risk of cardiovascular events was significantly lower in subjects with decreases in both BMI and WC (HR, 0.83; 95% CI, 0.69-0.99) and those with increased BMI and decreased WC (HR, 0.74; 95% CI, 0.59-0.94) when compared with those who showed increases in both BMI and WC. The effect of cardiovascular risk reduction among the group with increased BMI but decreased WC was particulary pronounced among those who had metabolic syndrome during the second check-up (HR, 0.63; 95% CI 0.43-0.93, p for interaction 0.02). CONCLUSIONS: Changes in BMI and WC were significantly associated with cardiovascular risk in NAFLD patients. NAFLD patients with increased BMI and decreased WC had the lowest cardiometabolic risk.

Ulnar neuropathy at the elbow: associations of pre-operative DTI parameters with clinical outcomes after cubital tunnel decompression.

OBJECTIVES: To evaluate whether DTI parameters of the ulnar nerve at the elbow are associated with clinical outcomes in patients receiving cubital tunnel decompression (CTD) surgery for ulnar neuropathy. METHODS: This retrospective study included 21 patients with cubital tunnel syndrome who received CTD surgery between January 2019 and November 2020. All patients underwent pre-operative elbow MRI, including DTI. Region-of-interest analysis was performed on the ulnar nerve at three levels around the elbow: above (level 1), cubital tunnel (level 2), and below (level 3). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated on three sections at each level. Clinical data on symptom improvement in respect to pain and tingling sensation after CTD were recorded. Logistic regression analysis was used to compare DTI parameters of the nerve at three levels and the entire nerve course between patients with and without symptom improvement after CTD. RESULTS: After CTD, 16 patients showed improvement in symptoms, but five did not. ROC analysis of DTI parameters showed that AUCs of FA, AD, and MD were higher at level 1 than at levels 2 and 3, with FA showing the highest AUC (level 1: FA, 0.7104 [95% CI, 0.5206-0.9002] vs AD, 0.6521 [95% CI, 0.4900-0.8142] vs MD, 0.6153 [95% CI, 0.4187-0.8119]). CONCLUSION: In patients who underwent CTD surgery for ulnar neuropathy at the elbow, the DTI parameters of FA, AD, and MD above the cubital tunnel level were associated with clinical outcomes, with FA showing the strongest associations. KEY POINTS: • After CTD surgery for ulnar neuropathy at the elbow, persistent symptoms may be observed, depending on symptom severity. • DTI parameters of the ulnar nerve at the elbow showed differences in their capacity for discriminating between patients with and without symptom improvement following CTD surgery, with this capacity depending on the nerve level at the elbow. • FA, AD, and MD measured above the cubital tunnel on pre-operative DTI may be associated with surgical outcomes, with FA showing the strongest association (AUC at level 1, 0.7104 [95% CI, 0.5206-0.9002]).

Dysregulation of Lipid Droplet Protein Expression in Adipose Tissues and Association with Metabolic Risk Factors in Adult Females with Obesity and Type 2 Diabetes.

BACKGROUND: Adipocyte dysregulation of lipid droplet (LD) metabolism caused by altered expression of LD proteins contributes to obesity-related metabolic diseases. OBJECTIVES: We aimed to investigate whether expression levels of PLIN1, CIDEA, and CIDEC were altered in adipose tissues of women with obesity and type 2 diabetes and whether their alterations were associated with metabolic risk factors. METHODS: Normal-weight (NW; 18.5 kg/m2 < BMI ≤ 25 kg/m2; n = 43), nondiabetic obese (OB; BMI > 30 kg/m2; n = 38), and diabetic obese (OB/DM; BMI > 30 kg/m2, fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%; n = 22) women were recruited. Metabolic parameters were measured, and expressions of PLIN1, CIDEA, CIDEC, and obesity-related genes were quantified in abdominal subcutaneous (SAT) and visceral adipose tissues (VAT). Effects of proinflammatory cytokines, endoplasmic reticulum (ER) stress inducers, and metabolic improvement agents on LD protein gene expressions were investigated in human adipocytes. RESULTS: PLIN1, CIDEA, and CIDEC expressions were lower in SAT and higher in VAT in OB subjects relative to NW subjects; however, they were suppressed in both fat depots in OB/DM subjects relative to OB (P < 0.05). Across the entire cohort, whereas VAT PLIN1 (r = 0.349) and CIDEC expressions (r = 0.282) were positively associated with BMI (P < 0.05), SAT PLIN1 (r = -0.390) and CIDEA expressions (r = -0.565) were inversely associated. After adjustment for BMI, some or all of the adipose LD protein gene expressions were negatively associated with fasting glucose (r = -0.259 or higher) and triglyceride levels (r = -0.284 or higher) and positively associated with UCP1 expression (r = 0.353 or higher) (P < 0.05). In adipocytes, LD protein gene expressions were 55-70% downregulated by increased proinflammatory cytokines and ER stress but 2-4-fold upregulated by the metabolic improvement agents exendin-4 and dapagliflozin (P < 0.05). CONCLUSIONS: The findings suggest that reduction of adipose LD protein expression is involved in the pathogenesis of metabolic disorders in women with obesity and type 2 diabetes and that increasing LD protein expression in adipocytes could control development of metabolic disorders.

Effects of Preoperative Breast MRI on Breast Cancer Survival Outcomes in Women Aged 35 Years and Younger.

Background The impact of preoperative breast MRI on the long-term outcomes in patients with breast cancer who are 35 years and younger has not been established. Purpose To evaluate the impact of preoperative breast MRI on recurrence-free survival (RFS) and overall survival (OS) in women with breast cancer who are 35 years and younger by using propensity score matching. Materials and Methods A total of 708 women who were 35 years and younger (mean age, 32 years ± 3 [SD]) and diagnosed with breast cancer from 2007 to 2016 were retrospectively identified. Patients who underwent preoperative MRI (MRI group) were matched with those who did not (no MRI group) according to 23 patient and tumor characteristics. RFS and OS were compared using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratios (HRs). Results Of 708 women, 125 patient pairs were matched. In the MRI group versus the no MRI group, the mean follow-up time was 82 months ± 32 versus 106 months ± 42, and the rates of total recurrence and death were 22% (104 of 478 patients) versus 29% (66 of 230 patients) and 5% (25 of 478 patients) versus 12% (28 of 230 patients), respectively. The time to recurrence was 44 months ± 33 in the MRI group and 56 months ± 42 in the no MRI group. After propensity score matching, the MRI and no MRI groups did not show significant differences in total recurrence (HR, 1.0; P = .99), local-regional recurrence (HR, 1.3; P = .42), contralateral breast recurrence (HR, 0.7; P = .39), or distant recurrence (HR, 0.9; P = .79). The MRI group showed a tendency toward better OS, but this was not statistically significant (HR, 0.47; P = .07). In the entire unmatched cohort, MRI was not an independent significant factor for predicting RFS or OS. Conclusion Preoperative breast MRI was not a significant prognostic factor for recurrence-free survival in women 35 years and younger with breast cancer. A tendency toward better overall survival was observed in the MRI group, but this was not significant. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim and Moy in this issue.