The Effect of Mobile Lifestyle Intervention Combined with High-Protein Meal Replacement on Liver Function in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Pilot Randomized Controlled Trial.

While many studies have explored dietary substitutes and mobile apps separately, a combined approach to metabolic dysfunction-associated steatotic liver disease (MASLD) has not been investigated. This study evaluated short-term mobile interventions coupled with partial meal replacement in patients with MASLD. Sixty adults with MASLD and a body mass index ≥25 kg/m2 from a health examination center were randomized into an intervention group using a mobile app with partial meal replacements or a control group receiving standard educational materials. Liver enzyme levels, lipid profiles, and anthropometric measurements were assessed at baseline and after 4 weeks. Twenty-five participants in the intervention group and 24 in the control group completed the trial. Significant reductions were observed in the intervention group for alanine aminotransferase (-28.32 versus [vs.] -10.67, p = 0.006) and gamma-glutamyl transferase (-27.76 vs. 2.79, p = 0.014). No significant changes in aspartate aminotransferase, body weight, or waist circumference were noted in the intervention group. Four weeks of mobile lifestyle intervention incorporating partial meal replacements improved liver enzyme profiles in patients with MASLD. This strategy demonstrated the potential for mitigating elevated liver enzyme levels without altering body weight or waist circumference. Comprehensive and longer-term research is needed to substantiate and elaborate these preliminary outcomes.

Time to initiation of extracorporeal membrane oxygenation in conventional cardiopulmonary resuscitation affects the patient survival prognosis.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes. METHODS: This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20-40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities. RESULTS: Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20-40 min, p = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20-40 min, p = 0.021). CONCLUSIONS: This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.

Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies.

BACKGROUND: To develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features. METHODS: Muscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs. RESULTS: In the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician. CONCLUSIONS: Combination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.

Pharmacist interventions in Asian healthcare environments for older people: a systematic review and meta-analysis on hospitalization, mortality, and quality of life.

BACKGROUND: Pharmaceutical interventions play a key role in the care of older people experiencing polypharmacy. Despite the rapid increase in the aging population in Asia, there is a lack of evidence regarding the effectiveness of pharmacist interventions on older adult's healthcare. This systematic review and meta-analysis assessed the effects of pharmacist interventions in Asian health care environments on hospitalization, mortality, and quality of life (QoL) among older people in Asia. METHODS: A comprehensive search was conducted across 5 databases, encompassing studies published from inception through June 2023. Only studies involving pharmacist interventions for people aged 65 years or older, residing in Asian countries, were considered. Studies without evidence of pharmacist involvement or conducted outside of Asia were excluded. Data extraction was performed by two reviewers, one reviewer (I.K.) performed the initial extraction, and another reviewer (G.R.) verified the extracted data. Forest plots were generated using a random effects model to obtain risk ratios or pooled standardized mean differences (SMDs). RESULTS: A total of 170 articles underwent thorough review, and ultimately, ten studies meeting the inclusion criteria were included in the meta-analyses. These studies encompassed diverse healthcare settings such as outpatient, inpatient, and nursing homes, with sample sizes ranging from 32 to 306 older people. Pharmacist interventions were found to significantly reduce hospitalization rates (n = 5, risk ratio = 0.57, 95% CI = 0.41-0.81) and mortality rates (n = 4, risk ratio = 0.57, 95% CI = 0.37-0.88) among older people. The analysis revealed less significant improvement in QoL in these patients than in those receiving usual care (n = 6, SMD = 0.36, P = 0.057). CONCLUSIONS: These findings highlight the crucial role of pharmacists within healthcare teams in Asian countries. Pharmacist interventions have an impact on reducing hospitalization and mortality rates among the elderly people, underscoring the importance of optimizing patient outcomes in Asia.

Statistical Methods for Comparing Predictive Values in Medical Diagnosis.

Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity, positive predictive value, and negative predictive value. Particularly when comparing the performance of two diagnostic tests applied on the same set of patients, these metrics are crucial for identifying the more accurate test. However, comparing predictive values presents statistical challenges because their denominators depend on the test outcomes, unlike the comparison of sensitivities and specificities. This paper reviews existing methods for comparing predictive values and proposes using the permutation test. The permutation test is an intuitive, non-parametric method suitable for datasets with small sample sizes. We demonstrate each method using a dataset from MRI and combined modality of mammography and ultrasound in diagnosing breast cancer.

Incidence and risk factors of age-related macular degeneration in patients with Parkinson's disease: a population-based study.

Background and objective: The association between age-related macular degeneration (AMD) and Parkinson' disease (PD) remains unclear. The aim of the present study was to assess the incidence of AMD in patients with PD, elucidate differences by age and sex, and investigate potential risk factors for AMD. Methods: Data were extracted from the Korean National Health Insurance System database, which covers 97% of the Korean population (2002 through 2019). We calculated the incidence of newly diagnosed AMD in patients with PD and used Cox proportional-hazards models to estimate risk factors for AMD, presenting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Results: Of 172,726 patients with PD, 15,800 were newly diagnosed with AMD during the follow-up, including 5,624 men and 10,176 women. The overall incidence of AMD in patients with PD was 13.59 per 1,000 person-years. Stratified by age group and sex, the incidence was higher in women aged 40-69, and conversely higher in men aged 70-89. Risk of AMD was high in older age groups (aHR = 4.36, 95% CI: 3.74-5.09 in the 70 s), female sex (aHR = 1.07, 95% CI: 1.04-1.11), patients with diabetes mellitus (DM) (aHR = 1.14, 95% CI: 1.10-1.18), and patients with hyperlipidemia (aHR = 1.17, 95% CI: 1.13-1.21). Conclusion: Our findings suggest that the AMD incidence is higher in patients with PD than in the general population, with varying patterns of sex differences across age groups. Particularly, old age, female sex, presence of DM, and hyperlipidemia are potential risk factors. Therefore, clinicians should pay greater attention to AMD in patients with PD.

Sex differences in prognosis factors in patients with lung cancer: A nationwide retrospective cohort study in Korea.

Large-scale studies elucidating sex differences in factors impacting prognosis and sex-specific prognossis factors scoring in patients with lung cancer are insufficient. The present study aimed to develop a model to predict sex-specific prognosis factors in Korean patients with lung cancer. This nationwide cohort study included 96,255 patients aged ≥19 years diagnosed with lung cancer and underwent Korean National Health Insurance Service health examinations between January 1, 2005 and December 31, 2015 and followed until 2020. Factors associated with prognosis were estimated using multivariable Cox proportional hazards regression analyses, and separate prognosis scores were calculated for male and female patients. The sex-specific risk scoring models were validated with Kaplan-Meier survival curves and c-statistic. During a mean follow-up of 2.8 years, 60.5% of the patients died. In male patients with lung cancer, age ≥ 65 years (24 points) had the highest mortality risk score, followed by chemotherapy in combination with radiotherapy (16 points), chemotherapy (14 points), and radiotherapy (11 points). In female patients with lung cancer, chemotherapy in combination with radiotherapy (19 points) had the highest mortality risk score, followed by chemotherapy (16 points), age ≥ 65 years (13 points), and radiotherapy (13 points). The analysis of patients categorized into three risk groups based on risk scores revealed that the fatality rates within 5 years were 7%, 54%, and 89% in the low-, intermediate-, and high-risk groups for male patients and 3%, 46%, 85% in the low-, intermediate-, and high-risk groups for female patients, respectively. The c-statistic was 0.86 for male patients and 0.85 for female patients. The strongest fatality risk factors in lung cancer were age ≥ 65 years in male patients and chemotherapy in female patients. The present study developed sex-specific prognosis scoring models to predict fatality risk in patients with lung cancer.

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).

Effect of pre-transplantation use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in kidney transplant recipients-propensity score-matched analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARBs) can cause acute kidney injury under dehydratation or in hemodynamically unstable conditions. Regarding kidney transplantation (KT), the risk of using ACEi/ARBs before surgery is not well established. Therefore, we evaluated the clinical outcomes to determine the effect of preoperative use of ACEi/ARBs on KT. METHODS: We retrospectively collected 1187 patients who received living-donor KT between January 2017 and December 2021. We conducted a propensity score-matched analysis between the ACEi/ARB(+) and ACEi/ARB(-) groups and evaluated the effects of ACEi/ARBs on delayed graft function, post-KT renal function, hyperkalemia events, rejection, and graft survival. RESULTS: The ACEi/ARB(+) group showed a similar incidence of delayed graft function as the ACEi/ARB(-) group (1.8% vs. 1.0%, P = 0.362). The risk of delayed graft function was not upregulated in the ACEi/ARB(+) group after propensity score-matching (odds ratio: 0.50, 95% confidence interval (CI) 0.13-2.00). Postoperative creatinine levels and the slope of creatinine levels after KT also were not significantly different between the two groups (creatinine slope from POD#0 to POD#7: - 0.73 ± 0.35 vs. - 0.75 ± 0.32 mg/dL/day, P = 0.464). Hyperkalemia did not occur more often in the ACEi/ARB(+) group than in the ACEi/ARB(-) group during perioperative days. Rejection-free survival (P = 0.920) and graft survival (P = 0.621) were not significantly different between the two groups. CONCLUSIONS: In KT, the preoperative use of ACEi/ARBs did not significantly affect clinical outcomes including delayed graft function, postoperative renal function, hyperkalemia events, incidence of rejection, and graft survival rates compared to the patients who did not receive ACEi/ARBs.

Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database.

BACKGROUND: Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are all immune-mediated chronic inflammatory liver diseases. Autoimmune liver diseases are rare, making identification and treatment difficult. To improve clinical outcomes and enhance patient quality of life, we performed an epidemiological study of autoimmune liver diseases based on real-world comprehensive data. RESULTS: We used National Health Insurance Service claims data in Korea from 2005 to 2019. Patients were identified using the International Classification of Disease 10th Revision code, and rare intractable disease codes assigned according to the strict diagnostic criteria. In the AIH cohort, 8,572 (83.9%) were females and the mean age at diagnosis was 56.3 ± 14.3 years. PBC also showed female dominance (83.3%) and the mean age was 57.8 ± 12.6 years. Patients with PSC showed no sex predominance and had a mean age of 57.8 ± 21.5 years. During the study period, there were 10,212, 6,784, and 888 AIH, PBC, and PSC patients, respectively. The prevalence of AIH, PBC, and PSC in 2019 were 18.4, 11.8, and 1.5 per 100,000 population, while the corresponding incidences were 2.3, 1.4, and 0.3 per 100,000 population, respectively. Analysis of sex-age-standardized data showed that the annual prevalence of these diseases is increasing. The 10-year survival rates were 89.8%, 74.9%, and 73.4% for AIH, PBC, and PSC, respectively. CONCLUSIONS: The number of patients with autoimmune liver disease in South Korea is increasing over time. Further research on autoimmune liver disease is needed to fulfill unmet clinical needs.

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.

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.

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.

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.

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.

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.

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.

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.