MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.

The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Patients and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen (44.8%) of the 29 patients achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Clinical and Radiological Outcomes in C2 Recapping Laminoplasty for the Pathologies in the Upper Cervical Spine.

OBJECTIVE: To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty. METHODS: Fourteen consecutive patients who underwent C2 recapping laminoplasty around C1-2 level were enrolled. To evaluate muscle preservation effect, the authors conducted a morphological measurement of extensor muscles between the operated and nonoperated side. Two surgeons measured the cross-sectional area (CSA) of obliquus capitis inferior (OCI) and semispinalis cervicis (SSC) muscle before and after surgery to determine atrophy rates (ARs). Additionally, we examined range of motion (ROM), sagittal vertical axis (SVA), neck visual analogue scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) score to assess potential changes in alignment and consequent clinical outcomes following posterior cervical surgery. RESULTS: We measured the CSA of OCI and SSC before surgery, and at 6 and 12 months postoperatively. Based on these measurements, the AR of the nonoperated SSC was 0.1% ± 8.5%, the AR of the operated OCI was 2.0% ± 7.2%, and the AR of the nonoperated OCI was -0.7% ± 5.1% at the 12 months after surgery. However, the AR of the operated side's SSC was 11.2% ± 12.5%, which is a relatively higher value than other measurements. Despite the atrophic change of SSC on the operated side, there were no prominent changes observed in SVA, C0-2 ROM, and C2-7 ROM between preoperative and 12 months postoperative measurements, which were 11.8 ± 10.9 mm, 16.3° ± 5.9°, and 48.7° ± 7.7° preoperatively, and 14.1 ± 11.6 mm, 16.1° ± 7.2°, and 44.0° ± 10.3° at 12 months postoperative, respectively. Improvement was also noted in VAS, NDI, and JOA scores after surgery with JOA recovery rate of 77.3% ± 29.6%. CONCLUSION: C2 recapping laminoplasty could be a useful tool for addressing pathologies around the upper cervical spine, potentially mitigating muscle atrophy and reducing postoperative neck pain, while maintaining sagittal alignment and ROM.

Mitral Valve Repair with Leaflet Resection versus Preservation for Degenerative Posterior Leaflet Prolapse.

OBJECTIVES: The optimal technique for repairing posterior mitral valve (MV) leaflet (PMVL) prolapse remains undetermined. We aimed to compare leaflet resection and neo-chordae implantation in patients undergoing MV repair for posterior leaflet prolapse, focusing on trans-mitral pressure gradient (PG) and recurrence of mitral regurgitation (MR). METHODS: We enrolled patients undergoing MV repair using either leaflet resection or neo-chordae implantation for single-segment prolapse of PMVL between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting (IPTW). Repeat echocardiographic measurements (n=3,473, 5.4/patient) of trans-mitral PG and significant (moderate or severe) MR recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. RESULTS: Among 639 patients, leaflet resection was used in 479 (75.0%) and neo-chordae implantation in 160 (25.0%). In the IPTW-adjusted cohort, the risk of death (P=0.623) and MV reoperation (P=0.340) did not significantly differ between the two groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs. 4.0 mmHg; P=0.442) and peak (9.6 vs. 10.4mmHg; P=0.131) PGs between groups, which persisted in most subgroup analyses. However, neo-chordae implantation was associated with a higher probability of significant MR recurrence compared to leaflet resection (at 5 years, 16.1% vs. 7.0%; P<0.001). CONCLUSIONS: Leaflet resection yielded similar clinical outcomes and trans-mitral PGs compared to neo-chordae implantation after MV repair, with a lower MR recurrence rate. These findings underscore the need to reassess the efficacy of neo-chordae implantation relative to leaflet resection.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT).

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

Neighbor effect on conformational spaces of alanine residue in azapeptides.

The conformational properties of Alanine (Ala) residue have been investigated to understand protein folding and develop force fields. In this work, we examined the neighbor effect on the conformational spaces of Ala residue using model azapeptides, Ac-Ala-azaGly-NHMe (3, AaG), and Ac-azaGly-Ala-NHMe (4, aGA1). Ramachandran energy maps were generated by scanning (φ, ψ) dihedral angles of the Ala residues in models with the fixed dihedral angles (φ = ±90°, ψ = ±0° or ±180°) of azaGly residue using LCgau-BOP and LCgau-BOP + LRD functionals in the gas and water phases. The integral-equation-formalism polarizable continuum model (IEF-PCM) and a solvation model density (SMD) were employed to mimic the solvation effect. The most favorable conformation of Ala residue in azapeptide models is found as the polyproline II (ßP), inverse γ-turn (γ'), ß-sheet (ßS), right-handed helix (αR), or left-handed helix (αL) depending on the conformation of neighbor azaGly residue in isolated form. Solvation methods exhibit that the Ala residue favors the ßP, δR, and αR conformations regardless of its position in azapeptides 3 and 4 in water. Azapeptide 5, Ac-azaGly-Ala-NH2 (aGA2), was synthesized to evaluate the theoretical results. The X-ray structure showed that azaGly residue adopts the polyproline II (ßP) and Ala residue adopts the right-handed helical (αR) structure in aGA2. The conformational preferences of aGA2 and the dimer structure of aGA2 based on the X-ray structure were examined to assess the performance of DFT functionals. In addition, the local minima of azapeptide 6, Ac-Phe-azaGly-NH2 (FaG), were compared with the previous experimental results. SMD/LCgau-BOP + LRD methods agreed well with the reported experimental results. The results suggest the importance of weak dispersion interactions, neighbor effect, and solvent influence in the conformational preferences of Ala residue in model azapeptides.

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer.

The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis. The likelihood of BM was evaluated using multivariate analysis and a predictive nomogram. Additionally, we prospectively monitored 177 samples from 46 LC patients initially without BM. Patients with BMs (n= 135) had significantly higher median sNfL (52.5 pg/mL) and sGFAP (239.2 pg/mL) levels compared to those without BMs (n = 565), with medians of 17.8 pg/mL and 141.1 pg/mL, respectively (p < 0.001 for both). The nomogram, incorporating age, sNfL, and sGFAP, predicted BM with an area under the curve (AUC) of 0.877 (95% CI 0.84-0.914), showing 74.8% sensitivity and 83.5% specificity. Over nine months, 93% of samples from patients without BM remained below the cutoff, while all patients developing BMs showed increased levels at detection. A nomogram incorporating age, sNfL, and sGFAP provides a valuable tool for identifying LC patients at high risk for BM, thereby enabling targeted MRI screenings and enhancing diagnostic efficiency.

Isotemporal substitution of accelerometer-derived sedentary behavior and physical activity on physical fitness in young children.

This study investigates the effects of different types of physical activity (PA) on the physical fitness (PF) of young children in Japan, with a particular focus on how substituting sedentary behavior (SB) with active behaviors influences PF. We conducted a cross-sectional analysis of 1843 participants aged 3-6 years from northeastern Japan. Using triaxial accelerometers, we quantified PA, and PF was assessed via standardized tests. The innovative application of isotemporal substitution modeling (ISM) allowed us to analyze the impact of reallocating time from SB to more active states, specifically moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA). Our findings reveal a robust association between increased MVPA and enhanced PF outcomes, underscoring the health benefits of reducing SB. Notably, replacing SB with LPA also showed beneficial effects on certain PF metrics, indicating LPA's potential role in early childhood fitness. These results highlight the critical importance of promoting MVPA and minimizing sedentary periods to bolster PF in young children. The study offers vital insights for shaping public health policies and emphasizes the need to cultivate an active lifestyle from an early age to secure long-term health advantages.

Photocatalytic Conversion of CO2 to Formate/CO by an (η6-para-Cymene)Ru(II) Half-Metallocene Catalyst: Influence of Additives and TiO2 Immobilization on the Catalytic Mechanism and Product Selectivity.

The catalytic efficacy of the monobipyridyl (η6-para-Cymene)Ru(II) half-metallocene, [(p-Cym)Ru(bpy)Cl]+ was evaluated in both mixed homogeneous (dye + catalyst) and heterogeneous hybrid systems (dye/TiO2/Catalyst) for photochemical CO2 reduction. A series of homogeneous photolysis experiments revealed that the (p-Cym)Ru(II) catalyst engages in two competitive routes for CO2 reduction (CO2 to formate conversion via RuII-hydride vs CO2 to CO conversion through a RuII-COOH intermediate). The conversion activity and product selectivity were notably impacted by the pKa value and the concentration of the proton source added. When a more acidic TEOA additive was introduced, the half-metallocene Ru(II) catalyst leaned toward producing formate through the RuII-H mechanism, with a formate selectivity of 86%. On the other hand, in homogeneous catalysis with TFE additive, the CO2-to-formate conversion through RuII-H was less effective, yielding a more efficient CO2-to-CO conversion with a selectivity of >80% (TONformate of 140 and TONCO of 626 over 48 h). The preference between the two pathways was elucidated through an electrochemical mechanistic study, monitoring the fate of the metal-hydride intermediate. Compared to the homogeneous system, the TiO2-heterogenized (p-Cym)Ru(II) catalyst demonstrated enhanced and enduring performance, attaining TONs of 1000 for CO2-to-CO and 665 for CO2-to-formate.

The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.

The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health.

Development of Hsp90 inhibitor to regulate cytokine storms in excessive delayed- and acute inflammation.

BACKGROUND: The surplus cytokines remaining after use in the early stages of the inflammatory response stimulate immune cells even after the response is over, causing a secondary inflammatory response and ultimately damaging the host, which is called a cytokine storm. Inhibiting heat shock protein 90 (Hsp90), which has recently been shown to play an important role in regulating inflammation in various cell types, may help control excessive inflammatory responses and cytokine storms. METHODS: We discovered an anti-inflammatory compound by measuring the inhibitory effect of CD86 expression on spleen DCs (sDCs) using the chemical compounds library of Hsp90 inhibitors. Subsequently, to select the hit compound, the production of cytokines and expression of surface molecules were measured on the bone marrow-derived DCs (BMDCs) and peritoneal macrophages. Then, we analyzed the response of antigen-specific Th1 cells. Finally, we confirmed the effect of the compound using acute lung injury (ALI) and delayed-type hypersensitivity (DTH) models. RESULTS: We identified Be01 as the hit compound, which reduced CD86 expression the most in sDCs. Treatment with Be01 decreased the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in BMDC and peritoneal macrophages stimulated by LPS. Under the DTH model, Be01 treatment reduced ear swelling and pro-inflammatory cytokines in the spleen. Similarly, Be01 treatment in the ALI model decreased neutrophil infiltration and lower levels of secreted cytokines (IL-6, TNF-α). CONCLUSIONS: Reduction of CD80 and CD86 expression on DCs by Be01 indicates reduced secondary inflammatory response by Th1 cells, and reduced release of pro-inflammatory cytokines by peritoneal macrophages may initially control the cytokine storm.

Sex or gender differences in treatment outcomes of sepsis and septic shock.

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Quantitative Assessment of Morphological Changes in Lipid Droplets and Lipid-Mito Interactions with Aging in Brown Adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT.

The complete mitochondrial genome of Membranipora villosa Hincks, 1880 (Bryozoa: Gymnolaemata: Cheilostomatida): phylogenetic relationship of two kelp-encrusting bryozoans within the suborder Membraniporina.

The two commonest kelp-encrusting bryozoans, Membranipora villosa and M. membranacea, are difficult to distinguish morphologically. Molecular studies of M. villosa should thus be helpful for the identification of both species because the mitogenome of M. membranacea was already sequenced. The complete mitogenome of M. villosa collected from Sinjido was determined in this study through Illumina NovaSeq sequencing. Maximum-likelihood (ML) analysis was based on concatenated 13 protein-coding genes dataset from nine bryozoan species. The mitogenome length was 15,407 bp, and its gene arrangement was similar to those of the mitogenome of other membraniporids, having 13 PCGs, two ribosomal RNAs, and 22 tRNAs. It had an overall A + T content of 63.7% (29.7% A, 16.7% C, 19.6% G, and 34.0% T). M. villosa and M. membranacea showed sequence differences of 20% for the total length of mitogenome and 16.1.% for 13 PCGs. Molecular data definitely consider them to be separate species. Phylogenetic analyses based on the amino acids of 13 PCGs indicated that M. villosa has the closest relationship with another kelp-encrusting bryozoan, M. membranacea of membraniporids. The phylogenetic position of genera and families within the suborder Membraniporina coincides with the Bayesian phylogenetic analysis of the mixed concatenated alignment consisting of three partitions.

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.

Tailored surgical strategies for mini-access open total arch repair.

Objective: Open arch repair is perceived as a challenging, high-risk procedure, with a barrier against the use of a minimally invasive approach. We aimed to present a mini-access total arch replacement performed by stratified approaches and to evaluate perioperative outcomes to contribute to the body of evidence. Methods: We evaluated 40 consecutive patients (aged 69.5 years; interquartile range, 65.6-76.3 years) undergoing elective total arch replacement using 5- to 8-cm upper mini-sternotomy between 2018 and 2022. Surgical strategies, including arterial inflow site and methods of branching vessel reconstruction, were systematically selected at the individual level. To evaluate comparative outcomes, contemporary cases undergoing total arch replacement via sternotomy with similar eligibility criteria served as a control group, and the inverse-treatment-weighting method was used to adjust for baseline characteristics. Results: Arch-first anastomosis using trifurcate graft, distal-first anastomosis using 4-branch graft, and island anastomosis were used in 18 (45%), 12 (30.0%), and 10 (25%) patients, respectively. Lower body and cardiac ischemic times were 23.4 minutes (interquartile range, 18.0-29.0 minutes) and 66.7 minutes (interquartile range, 50.1-78.2 minutes). There was no early (30-day or in-hospital) mortality, and 2 patients experienced disabling stroke (5.0%). The contemporary control group comprised 55 patients. After an adjustment, a mini-access group showed lower risks of stroke (odds ratio, 0.88; 95% CI, 0.78-1.00; P = .049) and a composite of major complications (odds ratio, 0.79; 95% CI, 0.68-0.92; P = .003), compared with a sternotomy approach. Conclusions: Based on present results, mini-access total arch replacement may be performed with reasonable safety and efficiency.

Preoperative COVID-19 and Postoperative Mortality in Cancer Surgery: A South Korean Nationwide Study.

BACKGROUND: We evaluated the impact of preoperative COVID-19 on early postoperative mortality in patients undergoing time-sensitive cancer surgery. METHODS: This retrospective, nationwide cohort study included adult patients who underwent various cancer (thyroid, breast, stomach, colorectal, hepatobiliary, genitourinary, lung, and multiple cancer) surgeries under general anesthesia in South Korea in 2022. Patients were grouped according to the duration from the date of COVID-19 confirmation to the date of surgery (0-2 weeks, 3-4 weeks, 5-6 weeks, and ≥7 weeks). Patients without preoperative COVID-19 also were included. Multivariable logistic regression analysis with Firth correction was performed to investigate the association between preoperative COVID-19 and 30-day and 90-day postoperative mortality. The covariates encompassed sociodemographic factors, the type of surgery, and vaccination status in addition to the aforementioned groups. RESULTS: Of the 99,555 patients analyzed, 30,933 (31.1%) were preoperatively diagnosed with COVID-19. Thirty-day mortality was increased in those who underwent surgery within 0-2 weeks after diagnosis of COVID-19 (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.02-2.12; P = 0.038); beyond 2 weeks, there was no significant increase in mortality. A similar pattern was observed for 90-day mortality. Full vaccination against COVID-19 was associated with reduced 30-day (OR 0.38; 95% CI 0.29-0.50; P < 0.001) and 90-day (OR 0.39; 95% CI 0.33-0.46; P < 0.001) mortality. CONCLUSIONS: Cancer surgery within 2 weeks of COVID-19 diagnosis was associated with increased early postoperative mortality. These findings support current guidelines that recommend postponing elective surgery for at least 2 weeks after the diagnosis of COVID-19.

Volatile Anesthetic Use Versus Total Intravenous Anesthesia for Patients Undergoing Heart Valve Surgery: A Nationwide Population-Based Study.

BACKGROUND: Many studies have suggested that volatile anesthetic use may improve postoperative outcomes after cardiac surgery compared to total intravenous anesthesia (TIVA) owing to its potential cardioprotective effect. However, the results were inconclusive, and few studies have included patients undergoing heart valve surgery. METHODS: This nationwide population-based study included all adult patients who underwent heart valve surgery between 2010 and 2019 in Korea based on data from a health insurance claim database. Patients were divided based on the use of volatile anesthetics: the volatile anesthetics or TIVA groups. After stabilized inverse probability of treatment weighting (IPTW), the association between the use of volatile anesthetics and the risk of cumulative 1-year all-cause mortality (the primary outcome) and cumulative long-term (beyond 1 year) mortality were assessed using Cox regression analysis. RESULTS: Of the 30,755 patients included in this study, the overall incidence of 1-year mortality was 8.5%. After stabilized IPTW, the risk of cumulative 1-year mortality did not differ in the volatile anesthetics group compared to the TIVA group (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07; P = .602), nor did the risk of cumulative long-term mortality (hazard ratio, 0.98; 95% confidence interval, 0.93-1.04; P = .579) at a median (interquartile range) follow-up duration of 4.8 (2.6-7.6) years. CONCLUSIONS: Compared with TIVA, volatile anesthetic use was not associated with reduced postoperative mortality risk in patients undergoing heart valve surgery. Our findings indicate that the use of volatile anesthetics does not have a significant impact on mortality after heart valve surgery. Therefore, the choice of anesthesia type can be based on the anesthesiologists' or institutional preference and experience.