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Objectives: The aim of this article is to assess the safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in routine clinical settings in Korea., Methods: This is a prospective, multi-centre post-marketing surveillance study. Data were prospectively collected within 6 months after the start of tofacitinib therapy. Safety was evaluated based on the presence of adverse events (AEs) observed in patients who received at least one dose of tofacitinib. Effectiveness was assessed according to the proportion of patients who achieved low disease activity and remission, American College of Rheumatology 20 criteria (ACR20), European League Against Rheumatism (EULAR) response, and change of Disease Activity Score in 28 Joints (DAS28)., Results: The incidence rates [patients with events per 100 patient-years (PY)] of AEs and serious AEs were 56.92 and 10.69, respectively. Regarding AEs of special interest, the incidence rates were 4.33 per 100 PY for serious infections and infestations, 5.78 per 100 PY for herpes zoster, no event of tuberculosis, 0.29 per 100 PY for malignancy, 0.29 per 100 PY for venous thromboembolism (one event of deep vein thrombosis and no event of pulmonary embolism), 0.87 per 100 PY for major adverse cardiovascular event, and 0.58 per 100 PY for mortality. Moreover, ∼40.48% and 21.60% of patients achieved low disease activity and remission of DAS28-erythrocyte sedimentation rate. The EULAR response was classified as good responders with 39.12% in the DAS28-erythrocyte sedimentation rate., Conclusions: The benefit/risk profile of tofacitinib in adult patients with rheumatoid arthritis in routine clinical settings in Korea was similar to long-term clinical trial data., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema., Methods: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation., Results: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3 + CD4 + IL-17 + T-cell population in the lung and spleen., Conclusion: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Backgruound: There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM)., Methods: This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics., Results: Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without., Conclusion: We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Cognitive impairment refers to notable declines in cognitive abilities including memory, language, and emotional stability leading to the inability to accomplish essential activities of daily living. Astrocytes play an important role in cognitive function, and homeostasis of the astrocyte-neuron lactate shuttle (ANLS) system is essential for maintaining cognitive functions. Aquaporin-4 (AQP-4) is a water channel expressed in astrocytes and has been shown to be associated with various brain disorders, but the direct relationship between learning, memory, and AQP-4 is unclear. We examined the relationship between AQP-4 and cognitive functions related to learning and memory. Mice with genetic deletion of AQP-4 showed significant behavioral and emotional changes including hyperactivity and instability, and impaired cognitive functions such as spatial learning and memory retention. 18  F-FDG PET imaging showed significant metabolic changes in the brains of AQP-4 knockout mice such as reductions in glucose absorption. Such metabolic changes in the brain seemed to be the direct results of changes in the expression of metabolite transporters, as the mRNA levels of multiple glucose and lactate transporters in astrocytes and neurons were significantly decreased in the cortex and hippocampus of AQP-4 knockout mice. Indeed, AQP-4 knockout mice showed significantly higher accumulation of both glucose and lactate in their brains compared with wild-type mice. Our results show that the deficiency of AQP-4 can cause problems in the metabolic function of astrocytes and lead to cognitive impairment, and that the deficiency of AQP4 in astrocyte endfeet can cause abnormalities in the ANLS system., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The outcomes of total knee arthroplasty (TKA) remain controversial, and we do not know which factors are important for successful outcomes. This study aimed to compare the mid-term outcomes of different conceptual designs by evaluating the radiological and clinical outcomes., Materials and Methods: A total of 478 total knee arthroplasties (TKAs) were enrolled and allocated into groups I [posterior stabilizing (PS) with anterior referencing (AR)], II [PS with posterior referencing (PR), and III [ultra-congruent (UC) TKA)]. Preoperative findings, last follow-up clinical outcomes, and final follow-up radiological and indirect assessments of the femoral rollback were compared between the groups., Results: The mean follow-up period was 72.6 ± 12.9 months. The tourniquet was used samely applied to every group. Flexion contracture was significantly larger in group III than in groups I and II (3.3 ± 2.7, p < 0.001), and further flexion was significantly smaller in group III (130.0° ± 2.7°, p < 0.001). Among the radiological parameters, posterior osteophyte formation was the most common in group III (67.8%). The rollback distance was significantly smaller in group III than in groups I and II (p < 0.001). The active deep flexion angle was affected by the posterior condylar offset (PCO) ratio, and the contact point changed the distance (p < 0.05)., Conclusion: PS TKAs showed better ROMs than UC TKAs; however, no differences were noted in the clinical outcome scales. The flexion angle was affected by the PCOR and rollback at both PS and UC TKAs. However, rollback negatively affected the flexion angle during UC TKAs. An inappropriate femoral rollback was identified, and femoral osteophyte formation was determined to be the most prominent in UC TKAs. Level of evidence Level III comparative study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Diabetes mellitus (DM) and sarcopenia (SP) are growing public health concerns in an aging society, which share common pathophysiological mechanisms and are associated with serious health consequences. We investigated the impact of DM and SP on all-cause and cardiovascular mortalities in a longitudinal nationwide population-based study., Methods: The study analyzed data from the Korea National Health and Nutrition Examination Survey conducted between 2008 and 2011, including information on appendicular skeletal muscle mass data. Mortality data up to December 2020 were retrieved from the National Death Registry., Results: Among the 17,920 participants, 14,737 (82.2 %) had neither DM nor SP (DM-/SP-), 1349 (7.5 %) had only DM (DM+/SP-), 1425 (8.0 %) had only SP (DM-/SP+), and 409 (2.3 %) had both DM and SP (DM+/SP+). Compared to the DM-/SP- group, the DM-/SP+ and DM+/SP+ groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.47 (95 % confidence interval [CI]: 1.14-1.89) and 1.85 (95 % CI: 1.28-2.69), respectively, while the DM+/SP- group did not (HR 1.29, 95 % CI: 0.97-1.74). The DM+/SP+ group demonstrated the highest risk of overall mortality (p-for-trend <0.001). Compared to the DM-/SP- group, only the DM+/SP+ group demonstrated increased cardiovascular mortality with HRs of 2.10 (95 % CI: 1.11-4.00) while the DM+/SP- (HR 1.35, 95 % CI: 0.79-2.30) and DM-/SP+ (HR 1.42, 95 % CI: 0.84-2.43) groups did not., Conclusions: The coexistence of DM and SP additively increased the risk of all-cause and cardiovascular mortality. Individuals with either disease may require more careful management to prevent the development of the other disease to reduce mortality., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate whether an additional module on realistic expectations following total knee arthroplasty (TKA) would lead to a higher proportion of satisfied patients compared to existing preoperative education., Methods: This was a single-center, randomized-controlled trial. A total of 172 patients who were scheduled for TKA between September 2020 and October 2021 were enrolled. Patients were randomized to receive either only standard preoperative education, or an additional module on realistic expectations following TKA. The primary outcome was patient satisfaction. Secondary outcomes were Short Form-36, Western Ontario and McMaster Universities Osteoarthritis Index, crepitus score, and range of motion. Subgroup analysis was performed based on central sensitization inventory (CSI) score stratification. Assessment was performed at the 3-month, 6-month, and > 1-year follow-up., Results: At more than 1 year, 65/78 (83.3%) patients in the intervention group and 52/80 (65.0%) patients in the control group were satisfied (P = 0.03). The mean satisfaction score was measured as 4.2 ± 0.9 in the intervention and 3.9 ± 0.9 in the control at > 1 year (P = 0.01). There were significant differences in Short Form-36 physical and mental component summary scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness scores at 6 months (P = 0.02, P = 0.02, P = 0.04, P = 0.04). The frequency of satisfaction and mean satisfaction score in the top 25 percentile CSI group were 15/16 (93.8%) and 4.6 ± 0.6 in those who received intervention and 12/19 (63.2%) and 3.8 ± 0.8 in those who did not (P = 0.01, P = 0.01)., Conclusions: Thorough preoperative education on realistic expectations following TKA showed effects on WOMAC pain and satisfaction at > 1 year after surgery. It was more prominent in the group with a higher CSI score at > 1-year follow-up., Level of Evidence: Level I., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

As an arousal hub region in the brain, the locus coeruleus (LC) has bidirectional connections with the autonomic nervous system. Magnetic resonance imaging (MRI)-based measures of LC structural integrity have been linked to cognition and arousal, but less is known about factors that influence LC structure and function across time. Here, we tested the effects of heart rate variability (HRV) biofeedback, an intervention targeting the autonomic nervous system, on LC MRI contrast and sympathetic activity. Younger and older participants completed daily HRV biofeedback training for five weeks. Those assigned to an experimental condition performed biofeedback involving slow, paced breathing designed to increase heart rate oscillations, whereas those assigned to a control condition performed biofeedback to decrease heart rate oscillations. At the pre- and post-training timepoints, LC contrast was assessed using turbo spin echo MRI scans, and RNA sequencing was used to assess cAMP-responsive element binding protein (CREB)-regulated gene expression in circulating blood cells, an index of sympathetic nervous system signaling. We found that left LC contrast decreased in younger participants in the experimental group, and across younger participants, decreases in left LC contrast were related to the extent to which participants increased their heart rate oscillations during training. Furthermore, decreases in left LC contrast were associated with decreased expression of CREB-associated gene transcripts. On the contrary, there were no effects of biofeedback on LC contrast among older participants in the experimental group. These findings provide novel evidence that in younger adults, HRV biofeedback involving slow, paced breathing can decrease both LC contrast and sympathetic nervous system signaling., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Endometriosis, which is the presence of endometrial stroma and glands outside the uterus, is one of the most frequently diagnosed gynecologic diseases in reproductive women. Patients with endometriosis suffer from various pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. The pathophysiology for chronic pain in patients with endometriosis has not been fully understood. Altered inflammatory responses have been shown to contribute to pain symptoms. Increased secretion of cytokines, angiogenic factors, and nerve growth factors has been suggested to increase pain. Also, altered distribution of nerve fibers may also contribute to chronic pain. Aside from local contributing factors, sensitization of the nervous system is also important in understanding persistent pain in endometriosis. Peripheral sensitization as well as central sensitization have been identified in patients with endometriosis. These sensitizations of the nervous system can also explain increased incidence of comorbidities related to pain such as irritable bowel disease, bladder pain syndrome, and vulvodynia in patients with endometriosis. In conclusion, there are various possible mechanisms behind pain in patients with endometriosis, and understanding these mechanisms can help clinicians understand the nature of the pain symptoms and decide on treatments for endometriosis-related pain symptoms.

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema., (© 2023. The Author(s).)

Objectives: To quantify the proportion of fat within the rotator cuff muscles using CT histogram analysis (HA) and to compare fat fraction (FF) values obtained from CT and T2*-corrected 6-echo three-dimensional gradient-echo Dixon sequences., Methods: Twenty-six patients who underwent both shoulder CT and MRI were enrolled. The FF of rotator cuff muscles was measured on FF maps of the Dixon technique. Using CT, the FF values were obtained in two ways: 1) CT mean Hounsfield Unit (HU) measurement-based fat quantification using subcutaneous fat and the teres major muscle as internal standards; and 2) CT HA-based fat quantification in which pixels from -190 to -30 HU were arbitrarily classified as fat, and those from -30 to 150 HU as muscle. Afterward, the relationship between FF values from MRI (FF-MR), CT mean HU-based analysis (FF-HU), and CT HA (FF-HA) was assessed., Results: There were strong positive correlations ( p < 0.001) between FF-MR and FF-HA, which were higher when compared with FF-HU ( r = 0.90 vs. 0.77 for total). For a total of 104 rotator cuff muscles, the intraclass correlation between FF-MR and FF-HA was excellent (ICC, 0.90), which was higher than that between FF-MR and FF-HU (ICC, 0.76). The ICCs showed excellent interobserver agreement between FF-MR, FF-HU, and FF-HA (ICCs, 0.93-0.96)., Conclusions: Fat quantification within the rotator cuff muscles using CT HA is both feasible and reliable., Advances in Knowledge: CT HA provides reliable quantification of intramuscular fat and has strengths regarding its retrospective applicability to conventional CT studies without additional radiation dose to subjecting patients.

Objectives: This study aimed to assess the status of the Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) and propose measures for its growth and development., Methods: The study was conducted using a questionnaire survey targeting members of the Korean Academy of Child and Adolescent Psychiatry. The six key elements analyzed were Access to the journal, Convenience following conversion to English, Recognition as an international journal and institutional achievements, Author perspectives on manuscript submission,Transition to an online-only journal, and Content and identity of the journal., Results: The survey revealed that email notification was highly effective for Journal Accessibility, with the website and search engines also frequently being used by members. Conversion to English in 2018 initially impacted readability and submission rates, but these concerns have decreased over time. However, the Recognition of JKACAP as an international academic journal was still not on par with SCIE journals, highlighting the need for further efforts towards SCIE inclusion. Despite these challenges and limited research opportunities, there was an active intention among members to submit manuscripts. Respondents showed a notable preference for the Transition to an online-only journal. Regarding content and identity of the JKACAP, members predominantly favored review articles and perceived the journal as a research and communication platform for Korean child and adolescent psychiatrists., Conclusion: The results indicate the need for JKACAP to enhance its digital accessibility, provide more support for domestic and international authors, and actively seek SCIE indexing. Addressing the varied content preferences of its members, improving the submission process, and transitioning to an online-only format could further its growth and solidify its position as an internationally recognized academic journal in the field of child and adolescent psychiatry., Competing Interests: Conflicts of Interest The editorial board of JKACAP was not involved in the editorial evaluation or decision to publish this article., (Copyright © 2023 Korean Academy of Child and Adolescent Psychiatry.)

Competing Interests: J.Y.J. and H.J.Y. are the employees and shareholders of Pfizer Inc. J.Y.S. received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, the Government-wide R&D Fund for Infectious Disease Research, and pharmaceutical companies, including Daiichi Sankyo, GSK, and Pfizer, outside the submitted work.

Prior studies suggest that sex differences in emotion regulation (ER) ability contribute to sex disparities in affective disorders. In behavioral studies, females rely more on maladaptive strategies to cope with emotional distress than males. Neuroimaging studies suggest that males more efficiently regulate emotion than females by showing less prefrontal cortex activity (suggesting less effort) for similar amygdala activity (similar regulation outcome). However, physiological studies involving heart rate variability (HRV) indicated that, compared with males, females have higher resting HRV, indicative of parasympathetic dominance and better control of emotion. To help resolve these apparently inconsistent findings, we examined sex differences in how resting HRV relates to brain activity while using cognitive reappraisal, one of the adaptive strategies. Based on 51 males and 49 females, we found that females showed different levels of self-rated emotional intensity and amygdala activity for negative versus positive emotions, while males did not. Females also showed greater overall prefrontal cortex activity but similar levels of amygdala activity compared to males. Sex differences in how resting HRV related to brain activity during ER were evident only during viewing or regulating positive emotion. The results suggest that sex differences in the neural correlates of ER and resting HRV might lie in valence more than arousal modulation., (© 2023. The Author(s).)

This descriptive correlational study was conducted to examine the mediating effect of disability acceptance on the relationship between family strength and life satisfaction in individuals who have a sibling with a disability. The responses of 144 non-disabled siblings of persons with a disability were analyzed using panel data from the Korea Institute for Persons with Disabilities, and a regression analysis was performed. Family strength and acceptance of disabilities significantly affected the life satisfaction of siblings without disability. Regarding the effect of family strength on life satisfaction, acceptance of a sibling's disability by siblings without disability had a significant mediating effect. Our results suggest that strategies to enhance the acceptance of disabilities and promote family strength are necessary to improve the life satisfaction of individuals without disability as well as their siblings with disabilities. Family-centered interventions are warranted to promote positive acceptance of disabilities., (© 2023 John Wiley & Sons Australia, Ltd.)

Unintended rotation of the distal tibia occurs during medial open-wedge high tibial osteotomy (MOWHTO). Computed tomography (CT) is the standard method of measuring lower limb alignment; however, the new low-dose EOS system allows three-dimensional limb modeling with automated measurements of lower limb alignment. This study investigated the differences between the changes in lower limb alignment profiles obtained using the EOS system and CT in patients who underwent MOWHTO. We investigated whether any factors contributed to the degree of deformation. Thirty patients were prospectively enrolled between October 2019 and February 2023. Changes in femoral and tibial torsion, femorotibial rotation, and posterior tibial slope were measured using pre- and post-MOWHTO CT and EOS images. We found no significant difference in pre- and postoperative tibial torsion or posterior tibial slope between CT and EOS. No variables showed a significant correlation with changes in the tibial torsion or posterior tibial slope. This study confirmed the possibility that the EOS system could replace CT in measuring changes in several parameters pre- and postoperatively. Furthermore, we confirmed that the distal tibia tended to be internally rotated after MOWHTO; however, we found no significantly related parameters related to deformation caused by MOWHTO.

Background: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA., Methods: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA., Results: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid., Conclusion: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Deltoid function critically influences the results of reverse total shoulder arthroplasty (RTSA), and spontaneous deltoid attrition tears are frequently detected in cuff tear arthropathy (CTA) patients; however, the clinical impacts of these tears on RTSA outcomes are undetermined. Our aim was to determine the effect of spontaneous deltoid attrition tears on postoperative outcomes after RTSA without an additional deltoid procedure., Methods: Seventy-two patients who underwent RTSA for CTA with preoperative magnetic resonance imaging (MRI) and a minimum clinical follow-up of 1 year (mean, 32 months) were retrospectively reviewed in the study. Patients with a history of previous shoulder surgery or injury were excluded. The presence and location of deltoid attrition tears were determined in preoperative MRI. Propensity score matching (1:1) was performed to construct tear and no-tear groups. Finally, 21 patients, matched with respect to age, sex, hand dominance, symptom duration, medical comorbidity (obesity, diabetes mellitus, and coronary artery disease), Hamada grade, and implant type, were assigned to each group. Clinical outcomes (functional scores, isometric power, and range of motion) in the two groups were compared., Results: Deltoid attrition tears were detected in 21 of the 72 enrolled cases (29.1%). Anterolateral deltoid was the most frequent location and no tear was detected in the posterior deltoid. The tear rate increased with disease severity (Hamada G2, 4.8%; G3, 23.8%; > G4, 71.4%). No pre- or postoperative clinical variables differed significantly between the tear and no tear groups., Conclusions: Deltoid attrition tears were detected in 29% of CTA patients who underwent RTSA. The most common site was the anterolateral region and tear prevalence tended to increase with CTA progression. However, RTSA was found to provide satisfactory outcomes regardless of the presence of a deltoid attrition tear., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T 1 -weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy ( 1 H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO 2 ) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform., (© 2023. The Author(s).)

Blood pressure variability (BPV), independent of mean blood pressure levels, is associated with cerebrovascular disease burden on MRI and postmortem evaluation. However, less is known about relationships with markers of cerebrovascular dysfunction, such as diminished spontaneous brain activity as measured by the amplitude of low frequency fluctuations (ALFF), especially in brain regions with vascular and neuronal vulnerability in aging. We investigated the relationship between short-term BPV and concurrent regional ALFF from resting state fMRI in a sample of community-dwelling older adults ( n  = 44) and healthy younger adults ( n  = 49). In older adults, elevated systolic BPV was associated with lower ALFF in widespread medial temporal regions and the anterior cingulate cortex. Higher systolic BPV in younger adults was also related to lower ALFF in the medial temporal lobe, albeit in fewer subregions, and the amygdala. There were no significant associations between systolic BPV and ALFF across the right/left whole brain or in the insular cortex in either group. Findings suggest a possible regional vulnerability to cerebrovascular dysfunction and short-term fluctuations in blood pressure. BPV may be an understudied risk factor for cerebrovascular changes in aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Acute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways., Methods: This study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct and indirect ARDS. Metabolite concentrations of five analyte classes (energy metabolism, free fatty acids, amino acids, phospholipids, sphingolipids) were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry by targeted metabolomics., Results: In total, 186 metabolites were detected. Among them, 102 metabolites could differentiate sepsis-induced ARDS patients from the non-ARDS controls, while 14 metabolites could discriminate sepsis-induced ARDS subphenotypes. Using partial least-squares discriminant analysis, we showed that sepsis-induced ARDS patients were metabolically distinct from the non-ARDS controls. The main distinguishing metabolites were lysophosphatidylethanolamine (lysoPE) plasmalogen, PE plasmalogens, and phosphatidylcholines (PCs). Sepsis-induced direct and indirect ARDS were also metabolically distinct subgroups, with differences in lysoPCs. Glycerophospholipid and sphingolipid metabolism were the most significant metabolic pathways involved in sepsis-induced ARDS biology and in sepsis-induced direct/indirect ARDS, respectively., Conclusion: Our study demonstrated a marked difference in metabolic patterns between sepsis-induced ARDS patients and non-ARDS controls, and between sepsis-induced direct and indirect ARDS subpheonotypes. The identified metabolites and pathways can provide clues relevant to the diagnosis and treatment of individuals with ARDS., (© 2023. The Author(s).)

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To track changes in the haemodynamic and respiratory indicators of patients and evaluate families' caring experiences via the visitation programme in the intensive care unit (ICU)., Background: Although most people recognise the importance of family care visitation programme in the ICU, objective research results on the effect on patients and caregivers are still insufficient., Design: Mixed methods., Methods: In this a quasi-experimental investigation and qualitative study, after executing the programme with families of ICU patients in a general hospital in South Korea from June to July 2019, changes in haemodynamic and respiratory indicators for control (n = 28) and experimental groups (n = 28) were analysed; the experimental group families' experiences were analysed through in-depth interviews; the qualitative study's reporting rigour was checked against the COREQ guidelines and TREND checklist for a quasi-experimental study. Qualitative and quantitative data were examined using content analysis and repeated-measures analysis of variance, respectively., Results: There was a significant change in systolic and diastolic blood pressure in the haemodynamic indicator, and the respiratory indicator in both groups increased slightly over time and then gradually stabilised; there were no significant differences or interactions between groups regarding time of systolic blood pressure. The respiratory rate significantly decreased only in the experimental group. There was a significant increase in oxygen saturation over time, as well as interactions between time and group and between groups. Four themes were extracted from families' experiences., Conclusion: The haemodynamic and respiratory indicators of the group using patient- and family-centred care (PFCC) showed a stable effect on critically ill patients, which increased families' satisfaction. In future, interventions should encourage family participation in the ICU for successful PFCC., Relevance to Clinical Practice: The findings provided evidence for the importance of PFCC through changes in objective haemodynamic and respiratory indicators., (© 2023 John Wiley & Sons Ltd.)

Background: As the metabolic significance of sarcopenic obesity (SO) is revealed, finding an appropriate index to detect SO is important, especially for type 2 diabetes mellitus (T2DM) patients with accompanying metabolic dysfunction., Methods: Participants (n=515) from the Korea Guro Diabetes Program were included to compare how well waist circumference (WC), waist hip ratio (WHR), waist height ratio (WHtR), and the weight-adjusted waist index (WWI) predict SO in newly diagnosed T2DM patients. Sarcopenia was defined based on guidelines from the 2019 Asian Working Group for Sarcopenia as both low muscle mass (appendicular skeletal muscle [ASM]/height 2 <7.0 kg/m 2 for men, <5.4 kg/m 2 for women) and strength (handgrip strength <28.0 kg for men, <18.0 kg for women) and/or reduced physical performance (gait speed <1.0 m/sec). Obesity was defined as a WC ≥90 cm in men and ≥85 cm in women. The WHR, WHtR, and WWI were calculated by dividing the WC by the hip circumference, height, and √ weight, respectively., Results: The WC, WHR, and WHtR correlated positively with the fat and muscle mass represented by truncal fat amount (TFA) and ASM, whereas the WWI was proportional to the TFA and inversely related to ASM. Of the four indices, the WWI showed the highest area under the receiver operative characteristic curve for SO. The WWI also exhibited a positive correlation with albuminuria and the mean brachial-ankle pulse wave velocity, especially in patients aged ≥65 years., Conclusion: The WWI is the preferable anthropometric index for predicting SO in T2DM patients, and it might be a proper index for predicting cardiometabolic risk factors in elderly people.

Objective: To evaluate the feasibility and clinical usefulness of deep learning (DL)-accelerated turbo spin echo (TSEDL) sequences relative to standard TSE sequences (TSES) for acute radius fracture patients wearing a splint., Methods: This prospective consecutive study investigated 50 patients' preoperative wrist MRI scans acquired between July 2021 and January 2022. Examinations were performed at 3 Tesla MRI with body array coils due to the wrist splint. Besides TSES obtained according to the routine protocol, TSEDL sequences for axial T2-, coronal T1-, and coronal PD-weighted TSE sequences were scanned for comparison. For quantitative assessment, the relative signal-to-noise ratio (rSNR), the relative contrast-to-noise ratio (rCNR), and the relative contrast ratio (rCR) were measured. For qualitative assessment, all images were assessed by two independent musculoskeletal radiologists in terms of perceived SNR, image contrast, image sharpness, artifacts disturbing evaluation, overall image quality and diagnostic confidence for injuries using a four- or five-point Likert scale., Results: The scan time was shortened approximately by a factor of two for TSEDL compared to TSES. TSEDL images showed significantly better rSNR, rCNR, and rCR values for all sequences, and scored significantly better in terms of both image quality and diagnostic confidence for both readers than TSES images (all p < .05). Interrater reliabilities were in almost perfect agreement., Conclusion: The DL-accelerated technique proved to be very helpful not only to reduce scan time but also to improve image quality for acute painful fracture patients wearing a splint despite using body array coils instead of a wrist-specific coil. Based on our study, the DL-accelerated technique can be very useful for MRI of any part of the extremities in trauma settings just with body array coils., Competing Interests: Three authors Dominik Nickel, Gregor Koerzdoerfer, and JaeKon Sung are employees of Siemens Healthineers. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflicts of interest to disclose., (Copyright: © 2023 Roh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear., Methods: We included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4-18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive-Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26., Results: Tic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70)., Conclusions: The IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD. Trial registration This study retrospectively registered participants., (© 2023. The Author(s).)

Background: Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics., Methods: Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated., Results: Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/μL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/μL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497)., Conclusions: Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Previous research suggests that implicit automatic emotion regulation relies on the medial prefrontal cortex (mPFC). However, most of the human studies supporting this hypothesis have been correlational in nature. In the current study, we examine how changes in mPFC-left amygdala functional connectivity relate to emotional memory biases. In a randomized clinical trial examining the effects of heart rate variability (HRV) biofeedback on brain mechanisms of emotion regulation, we randomly assigned participants to increase or decrease heart rate oscillations while receiving biofeedback. After several weeks of daily biofeedback sessions, younger and older participants completed an emotional picture memory task involving encoding, recall, and recognition phases as an additional measure in this clinical trial. Participants assigned to increase HRV (Osc+) (n = 84) showed a relatively higher rate of false alarms for positive than negative images than participants assigned to decrease HRV (Osc-) (n = 81). Osc+ participants also recalled relatively more positive compared with negative items than Osc- participants, but this difference was not significant. However, a summary bias score reflecting positive emotional memory bias across recall and recognition was significantly higher in the Osc+ than Osc- condition. As previously reported, the Osc+ manipulation increased left amygdala-mPFC resting-state functional connectivity significantly more than the Osc- manipulation. This increased functional connectivity significantly mediated the effects of the Osc+ condition on emotional bias. These findings suggest that, by increasing mPFC coordination of emotion-related circuits, daily practice increasing heart rate oscillations can increase implicit emotion regulation., (© 2023. The Author(s).)

Executive functioning (EF) is a cognitive process used to perform various daily activities throughout one's lifespan. Autistic adults without intellectual disabilities (ID) also experience difficulties with EF, which is closely associated with adaptive behaviors. For this reason, it is important to improve adaptive behaviors through enhanced use of EF for autistic adults to transition into adulthood successfully. This study aims to conduct a randomized controlled trial to evaluate the effectiveness of a newly developed and modified intervention program. Thirty autistic adults without ID were randomly assigned to the treatment or waitlist group. The participants and caregivers completed various assessments and self-report questionnaires to measure everyday EF and adaptive behaviors. We performed linear mixed-effect modeling to compare the two groups. Data collected at pre-, middle, post-, and follow-up based on participants who completed the program were used to explore changes across time. While there were significant differences in the EF utility-scale (F=5.46, p = .027) between the treatment and waitlist groups, no group x time interactions were detected in other measures. Everyday EF and adaptive behaviors improved when comparing measurements at different time points (p < .001). Our program is Korea's first evidence-based intervention to improve everyday EF and adaptive behaviors for autistic adults without ID., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Carotenoids and apocarotenoids function as pigments and flavor volatiles in plants that enhance consumer appeal and offer health benefits. Tomato (Solanum lycopersicum.) fruit, especially those of wild species, exhibit a high degree of natural variation in carotenoid and apocarotenoid contents. Using positional cloning and an introgression line (IL) of Solanum habrochaites "LA1777', IL8A, we identified carotenoid cleavage dioxygenase 4 (CCD4) as the factor responsible for controlling the dark orange fruit color. CCD4b expression in ripe fruit of IL8A plants was ∼8,000 times greater than that in the wild type, presumably due to 5' cis-regulatory changes. The ShCCD4b-GFP fusion protein localized in the plastid. Phytoene, ζ-carotene, and neurosporene levels increased in ShCCD4b-overexpressing ripe fruit, whereas trans-lycopene, β-carotene, and lutein levels were reduced, suggestive of feedback regulation in the carotenoid pathway by an unknown apocarotenoid. Solid-phase microextraction-gas chromatography-mass spectrometry analysis showed increased levels of geranylacetone and β-ionone in ShCCD4b-overexpressing ripe fruit coupled with a β-cyclocitral deficiency. In carotenoid-accumulating Escherichia coli strains, ShCCD4b cleaved both ζ-carotene and β-carotene at the C9-C10 (C9'-C10') positions to produce geranylacetone and β-ionone, respectively. Exogenous β-cyclocitral decreased carotenoid synthesis in the ripening fruit of tomato and pepper (Capsicum annuum), suggesting feedback inhibition in the pathway. Our findings will be helpful for enhancing the aesthetic and nutritional value of tomato and for understanding the complex regulatory mechanisms of carotenoid and apocarotenoid biogenesis., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05-22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low., (© 2023. The Author(s).)

Objectives: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH)., Methods: In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy., Results: The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393)., Conclusion: HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.

Background: As significant advances in the field of treatment for rheumatoid arthritis (RA), there is a great need to identify the healthcare outcomes such as treatment satisfaction and health-related quality of life (HRQoL) of patients with various treatment options. This study aims to identify the difference in the treatment satisfaction and HRQoL of patients with RA using different treatment options, by comparing the treatment satisfaction and HRQoL in patients with RA treated with tofacitinib and adalimumab in real-world settings in Korea, using propensity score methods., Methods: In this non-interventional, multicenter, cross-sectional study (NCT03703817), a total of 410 patients with RA diagnosis were recruited in 21 university-based hospitals throughout Korea. The treatment satisfaction and HRQoL were assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and EQ-5D questionnaires self-reported by the patients. This study compared outcomes between two drug groups in unweighted, greedy matching, and stabilized inverse probability of treatment weight (IPTW) samples using propensity score., Results: In all three samples, tofacitinib group showed higher convenience domain of TSQM than that in the adalimumab group, but not effectiveness, side effects, and global satisfaction domains. Multivariable analysis using the covariates of demographic and clinical characteristics of the participants also showed consistent results in TSQM. No statistical difference in EQ-5D-based HRQoL was identified between two drug groups in all three samples., Conclusions: This study identified that tofacitinib shows higher treatment satisfaction in the convenience domain of TSQM rather than adalimumab, suggesting that various factors such as drug formulation, route or frequency of administration, and storage can have an impact on the treatment satisfaction, especially the convenience domain. These findings may be useful to patients and physicians when determining treatment options., Trial Registration: ClinicalTrials.gov, NCT03703817., (© 2023. The Author(s).)

Background: Although acute myocardial infarction (AMI) requires timely intervention, limited nationwide data is available regarding the association between disruption of emergency services and outcomes of patients with AMI during the coronavirus disease 2019 (COVID-19) pandemic. Moreover, whether diabetes mellitus (DM) adversely affects disease severity in these patients has not yet been investigated., Methods: This nationwide population-based study analyzed 45,648 patients with AMI, using data from the national registry of emergency departments (ED) in Korea. Frequency of ED visits and disease severity were compared between the COVID-19 outbreak period (year 2020) and the control period (the previous year 2019)., Results: The number of ED visits by patients with AMI decreased during the first, second, and third waves of the outbreak period compared to the corresponding time period in the control period (all p -values < 0.05). A longer duration from symptom onset to ED visit ( p = 0.001) and ED stay ( p = 0.001) and higher rates of resuscitation, ventilation care, and extracorporeal membrane oxygen insertion were observed during the outbreak period than during the control period (all p -values < 0.05). These findings were exacerbated in patients with comorbid DM; Compared to patients without DM, patients with DM demonstrated delayed ED visits, longer ED stays, more intensive care unit admissions ( p < 0.001), longer hospitalizations ( p < 0.001), and higher rates of resuscitation, intubation, and hemodialysis (all p -values < 0.05) during the outbreak period. While in-hospital mortality was similar in AMI patients with and without comorbid DM during the two periods (4.3 vs. 4.4%; p = 0.671), patients with DM who had other comorbidities such as chronic kidney disease or heart failure or were aged ≥ 80 years had higher in-hospital mortality compared with those without any of the comorbidities (3.1 vs. 6.0%; p < 0.001)., Conclusion: During the pandemic, the number of patients with AMI presenting to the ED decreased compared with that of the previous year, while the disease severity increased, particularly in patients with comorbid DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Hwang, Park, Park, Jang, Choi, Baik and Yoo.)

Surgical debridement is an essential step in treating complex facial lacerations (CFL). As the CFL severity increases, conventional surgical debridement (CSD) of wound edges becomes difficult and may be insufficient. Because the severity and shape of each CFL vary, it is necessary to tailor the customized pre-excisional design, that is, tailored surgical debridement (TSD), for each case before performing surgical debridement. The use of TSD can enable effective debridement of CFL with higher severity. This study aimed to compare the cosmetic outcomes and complication incidence of CSD versus TSD according to CFL severity. In this retrospective observational study, eligible patients with CFL who visited the emergency department between August 2020 and December 2021 were examined. CFL severity was graded as Grades I and II. The outcomes of CSD and TSD were compared using the scar cosmesis assessment and rating (SCAR) scale, wherein a good cosmetic outcome was defined as a SCAR score of ≤ 2. The percentage of good cosmetic outcomes between the 2 groups was compared. The SCAR score and percentage of good cosmetic outcomes between the 2 groups were compared overall and by severity. For analyzing complication incidence, asymmetry, infection, and dehiscence incidence were compared. In total, 252 patients were enrolled [121 (48.0%) CSD and 131 (52.0%) TSD]. The median SCAR scores were 3 (1-5) and 1 (0-2) in all enrolled patients (P < .001), 2 (0-4), and 1 (0-1) in Grade I patients (P < .01), and 5 (4-6) and 1 (1-2) in Grade II patients (P < .001) in the CSD and TSD groups, respectively. The percentage of good cosmetic outcomes was 46.3% and 84.0% overall (P < .001), 59.6% and 85.0% in Grade I patients (P < .01), and 9.4% and 83.5% in Grade II patients (P < .001) in the CSD and TSD groups, respectively. The incidence of complications was significantly higher in the CSD group than in the TSD group, but this was limited to asymmetry. No significant difference was noted in infection or dehiscence. Compared with CSD, TSD can lead to an objectively good cosmetic prognosis at higher CFL severity and can reduce facial asymmetry occurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline., Materials and Methods: We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits., Results: Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference = -1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference = -0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group., Conclusions: Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline., (© 2022 John Wiley & Sons Ltd.)

Background: There are no clear guidelines to determine whether to perform D1 or D1+ lymph node dissection in early gastric cancer (EGC). This study aimed to develop a nomogram for estimating the risk of extraperigastric lymph node metastasis (LNM)., Materials and Methods: Between 2009 and 2019, a total of 4,482 patients with pathologically confirmed T1 disease at 6 affiliated hospitals were included in this study. The basic clinicopathological characteristics of the positive and negative extraperigastric LNM groups were compared. The possible risk factors were evaluated using univariate and multivariate analyses. Based on these results, a risk prediction model was developed. A nomogram predicting extraperigastric LNM was used for internal validation., Results: Multivariate analyses showed that tumor size (cut-off value 3.0 cm, odds ratio [OR]=1.886, P=0.030), tumor depth (OR=1.853 for tumors with sm2 and sm3 invasion, P=0.010), cross-sectional location (OR=0.490 for tumors located on the greater curvature, P=0.0303), differentiation (OR=0.584 for differentiated tumors, P=0.0070), and lymphovascular invasion (OR=11.125, P<0.001) are possible risk factors for extraperigastric LNM. An equation for estimating the risk of extraperigastric LNM was derived from these risk factors. The equation was internally validated by comparing the actual metastatic rate with the predicted rate, which showed good agreement., Conclusions: A nomogram for estimating the risk of extraperigastric LNM in EGC was successfully developed. Although there are some limitations to applying this model because it was developed based on pathological data, it can be optimally adapted for patients who require curative gastrectomy after endoscopic submucosal dissection., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

Background/objectives: The consumption of dietary supplements has shown an increase among young people in their 20s. We aimed to compare the use of dietary supplements and related factors between Chinese international and Korean college students living in South Korea., Subjects/methods: We conducted online surveys of 400 Chinese international students and 452 Korean college students from January to February 2021. We analyzed the factors related to the use of dietary supplements by these students using multi-group structural equation modeling and logistic regression analysis., Results: Approximately 65% of the Chinese international students and 93% of the Korean college students consumed dietary supplements at least once in the year preceding the survey. The common types of dietary supplements consumed by both groups of students were vitamin and mineral supplements, Lactobacillus products, and red ginseng products. Structural equation modeling showed that perception of the consumption of dietary supplements by family and friends positively influenced attitude toward dietary supplements. This effect was higher for Korean college students than for Chinese international students ( P < 0.01). Attitude toward dietary supplements positively influenced their use, and this effect was higher for Chinese international students than for Korean college students ( P < 0.001). Logistic regression analysis showed that the use of dietary supplements by Chinese international students was significantly associated with age, self-reported health status, interest in health, perception of and attitude toward dietary supplements, and length of residence in South Korea. Among Korean college students, it was associated with exercise frequency and attitude toward dietary supplements., Conclusion: This study showed significant differences in the use of dietary supplements and related factors between Chinese international and Korean college students. Therefore, nutrition education programs on dietary supplements need to have differentiated content for each group. Such differences also suggest that the industry should consider the relevant characteristics of college students while developing and marketing dietary supplements., Competing Interests: Conflicts of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Background and Aims: Liver cirrhosis is associated with an increased risk of developing erectile dysfunction (ED). The aim of this systematic review and meta-analysis was to evaluate the prevalence of ED and its risk factors in male patients with liver cirrhosis., Methods: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library, and other databases was performed for this review. Two investigators reviewed the abstracts obtained from the search and selected manuscripts for full-text review. The event rates were calculated with random-effects model and quality effects model., Results: Fourteen studies evaluating ED with the International Index of Erectile Function (IIEF) scores were selected. A total of 770 patients with liver cirrhosis were analyzed. The prevalence of ED in cirrhotic patients was 79% [decompensated: 88.4%, CI 35.95-70.84%, I 2 heterogeneity 85%; compensated: 53.6%, CI 77.64-32%, I 2 heterogeneity 80%]. Through a meta-regression analysis, we discovered that the presence of decompensation, use of beta-blocker and diuretics were related with ED. In addition, risk factors for ED included high body mass index [odds ratio (OR) 1.13, 95% CI 1.01-1.26], advanced Child-Pugh class (OR 2.29, 95% CI 1.12-4.72), MELD score (OR 1.19, 95% CI 1.05-1.35), diabetes (OR 3.44, 95% CI 1.38-8.57), and hypertension (OR 8.24, 95% CI 1.62-41.99)., Conclusion: ED is relatively common in male patients with cirrhosis, and presence of risk factors increases the prevalence of ED., Clinical Trial Number: PROSPERO (International Prospective Register of Systematic Reviews), CRD42020220411., (© 2021. Asian Pacific Association for the Study of the Liver.)

Slow paced breathing via heart rate variability (HRV) biofeedback stimulates vagus-nerve pathways that counter noradrenergic stress and arousal pathways that can influence production and clearance of Alzheimer's disease (AD)-related proteins. Thus, we examined whether HRV biofeedback intervention affects plasma Αβ40, Αβ42, total tau (tTau), and phosphorylated tau-181 (pTau-181) levels. We randomized healthy adults (N = 108) to use slow-paced breathing with HRV biofeedback to increase heart rate oscillations (Osc+) or to use personalized strategies with HRV biofeedback to decrease heart rate oscillations (Osc-). They practiced 20-40 min daily. Four weeks of practicing the Osc+ and Osc- conditions produced large effect size differences in change in plasma Aβ40 and Aβ42 levels. The Osc+ condition decreased plasma Αβ while the Osc- condition increased Αβ. Decreases in Αβ were associated with decreases in gene transcription indicators of β-adrenergic signaling, linking effects to the noradrenergic system. There were also opposing effects of the Osc+ and Osc- interventions on tTau for younger adults and pTau-181 for older adults. These results provide novel data supporting a causal role of autonomic activity in modulating plasma AD-related biomarkers.Trial registration: NCT03458910 (ClinicalTrials.gov); first posted on 03/08/2018., (© 2023. The Author(s).)

Background: The mainstay treatment for tenosynovial giant cell tumor (TGCT) is open excision. However, open excision is associated with the risk of stiffness, infection, neurovascular injury, and prolonged hospital stay and rehabilitation. The purpose of this study was to evaluate the efficacy of arthroscopic excision of tenosynovial giant cell tumor (TGCT) of the knee joint, including the diffuse type of TGCT., Methods: Patients who underwent arthroscopic excision of TGCT between April 2014 and November 2020 were retrospectively analyzed. TGCT lesions were divided into 12 distributions (nine intra- and three extra-articular lesions). The distribution of TGCT lesions, portals used, degree of excision, recurrence, and magnetic resonance imaging (MRI) scans were evaluated. The prevalence of intra-articular lesions in diffuse TGCT was also analyzed to validate the existence of a connection between intra- and extra-articular lesions., Results: Twenty-nine patients were included in the study. Fifteen patients (52%) had localized TGCT, and 14 patients (48%) had diffuse TGCT. The recurrence rates for localized, and diffuse TGCT were 0%, and 7%, respectively. Intra-articular posteromedial (i-PM), intra-articular posterolateral (i-PL), and extra-articular posterolateral (e-PL) lesions were found in all patients with diffuse TGCT. The prevalence rates of i-PM and i-PL lesions among e-PL lesions were both 100% (p = 0.026 and p < 0.001, respectively). Diffuse TGCT lesions were managed with posterolateral capsulotomy and viewed from the trans-septal portal., Conclusions: Arthroscopic excision of TGCT was effective in both localized and diffuse TGCT. However, diffuse TGCT was associated with posterior and extra-articular lesions. Therefore, technical modification such as posterior, trans-septal portal, and capsulotomy were required., Study Design: Retrospective case series; level Ⅳ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Recent 3-dimensional technology advancements have resulted in new techniques to improve the accuracy of intraoperative transfer. This study aimed to validate the accuracy of computer-aided design and manufacturing (CAD-CAM) customized surgical cutting guides and fixation plates on mandibular repositioning surgery performed in isolation or combined with simultaneous maxillary repositioning surgery., Methods: Sixty patients who underwent mandibular advancement surgery by the same surgeon were retrospectively evaluated by 3-dimensional surface-based superimposition. A 3-point coordinate system (x, y, z) was used to identify the linear and angular discrepancies between the planned movements and actual outcomes. Wilcoxon rank sum test was used to compare the outcomes between the mandible-only and the bimaxillary surgery groups with significance at P <0.05. Pearson correlation coefficient compared planned mandible advancement to the outcome from advancement planned. The centroid, which represents the mandible as a single unit, was computed from 3 landmarks, and the discrepancies were evaluated by the root mean square error (RMSE) for clinical significance set at 2 mm for linear discrepancies and 4° for angular discrepancies., Results: There was no statistically significant difference between the planned and actual position of the mandible in either group when considering absolute values of the differences. When considering raw directional data, a statistically significant difference was identified in the y-axis suggesting a tendency for under-advancement of the mandible in the bimaxillary group. The largest translational RMSE for the centroid was 0.77 mm in the sagittal dimension for the bimaxillary surgery group. The largest rotational RMSE for the centroid was 1.25° in the transverse dimension for the bimaxillary surgery group. Our results show that the precision and clinical feasibility of CAD-CAM customized surgical cutting guides and fixation plates on mandibular repositioning surgery is well within clinically acceptable parameters., Conclusion: Mandibular repositioning surgery can be performed predictably and accurately with the aid of CAD-CAM customized surgical cutting guides and fixation plates with or without maxillary surgery., (Copyright © 2022 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics., Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0., Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment., Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.

Previous research suggests that higher heart rate variability (HRV) is associated with better cognitive function. However, since most previous findings on the relationship between HRV and cognitive function were correlational in nature, it is unclear whether individual differences in HRV play a causal role in cognitive performance. To investigate whether there are causal relationships, we used a simple breathing manipulation that increases HRV through a 5-week HRV biofeedback intervention and examined whether this manipulation improves cognitive performance in younger and older adults (N = 165). The 5-week HRV biofeedback intervention did not significantly improve inhibitory control, working memory and processing speed across age groups. However, improvement in the Flanker score (a measure of inhibition) was associated with the amplitude of heart rate oscillations during practice sessions in the younger and older intervention groups. Our results suggest that daily practice to increase heart rate oscillations may improve inhibitory control, but future studies using longer intervention periods are warranted to replicate the present finding., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Appropriate prediction models can assist healthcare systems in delaying or reversing osteoarthritis (OA) progression. We aimed to identify a reliable algorithm for predicting the progression rate and fate of OA based on patient-specific information. From May 2003 to 2019, 83,280 knees were collected. Age, sex, body mass index, bone mineral density, physical demands for occupation, comorbidities, and initial Kellgren-Lawrence (K-L) grade were used as variables for the prediction models. The prediction targets were divided into dichotomous groups for even distribution. We compared the performances of logistic regression (LR), random forest (RF), and extreme gradient boost (XGB) algorithms. Each algorithm had the best precision when the model used all variables. XGB showed the best results in accuracy, recall, F1 score, specificity, and error rates (progression rate/fate of OA: 0.710/0.877, 0.542/0.637, 0.637/0.758, 0.859/0.981, and 0.290/0.123, respectively). The feature importance of RF and XGB had the same order up to the top six for each prediction target. Age and initial K-L grade had the highest feature importance in RF and XGB for the progression rate and fate of OA, respectively. The XGB and RF machine learning algorithms showed better performance than conventional LR in predicting the progression rate and fate of OA. The best performance was obtained when all variables were combined using the XGB algorithm. For each algorithm, the initial K-L grade and physical demand for occupation were the greatest contributors with superior feature importance compared with the others., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)