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June Hong Ahn, Jin Hong Chung, Kyeong-Cheol Shin, Eun Young Choi, Hyun Jung Jin, Mi Suk Lee, Mi Jeong Nam, Kwan Ho Lee Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Yeungnam University, Daegu, South KoreaCorrespondence: Kwan Ho LeeDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, South KoreaEmail ghlee@med.yu.ac.krObjective: Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. “Frequent exacerbator” phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.Methods: This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.Results: Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m2, lower forced expiratory volume in 1 s (FEV1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m2 (OR, 2.855, 95% CI, 1.247–6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072–2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021–3.999; p=0.044) were risk factors.Conclusion: Any critical error, BMI < 25 kg/m2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.Keywords: COPD, inhalation therapy, drug use error, disease exacerbation

Background: The use of proton pump inhibitors (PPIs) is thought to increase the incidence of microscopic colitis (MC), although the exact mechanisms are not fully understood. Increased infiltration of intraepithelial lymphocytes (IELs) is a pathologic finding of MC (including collagenous or lymphocytic colitis).Aims: We investigated whether PPI use is associated with increased IEL infiltration and inflammation in the lamina propria.Methods: We retrospectively reviewed the medical records and histological reports of 78 patients receiving PPIs who had no symptoms of diarrhea, and their age- and gender- matched controls. The levels of IELs and inflammation in the lamina propria were assessed independently by two pathologists using H&E and immunohistochemical staining for CD3 and CD8.Results: The IEL count was significantly higher in the PPI group than in controls (12.92 ± 6.27 vs. 8.10 ± 4.21 per 100 epithelial cells, p < 0.001), as was the extent of inflammation (1.74 ± 0.90 vs. 0.86 ± 0.78, p < 0.001). PPI use was associated with increased IEL infiltration in a multivariate analysis (OR, 3.232; 95 % CI, 1.631-6.404, p < 0.001). Within the PPI group, however, the IEL count was not significantly associated with gender, age, type of PPI, or duration of PPI use.Conclusions: The use of PPIs has a significant association with increased IEL infiltration for subjects without symptoms of diarrhea. This finding suggests that changes such histological alterations seen in the early phage seen in MC possibly represent the stage of the disease even before the onset of symptoms. [ABSTRACT FROM AUTHOR]

Objective To investigate clinical outcomes of exercise-induced pulmonary hypertension (PH) and implications of an increase in left ventricular (LV) filling pressure during exercise in subjects with preserved LV ejection fraction. Design Longitudinal follow-up study. Setting Subjects who were referred for diastolic stress echocardiography. Patients and methods The ratio of transmitral and annular velocities (E/Ea) and pulmonary artery systolic pressure (PASP) at rest and during exercise were measured in 498 subjects (57±11years; 201 male). Exercise-induced PH was defined as present if PASP >=50mm Hg at 50W of exercise, and an increase in LV filling pressure during exercise was present if E/Ea >=15 at 50W. Main outcome measures A combination of major cardiovascular events and any cause of death. Results During a median follow-up of 41months, there were 14 hospitalisations and four deaths. Subjects with exercise-induced PH had significantly worse clinical outcomes than those without (p=0.014). Subjects with exercise-induced PH associated with an increase in E/Ea during exercise had significantly worse outcomes than other groups (p<0.001). However, prognosis was similar between subjects with exercise-induced PH without an increase in E/Ea and those without exercise-induced PH. In subjects with exercise-induced PH, E/Ea at 50W was an independent predictor of adverse outcomes (HR 1.37; 95% CI 1.02 to 1.83; p=0.036). Conclusions Exercise-induced PH provides prognostic information in subjects with preserved LV ejection fraction. The excess risk of exercise-induced PH is restricted to subjects with an increase in estimated LV filling pressure during exercise. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate atrial myocardial properties through two-dimensional (2D) myocardial imaging in patients with atrial fibrillation (AF) and its predictive role for recurrence after catheter ablation.Methods and Results: Echocardiographic examinations were performed in 40 patients with paroxysmal AF before catheter ablation and 40 age- and gender-matched healthy control subjects. Using a software package, bidimensional acquisitions were analyzed to measure longitudinal strain and strain rate for the left atrium (LA). Systolic strain and strain rate in all eight segments, and its average values, were significantly reduced in AF patients compared to controls. During 9 months of follow-up after catheter ablation for AF, 11 of 40 AF patients had AF recurrence. AF recurrence was associated with gender, LA volume index, and average values of systolic strain and strain rate. By multivariate analysis, only average strain was an independent predictor of AF recurrence (OR = 0.88, 95% CI 0.79-0.98, p = 0.018).Conclusions: Lower systolic strain of LA was strongly associated with recurrence after catheter ablation. Thus, diverse adjunctive ablation strategies should be considered to reduce recurrence in patients with lower systolic strain. [ABSTRACT FROM AUTHOR]

Aims: Despite the prognostic importance of ventricular filling and ventricular-arterial interaction in patients with advanced systolic heart failure, the structural determinants of these parameters have not been fully studied. We aimed to investigate whether patterns of late gadolinium enhancement (LGE) on cardiac magnetic resonance affect ventricular elastic properties or performance in patients with non-ischaemic dilated cardiomyopathy (DCM). Methods and Results: Patients (n = 49) with markedly reduced systolic function (left ventricular (LV) ejection fraction <35%) due to longstanding non-ischaemic DCM underwent contrast-enhanced cardiac magnetic resonance after comprehensive echo-Doppler evaluations. The single beat-derived end-diastolic elastance, end-systolic elastance, arterial elastance, and dyssynchrony indices were measured by echo. On the basis of LGE patterns, patients could be divided into three groups: non-LGE (n = 18), non-midwall LGE (n = 13), and midwall LGE (n = 18). The midwall LGE group had lower LV systolic longitudinal velocity (4.6 +/- 1.7 for non-LGE vs. 4.3 +/- 1.2 for non-midwall LGE vs. 3.5 +/- 1.0 cm/s for midwall LGE, P = 0.025), higher end-diastolic elastance index (0.41 +/- 0.21 vs. 0.46 +/- 0.31 vs. 0.85 +/- 0.51 respectively, P = 0.008), and a more impaired ventriculoarterial coupling index (3.14 +/- 1.53 vs. 2.88 +/- 1.94 vs. 5.52 +/- 3.18, P = 0.006) than other subgroups. Conclusion: Patients with midwall LGE had a higher ventricular stiffness index and more impaired ventriculoarterial coupling when compared with other non-ischaemic DCM patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with similar grade diastolic dysfunction at rest may have a spectrum of alterations in diastolic function during exercise. OBJECTIVE: To evaluate (a) whether exercise could unmask further diastolic abnormalities not evident during rest; (b) whether diastolic functional reserve during exercise is associated with exercise capacity. METHODS: 141 subjects (77 male, mean (SD) age 62 (9)) with abnormal left ventricular (LV) relaxation (mitral E/A <0.75) and/or deceleration time >240 ms, underwent graded supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. Mitral inflow and annular velocities were measured at rest and during exercise. The LV diastolic function reserve index (DFRI) was calculated. RESULTS: Patients were classified into two groups: group 1 (n = 64), DFRI <13.5; group 2 (n = 77), DFRI >or=13.5. The ratio of E/E' to stroke volume was used as an index of ventricular elastance (Ed). No significant differences between the groups in mitral inflow and annular velocities at rest were found. Mean (SD) Ed was not significantly different at rest between the groups (0.19 (0.07) vs 0.18 (0.06), p = 0.29). Ed was significantly higher during exercise in group 1 than in group 2 (25 W, 0.21 (0.09) vs 0.14 (0.04), p<0.001; 50 W, 0.22 (0.10) vs 0.15 (0.04), p<0.001). Group 1 subjects had a shorter exercise duration (8.2 (2.7) vs 9.4 (3.7) min, p = 0.04) and lower peak oxygen consumption (17.5 (4.5) vs 20.2 (5.4) ml/kg/min, p = 0.005). CONCLUSIONS: Despite similar mitral flow and annular velocities at rest, different responses to exercise were seen in patients with abnormal LV relaxation at rest. Lower LV diastolic functional reserve was associated with higher ventricular elastance during exercise, and reduced exercise capacity. [ABSTRACT FROM AUTHOR]

Background: Subclinical myocardial dysfunction occurs in a significant number of patients with type 2 diabetes. Assessment of ventricular long-axis function by measuring mitral annular velocities using tissue Doppler echocardiography (TDE) is thought to provide a more sensitive index of systolic and diastolic function. We hypothesised that augmentation of left ventricular (LV) longitudinal contraction and relaxation during exercise would be blunted in patients with type 2 diabetes. Methods: Mitral annular systolic (S') and early diastolic (E') velocities were measured at rest and during supine bicycle exercise (25 W, 3 min increments) in 53 patients (27 male, mean age 53+/-14 years) with type 2 diabetes and 53 subjects with age and gender-matched control. None had echocardiographic evidence of resting or inducible myocardial ischaemia. Results: There were no significant differences in mitral inflow velocities at rest between the two groups. E' and S' at rest were also similar between the groups. However, S' (7.1+/-1.3 vs 8.3+/-1.8 cm/s at 25 W, p = 0.0021; 8.1+/-1.5 vs 9.1+/-2.0 cm/s at 50 W, p = 0.026) and E' (8.5+/-2.3 vs 9.9+/-3.1 cm/s at 25 W, p = 0.054; 9.1+/-2.1 vs 10.9+/-2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly lower in patients with diabetes compared with controls. Longitudinal systolic and diastolic function reserve indices were significantly lower in patients with diabetes compared with that of controls (systolic index, 0.6+/-0.70 vs 1.2+/-1.5 cm/s at 25 W, p = 0.029; 1.2+/-1.2 vs 2.1+/-1.6 cm/s at 50 W, p = 0.009; diastolic index, 1.9+/-1.2 vs 2.5+/-2.2 cm/s at 25 W, p = 0.07; 2.3+/-1.3 vs 3.2+/-2.2 cm/s at 50 W, p = 0.031). Conclusion: In conclusion, unlike resting mitral inflow and annular velocities, changes of systolic and diastolic velocities of the mitral annulus during exercise were significantly reduced in patients with type 2 diabetes compared with the control group. The assessment of LV longitudinal functional reserve with exercise using TDE appears to be helpful in identifying early myocardial dysfunction in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not been explored previously. This study was sought to determine the relationship between diastolic mitral annular velocities combined with conventional Doppler indexes and exercise capacity in patients with ApHCM. Patients: Twenty-nine patients with ApHCM (24 men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. Results: The mitral inflow velocities (early filling [E], late filling, and deceleration time) were traced and measured. Early diastolic mitral annular velocity (E') was measured at the septal corner of mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view. Pro-brain natriuretic peptide (proBNP) was measured at the time of echocardiography using a quantitative electrochemiluminescence immunoassay. E/E' ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p = 0.0106]. There was a significant positive correlation between E' and Vo(2)max (r = 0.41, p = 0.024). However, no correlation was found between conventional two-dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the echocardiographic and clinical parameters assessed, E/E' ratio had the best correlation with exercise capacity (r - 0.47) and was the strongest independent predictor of Vo(2)max by multivariate analysis (p = 0.0106). Conclusions: DTI-derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV filling pressures, correlate with exercise capacity in patients with ApHCM, suggesting that abnormal diastolic function may be a factor limiting exercise capacity. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cells show remarkable efficacy for some hematological malignancies. However, CAR targets that are expressed at high level and selective to tumors are scarce. Several strategies have been proposed to tackle the on-target off-tumor toxicity of CAR-T cells that arise from suboptimal selectivity, but these are complicated, with many involving dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40. Our system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which we show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. Simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag may further enhance safety by enabling permanent in vivo depletion of the switchable CAR-T cells when necessary. In summary, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the range of CAR targets., Competing Interests: Competing interests K.C. and E.Y.C. are founders and shareholders of Ticaros Inc. H.B.P., J.E.L., and G.R.J. are currently employees of Ticaros. K.C., J.C., H.B.P., K.H.K., S.I.K., and G.R.J. are co-inventors on the pending patent for anti-CD40 switchable CAR T cells. The other authors declare no competing interests., (© 2024. The Author(s).)

Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions. However, there are no treatments to induce motile ciliogenesis. Forkhead box transcription factor J1 (FOXJ1), the master regulator, has been implicated in motile cilia formation. Mice lacking the Foxj1 gene show loss of axoneme, a key component of cilia, that further highlights the importance of FOXJ1 in motile cilia formation. This prompted us to identify new small molecules that could induce motile ciliogenesis. A phenotype-based high-throughput screening (HTS) in a Tg(foxj1a:eGFP) zebrafish model was performed and a novel hit compound was identified. Among the synthesized compounds, compound 16c effectively enhanced motile ciliogenesis in a transgenic zebrafish model. To further test the efficacy of compound 16c on a mammalian airway system consisting of multiciliated cells (MCCs), ex vivo mice tracheal epithelial cell culture was adopted under an air-liquid interface system (ALI). Compound 16c significantly increased the number of MCCs by enhancing motile ciliogenesis. In addition, compound 16c exhibited good liver microsomal stability, in vivo PK profiles with AUC, and oral bioavailability. There was no significant inhibition of CYP and hERG, and no cell cytotoxicity was shown. In an elastase-induced COPD (chronic obstructive pulmonary disease) mouse model, compound 16c effectively prevented the development and onset of COPD. Taken together, compound 16c has great promise as a therapeutic agent for treating and alleviating motile ciliopathies., 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 © 2024 Elsevier Masson SAS. All rights reserved.)

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), ventrolateral PFC (vlPFC), and dorsal PFC (dPFC) of macaque monkeys. Rs-fMRI seeds at the same regions of NHP and homologous regions of human brains showed connectivity maps in the striatum mostly consistent with those observed in the tracer data. We then examined the location of overlap in striatal projection zones. The medial rostral dorsal caudate connected with all five frontocortical regions evaluated in this study in both modalities (tract-tracing and rs-fMRI) and species (NHP and human). Other locations in the caudate also presented an overlap of four frontocortical regions, suggesting the existence of different locations with lower levels of input diversity. Small retrograde tracer injections and rs-fMRI seeds in the striatum confirmed these cortical input patterns. This study sets the ground for future studies evaluating rs-fMRI in clinical samples to measure anatomical corticostriatal circuit dysfunction and identify connectional hubs to provide more specific treatment targets for neurological and psychiatric disorders., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature Working Group criteria., Methods: Using the medical records of the patients, the authors reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on Standardization of Uveitis Nomenclature criteria and compared the result with the clinical diagnosis., Results: Of 100 eyes, 29 eyes (29%) were diagnosed as punctate inner choroidopathy and 15 eyes (15%) were diagnosed as MCP using Standardization of Uveitis Nomenclature criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed punctate inner choroidopathy eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using Standardization of Uveitis Nomenclature criteria., Conclusion: The existing diagnostic criteria showed limitations in capturing all clinical cases of punctate inner choroidopathy or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia could be considered to enhance diagnostic accuracy.

Objectives: Exposure to stressful neighborhood environments is a well-established risk factor for health deterioration and premature death. However, the biological underpinnings are not fully understood. Epigenetic aging may function as a key molecular pathway to adverse health outcomes among residents of high-stress neighborhoods. This study examines the associations between neighborhood social stressors (socioeconomic deprivation, observed and perceived disorder, and low social cohesion) and epigenetic age (DunedinPACE and Principal component adjusted (PC) PCHorvath, PCHannum, PCPhenoAge, PCGrimAge). Further, we identify sub-populations most vulnerable to neighborhood stressors., Methods: Respondent data are from the 2016 Health and Retirement Study (HRS) DNA Methylation subsample. Neighborhood data come from respondent reports (2014/2016) and the census (2012-2016 ACS). The analytic sample included 3,146 adults ages 56 and older (mean age=68.8), of whom 54.9% were women and 19.3% were non-white., Results: In multilevel regression models adjusting for sociodemographic covariates, all neighborhood stressors were associated with faster DunedinPACE (B=0.008 to 0.017). Neighborhood deprivation, perceived disorder, and low cohesion were associated with PCPhenoAge (B=0.27 to 0.40) or PCGrimAge acceleration (B= 0.23). Health behaviors explained these associations to some degree. However, no significant associations were found with PCHorvath and PCHannum. In interaction analyses, adverse associations with deprivation, observed disorder, and low cohesion were more pronounced for women. No consistent interactions were found for race/ethnic and education groups., Discussion: Our findings indicate that neighborhood stressors can accelerate epigenetic aging, with older women particularly vulnerable to their effects. These findings provide insights into the biological foundations of health disparities rooted in neighborhood environments., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: The author declares no competing financial interests.

Hopelessness is one of the strongest predictors of health and mortality, particularly for older populations. Prior research has found associations between individual-level socioeconomic factors and hopelessness, but less is known about the potential importance of neighborhood-level socioeconomic contexts for hopelessness. In particular, the role of neighborhood disorder as a potential explanatory factor for poor psychological well-being remains underexplored. This study investigates whether neighborhood poverty is associated with a sense of hopelessness among older adults and if perceived neighborhood disorder mediates the link between poverty and hopelessness. Individual-level data came from the 2014/2016 Health and Retirement Study and were merged with neighborhood-level poverty data from the 2012-2016 and 2014-2018 American Community Survey. Linear regression models were employed to examine the association between neighborhood poverty, disorder, and hopelessness. Respondents in neighborhoods with higher poverty levels reported a greater sense of hopelessness (b = 0.11, 95% CI = 0.08, 0.15, p < .001), controlling for individual-level sociodemographic and health characteristics. Greater perceived neighborhood disorder was also positively associated with a sense of hopelessness (b = 0.16, 95%CI = 0.14, 0.18). When we included both neighborhood poverty and disorder in the same model, the association between neighborhood poverty and hopelessness was reduced by two thirds (b = 0.04, 95%CI = 0.0003, 0.07), while the association between perceived disorder and hopelessness remained robust (b = 0.16, 95%CI = 0.14, 0.18). We further examined the formal mediating effects of neighborhood disorder using structural equation modeling. The total effect of neighborhood poverty on hopelessness was significant (β = 0.08, bootstrapped 95%CI = 0.05, 0.10). The direct effect of neighborhood poverty was not significant (β = 0.02, bootstrapped 95% CI = -0.01, 0.04), while the indirect effect through neighborhood disorder was significant (β = 0.06, bootstrapped 95% CI = 0.05, 0.07). Neighborhood disorder mediated 75% of the association between neighborhood poverty and hopelessness. In light of these findings, improving neighborhood conditions, such as signs of disorder, may alleviate feelings of hopelessness in older adults residing in impoverished neighborhoods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choi 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.)

Objective: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data., Patients and Methods: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed., Results: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%)., Conclusion: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Psychological support programs can help nurses who involved in patient safety incidents. However, most of these programs are operated internally by healthcare providers and utilize peer supporters, which may take a long time to implement. Therefore, there is a need to develop programs that can be used by healthcare providers in healthcare institutions that have difficulty implementing their own programs. This feasibility study aimed to develop an external support program for nurses as second victims and to examine the feasibility, acceptability, and impact of the program., Methods: This study was conducted using a single-group pretest-posttest design. Nurses who experienced patient safety incidents were recruited through posters at three advanced general hospitals, as well as open online recruitment and via a research agency panel from September 2020 to April 2021. The 11 participants attended a total of three one-on-one counseling sessions. Feasibility was evaluated based on participant recruitment and retention, resource availability, program procedures, and the practicability of data collection. Acceptability was assessed through program satisfaction and participant feedback. Psychological impact was measured using the Impact of Event Scale-Revised Korean version., Results: Out of 26 applicants, 11 (42.3%) completed the program, with 10 (38.5%) participants completing both pre and post-program surveys. Most participants responded that they were satisfied with the program and expressed their intention to recommend the program to others and participate in it again if similar situations arise. The participants' median total IES-R-K score decreased significantly from 30.0 to 16.0 (p = 0.028, r = 0.67)., Conclusion: This study demonstrates the feasibility of an external second victim support program and provides preliminary data suggesting its potential to alleviate the psychological impact of participants. To overcome the limitations of this study, it is necessary to conduct additional controlled trials with a longer follow-up period and a larger sample size., (© 2024. The Author(s).)

The use of prostaglandin infusion to maintain patency of the ductus arteriosus in patients with critical coarctation of the aorta (CoA) to support systemic circulation is the standard of care. However, pulmonary overcirculation resulting from a patent ductus arteriosus in patients with critical CoA is not well described in the literature. We report two cases of critical CoA that required invasive measures to control pulmonary blood flow before surgical repair of the CoA. Both patients had signs of decreased oxygen delivery, hyperlactatemia, and systemic to pulmonary flow via the ductus arteriosus. One patient required surgical pulmonary artery banding and the second patient underwent pulmonary flow restrictor device placement for the control of pulmonary blood flow. A rapid improvement in oxygen delivery and normalization of lactate levels were observed after control of pulmonary overcirculation. Both patients underwent successful surgical repair of the coarctation A and were discharged home., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Anti-tumor necrosis factor (anti-TNF) therapy may improve insulin sensitivity, and its impact during pregnancy remains unclear. We aimed to assess the risk of gestational diabetes mellitus (GDM) associated with anti-TNF treatment among pregnant women with inflammatory bowel disease (IBD)., Methods: This nationwide cohort study included patients with IBD in Korea from 2010 to 2021. Anti-TNF exposure was identified from the last menstrual period (LMP) to LMP + 140 days. The development of GDM was assessed from LMP + 141 days to delivery. We performed overlap weighting to balance the covariates and used a generalized linear mixed model to measure the risk ratio (RR) and 95% confidence intervals (CIs). The anti-TNF group was compared with the unexposed group, as well as with the immunosuppressant, 5-aminosalicylate, and untreated groups., Results: A total of 3,695 pregnancies in women with IBD were identified, of which 338 (9.2%) were exposed to anti-TNFs. GDM was found in 7.1% of the pregnancies exposed to anti-TNFs as compared with 11.0% of those unexposed. The crude and weighted RRs for GDM risk were 0.64 (95% CI 0.43-0.96) and 0.68 (95% CI 0.55-0.84), respectively. The weighted RR when compared with the immunosuppressant, 5-aminosalicylate, and untreated groups was 0.70 (95% CI 0.41-1.18), 0.71 (95% CI 0.52-0.95), and 0.85 (95% CI 0.59-1.24), respectively., Discussion: This nationwide cohort reported a decreased risk of GDM among patients who used anti-TNFs during early pregnancy compared with those unexposed. GDM risk may become a consideration in the decision-making process when choosing treatment options for pregnant women with a risk factor for GDM., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Medical therapy for aortic stenosis (AS) remains an elusive goal., Objectives: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression., Methods: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18 F-sodium fluoride positron emission tomography ( 18 F-NaF PET)., Results: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm 3 ; 95% CI: 108-163 vs 102 mm 3 ; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18 F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group., Conclusions: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18 F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883)., Competing Interests: Funding Support and Author Disclosures This is a sponsor-initiated trial, and the DongA ST company (Seoul, South Korea), which produces evogliptin, provided the research funding. Dr Song works as the chief medical officer of REDNVIA, a venture company dedicated to the development of drugs for the medical treatment of calcific aortic valve disease. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each area's preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.