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Background: To evaluate the diagnostic accuracy of (18)F-FDG PET/CT in detection of recurrent differentiated thyroid cancer (DTC) in patients with elevated stimulated thyroglobulin (Tg) or anti-Tg antibody (Ab) levels, and negative (131)I whole body scan according to the Tg level. Methods: PET/CT images of well DTC patients who had total thyroidectomy and radioiodine ablation were included. Patients showing elevated Tg titer (≥2.0 ng/ml after TSH stimulation) or elevated anti-Tg titer (≥70.0 IU/ml) while diagnostic radioiodine scan was negative were enrolled. PET/CT was classified as positive or negative on the basis of visual interpretation. The maximum standard uptake values (SUVmax) of the suspected lesions on PET/CT were also recorded. The PET/CT findings were compared with histological or clinical follow-up results based on other imaging modalities and serum Tg/anti-Tg Ab titers. The diagnostic performance of PET/CT was compared among 4 subgroups according to the Tg level [2 ng/ml ≤ stimulated Tg (sTg) < 5 ng/ml, 5 ng/ml ≤ sTg < 10 ng/ml, 10 ng/ml ≤ sTg < 20 ng/ml, and ≥20 ng/ml]. Results: A total of 68 PET/CT images from 60 patients were included, and histological confirmations were available in 32 images. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 69.4, 66.7, 69.1, 95.6, and 17.4%, respectively. There were 3 PET/CT cases with high anti-Tg Ab level, and low (<2 ng/ml) Tg level, and all 3 were positive of recurrence. The mean SUVmax of the suspected lesions on PET/CT was 2.9 ± 4.5 (range 1.3-29.7). The sensitivity of PET/CT according to Tg levels was 28.6% when Tg was between 2 and 5, 57.1% between 5 and 10, 60.0% between 10 and 20, and 85.7% when Tg was equal to or greater than 20 ng/ml sub-groups, respectively. Conclusion: Diagnostic accuracy of FDG PET in radioiodine negative thyroid cancer may vary depending on serum Tg levels at imaging. (18)F-FDG PET/CT is useful in detection and localization of recurrent thyroid cancer in patients with negative diagnostic radioiodine scan despite elevated Tg greater than 20 ng/ml or high anti-Tg Ab titers. In contrast, PET/CT provides little additional information when the Tg is less than 5 ng/ml. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing InterestsYeongjoo Lee and Sae Jung Na declare that they have no conflict of interest.

Background: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA)., Methods: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage., Results: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889)., Conclusion: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Cardiac 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG PET) is widely used to assess myocardial viability in patients with ischemic heart disease. While sufficient glucose uptake is a prerequisite for accurate interpretation of cardiac viability, there are a lack of data on which clinical variables have the most significant impact on myocardial glucose metabolism. Therefore, this study was designed to evaluate several clinical variables that could affect myocardial glucose metabolism., Methods: A total of 214 consecutive cases were retrospectively enrolled in this study. All subjects received 250 mg of acipimox and underwent glucose loading as preparation for cardiac FDG PET/CT. Three-dimensional regions of interest (ROIs) were drawn on PET/CT fusion images. Myocardial glucose uptake ratio (MGUR = SUVmax of LV myocardium/SUVmean of liver) was then calculated. Multiple clinical variables including body mass index (BMI), blood glucose levels at different times, administered insulin dosage, lipid profiles, and ejection fraction were measured and analyzed for correlation with myocardial glucose uptake. After dichotomizing the subjects based on a BMI of 25, each group's MGUR was compared., Results: Myocardial uptake showed significant correlations with BMI (r = -0.162, p = 0.018), HbA1c (r = -0.150, p = 0.030), and triglyceride levels (r = -0.137, p = 0.046). No other clinical variables showed a significant correlation with myocardial glucose uptake. After multiple linear regression analysis, BMI ( p = 0.032) and HbA1c ( p = 0.050) showed a correlation with MGUR. In group analysis, after dividing patients based on BMI, the obese group showed significantly lower myocardial uptake than the non-obese group (3.8 ± 1.9 vs. 4.4 ± 2.1, p = 0.031)., Conclusions: Among several clinical variables, BMI and HbA1c levels were related to myocardial glucose uptake. A prospective study would be needed to examine whether a protocol that additionally considers BMI and HbA1c levels is necessary for the current cardiac FDG PET protocol.

Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p < 0.001). Similarly, among the 160 patients who required intensive care unit admission, significantly more patients in the low QRS group died in the intensive care unit (35.9% vs. 18.2%, p = 0.021). Low QRS voltage was associated with increased hospital mortality in patients with sepsis., (© 2024. The Author(s).)

Introduction and Objectives: Delirium, recognized as a crucial prognostic factor in the cardiac intensive care unit (CICU), has evolved in response to the changing demographics among critically ill cardiac patients. This study aimed to create a predictive model for delirium for patients in the CICU., Methods: This study included consecutive patients admitted to the CICU of the Samsung Medical Center. To assess the candidate variables for the model: we applied the following machine learning methods: random forest, extreme gradient boosting, partial least squares, and Plmnet-elastic.net. After selecting relevant variables, we performed a logistic regression analysis to derive the model formula. Internal validation was conducted using 100-repeated hold-out validation., Results: We analyzed 2774 patients, 677 (24.4%) of whom developed delirium in the CICU. Machine learning-based models showed good predictive performance. Clinically significant and frequently important predictors were selected to construct a delirium prediction scoring model for CICU patients. The model included albumin level, international normalized ratio, blood urea nitrogen, white blood cell count, C-reactive protein level, age, heart rate, and mechanical ventilation. The model had an area under the receiver operating characteristics curve (AUROC) of 0.861 (95%CI, 0.843-0.879). Similar results were obtained in internal validation with 100-repeated cross-validation (AUROC, 0.854; 95%CI, 0.826-0.883)., Conclusions: Using variables frequently ranked as highly important in four machine learning methods, we created a novel delirium prediction model. This model could serve as a useful and simple tool for risk stratification for the occurrence of delirium at the patient's bedside in the CICU., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Unplanned intensive care unit (ICU) readmissions contribute to increased morbidity, mortality, and healthcare costs. The severity of patient illness at ICU discharge may predict early ICU readmission. Thus, in this study, we investigated the association of cardiac ICU (CICU) discharge Sequential Organ Failure Assessment (SOFA) score with unplanned CICU readmission in patients admitted to the CICU., Methods and Results: We retrospectively reviewed the hospital medical records of 4659 patients who were admitted to the CICU from 2012 to 18. Sequential Organ Failure Assessment scores at CICU admission and discharge were obtained. The predictive performance of organ failure scoring was evaluated by using area under the receiver operating characteristic (AUROC) curves. The primary outcome was unplanned CICU readmission. Of the 3949 patients successfully discharged from the CICU, 184 (4.7%) had an unplanned CICU readmission or they experienced a deteriorated condition but died without being readmitted to the CICU (readmission group). The readmission group had significantly higher rates of organ failure in all organ systems at both CICU admission and discharge than the non-readmission group. The AUROC of the discharge SOFA score for CICU readmission was 0.731, showing good predictive performance. The AUROC of the discharge SOFA score was significantly greater than that of either the initial SOFA score (P = 0.020) or the Acute Physiology and Chronic Health Evaluation II score (P < 0.001). In the multivariable regression analysis, SOFA score, overweight or obese status, history of heart failure, and acute heart failure as reasons for ICU admission were independent predictors of unplanned ICU readmission during the same hospital stay., Conclusion: The discharge SOFA score may identify patients at a higher risk of unplanned CICU readmission, enabling targeted interventions to reduce readmission rates and improve patient outcomes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment., Methods: The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models., Results: Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis., Conclusion: High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

This study aimed to evaluate the spherical aberration (SA) in different corneal areas before and after femtosecond laser-assisted in situ keratomileusis (fLASIK) and transepithelial photorefractive keratectomy (tPRK), with the goal of identifying the limitations of and potential improvements in using SA within a 6 mm area. The study included 62 patients who underwent fLASIK and tPRK. Complete eye examinations including keratometry, corneal epithelial thickness, central corneal thickness, and topography were performed preoperatively and postoperatively. Anterior, posterior, and total corneal aberrations were measured preoperatively and three months postoperatively, with pupil diameters ranging from 2 to 8 mm. In the fLASIK group, compared to the preoperative SA, the anterior and total SA increased postoperatively in the 6 and 7 mm areas. In the tPRK group, meanwhile, the anterior and total SA of the 5 mm or larger areas increased postoperatively. An area of 6 mm or larger showed an increase in correlation with the changes in Q value and refractive correction. As the corneal SA and asphericity in the 6 mm zone cannot specifically demonstrate the status of areas smaller than 6 mm or changes in the optical zone after laser refractive surgery, comparison with normal values in various areas of the cornea is necessary.

Abstract: Frontotemporal dementia is a clinical syndrome that is characterized by a progressive deterioration in behavior, personality, and/or language, with relative preservation of memory, and its phenotype and molecular basis are heterogeneous. We present a case of a 62-year-old female patient who underwent 18 F-FDG PET/CT and 18 F-FP-CIT PET/CT for differential diagnosis of psychiatric disease and types of dementia. 18 F-FDG PET/CT image showed a compatible finding for frontotemporal dementia, and 18 F-FP-CIT PET/CT image showed dominantly decreased dopamine transporter activity in the bilateral caudate nucleus., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The growing beekeeping industry in South Korea has led to the establishment of new honey plant complexes. However, studies on honey production from each species are limited. This study aimed to assess the honey production potential of various Brassica napus cultivars and two wildflower species. The nectar characteristics of B. napus varied significantly among the cultivars. Absolute sugar concentrations differed among the cultivars, but sugar composition ratios were similar. In contrast, the amino acid content remained relatively uniform regarding percentage values, irrespective of the absolute concentrations. Estimations of honey potential production per hectare (kg/ha) resulted in the following ranking among cultivars: 'JM7003' (107.1) > 'YS' (73.0) > 'JM7001' (63.7) > 'TL' (52.7) > 'TM' (42.4). The nectar volume of Pseudolysimachion rotundum var. subintegrum and Leonurus japonicus increased during the flowering stage. P. rotundum var. subintegrum was sucrose-rich and L. japonicus was sucrose-dominant. Both species predominantly contained phenylalanine, P. rotundum var. subintegrum had glutamine as the second most abundant amino acid, and L. japonicus had tyrosine. The honey production potential was 152.4 kg/ha for P. rotundum var. subintegrum and 151.3 kg/ha for L. japonicus . These findings provide a basis for identifying food resources for pollinators and selecting plant species to establish honey plant complexes.

Purpose: This study aims to investigate how medical schools in Korea managed their academic affairs and student support in response to the coronavirus disease 2019 (COVID-19) pandemic and their plans for the post-COVID-19 era., Methods: An online survey was conducted, and a link to a questionnaire was distributed to all the administrators of the 40 medical schools in Korea. The final analysis data involved responses from 33 medical schools and 1,342 students. Frequency analysis, cross-tabulation analysis, Fisher's exact test, and one-way analysis of variance were applied for statistical analysis., Results: Regarding instruction methods, most medical schools in Korea transitioned from in-person learning to video-on-demand learning (51.5%) and real-time online learning (42.4%). Among the school leaders, 36.4% planned to continue offering online classes combined with in-person classes beyond the end of the pandemic. Among the students, the online class concentration and participation score was 3.0 points or lower, but the class understanding score was 3.6 points, above a moderate level., Conclusion: Students cited the shorter times needed to attend school and being able to take classes repeatedly as advantages of online classes, and over one-third of medical schools intended to continue with a hybrid of in-person and online learning even after the COVID-19 pandemic restrictions end.

Herpes simplex virus 1 (HSV-1) is double-stranded DNA virus that belongs to the Orthoherpesviridae family. It causes serious neurological diseases of the central nervous system, such as encephalitis. The current U.S. Food and Drug Administration (FDA)-approved drugs for preventing HSV-1 infection include acyclovir (ACV) and valacyclovir; however, their long-term use causes severe side effects and often results in the emergence of drug-resistant strains. Therefore, it is important to discover new antiviral agents that are safe and effective against HSV-1 infection. Korean chestnut honey (KCH) has various pharmacological activities, such as antioxidant, antibacterial, and anti-inflammation effects; however, antiviral effects against HSV-1 have not yet been reported. Therefore, we determined the antiviral activity and mechanism of action of KCH after HSV-1 infection on the cellular level. KCH inhibited the HSV-1 infection of host cells through binding and virucidal steps. KCH decreased the production of reactive oxygen species (ROS) and calcium (Ca 2+ ) following HSV-1 infection and suppressed the production of inflammatory cytokines by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) activity. Furthermore, we found that KCH inhibited the expression of the nod-like receptor protein 3 (NLRP3) inflammasome during HSV-1 infection. Taken together, the antiviral effects of KCH occur through multiple targets, including the inhibition of viral replication and the ROS-mediated NLRP3 inflammasome pathway. Our findings suggest that KCH has potential for the treatment of HSV-1 infection and related diseases.

In this presented case, a 77-year-old woman with an implanted prosthesis and ongoing knee pain underwent a bone scan using 99m Tc-hydroxydiphosphonate (HDP) in suspicion for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient's medical records, she received 1000 mg of ferric carboxymaltose for iron-deficient anemia the day before the 99m Tc-HDP bone scan. Therefore, it was assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share these bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.

Background: This study aimed to evaluate whether the effect of tachycardia varies according to the degree of tissue perfusion in septic shock., Methods: Patients with septic shock admitted to the intensive care units were categorized into the tachycardia (heart rate > 100 beats/min) and non-tachycardia (≤ 100 beats/min) groups. The association of tachycardia with hospital mortality was evaluated in each subgroup with low and high lactate levels, which were identified through a subpopulation treatment effect pattern plot analysis., Results: In overall patients, hospital mortality did not differ between the two groups (44.6% vs. 41.8%, P = 0.441), however, tachycardia was associated with reduced hospital mortality rates in patients with a lactate level ≥ 5.3 mmol/L (48.7% vs. 60.3%, P = 0.030; adjusted odds ratio [OR], 0.59, 95% confidence interval [CI], 0.35-0.99, P = 0.045), not in patients with a lactate level < 5.3 mmol/L (36.5% vs. 29.7%, P = 0.156; adjusted OR, 1.39, 95% CI, 0.82-2.35, P = 0.227)., Conclusion: In septic shock patients, the effect of tachycardia on hospital mortality differed by serum lactate level. Tachycardia was associated with better survival in patients with significantly elevated lactate levels., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Distant metastasis of cholangiocarcinoma is most commonly diagnosed in the liver; however, it can also be found in the lungs, distant lymph nodes, bones, and brain. Distant lymph node metastasis outside the abdominal region without concurrent abdominal metastasis is exceedingly rare in extrahepatic cholangiocarcinoma. Herein, we present interesting 18 F-FDG PET/CT images of a 49-year-old male patient with common bile duct cancer. In this case, the patient, who was scheduled for surgery, unexpectedly showed axillary lymph node metastasis on a preoperative 18 F-FDG PET scan, which was subsequently confirmed via histological examination. Although such cases are exceptionally rare, this accurate diagnosis prompted a modification of the treatment plan, leading to a positive therapeutic response.

Background: Patient-centered outcomes can be achieved when common core and specialist competencies are achieved in a balanced manner. This study was conducted to assess the need to fill the gap between the defined competencies and learners' achievement, in order to improve the internal medicine (IM) training education curriculum for promoting patient-centered outcomes., Methods: A cross-sectional online survey was conducted. The participants were 202 IM specialists who obtained board certification in 2020-2021. We developed a questionnaire to investigate the self-evaluation of common core competencies and achievement level of IM essential competencies. For analysis, frequency tests, paired t -test, Borich priority formula, and χ² were performed., Results: In common core competencies, IM specialists recognized that their achievement levels in all competency categories were lower than their importance level ( P < 0.001), and the highest educational demands were related to self-management. They assessed their five essential procedure skill levels as novice or advanced beginner status. The achievement level for the essential symptoms and signs that IM specialists should be able to manage was predominantly competent level. However, on average, 34.9% answered that they had never assessed during training for essential skills, and 29.7% answered the same for essential symptoms and signs., Conclusion: We identified the priorities of core competencies, the level of achievement in essential procedures and patient care with essential symptoms and signs for IM training, and the related educational methods and assessment status. This study is expected to be used as basic data for developing and revising IM training educational curriculum., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

A 3D numerical model of heat transfer and fluid flow of molten pool in the process of laser wire deposition was presented by computational fluid dynamics technique. The simulation results of the deposition morphology were also compared with the experimental results under the condition of liquid bridge transfer mode. Moreover, they showed a good agreement. Considering the effect of recoil pressure, the morphology of the deposit metal obtained by the simulation was similar to the experiment result. Molten metal at the wire tip was peeled off and flowed into the molten pool, and then spread to both sides of the deposition layer under the recoil pressure. In addition, the results of simulation and high-speed charge-coupled device presented that a wedge transition zone, with a length of ∼6 mm, was formed behind the keyhole in the liquid bridge transfer process, where the height of deposited metal decreased gradually. After solidification, metal in the transition zone retained the original melt morphology, resulting in a decrease in the height of the tail of the deposition layer., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Background: Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group., Methods: This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19-50 years, 50-80 years, and ≥ 80 years old individuals., Results: During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02-1.29). Interestingly, in the age 19-50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35-0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19-50 groups (adjusted OR = 0.29, 95% CI = 0.12-0.69)., Conclusions: Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis., (© 2023. The Author(s).)

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck. However, the molecular mechanisms governing the development of HNSCC have not been fully elucidated. Materials and Methods: Differentially expressed genes (DEGs) were screened out from The Cancer Genome Atlas (TCGA) and GSE23036 datasets. Weighted gene coexpression network analysis (WGCNA) was used to reveal the correlations among genes and to search for significantly correlated gene modules. The expression levels of genes in HNSCC and normal samples according to antibody-based detected methods was assessed by utilizing the Human Protein Atlas (HPA). The impact of the selected hub genes on the prognosis of HNSCC patients was assessed by analysing immunohistochemistry (IHC) and immunofluorescence (IF) expression levels and clinical data. Results: Twenty-four genes positively correlated with tumour status and 15 genes negatively correlated with tumour status were screened out by WGCNA. PLAU and LAMC2 were associated with a poor prognosis in patients with HNSCC and were finally screened out and verified by GEPIA and HPA database analysis. Immunohistochemistry of samples collected from 175 patients with HNSCC and subsequent statistical analysis also showed that PLAU and LAMC2 were associated with a poor prognosis in patients with HNSCC, and the levels of these two factors were positively correlated. The expression and co-localization of PLAU and LAMC2 in HNSCC tissues were confirmed by double immunofluorescence labeling. Conclusions: There was a positive correlation between PLAU and LAMC2 expression in HNSCC samples, and PLAU and LAMC2 might be independent prognostic biomarkers for HNSCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: In Korea, winter can cause skin dryness due to low relative humidity (RH); moreover, indoor heating devices promote moisture loss and air pollution. If dryness persists, dead skin cells accumulate, leading to skin problems; therefore, careful skin care is required. This study aimed to compare changes in skin conditions when exposed to an indoor environment for a short period of 6 h in winter, and to suggest proper winter skin care practices., Methods: A randomized, split-face clinical study was conducted in which healthy female participants with normal skin were exposed to an indoor environment with a heater turned on for a short period at least 6 h per day in the winter season, and cream was applied to one side of the face. Skin temperature, hydration, sebum, transepidermal water loss (TEWL), elasticity, texture, pores, redness, and wrinkles were measured at the treated and nontreated sites., Results: After 6 h of exposure, skin temperature, pores, roughness, redness, and wrinkles significantly increased (p < 0.05) on the face, whereas TEWL significantly increased on the forearm (p < 0.05). However, sebum secretion appeared to function as a barrier to maintain homeostasis in the facial skin. Elasticity, pores, texture, and wrinkles in the cream-treated ceramide site improved compared to those in the nontreated site (p < 0.05). The moisture content was also significantly higher in the forearm (p < 0.05)., Conclusion: Changes in skin parameters of participants with healthy skin were observed even after short-term exposure to an indoor environment in winter. Creams containing ceramide maintain skin homeostasis and protect the skin barrier; therefore, it is recommended to use such creams to prevent skin damage and maintain healthy skin, particularly during prolonged exposure to indoor environments during winter., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Respiratory quotient (RQ) may be used as a tissue hypoxia marker in various clinical settings but its prognostic significance in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) is not known., Methods: Medical records of adult patients admitted to the intensive care units after ECPR in whom RQ could be calculated from May 2004 to April 2020 were retrospectively reviewed. Patients were divided into good neurologic outcome and poor neurologic outcome groups. Prognostic significance of RQ was compared to other clinical characteristics and markers of tissue hypoxia., Results: During the study period, 155 patients were eligible for analysis. Of them, 90 (58.1%) had a poor neurologic outcome. The group with poor neurologic outcome had a higher incidence of out-of-hospital cardiac arrest (25.6% vs. 9.2%, P=0.010) and longer cardiopulmonary resuscitation to pump-on time (33.0 vs. 25.2 minutes, P=0.001) than the group with good neurologic outcome. For tissue hypoxia markers, the group with poor neurologic outcome had higher RQ (2.2 vs. 1.7, P=0.021) and lactate levels (8.2 vs. 5.4 mmol/L, P=0.004) than the group with good neurologic outcome. On multivariable analysis, age, cardiopulmonary resuscitation to pump-on time, and lactate levels above 7.1 mmol/L were significant predictors for a poor neurologic outcome but not RQ., Conclusions: In patients who received ECPR, RQ was not independently associated with poor neurologic outcome.

This study aimed to determine the effects of progressive resistive exercise (PRE), including complex decongestive physical therapy (CDPT), on edema volume, handgrip strength, upper extremity function, and quality of life (QoL) in patients with breast cancer-related lymphedema (BCRL). Twenty patients were randomized between the progressive resistance exercise group (PREG) and the self-home resistance exercise group (SREG). Two patients in each group dropped out of the study, leaving 16 patients: n=8 in the exercise group and n=8 in the SREG. First, the PREG and the SREG received CDPT. Subsequently, the patients in the PREG performed PRE, whereas the patients in the SREG performed self-home resistance exercises. Interventions were performed for 50 min, 3 times a week, for 6 weeks. The results showed that, for the edema volume, a significant intergroup variation was absent, whereas the intragroup variation was significant. The inter- and intragroup variations were significant for both handgrip strength and upper extremity function. Regarding QoL, a significant difference was observed in global health status/QoL and role function between the groups. Furthermore, significant differences were observed within the PREG in global health status/QoL; physical, role, and cognitive function; and dyspnea. No significant differences were observed within the SREG. The results collectively suggest that the exercise program was an intervention with a greater potential contribution to reducing edema and enhancing physical function in patients with BCRL., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 Korean Society of Exercise Rehabilitation.)

Background: This study aimed to determine the optimal position of venovenous extracorporeal membrane oxygenation (V-V ECMO) draining cannulas for refractory respiratory failure based on short-term clinical results., Methods: In total, 278 patients underwent V-V ECMO at our hospital between 2012 and 2020. Those who underwent V-V ECMO with a femorojugular configuration were included. In the final cohort, 96 patients were divided into groups based on the draining cannula tip site: an inferior vena cava (IVC) group (n = 35) and a right atrium (RA) group (n = 61). The primary outcome was the change in fluid balance and ratio of awake ECMO 72 hours after V-V ECMO initiation., Results: The only significant difference in baseline characteristics before V-V ECMO between the groups was a higher PaO 2 /FiO 2 ratio in the RA group than in the IVC group (79.1 ± 26.21 vs 64.7 ± 14, P = .001). The degree of recirculation and arterial oxygenation, 90-day mortality, and clinical outcomes were similar between the groups. However, more patients achieved negative intake and output fluid balances (57.4% vs 31.4%, P = .01) and reductions in body weight (68.9% vs 40%, P = .006) in the RA group. At 72 hours after V femoral -V jugular ECMO initiation, more patients in the RA group than in the IVC group were managed under awake ECMO (42.6% vs 22.9%, P =.047)., Conclusions: Placement of a V-V ECMO draining cannula in the RA rather than the IVC is more effective for restricted fluid management and awake ECMO without significant recirculation., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Limited data are available on the association of malnutrition with the occurrence of delirium in the cardiac intensive care unit (CICU). Thus, we aimed to analyze whether nutritional indices and their components can predict the development of delirium in CICU., Methods: We enrolled 2,783 patients admitted to the CICU of Samsung Medical Center for more than 24 h between September 2012 and December 2018. We assessed the nutritional status at admission using three indices, the Prognostic Nutrition Index (PNI), the Geriatric Nutritional Risk Index (GNRI), and the Controlling Nutritional Status (CONUT). Then, we compared predictive performances for the occurrence of delirium among nutritional indices using Delong's test., Results: Delirium developed in 678 patients (24.3%) assessed three times daily for 7 days of CICU stay. Nutritional indices had fair predictive performance for development of delirium in critically ill cardiac patients using the area under the receiver-operating characteristic curve (AUROC: 0.729 for the GNRI, 0.728 for PNI, and 0.762 for CONUT). Furthermore, the AUROC of albumin alone (0.77, 95% CI, 0.75-0.79) was significantly greater than that of either GNRI ( p < 0.001) or PNI ( p < 0.001). In a multivariable analysis including each component of nutritional indices, albumin was a significant predictor for delirium but not absolute lymphocyte count, bodyweight/ideal bodyweight, or total cholesterol level as a component of nutritional indices., Conclusion: Predictive performances of nutritional indices for the occurrence of delirium were acceptable in patients admitted to CICU. Albumin alone might be a helpful and straightforward indicator for the occurrence of delirium., 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 Kim, Ko, Na, Chung, Choi, Park and Yang.)

Background and Objective: Inflammation is an important factor in the development of aneurysm, and has been identified as a key characteristic predictive of rupture of intracranial aneurysm (IA). However, the role of inflammatory peripheral blood cell ratios in patients with IA has not been well delineated., Methods: A total of 1,209 patients, including 1,001 with unruptured IA and 208 with ruptured IA, were enrolled in this study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white-blood-cell ratio (PWR) were compared between ruptured and unruptured IA., Results: Compared with the ruptured IA group, the unruptured IA group had higher PNR {median, 65.96 [interquartile range (IQR) 48.95-85.05] vs. 37.78 (IQR, 23.17-54.05); p < 0.001} and PWR [median, 36.89 (IQR 29.38-44.56) vs. 22.39 (IQR, 16.72-29.29); p < 0.001]. In multivariate analysis, PNR and PWR were independently associated with ruptured IA ( p = 0.001 and p < 0.001, respectively). Unruptured IA subgroup analyses according to the PHASES scores showed that a higher PHASES score was associated with significantly higher NLR and erythrocyte sedimentation rate ( p < 0.001 and p = 0.025) and lower PNR and PWR ( p < 0.001 and p = 0.007)., Conclusions: We demonstrated that lower PNR and PWR levels are associated with ruptured IA and a higher PHASES score. Unlike many other inflammatory markers and bioassays, peripheral blood cell ratios are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm. However, a long-term prospective study is needed to clarify this matter., 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 © 2022 Kim, Lee, Oh, Lee, Choo, Kim, Kim, Kim, Na and Heo.)

Background: Only a few observational studies using small patient samples and one subgroup analysis have compared norepinephrine and dopamine for the treatment of cardiogenic shock (CS). The objective of the present study was to investigate whether the use of norepinephrine was associated with improvements in clinical outcomes in CS patients compared to dopamine., Methods: We retrospectively reviewed hospital medical records of patients who were admitted to cardiac intensive care unit from 2012 to 2018. We included 520 patients with CS in this analysis. The primary outcome was in-hospital mortality, and serial hemodynamic data were also assessed., Results: As a first-line vasopressor, dopamine was used in 156 patients (30%) and norepinephrine in 364 patients (70%). Overall, the norepinephrine group had significantly higher severity of shock, arrest at presentation, vital signs, and lactic acid than did the dopamine group at the time of vasopressor initiation. Nevertheless, in the norepinephrine group, additional vasopressor was required in 123 patients (33.8%), which was a significantly smaller percentage than the 92 patients (56.4%) in the dopamine group who required additional vasopressor (p < 0.001). There was no significant difference in in-hospital mortality between the two groups (26.9% and 31.9%, respectively, p = 0.26). In addition, the incidence of arrhythmia was not different between the two groups (atrial fibrillation, 12.2% vs. 15.7%, p = 0.30; ventricular tachyarrhythmia, 19.9% vs. 25.3%, p = 0.18)., Conclusions: The use of norepinephrine as a first-line vasopressor was not associated with reductions of in-hospital mortality or arrythmia but could reduce use of additional vasopressors in CS patients., Competing Interests: The authors have declared that no competing interests exist.

Background: People whose skin type is oily have experienced an esthetic and hygienic discomfort due to the excessive secretion of the sebum during the day and night time, and therefore sebum control is required. In this study, we aimed to find out whether the skin status between the oily and nonoily skin indicates a significant difference before and after sleep., Materials and Methods: Forty Korean males and females whose skin type was oily or nonoily participated in this study. To investigate the difference of the skin between oily and nonoily skin before and after sleep, we measured the sebum, skin pore, texture, and redness on their cheek at baseline and after 4-h sleep. Moreover, the significant level was determined at p < 0.05., Results: Parameters of sebum and skin pore significantly increased after 4-h sleep compared with baseline in the oily and nonoily skin (p < 0.05). Moreover, the increment of sebum and pore parameters in the oily skin was significantly higher than those in the nonoily skin (p < 0.05). In the case of skin texture and redness, parameters of them were significantly changed after 4-h sleep compared with baseline only in the oily skin (p < 0.05), and there was no significant difference among groups., Conclusions: We found that the change rates of the sebum secretion and skin pore in oily skin were significantly higher than those in nonoily skin after 4-h sleep. These results suggest the necessity of the skin care depending on the skin type before sleeping., (© 2022 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

In this study, we focus on the correctness of oil condition monitoring, specifically of a tuning forks sensor in hydraulic systems. We also aim to analyze the correlation between the online monitoring sensor signal and offline oil analysis by periodically sampling the hydraulic oil. In recent years, condition-based monitoring (CBM) of hydraulic oils has played a key role in extending earthmoving machinery uptime and reducing maintenance costs. We performed rig test and field test to develop a condition monitoring system based on oil analysis for construction equipment. Using the rig test, a reference line for the diagnosis of viscosity and dielectric constant for the new hydraulic oil was derived, and the characteristics of each sensor parameter for artificial contamination and oxidation were confirmed. In order to affirm the validity of oil diagnosis using oil sensors, the oil sensors were applied to four excavators to detect changes in oil conditions over 12 months. It was found that monitoring hydraulic oil with an oil sensor detecting the change in oil properties and contamination can provide reliable information for establishing diagnostic criteria. The finding allows us to predict the remaining oil life and to determine the oil change intervals based on the diagnosis of the oil condition.

Background: Oculomotor nerve palsy (ONP) may result from posterior communicating artery (PcomA) aneurysms. We aimed to evaluate the resolution of ONP after endovascular treatment with the intention of clarifying predictors of nerve recovery in a relatively large series., Methods: A total of 211 patients with ONP caused by PcomA aneurysms underwent endovascular coiling between May 2010 and December 2020 in four tertiary hospitals. We evaluated the demographics, clinical characteristics, aneurysm morphology parameters and ONP resolution to analyze the predictors of ONP recovery using univariate and multivariate analyses., Results: At the last available clinical follow-up, ONP resolution was complete in 126 (59.7%) patients, partial in 73 (34.6%) patients, and no recovery in 12 (5.7%) patients. The median resolution time after endovascular treatment was 55 days (interquartile range: 40-90 days). In multivariate analysis, degree of ONP (incomplete palsy) on admission (OR 5.396; 95% CI 2.836-10.266; P < 0.001), duration of ONP (≤ 14 days) before treatment (OR 5.940; 95% CI 2.724-12.954; P < 0.001) were statistically significant predictors of complete recovery of ONP. In the subgroup analysis of patients with unruptured aneurysms, aspirin showed a higher complete recovery rate in univariate analysis (OR 2.652; 95% CI 1.057-6.656; P = 0.038)., Conclusion: Initial incomplete ONP and early management might predict better recovery of ONP after endovascular treatment., (© 2022. The Author(s).)

We aimed to explore whether the imaging of antiporter system x C - of immune cells with (4 S )-4-(3- 18 F-fluoropropyl)-l-glutamate ( 18 F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18 F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x C - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18 F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18 F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18 F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18 F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68 + xCT + and CD3 + xCT + cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68 + xCT + cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x C - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18 F-FSPG PET imaging of system x C - activity may noninvasively assess the IBD activity., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To evaluate the efficacy of liquid embolization agents for treating various hemorrhagic peripheral intracranial aneurysms. Methods : We retrospectively analyzed 38 patients who suffered from hemorrhagic peripheral intracranial aneurysms and were treated with liquid embolization agents. We used the modified Rankin scale for follow-up at 6 months postoperatively, and digital subtraction angiography follow-up was performed 6 months postoperatively. Results : Of the 38 patients (ten of simple peripheral intracranial aneurysms, six of Moyamoya disease (MMD), and 22 of arteriovenous malformation (AVM)), posterior circulation accounted for the most significant proportion (57.9%), followed by anterior circulation (21.1%) and intranidal aneurysms (21.1%). Intraoperative hemorrhage occurred in four cases, postoperative cerebral infarction occurred in four cases, two patients encountered microcatheter retention, and intraoperative thrombosis took place in the basilar artery of a patient with an arteriovenous malformation. A postoperative hemorrhage occurred in only one patient. At 6-month follow-up, 84.2% of patients had good prognosis outcomes, and 13.5% had poor outcomes. Conclusion: Liquid embolization agents are effective for hemorrhagic peripheral intracranial aneurysms; however, safety depends on the subtypes. For peripheral hemorrhagic aneurysms in MMD, the vessel architecture must be carefully evaluated before embolization.

Objective: Continuous renal replacement therapy (CRRT) is the standard treatment for critically ill patients with acute kidney injury (AKI). Electrolyte disturbance such as hypokalemia or hypophosphatemia occurs paradoxically in patients undergoing CRRT due to high clearance. We developed a fluid management protocol for dialysate and replacement fluid that depends on serum electrolytes and focuses on potassium and phosphate levels to prevent electrolyte disturbance during CRRT. The impact of our new fluid protocol on electrolyte stability was evaluated., Methods: Adult patients who received CRRT between 2013 and 2017 were included. Patients treated 2 years before (2013-2014; pre-protocol group) and 2 years following development of the fluid protocol (2016-2017; protocol group) were compared. The primary outcomes were individual coefficient of variation (CV) and abnormal event rates of serum phosphate and potassium. Secondary outcomes were frequency of electrolyte replacement and incidence of cardiac arrhythmias. Individual CV and abnormal event rates for each electrolyte were analyzed using the Wilcoxon rank-sum test and Chi-square test with Yates' continuity correction., Results: A total of 1,448 patients was included. Both serum phosphate and potassium were higher in the protocol group. The CVs of serum phosphate (pre-protocol vs. protocol, 0.275 [0.207-0.358] vs. 0.229 [0.169-0.304], p < 0.01) and potassium (0.104 [0.081-0.135] vs. 0.085 [0.064-0.110], p < 0.01) were significantly lower in the protocol group. The abnormal event rates of serum phosphate (rate [95% CI], 0.410 [0.400-0.415] vs. 0.280 [0.273-0.286], p < 0.01) and potassium (0.205 [0.199-0.211] vs. 0.083 [0.079-0.087], p < 0.01) were also significantly lower in the protocol group., Conclusion: The protocolized management of fluid in CRRT effectively prevented hypophosphatemia and hypokalemia by inducing excellent stability of serum phosphate and potassium levels., 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 © 2022 Baeg, Jeon, Kang, Na, Cho, Kim, Yang, Chung, Lee, Huh, Suh, Kim, Kim and Jang.)

Background: No data is available on delirium prediction models in the cardiac intensive care unit (CICU), although preexisting delirium prediction models [PREdiction of DELIRium in ICu patients (PRE-DELIRIC) and Early PREdiction of DELIRium in ICu patients (E-PRE-DELIRIC)] were developed and validated based on a population admitted to the general intensive care unit (ICU). Therefore, we externally validated the usefulness of the PRE-DELIRIC and E-PRE-DELIRIC models and compared their predictive performance in patients admitted to the CICU., Methods: A total of 2,724 patients admitted to the CICU were enrolled between September 2012 and December 2018. Delirium was defined as at least one positive Confusion Assessment Method for the ICU (CAM-ICU) which was screened at least once every 8 h. The PRE-DELIRIC value was calculated within 24 h of CICU admission, and the E-PRE-DELIRIC value was calculated at CICU admission. The predictive performance of the models was evaluated by using the area under the receiver operating characteristic (AUROC) curve, and the calibration slope was assessed graphically by plotting., Results: Delirium occurred in 677 patients (24.8%) when the patients were assessed thrice daily until 7 days of the CICU stay. The AUROC curve for the prediction of delirium was significantly greater for PRE-DELIRIC values [0.84, 95% confidence interval (CI): 0.82-0.86] than for E-PRE-DELIRIC values (0.79, 95% CI: 0.77-0.80) [z score of -6.24 ( p < 0.001)]. Net reclassification improvement for the prediction of delirium increased by 0.27 (95% CI: 0.21-0.32, p < 0.001). Calibration was acceptable in the PRE-DELIRIC model (Hosmer-Lemeshow p = 0.170) but not in the E-PRE-DELIRIC model (Hosmer-Lemeshow p < 0.001)., Conclusion: Although both models have good predictive performance for the development of delirium, even in critically ill cardiac patients, the performance of the PRE-DELIRIC model might be superior to that of the E-PRE-DELIRIC model. Further studies are required to confirm our results and design a specific delirium prediction model for CICU patients., 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 © 2022 Kim, Ko, Na, Chung, Choi, Kim, Park, Lee, Song, Choi, Hahn, Choi, Gwon and Yang.)

Background: Sepsis is a leading cause of mortality in patients with neutropenia; however, data on whether neutropenic sepsis is associated with distinct clinical characteristics and outcomes are limited. Thus, this study was designed to clarify the clinical characteristics and outcomes of patients with neutropenic sepsis compared with those of patients without neutropenic sepsis diagnosed based on the Third International Consensus Definitions for Sepsis and Septic Shock criteria., Methods: We analyzed data from the Korean Sepsis Alliance, a nationwide prospective multicenter cohort study evaluating the clinical characteristics, management, and outcomes of patients with sepsis from September 2019 to February 2020. Eligible patients were divided into the neutropenic (absolute neutrophil count of less than 1,500/mL) and non- neutropenic groups. The characteristics and outcomes were compared between the two groups., Results: During the study period, 2,074 patients were enrolled from 16 tertiary referral or university-affiliated hospitals. Of them, 218 (10.5%) had neutropenia. The neutropenia group was younger and had a lower proportion of patients with chronic diseases compared with the non-neutropenia group. However, solid tumors (50.0% vs. 34.1%; P  > 0.001) and hematological malignancies (40.8% vs. 3.8%; P  < 0.001) were more common in the neutropenia group. The neutropenia group had a higher incidence of septic shock (43.6% vs. 22.9%; P  < 0.001) and higher Sequential Organ Failure Assessment score (7 vs. 5; P  < 0.001) than the nonneutropenia group. However, no significant differences in microbiologically confirmed infections and its pathogen distribution and the incidence of multidrug resistance were observed between the two groups. The neutropenic group had a higher hospital mortality than the non-neutropenic group (42.2% vs. 26.3%; P  < 0.001), and the Kaplan-Meier survival curve demonstrated a significant difference in survival within 1 week after diagnosing sepsis (log-rank test, P = 0.002). The incidence of adverse events during intensive care unit admission was not different between the two groups. Among hospital survivors, the neutropenic group was more frequently discharged to home (72.2% vs. 57.8%; P = 0.002)., Conclusions: Neutropenic sepsis is associated with a higher-grade organ dysfunction during the diagnosis of sepsis and higher mortality without difference in the pathogen isolated., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Background: Randomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown., Aim: To investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS., Methods: 5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality., Results: Spironolactone was prescribed in 2,402 (46.8%) at discharge: <25 mg in 890 patients (37.1%), ≥25 mg, and <50 mg in 1,154 patients (48.0%), and ≥50 mg in 358 patients (14.9%). Patients treated with spironolactone had a lower proportion of chronic renal failure and renal replacement therapy during hospitalization and had lower serum creatinine level than those who did not. In overall patients, 3-year mortality was not different in both groups (35.9 vs. 34.5%, P = 0.279). The incidence of renal injury and hyperkalemia was 2.2% and 4.3%, respectively, at the first follow-up visit. The treatment effect of spironolactone on mortality was different across subpopulations according to LVEF. The use of spironolactone was associated with a significant reduction in 3-year morality in patients with LVEF ≤ 26% (33.8 vs. 44.3%, P < 0.001; adjusted HR 0.79, 95% CI 0.64-0.97, P = 0.023), but not in patients with LVEF > 26%., Conclusions: Although spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings., 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 © 2022 Na, Youn, Lee, Jeon, Lee, Cho, Choi, Jeon, Lee, Kim, Kim, Hwang, Cho, Chae, Kang, Choi, Yoo, Kim, Oh and Baek.)

Background: Recent guidelines recommended conducting spontaneous breathing trial (SBT) with modest inspiratory pressure augmentation rather than T-piece or continuous positive airway pressure. However, it was based on few studies focused on the outcomes of extubation rather than the weaning process, despite the existence of various weaning situations in clinical practice. This study was designed to investigate the effects of SBT with pressure support ventilation (PSV) or T-piece on weaning outcomes., Methods: All consecutive patients admitted to two medical intensive care units (ICUs) and those requiring mechanical ventilation (MV) for more than 24 h from November 1, 2017 to September 30, 2020 were prospectively registered. T-piece trial was used until March 2019, and then, pressure support of 8 cmH 2 O and 0 positive end-expiratory pressure were used for SBT since July 2019, after a 3-month transition period for the revised SBT protocol. The primary outcome of this study was successful weaning defined according to the WIND (Weaning according to a New Definition) definition and were compared between the T-piece group and PSV group. The association between the SBT method and weaning outcome was evaluated with logistic regression analysis., Results: In this study, 787 eligible patients were divided into the T-piece (n = 473) and PSV (n = 314) groups after excluding patients for a 3-month transition period. Successful weaning was not different between the two groups (85.0% vs. 86.3%; p = 0.607). However, the PSV group had a higher proportion of short weaning (70.1% vs. 59.0%; p = 0.002) and lower proportion of difficult weaning (13.1% vs. 24.1%; p < 0.001) than the T-piece group. The proportion of prolonged weaning was similar between the two groups (16.9% vs. 16.9%; p = 0.990). After excluding patients who underwent tracheostomy before the SBTs, similar results were found. Reintubation rates at 48 h, 72 h, and 7 days following the planned extubation were not different between the PSV and T-piece groups. Moreover, no significant differences in intensive care unit and hospital mortality and length of stay were observed., Conclusions: In critically ill medical patients, SBT using PSV was not associated with a higher rate of successful weaning compared with SBT using T-piece. However, PSV could shorten the weaning process without increasing the risk of reintubation., (© 2022. The Author(s).)

Background: Agitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated., Methods: For cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated., Results: Pentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617-1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631-1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785-1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524-0.865, p = 0.029333)., Conclusion: Pentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients., (© 2022. The Author(s).)

Background: Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock., Methods: This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock., Results: Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61-0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44-0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64-1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock., Conclusion: Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock., (© 2022. The Author(s).)

Background: Patients who need prolonged mechanical ventilation (MV) have high resource utilization and relatively poor outcomes. The pathophysiologic mechanisms leading to weaning failure in this group may be complex and multifactorial. The aim of this study was to investigate the factors associated with prolonged weaning based on the Weaning Outcome according to a New Definition (WIND) classification., Methods: This is a prospective observational study with consecutive adult patients receiving MV for at least two calendar days in medical intensive care units from 1 November 2017 to 30 September 2020. Eligible patients were divided in a non-prolonged weaning group, including short and difficult weaning, and in a prolonged weaning group according to the WIND classification. The risk factors at the time of first separation attempt associated with prolonged weaning were analyzed using a multivariable logistic regression model., Results: Of the total 915 eligible patients, 172 (18.8%) patients were classified as prolonged weaning. A higher proportion of the prolonged weaning group had previous histories of endotracheal intubation, chronic lung disease, and hematologic malignancies. When compared with the non-prolonged weaning group, the median duration of MV before the first spontaneous breathing trial (SBT) was longer and the proportion of tracheostomized patients was higher in prolonged weaning group. In addition, the prolonged weaning group used higher peak inspiratory pressures and yielded lower PaO 2 /FiO 2 ratios at the day of the first SBT compared with the non-prolonged weaning group. In multivariate analyses, the duration of MV before first SBT (adjusted odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.06-1.22, p  < 0.001), tracheostomy state (adjusted OR = 1.95, 95% CI = 1.04-3.63, p  = 0.036), PaO 2 /FiO 2 ratio (adjusted OR = 1.00, 95% CI = 0.99-1.00, p  = 0.023), and need for renal replacement therapy (adjusted OR = 2.68, 95% CI = 1.16-6.19, p  = 0.021) were independently associated with prolonged weaning. After the exclusion of patients who underwent tracheostomy before the SBTs, similar results were obtained., Conclusion: Longer duration of MV before the first SBT, tracheostomy status, poor oxygenation, and need for renal replacement therapy at the time of first SBT can predict prolonged weaning., Trial Registration: ClinicalTrials.gov Identifier NCT05134467.

Purpose: This study aimed to gather opinions from medical educators on the possibility of introducing an interview to the Korean Medical Licensing Examination (KMLE) to assess professional attributes. Specifically following topics were dealt with: the appropriate timing and tool to assess unprofessional conduct; the possiblity of prevention of unprofessional conduct by introducing an interview to the KMLE; and the possibility of implementation of an interview to the KMLE., Methods: A cross-sectional study approach based on a survey questionnaire was adopted. We analyzed 104 pieces of news about doctors’ unprofessional conduct to determine the deficient professional attributes. We derived 24 items of unprofessional conduct and developed the questionnaire and surveyed 250 members of the Korean Society of Medical Education 2 times. Descriptive statistics, cross-tabulation analysis, and Fisher’s exact test were applied to the responses. The answers to the open-ended questions were analyzed using conventional content analysis., Results: In the survey, 49 members (19.6%) responded. Out of 49, 24 (49.5%) responded in the 2nd survey. To assess unprofessional conduct, there was no dominant timing among basic medical education (BME), KMLE, and continuing professional development (CPD). There was no overwhelming assessment tool among written examination, objective structured clinical examination, practice observation, and interview. Response rates of “impossible” (49.0%) and “possible” (42.9%) suggested an interview of the KMLE prevented unprofessional conduct. In terms of implementation, “impossible” (50.0%) was selected more often than “possible” (33.3%)., Conclusion: Professional attributes should be assessed by various tools over the period from BME to CPD. Hence, it may be impossible to introduce an interview to assess professional attributes to the KMLE, and a system is needed such as self-regulation by the professional body rather than licensing examination.

Background: Timely recognition of warning signs from deteriorating patients and proper treatment are important in improving patient safety. In comparison to the traditional medical emergency team (MET) activation triggered by phone calls, automated activation of MET may minimize activation delays. However, limited data are available on the effects of automated activation systems on the time from derangement to MET activation and on clinical outcomes. The objective of this study was to determine the impact of an automated alert and activation system for MET on clinical outcomes in unselected hospitalized patients., Methods: This is an observational study using prospectively collected data from consecutive patients managed by the MET at a university-affiliated, tertiary hospital from March 2013 to December 2019. The automated alert system automatically calculates the Modified Early Warning Score (MEWS) and subsequently activates MET when the MEWS score is 7 or higher, which was implemented since August 2016. The outcome measures of interest including hospital mortality in patients with MEWS of 7 or higher were compared between pre-implementation and post-implementation groups of the automated alert and activation system in the primary analysis. The association between the implementation of the system and hospital mortality was evaluated with logistic regression analysis., Results: Of the 7678 patients who were managed by MET during the study period, 639 patients during the pre-implementation period and 957 patients during the post-implementation period were included in the primary analysis. MET calls due to abnormal physiological variables were more common during the pre-implementation period, while MET calls due to medical staff's worries or concern about the patient's condition were more common during the post-implementation period. The median time from deterioration to MET activation was significantly shortened in the post-implementation period compared to the pre-implementation period (34 min vs. 60 min, P < 0.001). In addition, unplanned ICU admission rates (41.2% vs. 71.8%, P < 0.001) was reduced during the post-implementation period. Hospital mortality was decreased after implementation of the automated alert system (27.2% vs. 38.5%, P < 0.001). The implementation of the automated alert and activation system was associated with decreased risk of death in the multivariable analysis (adjusted OR 0.73, 95% CI 0.56-0.90)., Conclusions: After implementing an automated alert and activation system, the time from deterioration to MET activation was shortened and clinical outcomes were improved in hospitalized patients., (© 2021. The Author(s).)

Background: Adenovirus infection can cause severe pneumonia even in immunocompetent adults. However, there is limited data on the benefits of cidofovir treatment in severe adenovirus pneumonia. The objective of this study was to evaluate the association of cidofovir treatment with clinical improvement in immunocompetent adult patients with severe adenovirus pneumonia., Methods: We evaluated 22 male patients who admitted to intensive care unit (ICU) with severe adenovirus pneumonia between January 2014 and December 2019. The patients were divided into 2 groups, patients treated with cidofovir or not. Clinical outcomes including time to defervescence and stopping of oxygen supplement, length of stay in ICU and hospital, and the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) were compared between the 2 groups., Results: Among 22 patients, 13 patients (59%) were treated with cidofovir and 9 (41%) were not. The difference in mean time (95% confidence interval [CI]) to defervescence and stopping of oxygen supplement between cidofovir group and no cidofovir group was 2.1 (-5.7 to 10.0) and 1.0 (-14.9 to 16.8) days, respectively. The difference in mean length of stay (95% CI) in ICU and hospital between the 2 groups was 0.2 (-7.1 to 7.5) and -0.4 (-18.3 to 17.5) days, respectively. The differences in proportion of patients requiring MV and ECMO between the 2 groups was 28.2 (-17.4 to 73.8) % and -10.3 (-52.2 to 31.7) %, respectively., Conclusions: The treatment with cidofovir for severe adenovirus pneumonia in immunocompetent patients did not improve clinical outcomes. Further studies with larger samples with prospective design are warranted.

Background: The inflammatory process is involved in the pathogenesis of atherosclerosis and brain tissue injury following cerebral ischemia. Human resistin is a member of small cysteine-rich secreted proteins and has been implicated in inflammatory responses. This study investigated the association of serum resistin level with acute cerebral infarction (ACI). We also investigated its association with the short-term functional outcome., Methods: This study included 106 patients with ACI and 106 age-matched and sex-matched healthy control subjects. Serum resistin level was assessed by using enzyme-linked immunosorbent sandwich assay. The association of serum resistin levels with ACI was analyzed by logistic regression analysis., Results: The serum resistin level was significantly higher in patients with ACI than the control group [median (interquartile range), 35.7 ng/mL (13.0 to 70.5) ng/mL vs. 10.5 ng/ml (15.4 to 16.6), P<0.001]. Logistic regression analysis showed that serum resistin level was associated with an ACI (odds ratio=1.055, 95% confidence interval: 1.035-1.074, P<0.001). Among stroke subtypes, the serum resistin level was higher in the patients with large artery atherosclerosis than those with other subtypes (P=0.013). High resistin levels were also significantly associated with unfavorable functional outcome at discharge (odds ratio=1.043, 95% confidence interval: 1.024-1.063, P<0.001)., Conclusions: This study suggests the potential association of resistin with stroke and cerebral atherosclerosis. Increased serum resistin levels were also associated with early unfavorable neurological outcome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom's taxonomy in the development of formative assessment items., Methods: We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students' perceptions of formative assessment through a survey., Results: It is designed to consist of 2-3 learning outcomes per hour of class and to conduct the formative assessment with 1-2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine "knowledge" items, 40 "comprehension" items, and 55 "application" items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students' perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes., Conclusion: The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. "Integration of lesson and assessments" was maximized by solving the assessment items as well as through the instructor's immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom's taxonomy allow students to remember, understand, and apply to clinical contexts.