ER-to-lysosome Ca2+ refilling followed by K+ efflux-coupled store-operated Ca2+ entry in inflammasome activation and metabolic inflammation.

We studied lysosomal Ca2+ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca2+ ([Ca2+]Lys) and increased [Ca2+]i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ER→lysosome Ca2+ refilling occurred after lysosomal Ca2+ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+ efflux whose inhibition reduced ER Ca2+ content ([Ca2+]ER) and impaired [Ca2+]Lys recovery. LPS + PA activated KCa3.1 channel, a Ca2+-activated K+ channel. Inhibitors of KCa3.1 channel or Kcnn4 KO reduced [Ca2+]ER, attenuated increase of [Ca2+]i or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+ release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+ release sustained by ER→lysosome Ca2+ refilling and K+ efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.

Optimizing Treatment for Carbapenem-Resistant Acinetobacter baumannii Complex Infections: A Review of Current Evidence.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively.

Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Magnetic field control device for transplantation of corneal endothelial tissue with magnetic filaments.

The corneal endothelial transplantation involves the transfer and attachment of a single-layered corneal endothelial tissue to the narrow space between the cornea and iris. Given the high risk of damage to the endothelial tissue and surrounding corneal tissues when using sharp instruments inserted externally to apply force during the process, the development of a device capable of transferring corneal endothelial tissue using a magnetic field became necessary. This study aims to develop a magnetic control device for transferring corneal endothelial tissue with attached magnetic particles to the transplant site, validate its appropriate transfer capabilities, and assess its applicability to corneal endothelial transplantation. For this purpose, a magnetic field-generating manipulation device equipped with four electromagnets controlled by a joystick and microcomputer was developed. Through simulated experiments, the strength of the magnetic field and the attraction force on the tissue were predicted, and the actual magnetic field strength was measured for validation. To measure the magnetic transfer force, experiments were conducted by towing corneal endothelial tissue fixed with 6 mg, 12 mg, and 18 mg plastic weights. Subsequently, the tissue's transfer speed was measured after applying continuous and pulsed magnetic fields. The results confirmed the feasibility of tissue transfer using the magnetic control device, and it was observed that pulsed magnetic fields led to faster transfer speeds and easier control compared to continuous magnetic fields. Exploratory animal experiments using rabbits were conducted to simulate real surgical conditions, confirming the feasibility of corneal endothelial tissue transfer and attachment.

Current practices of cervical epidural block for cervical radicular pain: a multicenter survey conducted by the Korean Pain Society.

Background: Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea. Methods: Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail. Results: Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group. Conclusions: This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Differences in cognitive trajectories of dementia: Comparison Alzheimer's disease dementia and Dementia with Lewy bodies in Korean patient cohort.

BACKGROUND AND PURPOSE: Prediction of the dementia progression is important for patient management. We aimed to investigate the cognitive trajectories of Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLB) according to the initial structural change measured by comprehensive visual rating scales (CVRS). Methods We retrospectively included the patients who initially visited the Dementia Clinic of Chonnam National University Hospital between 2010 to 2012. All patients underwent dementia work up including neuropsychological battery (Seoul Neuropsychological Screening Battery, SNSB). We recruited the participant who underwent SNSB annually for three years successively. Total 136 patients of ADD and 63 patients of DLB were included for analyze. We analyzed the decline pattern of cognitive profile according to the initial brain structural changes. Results The general cognitive trajectories between ADD and DLB patients were not different. However, DLB patients showed more rapid decline of cognitive function in language and related function, visual memory function, and frontal executive function. The scores were lower in participants with DLB with lesser atrophy group in attention, visuospatial function, and frontal executive function. In analysis of the cognitive trajectories, the visual memory domain declined rapidly in DLB with lesser atrophy group compared with the ADD with lesser atrophy group. Conclusion We founded that the differences in visual cognitive profile in ADD and DLB patients in serial follow up of neuropsychological tests. It is prominent in the mild structural change group of ADD and DLB.

Effectiveness of the Cooled Radiofrequency Ablation of Genicular Nerves in Patients with Chronic Knee Pain Due to Osteoarthritis: A Double-Blind, Randomized, Controlled Study.

Background: Increasing evidence supporting the clinical effectiveness of cooled radiofrequency ablation (RFA) therapy for genicular nerves in patients with chronic knee osteoarthritis (OA) exists. However, no study has been conducted to eliminate the potential influence of a placebo effect associated with this procedure. Therefore, we evaluated the efficacy of cooled RFA compared with a sham procedure in patients with painful knees due to OA. Methods: In this double-blind, randomized, controlled study, participants were randomly assigned to receive cooled RFA of the knee (cooled RFA group, n = 20) or a sham procedure (sham group, n = 20). The primary outcome was the proportion of successful responders at the three-month follow-up. The secondary outcomes were successful responders at one and six months; pain intensity of the knee; functional status; medication; and satisfaction at one, three, and six months after the procedures. Results: For the primary outcome, the successful responder rate was significantly higher in the cooled RFA group (76.5%) than in the sham group (33.3%) (p = 0.018). For the secondary outcome, more successful responders were observed in the cooled RFA group than in the sham group at one and six months after the procedure (p = 0.041 and 0.007, respectively). The decreased knee pain intensity was maintained throughout the six-month follow-up period in the cooled RFA group. No differences were observed in functional status, medication change, or satisfaction in both groups. Conclusions: The cooled RFA of genicular nerves offers significant pain relief and surpasses the effects attributable to a placebo.

Effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents.

OBJECTIVE: The daily lives of adolescents have changed significantly because of COVID-19 pandemic. We investigated the effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents. METHODS: Data from the 2021 Korea Youth Risk Behavior Survey were used. In total, 54,848 survey participants were included in the analysis. Allergic diseases included allergic rhinitis, atopic dermatitis, and asthma. Changes attributed to COVID-19 included family economic difficulties, physical activity, breakfast skipping frequency, alcohol consumption, smoking, and depressive moods. Chi-square tests and multiple logistic regression analyses were conducted to examine the impact of changes in daily life attributed to COVID-19 on allergic diseases. RESULTS: Among the Korean adolescents surveyed, 29.8% experienced a deterioration in their economic status due to COVID-19, 49.1% reported decreased physical activity, 2.8% reported increased alcohol consumption, 1.0% reported an increase in their smoking behavior, and 36.9% reported an increase in depressive moods. Those diagnosed with atopic dermatitis, allergic rhinitis, or asthma within the previous 12 months accounted for 17.1%, 6.2%, and 1.0% of the population, respectively. Adolescents who were significantly affected by COVID-19 in their daily lives were frequently diagnosed with allergic diseases within the last 12 months. CONCLUSION: Changes in daily life due to COVID-19, including decreased physical activity and increased depressive mood, were common in adolescents and were associated with an increased prevalence of allergic diseases. Since changes in daily life due to the pandemic may increase the burden of allergic disease, additional interventions for disease management should be considered.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Here we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (TREG) cells from patients with chronic HCV infection according to DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response (SVR) by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of TREG cells were investigated through flow cytometry analysis. Moreover, transcriptomic and epigenetic landscape of TREG cells were analyzed using RNA-seq and ATAC-seq analysis. RESULTS: The TREG cell population-especially the activated TREG cell subpopulation-was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA-seq analysis revealed that viral clearance did not abrogate the inflammatory features of these TREG cells, such as TREG activation and TNF signal. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of TREG cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that TREG cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded TREG cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the TREG cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of DAAs led to a high cure rate of chronic HCV infection. Nevertheless, we have demonstrated that inflammatory features of TREG cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Requirement of ß subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A.

Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.

hMAGEA2 Accelerates the Progression of Prostate Cancer via the EFNA3-Erk1/2 Signaling Pathway.

BACKGROUND/AIM: Human melanoma-associated antigen A2 (hMAGEA2) family members play several roles in many types of cancer and have been explored as potential prognostic markers. In this study, we investigated the molecular mechanism underlying hMAGEA2-mediated tumorigenesis of prostate cancer. MATERIALS AND METHODS: Immunohistochemistry and western blot were used to assess protein expression whereas microarray and quantitative reverse transcription-PCR determined mRNA expression. CCK-8 assay was used to determine cell proliferation. Colony formation assay was used to examine tumorigenesis. Migration and invasion were examined using a transwell assay. Propidium iodide (PI)/Annexin V double staining was performed to measure apoptosis. Transcriptional activity was measured using Dual-luciferase reporter assay. RESULTS: hMAGEA2 was highly over-expressed in human prostate cancer tissues compared to benign prostatic hyperplasia tissues. To elucidate its biological function in prostate cancer, we established two stable hMAGEA2-knockdown prostate cancer cell lines, PC3M and 22RV1, and found that they presented significantly decreased proliferation, anchorage-independent colony formation, migration, and invasion. As hMAGEA2 knockdown suppressed prostate cancer cell growth, we examined its potential influence on tumor apoptosis. hMAGEA2-knockdown cell lines displayed early apoptosis. Moreover, knockdown of hMAGEA2 resulted in the down-regulation of EFNA3 expression. Luciferase assay showed that hMAGEA2 bound to the EFNA promoter region and regulated its transcription. Down-regulation of EFNA3 expression led to decreased Ras/Braf/MEK/Erk1/2 phosphorylation and, consequently, inhibited prostate cancer progression. CONCLUSION: hMAGEA2 promotes prostate cancer growth, metastasis, and tumorigenesis by regulating the EFNA3-Erk1/2 signaling pathway, indicating its potential as a therapeutic marker for prostate cancer.

Performance Comparison of Convolutional Neural Network-Based Hearing Loss Classification Model Using Auditory Brainstem Response Data.

This study evaluates the efficacy of several Convolutional Neural Network (CNN) models for the classification of hearing loss in patients using preprocessed auditory brainstem response (ABR) image data. Specifically, we employed six CNN architectures-VGG16, VGG19, DenseNet121, DenseNet-201, AlexNet, and InceptionV3-to differentiate between patients with hearing loss and those with normal hearing. A dataset comprising 7990 preprocessed ABR images was utilized to assess the performance and accuracy of these models. Each model was systematically tested to determine its capability to accurately classify hearing loss. A comparative analysis of the models focused on metrics of accuracy and computational efficiency. The results indicated that the AlexNet model exhibited superior performance, achieving an accuracy of 95.93%. The findings from this research suggest that deep learning models, particularly AlexNet in this instance, hold significant potential for automating the diagnosis of hearing loss using ABR graph data. Future work will aim to refine these models to enhance their diagnostic accuracy and efficiency, fostering their practical application in clinical settings.

Carboxylate ester-based electrolytes for Na-ion batteries.

Sodium-ion batteries (SIBs) is a promising technology for next-generation energy storage. However, their performance is limited at low temperatures due to the inferior bulk and interfacial resistance of current electrolytes. Here we present a systematic study to evaluate carboxylate ester-based electrolytes for SIB applications, due to their favorable properties (i.e., low melting point, low viscosity and high dielectric constant). The effects of salt, concentration and solvent molecular structure were systematically examined and compared with those of carbonate-based electrolytes. By combining electrochemical tests with spectroscopic characterization, the performance of selective carboxylate ester-based electrolytes in hard carbon/Na and Na3V2(PO4)3/Na half-cells was evaluated. We found carboxylates enable high electrolyte conductivities, especially at low temperatures. However, carboxylates alone are inadequate to form a stable interphase due to their high reactivity, which can be addressed by choosing a suitable anion and facilitating anion-rich Na+ solvation by increasing salt concentration. Fundamental knowledge on the chemistry-property-performance correlation of this new family of electrolytes was obtained, and their benefits and pitfalls were thoroughly discussed. These discoveries and knowledge will shed light on the potential of carboxylate ester-based electrolytes and provide the foundation for further electrolyte engineering.

DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy.

More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.

Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Effects of Pulsed Radiofrequency Duration in Patients With Chronic Lumbosacral Radicular Pain: A Randomized Double-Blind Study.

OBJECTIVES: We hypothesized that the duration of pulsed radiofrequency (PRF) application may affect the effectiveness of PRF in patients with chronic lumbosacral radicular pain (LRP). MATERIALS AND METHODS: In this prospective, double-blind, randomized study, 68 patients were randomly allocated to two groups: a 6-minute group, in which PRF was applied at 42 °C for 2 minutes followed by a 2-minute pause, repeated three times; and a 12-minute group, with a continuous application at 42 °C for 12 minutes. The total application time in each group was equal. After PRF, 2 to 3 mL of 1% lidocaine with 5 mg of dexamethasone was injected. The primary outcome was the intensity of leg pain measured using a numerical rating scale (NRS) three months after the procedure. The secondary outcomes were intensities of leg and back pain, the Oswestry Disability Index (ODI), the Medication Quantification Scale III (MQS), the Global Perceived Effect of Satisfaction (GPES), and the incidence of adverse events during follow-up. Primary and secondary outcomes were analyzed using a linear mixed-effect model in the modified intention-to-treat population. RESULTS: Each group comprised 34 patients. Three patients in each group did not receive the allocated intervention owing to alleviation of pain. The estimated NRS mean of leg pain at three months was 4.0 (95% CI, 3.2-4.9) and 4.5 (95% CI, 3.6-5.4) in the 6- and 12-minute groups, respectively, with no significant difference between groups (estimated mean difference, -0.5; 95% CI, -1.8 to 0.8; p = 0.436). Regarding the intensities of leg and back pain, ODI, MQS, and GPES, there was no significant difference between the two groups except for GPES at six months. No adverse events were observed in the groups. CONCLUSIONS: Among patients with chronic LRP, a prolonged PRF application of 12 minutes, compared with 6 minutes, caused no significant difference in leg pain intensity. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number under the Clinical Trial Registry of Korea for the study is KCT0003850; https://cris.nih.go.kr.

The Role of Index of Microcirculatory Resistance in Left Anterior Descending Artery ST Segment Elevation Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: Our aim was to assess the relationship of the index of microvascular resistance (IMR) in left anterior descending (LAD) artery involved STEMI patients. Methods: Data of 316 STEMI patients who had undergone primary percutaneous coronary intervention (PCI) were collected from three cardiovascular centers from 2005 to 2015. In total, 246 patients with LAD STEMI were enrolled for IMR evaluation. Patients were divided into two groups respective of the cut-off IMR value of 30. All-cause mortality, left ventricular function, improvement of systolic function, and cardiac biomarkers were analyzed and compared. Results: A total of 246 patients were enrolled. The number of patients in the IMR above 30 group was 93 and below 30 was 153. The mean ages for each group were 57.91 ± 11.99 and 54 ± 10.63, respectively. The peak creatinine kinase (CK) (3936.85 ± 2827.32 IU/L vs. 2218.08 ± 2310.41 IU/L, p < 0.001) and CKmb (336.15 ± 195.08 mg/mL vs. 231.53 ± 179.53 mg/mL, p < 0.001) levels were higher for an IMR above the 30 group. The left ventricular ejection fraction (LVEF) (44.57 ± 6.685% vs. 47.35 ± 8.17%, p = 0.006) and improvement of LVEF (2.81 ± 7.135% vs. 5.88 ± 7.65%, p = 0.004) was lower in the IMR above 30 group. All-cause mortality (7.5% vs. 1.3%, p = 0.012) was higher in the IMR above 30 group, and a Cox regression analysis showed that an IMR above 30 was a poor prognostic factor regarding all-cause mortality (HR: 5.151, 95% CI 1.062-24.987, p = 0.042) even after adjusting for classical clinical risk factors. Conclusions: An elevated IMR value represented larger infarct size, more severe LV dysfunction, and higher mortality in LAD STEMI patients after successful PCI.