NgR1 is an NK cell inhibitory receptor that destabilizes the immunological synapse.

The formation of an immunological synapse (IS) is essential for natural killer (NK) cells to eliminate target cells. Despite an advanced understanding of the characteristics of the IS and its formation processes, the mechanisms that regulate its stability via the cytoskeleton are unclear. Here, we show that Nogo receptor 1 (NgR1) has an important function in modulating NK cell-mediated killing by destabilization of IS formation. NgR1 deficiency or blockade resulted in improved tumor control of NK cells by enhancing NK-to-target cell contact stability and regulating F-actin dynamics during IS formation. Patients with tumors expressing abundant NgR1 ligand had poor prognosis despite high levels of NK cell infiltration. Thus, our study identifies NgR1 as an immune checkpoint in IS formation and indicates a potential approach to improve the cytolytic function of NK cells in cancer immunotherapy.

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment.

BACKGROUND: The outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact. CASE PRESENTATION: A 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours-conforming to the criteria of the Korean Disease Control and Prevention Agency-the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered. CONCLUSION: This case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study.

BACKGROUND: Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach. OBJECTIVE: We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers. METHODS: The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls. RESULTS: The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%). CONCLUSIONS: The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.

Association between high-risk extracranial carotid plaque and covert brain infarctions and cerebral microbleeds.

PURPOSE: Covert brain infarctions (CBIs) and cerebral microbleeds (CMBs) represent subclinical sequelae of ischemic and hemorrhagic cerebral small vessel disease, respectively. In addition to thromboembolic stroke, carotid atherosclerosis has been associated with downstream vascular brain injury, including inflammation and small vessel disease. The specific plaque features responsible for this are unknown. We aimed to determine the association of specific vulnerable carotid plaque features to CBIs and CMBs to better understand the relation of large and small vessel disease in a single-center retrospective observational study. METHODS: Intraplaque hemorrhage (IPH) and plaque ulceration were recorded on carotid MRA and total, cortical, and lacunar CBIs and CMBs were recorded on brain MR in 349 patients (698 carotid arteries). Multivariable Poisson regression was performed to relate plaque features to CBIs and CMBs. Within-subject analysis in those with unilateral IPH and ulceration was performed with Poisson regression. RESULTS: Both IPH and plaque ulceration were associated with total CBI (prevalence ratios (PR) 3.33, 95% CI: 2.16-5.15 and 1.91, 95% CI: 1.21-3.00, respectively), after adjusting for stenosis, demographic, and vascular risk factors. In subjects with unilateral IPH, PR was 2.83, 95% CI: 1.76-4.55, for CBI in the ipsilateral hemisphere after adjusting for stenosis. Among those with unilateral ulceration, PR was 1.82, 95% CI: 1.18-2.81, for total CBI ipsilateral to ulceration after adjusting for stenosis. No statistically significant association was seen with CMBs. CONCLUSION: Both IPH and plaque ulceration are associated with total, cortical, and lacunar type CBIs but not CMBs suggesting that advanced atherosclerosis contributes predominantly to ischemic markers of subclinical vascular injury.

Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models.

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.

Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.

BACKGROUND: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. METHODS: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. RESULTS: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. CONCLUSION: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway.

The DPA-derivative 11S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM10.

11 S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid (DoPE) is a derivative of docosapentaenoic acid, a specialized pro-resolving mediator of inflammation such as lipoxins, resolvins, maresins, and protectins. PM10 is a fine dust particle that induces oxidative stress, DNA damage, inflammation, aging, and cancer. The anti-inflammatory mechanism of DoPE, however, has not yet been elucidated. In these studies, we investigated whether DoPE has anti-inflammatory effects in human keratinocyte HaCaT cells. We demonstrated that DoPE suppressed PM10-induced expressions of IL-6 mRNA and protein in human HaCaT keratinocytes. We also investigated the modulating effects of DoPE on reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK). ROS production, extracellular signal regulated kinase (ERK) phosphorylation, and translocation of nuclear factor-kappa B (NF-kB) p65 and NF-kB activity were suppressed by DoPE in PM10-stimulated HaCaT cells. Collectively, our results demonstrated that DoPE inhibited IL-6 expression by reducing ROS generation, suppressing ERK phosphorylation, and inhibiting translocation of NF-kB p65 and NF-kB activity in PM10-stimulated HaCaT cells, suggesting that DoPE can be useful for the resolution of the inflammation caused by IL-6.

Annual Case Volume and One-Year Mortality for Endovascular Treatment in Acute Ischemic Stroke.

BACKGROUND: The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context. METHODS: National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data. RESULTS: We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis. CONCLUSION: Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.

Omega-3 fatty acid and menaquinone-7 combination are helpful for aortic calcification prevention, reducing osteoclast area of bone and Fox0 expression of muscle in uremic rats.

BACKGROUND: Osteopenia, sarcopenia, and vascular calcification (VC) are prevalent in patients with chronic kidney disease and often coexist. In the absence of proven therapies, it is necessary to develop therapeutic or preventive nutrients supplementation for osteopenia, sarcopenia, and VC. The present study investigated the effect of omega-3 fatty acid (FA) and menaquinone-7 (MK-7) on osteopenia, sarcopenia, and VC in adenine and low-protein diet-induced uremic rats. METHODS: Thirty-two male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Rats were randomly divided into four groups that were fed diets containing 2.5% protein for four weeks: adenine control (0.9% saline), omega-3 FA (300 mg/kg/day), MK-7 (50 µg/kg/day), and omega-3 FA/MK-7. Von Kossa staining for aortic calcification assessment was performed. Osteoclast surface/bone surface ratio (OcS/BS) of bone and muscle fiber were analyzed using hematoxylin and eosin staining. Osteoprotegerin (OPG) immunohistochemical staining was done in the aorta and bone. Molecules related with sarcopenia were analyzed using western blotting. RESULTS: Compared to the normal control, OcS/BS and aortic calcification, and OPG staining in the aorta and bone were significantly increased in the adenine controls. OPG staining and aortic calcification progressed the least in the group supplemented with both omega-3 FA/MK-7. In the adenine controls, the regular arrangement of muscle fiber was severely disrupted, and inflammatory cell infiltration was more prominent. These findings were reduced after combined supplementation with omega-3 FA/MK-7. Furthermore, decreased mammalian target of rapamycin and increased Forkhead box protein 1 expression was significantly restored by combined supplementation. CONCLUSIONS: Combined nutrients supplementation with omega-3 FA and MK-7 may be helpful for aortic VC prevention, reducing osteoclast activation and improving sarcopenia-related molecules in adenine and low-protein diet induced uremic rats.

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10-3  mm2 /s, p < 0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10-3  mm2 /s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10-3  mm2 /s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.

Relationship between Coronary Artery Calcification and Central Chorioretinal Thickness in Patients with Subclinical Atherosclerosis.

PURPOSE: To evaluate the relationship between coronary artery calcification and subfoveal thicknesses of individual chorioretinal layers in subjects with subclinical atherosclerosis by using enhanced-depth imaging optical coherence tomography. METHODS: In this retrospective, noninterventional, cross-sectional study, we included 193 eyes from 193 subjects and divided them into three cardiovascular (CV) risk groups based on coronary artery calcification (CAC) scores calculated from cardiac-gated computed tomography: low (CAC = 0; n = 77), intermediate (CAC = 1-300; n = 83), and high (CAC >300; n = 33). Central macula individual retinal layer thicknesses and subfoveal choroidal thickness were measured and compared among groups. Multivariate linear regression was used to evaluate associations of subfoveal choroidal thickness or central retinal thickness with CAC scores. RESULTS: Average subfoveal choroidal thickness differed significantly among low, intermediate, and high CV risk groups (all p < 0.05). There were no statistically significant changes in segmented retinal layer thickness of the central macula. Multivariate regression analyses showed that higher CAC scores were significantly negatively associated with subfoveal choroidal thickness (ß = -2.169, p < 0.001). CONCLUSIONS: Higher CAC scores were significantly associated with subfoveal choroidal thinning in subjects with subclinical atherosclerosis. Prominent reductions in the subfoveal choroidal layer could provide a useful biomarker for predicting CV risk in patients of advanced age with subclinical atherosclerosis.

Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.

Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.

State-space multitaper time-frequency analysis.

Time series are an important data class that includes recordings ranging from radio emissions, seismic activity, global positioning data, and stock prices to EEG measurements, vital signs, and voice recordings. Rapid growth in sensor and recording technologies is increasing the production of time series data and the importance of rapid, accurate analyses. Time series data are commonly analyzed using time-varying spectral methods to characterize their nonstationary and often oscillatory structure. Current methods provide local estimates of data features. However, they do not offer a statistical inference framework that applies to the entire time series. The important advances that we report are state-space multitaper (SS-MT) methods, which provide a statistical inference framework for time-varying spectral analysis of nonstationary time series. We model nonstationary time series as a sequence of second-order stationary Gaussian processes defined on nonoverlapping intervals. We use a frequency-domain random-walk model to relate the spectral representations of the Gaussian processes across intervals. The SS-MT algorithm efficiently computes spectral updates using parallel 1D complex Kalman filters. An expectation-maximization algorithm computes static and dynamic model parameter estimates. We test the framework in time-varying spectral analyses of simulated time series and EEG recordings from patients receiving general anesthesia. Relative to standard multitaper (MT), SS-MT gave enhanced spectral resolution and noise reduction ([Formula: see text]10 dB) and allowed statistical comparisons of spectral properties among arbitrary time series segments. SS-MT also extracts time-domain estimates of signal components. The SS-MT paradigm is a broadly applicable, empirical Bayes' framework for statistical inference that can help ensure accurate, reproducible findings from nonstationary time series analyses.

Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

BACKGROUND: South Korea has been experiencing a third wave of coronavirus disease 2019 (COVID-19) since mid-November 2020. Our hospital in Gwangju metropolitan city experienced a healthcare-associated COVID-19 outbreak early in the third wave. The first confirmed COVID-19 patient was a symptomatic neurosurgery resident with high mobility throughout the hospital. We analyzed the transmission routes of nosocomial COVID-19 and discussed infection control strategies. METHODS: We retrospectively analyzed the severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction (RT-PCR) testing results according to time point and evaluated transmission routes. RESULTS: Since COVID-19 was first confirmed in a healthcare worker (HCW) on 11/13/2020, we performed RT-PCR tests for all patients and caregivers and four complete enumeration surveys for all HCWs. We detected three clusters of nosocomial spread and several sporadic cases. The first cluster originated from the community outbreak spot, where an asymptomatic HCW visited, which led to a total of 22 cases. The second cluster, which included patient-to-patient transmission, originated from a COVID-19 positive caregiver before diagnosis and the third cluster involved a radiologist and a banker. We took measures to isolate Building 1 of the hospital for 17 days and controlled the outbreak during a period of increasing community COVID-19 prevalence. Universal screening of all inpatients upon admission and resident caregivers was made mandatory and hospital-related employees are now screened monthly. CONCLUSION: Infection control strategies to prevent the nosocomial transmission of emerging infectious diseases must correspond with community disease prevalence. Our data reinforce the importance of multi-time point surveillance of asymptomatic HCWs and routine surveillance of patients and caregivers during an epidemic.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Comparison of clinical outcome between incremental peritoneal dialysis and conventional peritoneal dialysis: a propensity score matching study.

BACKGROUND: Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not. METHODS: We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day. RESULTS: The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM. CONCLUSIONS: Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.

Cap-Assisted Chromoendoscopy Using a Mounted Cap Versus Standard Colonoscopy for Adenoma Detection.

OBJECTIVES: Some neoplastic lesions remain undetected on colonoscopy. To date, no studies have investigated whether combining cap-assisted colonoscopy with chromoendoscopy increases the adenoma detection rate (ADR). This study aimed to compare cap-assisted chromoendoscopy (CAP/CHROMO) with standard colonoscopy (SC) with respect to their efficacy in detecting adenomas. METHODS: This prospective, multicenter, randomized controlled trial included asymptomatic subjects aged 45-75 years who underwent colonoscopy for the first time at 14 university hospitals. Subjects were randomized to either the CAP/CHROMO group (with 0.09% indigo carmine spraying using a cap-mounted catheter at the tip of the colonoscope) or the SC group. All polyps were resected, but only histologically confirmed neoplastic lesions were considered for analysis. The primary outcome was ADR, defined as the proportion of subjects with at least 1 adenoma. RESULTS: A total of 1,905 subjects were randomized to the CAP/CHROMO (n = 948) or SC (n = 957) group at 14 centers. Subjects' demographic characteristics were similar between both groups. The CAP/CHROMO group had significantly higher ADR than the SC group (54.4% vs 44.9%, P < 0.001). Significantly, more subjects with at least 1 proximal colon adenoma were identified by CAP/CHROMO (38.6%) than by SC (31.2%) (P = 0.001). The proximal serrated polyp detection rate by CAP/CHROMO was significantly higher in the female subgroup vs SC. However, advanced ADR was not different between the CAP/CHROMO and SC groups (9.3% vs 7.6%, P = 0.180). DISCUSSION: CAP/CHROMO markedly improved the ADR and enhanced the detection of proximal adenoma. CAP/CHROMO is feasible for routine application and will allow for a more effective surveillance program.

Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation.

We previously reported that syndecan-2 expression is increased on the colonic epithelium during chronic inflammation. Here, we report that syndecan-2 exhibits a different pattern of site-specific colonic expression during acute inflammation. Syndecan-2 expression was up-regulated predominantly in the proximal colon of dextran sulfate sodium-induced colitis mice. The colitis-associated up-regulation of syndecan-2 was barely detected in Rag-1-/- (recombination activating gene 1 knockout) mice under colitis-inducing conditions. Increased syndecan-2 expression correlated with increased levels of infiltrated CD4+ IL-17A+ T cells in the proximal colon. Serum levels of IL-17A were increased during the acute inflammatory response in normal mice but not Rag-1-/- mice. IL-17A directly induced IL-17 receptor (IL-17RA) and syndecan-2 expression in ex vivo-cultured proximal colon tissues and adenoma cell lines from proximal colon. IL-17RA knockdown reduced the IL-17A-mediated syndecan-2 expression in SNU1235 cells. No elevation of syndecan-2 or IL-17RA was observed in colonic tissues from IL-17A-/- mice during colitis induction. Finally, increased expression of syndecan-2 and IL-17RA was observed in the proximal colons of cecal ligation and puncture-induced sepsis mice and infectious pan colitis patients. Together, these data suggest that acute inflammation induces syndecan-2 expression predominantly in the proximal colon via IL-17A-IL-17RA signaling during the early stage of the inflammatory response and that proximal colonic syndecan-2 might be a biomarker for acute inflammation.-Hong, H., Song, H.-K., Hwang, E. S., Lee, A. R., Han, D. S., Kim, S.-E., Oh, E.-S. Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation.

Impacts of age and sedation on cardiocerebrovascular adverse events after diagnostic GI endoscopy: a nationwide population-based study.

BACKGROUND AND AIMS: Data are limited regarding the impact of age and sedation on cardiocerebrovascular disease (CCD) adverse events after GI endoscopy. We investigated the incidence of and risk factors for CCD adverse events after diagnostic GI endoscopy and the impact of age and sedation on these unfavorable outcomes. METHODS: In this nationwide population-based study, the incidence of and risk factors for newly diagnosed CCD within 14 days after diagnostic endoscopy were analyzed using Health Insurance Review and Assessment Service data from January to December 2015. RESULTS: Among 1,943,150 subjects, CCD adverse events occurred in approximately 2.23% within 14 days after endoscopy. According to the performance of sedation during endoscopy (60.1% nonsedation vs 39.9% sedation, midazolam alone [96.4%]), the incidence rates of CCD adverse events (per 10,000 persons) were 275.8 versus 302.8 for EGD, 116.9 versus 143.8 for colonoscopy, and 230.4 versus 243.2 for EGD + colonoscopy, respectively. On multivariate analysis, older age (70-99 years) and sedation were independent risk factors for CCD adverse events. Regarding CCD risk stratified by age and sedation, older age had a significant impact on CCD adverse events in individuals who underwent EGD only or EGD + colonoscopy, but sedation did not. However, both older age and sedation had considerable influence on CCD adverse events in individuals who underwent colonoscopy only. Sedation during endoscopy was significantly associated with minor but not major CCD adverse events. CCD adverse events were significantly higher for inpatients. CONCLUSION: CCD adverse events after diagnostic endoscopy were significantly frequent in individuals with older age (70-99 years) and/or sedation during endoscopy. Stratification by age and sedation shows that the impact of these 2 factors on CCD adverse events differs according to endoscopy type.

Case report: nosocomial fungemia caused by Candida diddensiae.

BACKGROUND: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases. CASE PRESENTATION: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 µg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements. CONCLUSION: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.