SiameseCPP: a sequence-based Siamese network to predict cell-penetrating peptides by contrastive learning.

BACKGROUND: Cell-penetrating peptides (CPPs) have received considerable attention as a means of transporting pharmacologically active molecules into living cells without damaging the cell membrane, and thus hold great promise as future therapeutics. Recently, several machine learning-based algorithms have been proposed for predicting CPPs. However, most existing predictive methods do not consider the agreement (disagreement) between similar (dissimilar) CPPs and depend heavily on expert knowledge-based handcrafted features. RESULTS: In this study, we present SiameseCPP, a novel deep learning framework for automated CPPs prediction. SiameseCPP learns discriminative representations of CPPs based on a well-pretrained model and a Siamese neural network consisting of a transformer and gated recurrent units. Contrastive learning is used for the first time to build a CPP predictive model. Comprehensive experiments demonstrate that our proposed SiameseCPP is superior to existing baseline models for predicting CPPs. Moreover, SiameseCPP also achieves good performance on other functional peptide datasets, exhibiting satisfactory generalization ability.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

The origin of sequence type 72 community-associated methicillin-resistant Staphylococcus aureus (MRSA) and fusidic acid (FA) resistant sequence type 5 MRSA: Analysis of FA resistance and spa type in a single center in South Korea.

INTRODUCTION: We investigated the prevalence of fusidic acid (FA) resistance in MSSA and MRSA stratified by sequence (ST) and spa types, and determined the prevalence of FA resistance mechanisms. METHODS: From August 2014 to April 2020, S. aureus blood isolates were collected in Asan Medical Center, Seoul, South Korea. Antimicrobial susceptibility tests were performed using broth microdilution and interpreted according to EUCAST's FA criteria. We performed spa typing for fusA mutation presence and acquired FA resistance determinants (fusB, fusC, and fusD) by PCR. RESULTS: Of the 590 MRSA isolates, 372 were FA resistant, and among 425 MSSA isolates, 136 were resistant. Of the 380 ST5-MRSA isolates, 350 were FA resistant, whereas only 1 of 14 ST5-MSSA isolates was FA resistant. Conversely, of the 163 ST72-MRSA isolates, only 8 were resistant, whereas 37 of 42 ST72-MSSA were resistant. The fusA mutation (80%) was the most common determinant. The one FA resistant ST5-MSSA isolate belonged to the t2460 spa type, the most common spa type (24 of 35 isolates) of FA resistant ST5-MRSA. In addition, t324 and t148, which are minor spa types of ST72-MSSA, were susceptible to FA, in contrast to other ST72-MSSA spa types, and the major spa type of ST72-MRSA (110 of 163 isolates). CONCLUSIONS: FA resistance was common in ST5-MRSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. Our findings suggest that minor clones of ST5-MSSA isolates, with the fusA mutation and minor clones of ST72-MSSA susceptible to FA, may have evolved to harbor the mecA gene.

Clinical safety of remdesivir therapy in COVID-19 patients with renal insufficiency.

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-ß-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.

Comparison of the Clinical Outcomes Between Early and Delayed Transplantation After SARS-CoV-2 Infection.

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

Deep learning-based EEG analysis to classify normal, mild cognitive impairment, and dementia: Algorithms and dataset.

For automatic EEG diagnosis, this paper presents a new EEG data set with well-organized clinical annotations called Chung-Ang University Hospital EEG (CAUEEG), which has event history, patient's age, and corresponding diagnosis labels. We also designed two reliable evaluation tasks for the low-cost, non-invasive diagnosis to detect brain disorders: i) CAUEEG-Dementia with normal, mci, and dementia diagnostic labels and ii) CAUEEG-Abnormal with normal and abnormal. Based on the CAUEEG dataset, this paper proposes a new fully end-to-end deep learning model, called the CAUEEG End-to-end Deep neural Network (CEEDNet). CEEDNet pursues to bring all the functional elements for the EEG analysis in a seamless learnable fashion while restraining non-essential human intervention. Extensive experiments showed that our CEEDNet significantly improves the accuracy compared with existing methods, such as machine learning methods and Ieracitano-CNN (Ieracitano et al., 2019), due to taking full advantage of end-to-end learning. The high ROC-AUC scores of 0.9 on CAUEEG-Dementia and 0.86 on CAUEEG-Abnormal recorded by our CEEDNet models demonstrate that our method can lead potential patients to early diagnosis through automatic screening.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City region.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.

Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models†.

The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.

Clinical and microbiological characteristics of rifampicin-resistant MRSA bacteraemia.

OBJECTIVES: The clinical significance of rifampicin resistance in Staphylococcus aureus infections has not been demonstrated. Here, we evaluated the clinical characteristics of rifampicin-resistant S. aureus infection. METHODS: Data were collected from adult patients who were hospitalized with MRSA bacteraemia between March 2007 and May 2020 at a tertiary hospital in South Korea. The clinical characteristics and treatment outcomes of patients infected with rifampicin-resistant MRSA were compared with those of rifampicin-susceptible isolates. All-cause death and recurrence of MRSA infection were assessed for 90 days. RESULTS: Of the 961 patients with MRSA bacteraemia, 61 (6.3%) were infected by rifampicin-resistant isolates. The type of infection focus and duration of bacteraemia did not significantly differ between the two groups. Rifampicin-resistant MRSA isolates were more likely to have multidrug resistance and a higher vancomycin MIC relative to the rifampicin-susceptible isolates. The 90-day recurrence rate was higher in the patients infected with rifampicin-resistant MRSA compared with those with rifampicin-susceptible MRSA (18.0% versus 6.2%, P < 0.001), whereas the 90-day mortality was comparable between the two groups (27.9% versus 29.2%, P = 0.94). After adjusting for potential confounding factors, rifampicin resistance was significantly associated with 90-day recurrence (subdistributional HR: 2.31; 95% CI: 1.05-5.10; P = 0.04). CONCLUSIONS: Rifampicin-resistant MRSA isolates showed distinct microbiological features in terms of multidrug resistance and a high vancomycin MIC. Although the management of MRSA bacteraemia was not significantly different between the two groups, recurrence was significantly more common in the rifampicin-resistant group. Rifampicin resistance may play a significant role in infection recurrence.

Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and Omicron variants: A prospective cohort study.

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1-7], vs. 8.5 days, IQR [5-12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.

Ablation of apparent diffusion coefficient hyperintensity clusters in mesial temporal lobe epilepsy improves seizure outcomes after laser interstitial thermal therapy.

OBJECTIVE: Laser interstitial thermal therapy (LiTT) is a minimally invasive surgical procedure for intractable mesial temporal epilepsy (mTLE). LiTT is safe and effective, but seizure outcomes are highly variable due to patient variability, suboptimal targeting, and incomplete ablation of the epileptogenic zone. Apparent diffusion coefficient (ADC) is a magnetic resonance imaging (MRI) sequence that can identify potential epileptogenic foci in the mesial temporal lobe to improve ablation and seizure outcomes. The objective of this study was to investigate whether ablation of tissue clusters with high ADC values in the mesial temporal structures is associated with seizure outcome in mTLE after LiTT. METHODS: Twenty-seven patients with mTLE who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (International League Against Epilepsy [ILAE] Class I) and residual seizures (ILAE Class II-VI). Volumes of hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. Proportion of cluster volume and number ablated were associated with seizure outcomes. RESULTS: The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p = .013) and number (p = .03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p = .026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated (area under the curve [AUC] = 0.7670, p = .02). SIGNIFICANCE: Seizure outcome after LiTT in patients with mTLE was associated significantly with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcome after LiTT in mTLE.

Clinical significance and outcomes of Clostridium tertium bacteremia: analysis of 62 cases in neutropenic and non-neutropenic patients.

The clinical significance of Clostridium tertium bacteremia is still uncertain. We evaluated the incidence, clinical characteristics, and outcomes of C. tertium bacteremia and identified differences between neutropenia and non-neutropenia. All adult patients with C. tertium bacteremia in a 2700-bed tertiary center between January 2004 and November 2021 were retrospectively enrolled. The first episode of C. tertium bacteremia in each patient was included in the analysis. Among 601 patients with Clostridium species bacteremia, 62 (10%) had C. tertium bacteremia, and of these 62 patients, 39 (63%) had had recent chemotherapy, and 31 (50%) had neutropenia or hematologic malignancy. C. tertium bacteremia originated frequently from a gastrointestinal tract infection such as enterocolitis (34%), primary bacteremia (29%), and secondary peritonitis (18%), and 34% of patients had polymicrobial bacteremia. Hematologic malignancy, prior antibiotic treatment, neutropenic enterocolitis, and primary bacteremia were significantly associated with C. tertium bacteremia in neutropenic patients, whereas solid tumor, hepatobiliary disease, secondary peritonitis, polymicrobial bacteremia, and a higher frequency of eradicable infection foci were significantly associated with C. tertium bacteremia in non-neutropenic patients. There was 15% 30-day mortality. APACHE II score (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-2.1) and secondary peritonitis (aOR, 25.9; 95% CI, 3.0-224.7) were independent risk factors for 30-day mortality. The prevalence of C. tertium bacteremia is low, and the characteristics of C. tertium bacteremia are significantly different between neutropenic and non-neutropenic patients. Appropriate investigation for gastrointestinal mucosal injury should be performed to improve treatment outcomes in this form of bacteremia.

Clinical impact of metformin exposure during Staphylococcus aureus bacteremia in patients with diabetes mellitus.

PURPOSE: Increasing evidence has suggested that metformin may play positive roles in a wide range of infectious diseases. This study aimed to investigate the clinical impact of metformin exposure during Staphylococcus aureus bacteremia (SAB) in patients with diabetes. METHODS: A 3-year observational cohort study of 452 patients (aged ≥ 16 years) with SAB was performed at a tertiary care hospital. Metformin exposure was defined as receiving metformin during SAB, regardless of metformin use before the onset of bacteremia. RESULTS: Of 452 patients, 51 (11.3%) were classified in Group A (diabetes with metformin exposure), 115 (25.4%) in Group B (diabetes without metformin exposure), and 286 (63.3%) in Group C (no diabetes). The 30-day mortality rate in Group A was significantly lower than that in Group B (3.9% [2/51] versus 14.8% [17/115]; p = 0.04) and lower than that in Group C (3.9% [2/51] versus 17.1% [49/286]; p = 0.02). The mortality rates did not differ between Group B and Group C (14.8% [17/115] versus 17.1% [49/286]; p = 0.57). The rates of persistent and recurrent bacteremia were comparable among the three groups. Multivariate analysis indicated that metformin exposure was significantly associated with reduced mortality (adjusted odds ratio, 0.20; 95% confidence interval, 0.04-0.88; p = 0.03). CONCLUSIONS: Metformin exposure during SAB appears to be an independent predictor of survival in patients with diabetes.

False positive Aspergillus galactomannan assay results caused by specific parenteral nutrition.

In September 2022, the proportion of clinically false positive results with high index values for the galactomannan (GM) assay increased dramatically in our hospital and remained high until November 2022. We aimed to identify the possible causative agent that led to the dramatic increase in false positivity in GM assay. A case-control-control study was conducted, and patients admitted to two intensive care units between September and November 2022 were included. We defined each time point at which the GM assay was conducted in a patient as an episode and classified episodes into strong-positive (≥10.0 index; case), positive (control), and negative (<0.5 index; control) groups. We compared the medications administered in three groups and measured GM levels in relevant medications, including parenteral nutrition (PN). In total, 118 episodes in 33 patients were classified into three groups. There were 46 negative, 23 positive, and 49 strong-positive episodes, and there was a significant difference in the use of Winuf® PNs (P < .001) between the three groups. Forty episodes (82%) in the strong-positive group received Winuf®, compared with three (6.5%) in the negative group and one (4.3%) in the positive group (P < .001). All samples of Winuf® PNs used in the five patients whose GM results were repeatedly strong-positive were strongly positive for GM. False positivity in GM assay can be caused by the administration of specific PNs. A thorough investigation of prescribed medications should be considered when there is an abrupt increase in the proportion of strong-positive or positive GM results.

In vitro and in vivo evaluation of the antiviral activity of arctigenin, ribavirin, and ivermectin against viral hemorrhagic septicemia virus infection.

Viral hemorrhagic septicemia virus (VHSV) causes a severe and often lethal infection in olive flounder (Paralichthys olivaceus) in Korea, resulting in mass mortality and substantial economic loss. As a potential prevention strategy for infectious viral diseases, this study aimed to evaluate the antiviral activity of three compounds (arctigenin [ARG], ribavirin [RBV], and ivermectin [IVM]) against VHSV infection in vitro and in vivo. In epithelioma papulosum cyprini cells, the expression of both VHSV glycoprotein (G) and nucleoprotein (N) genes were significantly suppressed by the three compounds in a dose-dependent manner (P < 0.05). Also, cell morphology and viability were maintained at the following concentrations: ARG 1.5 mg/L, RBV 2.5 mg/L, and IVM 10 mg/L. The fish that were treated with RBV (8.33 mg/kg) and IVM (0.25 mg/kg) before VHSV infection and those treated with IVM (0.25 mg/kg) after VHSV infection showed significant improvements in the survival rate, a reduction in the viral shedding rate, and downregulation of viral gene expression compared to those seen in fish with naïve VHSV infections. Furthermore, among the innate immune genes studied, persistent expression of Mx and upregulation of tumor necrosis factor-α gene expression in VHSV-infected fish treated with RBV and IVM revealed that these compounds might induce an immunostimulatory effect as one of their antiviral activities. Overall, this study supports the use of RBV and IVM as antiviral agents to control VHSV infections in olive flounder.

Clinical Response to Low-dose Omalizumab Treatment in Chronic Spontaneous Urticaria: A Retrospective Study of 179 Patients.

Omalizumab is effective in chronic spontaneous urticaria unresponsive to antihistamines. Of the licensed dosing schedules, Korean patients prefer a low dose, of 150 mg/month, for financial reasons. However, real-world experiences of low-dose omalizumab consumption have not been reported. The aim of this retrospective study was to assess the treatment outcomes and long-term clinical course of patients with chronic spontaneous urticaria who were treated with low-dose omalizumab. The study included 179 patients aged ≥ 20 years who were treated with omalizumab 150 mg/month for ≥ 12 weeks. Baseline disease activity was mild, moderate, and severe in 54.7%, 35.2%, and 10.1% of patients, respectively. A complete response was observed in 133 patients at 12 weeks, among whom 88 patients showed early responses within 4 weeks. Overall, 158 patients finally achieved a complete response. Multivariate analyses revealed that baseline disease activity is more likely to be mild in patients who experience early and final complete responses. The absence of atopic comorbidities correlated with an early response. Smoking was associated with a final complete response. This study shows that low-dose omalizumab provides favourable treatment outcomes in antihistamine-refractory chronic spontaneous urticaria. Disease severity, atopic comorbidity, and smoking may be predictive factors for studying the response to omalizumab.

Clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea.

BACKGROUND: Invasive fusariosis mainly affects immunocompromised patients including haematopoietic stem cell transplant recipients and those with haematologic malignancy. There are limited studies on invasive fusariosis in the Asia-Pacific region. OBJECTIVE: To describe the clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea. PATIENTS/METHODS: From 2005 to 2020, patients with fusariosis who met the revised European Organisation for Research and Treatment of Cancer and the Mycoses Study Group criteria for the definition of proven or probable invasive fusariosis, and those with non-invasive fusariosis were retrospectively reviewed in a tertiary medical centre in Seoul, South Korea. RESULTS: Overall, 26 and 75 patients had invasive and non-invasive fusariosis, respectively. Patients with invasive fusariosis commonly had haematologic malignancy (62%), were solid organ transplant recipients (23%), and had a history of immunosuppressant usage (81%). In non-invasive fusariosis, diabetes mellitus (27%) and solid cancer (20%) were common underlying conditions. Disseminated fusariosis (54%) and invasive pulmonary disease (23%) were the most common clinical manifestations of invasive fusariosis; skin infection (48%) and keratitis (27%) were the most common manifestations of non-invasive fusariosis. Twenty-eight-day and in-hospital mortalities were high in invasive fusariosis (40% and 52%, respectively). In multivariate analysis, invasive fusariosis (adjusted odds ratio, 9.6; 95% confidence interval 1.3-70.8; p = .03) was an independent risk factor for 28-day mortality. CONCLUSIONS: Patients with invasive fusariosis were frequently immunocompromised, and more than half had disseminated fusariosis. Invasive fusariosis was associated with poor prognosis.

The relationship between organising pneumonia and invasive mould disease in patients with haematologic malignancy.

BACKGROUND: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. OBJECTIVE: To investigate molecular evidence of invasive mould pneumonia in paraffin-embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. PATIENTS/METHODS: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus- and Mucorales-specific DNA within OP lung tissue sections. RESULTS: Forty-seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8-114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin-embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus- and Mucorales-specific DNA. CONCLUSIONS: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus-specific PCR in lung tissues, likely associated with concurrent or prior fungal infection.