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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

OBJECTIVE One-fourth of cerebral cavernous malformation (CCM) patients are children, but studies on these patients are scarce. This study aimed to identify the clinical presentation of pediatric CCM patients and to investigate clinical outcomes according to the treatment modalities applied on the basis of our institution’s treatment strategy. METHODS The authors performed a retrospective analysis of 124 pediatric CCM patients with a follow-up of more than 1 year from 2000 to 2019. They performed resection (n = 62) on lesions causing intractable seizure, rebleeding, or mass effect and observed the clinical courses of patients with lesions in deep or eloquent areas without persistent symptoms (n = 52). Radiosurgery (n = 10) was performed when the patient refused resection or strongly desired radiosurgery. The authors investigated the clinical characteristics, performance status (modified Rankin Scale [mRS] score), and rebleeding rate at the 1-year and last follow-up examinations and compared these among 3 groups classified on the basis of treatment applied. The authors evaluated seizure outcomes at the 1-year and last follow-up examinations for the surgery (n = 32) and observation (n = 17) groups. Finally, the authors drew cumulative incidence curves for the discontinuation of antiepileptic drugs (AEDs) for patients in the surgery (n = 30) and observation (n = 9) groups. RESULTS The 3 groups showed slight differences in initial symptoms, lesion locations, and rates of recent hemorrhage. The proportion of patients with improved mRS score at the 1-year follow-up was significantly greater in the surgery group than in the other groups (67% of the surgery group, 52% observation group, and 40% radiosurgery group; p = 0.078), as well as at the last follow-up (73% surgery group, 54% observation group, and 60% radiosurgery group; p = 0.097). The surgery group also had the lowest rebleeding rate during the follow-up period (2% surgery group, 11% observation group, and 20% radiosurgery group; p = 0.021). At the 1-year follow-up, the proportion of seizure-free patients without AEDs was significantly higher in the surgery group than the observation group (88% surgery group vs 53% observation group, p < 0.001), and similar results were obtained at the last follow-up (91% surgery group vs 56% observation group, p = 0.05). The 5-year AED-free rates for the surgery and observation groups were 94% and 50%, respectively, on the cumulative incidence curve (p = 0.049). CONCLUSIONS The clinical presentation of pediatric CCM patients was not significantly different from that of adult patients. Lesionectomy may be acceptable for pediatric CCM patients with indications of persistent seizures despite AED medications, rebleeding, and mass effects.

We investigate whether the bank examination process provides useful insight into bank future outcomes. We do this by conducting textual analysis on about 5,500 small to medium-sized commercial bank examination reports from 2004 to 2016. These confidential examination reports provide textual context to the components of supervisory ratings: capital adequacy, asset quality, management, earnings, and liquidity. Each component is given a categorical rating, and each bank is assigned an overall composite rating, which are used to determine the safety and soundness of banks. We find that, controlling for a variety of factors, including the ratings themselves, the sentiment supervisors express in describing most of the components predict relevant future bank outcomes. The sentiment conveyed in the asset quality, management, and earnings sections provides significant information in predicting future outcomes for problem loans, supervisory actions, and profitability, respectively, for all banks. Sentiment conveyed in the capital adequacy section appears to be predictive of future capital ratios for weak banks. These relationships suggest that bank supervisors play a meaningful role in the surveillance of the banking system.

Although posterior reversible encephalopathy syndrome (PRES) is induced by various causes, a few cases have occurred after severe anemia correction. In this case report, a 45-year-old female patient visited emergency department with a chief complaint of dizziness due to severe anemia related to hypermenorrhea caused by uterine myoma. Before her operation, she had an abrupt headache and seizure during anemia correction with transfusion and injection of gonadotropin-releasing hormone agonist. Immediately after the operation, she experienced visual disturbances, followed by limb weakness and tonic-clonic movements. Magnetic resonance imaging showed alterations in parietal and occipital lobes suggesting cerebrovascular edema with hypoperfusion. Here, we presented and discussed the clinical and radiologic features of PRES related to anemia correction.

Purpose The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer.Materials and Methods Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed.Results At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee.Conclusion Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

Background Not many imaging techniques have been reported in Eustachian tube imaging. Purpose To investigate the role of selective Eustachian tubography (SET) and Valsalva computed tomography (CT) in patients who underwent Eustachian tube balloon dilation (ETBD). Material and Methods Eligible patients were aged 18 years and older with chronic Eustachian tube dysfunction who had failed medical treatment. On the day of the procedure, Valsalva CT and SET were performed. Participants underwent fluoroscopic ETBD with a 6×20-mm balloon catheter. Clinical examinations to check for the ability to perform the Valsalva maneuver and ETDQ-7 score change were conducted at one week and then at one, two, and six months. Follow-up Valsalva CT was performed in the one-month follow-up. Results A total of 30 ears in 23 patients (16 right ears, 14 left ears; 10 women, 13 men) underwent ETBD from August 2018 to November 2019. Positive CT patency was higher in follow-up Valsalva CT than baseline Valsalva CT (40% and 23.3%, respectively) ( P = 0.006). In SET, positive patency was observed in 13 of 25 ears. Response to balloon dilation was observed in 18 of 25 patients. Clinical success was achieved in 16 of 27 ears. Response to balloon dilation was the only significant predictor of clinical success ( P = 0.012). Conclusion SET depicted the lumen of the Eustachian tube; thereby, it could be a potentially valuable tool in ETBD. Valsalva CT provides additional information about the cartilaginous portion of the Eustachian tube.

LMB-100 is a novel immune-conjugate (immunotoxin) that targets mesothelin. A phase 1/2 clinical trial was conducted (NCT02810418) with primary objectives assessing the safety and efficacy of LMB-100 ± nab-paclitaxel. Participant blood samples were analyzed for changes in serum cytokines and circulating immune cell subsets associated with response or toxicity. On Arm A, participants (n = 20) received standard 30-minute LMB-100 infusion with nab-paclitaxel. Although clinical efficacy was observed, the combination caused intolerable capillary leak syndrome (CLS), a major toxicity of unclear etiology that affects many immunotoxin drugs. Participants developing CLS experienced rapid elevations in IFNγ and IL-8 compared to those without significant CLS, along with midcycle increases in Ki-67- CD4 T cells that were CD38, HLA-DR, or TIM3 positive. Additionally, a strong increase in activated CD4 and CD8 T cells and a concurrent decrease in Tregs were seen in the single Arm A patient achieving a partial response. In Arm B, administration of single agent LMB-100 to participants (n = 20) as a long infusion given over 24-48 h was investigated based on pre-clinical data that this format could reduce CLS. An optimal dose and schedule of long infusion LMB-100 were identified, but no clinical efficacy was observed even in patients receiving LMB-100 in combination with nab-paclitaxel. Despite this, both Arm A and B participants experienced increases in specific subsets of proliferating CD4 and CD8 T cells following Cycle 1 treatment. In summary, LMB-100 treatment causes systemic immune activation. Inflammatory and immune changes that accompany drug associated CLS were characterized for the first time.

To compare the effectiveness of long-pulsed alexandrite laser (LPAL) with that of pulsed-dye laser (PDL) for rosacea.This was a single-blind randomized controlled trial on 27 patients who were clinically diagnosed with rosacea. Randomly assigned split face in each patient received four times monthly treatment of LPAL plus low-fluence Nd:YAG with the contralateral side serving as the control treated with PDL. At every visit, the erythema index (EI) was measured with skin analysis systems, and two independent dermatologists evaluated digital photographs for five-point global aesthetic improvement scale (GAIS).The EI significantly decreased on both treated sides (LPAL 366.5 ± 101.0 vs. 295.8 ± 90.2, p 0.001, PDL 369.0 ± 124.3 vs. 302.7 ± 92.1, p 0.001) 1 month after fourth treatment (visit 5). Also 3 months after the fourth treatment (visit 6), the reduction in the EI was well maintained on both sides (LPAL 360.3 ± 96.8 vs. 282.0 ± 89.2, p 0.001, PDL 364.3 ± 121.6 vs. 281.6 ± 97.8, p 0.001). When comparing the improvement in the EI between the two groups, the percentage reduction in the EI on the LPAL-treated side was not inferior to the PDL-treated side (visit 5: LPAL 18.7 ± 15.7% vs. PDL 16.4 ± 12.9%, p = 0.501 and visit 6: LPAL 21.7 ± 13.9% vs. PDL 21.9 ± 15.2%, p = 0.943). The GAIS and patient satisfaction were comparable between the LPAL and PDL sides and did not show any significant difference. No serious adverse events occurred on either of the treated sides.This study showed that the decrease in EI in the treatment of rosacea was comparable between PDL and LPAL. Therefore, LPAL could be a promising alternative treatment option with good merits for rosacea, considering no consumables are required for device maintenance.

OBJECTIVE Gamma Knife surgery (GKS) is a well-established treatment for benign intracranial meningiomas; however, the dosimetric factors associated with long-term GKS efficacy and safety remain to be elucidated. Using data obtained with at least 10 years of follow-up, the authors aimed 1) to analyze GKS efficacy and safety for the treatment of benign meningiomas confined to non–skull base, nonperioptic supratentorial locations and 2) to determine the radiation dose window that allows for long-term efficacy and safety, namely the minimum dose to achieve long-term local control (LC) and the maximum safe dose to avoid adverse radiation effects (AREs). METHODS A retrospective analysis was performed on patients who underwent GKS for benign meningiomas in the abovementioned location at the authors’ institution between 1998 and 2010 and who received follow-up for more than 10 years. The authors meticulously extracted the values of various dosimetric factors by using a dose-volume histogram. Cox proportional hazard regression analyses were performed to investigate the dosimetric factors associated with LC and ARE. RESULTS Fifty-five patients (male/female ratio 1:4.2) with 68 tumors were enrolled. The median (range) gross target volume and marginal dose were 4.2 (0.2–31.7) cm3 and 14.3 (9–20) Gy, respectively. In total, 23.5% of tumors progressed at an average of 72 months, with 10- and 15-year progression-free survival rates of 80.9% and 73.5%, respectively. In univariate analysis, higher marginal dose, coverage (%), Dmin, D98%, Dmean, D2%, Dmax, and Paddick conformity index were significantly associated with LC. In multivariate analysis, D98% was the significant factor, with a cutoff value of 11 Gy (HR 0.754, p < 0.001). Symptomatic AREs occurred in 7 patients at an average of 7 months after GKS. AREs were significantly associated with the volume of normal tissue irradiated with more than 14 Gy (nV14Gy), with a cutoff value of 0.66 cm3 (HR 2.459, p = 0.002). CONCLUSIONS D98% was a barometer of the minimum required dose associated with long-term LC, and nV14Gy was related to symptomatic AREs. The authors recommend a marginal dose ranging from 11 to 14 Gy to achieve long-term efficacy and safety in patients with non–skull base, nonperioptic benign supratentorial meningiomas, with the assumption of thorough tumor coverage.

BACKGROUND: In this study, we evaluate the clinical impact of psychiatric illnesses (PI) on the hospital outcomes of patients admitted with alcoholic liver disease (ALD). METHODS: From the National Inpatient Sample from 2012–2017, patients with alcoholic cirrhosis or alcoholic hepatitis were selected and stratified using the presence/absence of PI (which was a composite of psychiatric conditions). The cases were propensity score-matched to PI-absent controls and were compared to the following endpoints: mortality, death due to suicide, length of stay (LOS), hospitalization charges, and hepatic complications. RESULTS: After matching, there were 122907 PI with and 122907 without PI. Those with PI were younger (51.8 vs. 51.9 years p=0.02) and more likely to be female (39.2 vs. 38.7% p=0.01); however, there was no difference in race. Patients with PI had lower rates of alcoholic cirrhosis but higher rates of alcoholic hepatitis/alcoholic hepatic steatosis. In multivariate, patients with PI had lower rates of all-cause mortality (aOR 0.51 95%CI 0.49–0.54); however, they experienced higher rates of deaths due to suicide (aOR 3.00 95%CI 1.56–5.78) and had longer LOS (aOR 1.02 95%CI 1.01–1.02). CONCLUSION: Presence of PI in ALD patients is associated with prolonged hospital stay and higher rates deaths due to suicide.