Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.

To assess telomerase as a cancer therapeutic target and determine adaptive mechanisms to telomerase inhibition, we modeled telomerase reactivation and subsequent extinction in T cell lymphomas arising in Atm(-/-) mice engineered with an inducible telomerase reverse transcriptase allele. Telomerase reactivation in the setting of telomere dysfunction enabled full malignant progression with alleviation of telomere dysfunction-induced checkpoints. These cancers possessed copy number alterations targeting key loci in human T cell lymphomagenesis. Upon telomerase extinction, tumor growth eventually slowed with reinstatement of telomere dysfunction-induced checkpoints, yet growth subsequently resumed as tumors acquired alternative lengthening of telomeres (ALT) and aberrant transcriptional networks centering on mitochondrial biology and oxidative defense. ALT+ tumors acquired amplification/overexpression of PGC-1ß, a master regulator of mitochondrial biogenesis and function, and they showed marked sensitivity to PGC-1ß or SOD2 knockdown. Genetic modeling of telomerase extinction reveals vulnerabilities that motivate coincidental inhibition of mitochondrial maintenance and oxidative defense mechanisms to enhance antitelomerase cancer therapy.

Oncogenic Kras drives invasion and maintains metastases in colorectal cancer.

Human colorectal cancer (CRC) is a major cause of cancer mortality and frequently harbors activating mutations in the KRAS gene. To understand the role of oncogenic KRAS in CRC, we engineered a mouse model of metastatic CRC that harbors an inducible oncogenic Kras allele (Krasmut ) and conditional null alleles of Apc and Trp53 (iKAP). The iKAP model recapitulates tumor progression from adenoma through metastases. Whole-exome sequencing revealed that the Krasmut allele was heterogenous in primary tumors yet homogenous in metastases, a pattern consistent with activated Krasmut signaling being a driver of progression to metastasis. System-level and functional analyses revealed the TGF-ß pathway as a key mediator of Krasmut -driven invasiveness. Genetic extinction of Krasmut resulted in specific elimination of the Krasmut subpopulation in primary and metastatic tumors, leading to apoptotic elimination of advanced invasive and metastatic disease. This faithful CRC model provides genetic evidence that Krasmut drives CRC invasion and maintenance of metastases.

Antimicrobial Use and Carbapenem-Resistant Enterobacterales in Korea: A Nationwide Case-Control Study With Propensity Score Matching.

BACKGROUND: Nationwide research on the association between carbapenem-resistant Enterobacterales (CREs) and antibiotic use is limited. METHODS: This nested case-control study analyzed Korean National Health Insurance claims data from April 2017 to April 2019. Based on the occurrence of CRE, hospitalized patients aged ≥ 18 years were classified into CRE (cases) and control groups. Propensity scores based on age, sex, modified Charlson comorbidity score, insurance type, long-term care facility, intensive care unit stay, and acquisition of vancomycin-resistant Enterococci were used to match the case and control groups (1:3). RESULTS: After matching, the study included 6,476 participants (1,619 cases and 4,857 controls). Multivariable logistic regression analysis revealed that the utilization of broad-spectrum antibiotics, such as piperacillin/tazobactam (adjusted odds ratio [aOR], 2.178; 95% confidence interval [CI], 1.829-2.594), third/fourth generation cephalosporins (aOR, 1.764; 95% CI, 1.514-2.056), and carbapenems (aOR, 1.775; 95% CI, 1.454-2.165), as well as the presence of comorbidities (diabetes [aOR, 1.237; 95% CI, 1.061-1.443], hemiplegia or paraplegia [aOR, 1.370; 95% CI, 1.119-1.679], kidney disease [aOR, 1.312; 95% CI, 1.105-1.559], and liver disease [aOR, 1.431; 95% CI, 1.073-1.908]), were significantly associated with the development of CRE. Additionally, the CRE group had higher mortality (8.33 vs. 3.32 incidence rate per 100 person-months, P < 0.001) and a total cost of healthcare utilization per person-month (15,325,491 ± 23,587,378 vs. 5,263,373 ± 14,070,118 KRW, P < 0.001) than the control group. CONCLUSION: The utilization of broad-spectrum antibiotics and the presence of comorbidities are associated with increasing development of CRE. This study emphasizes the importance of antimicrobial stewardship in reducing broad-spectrum antibiotic use and CRE disease burden in Korea.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Post-acute COVID-19 syndrome in patients after 12 months from COVID-19 infection in Korea.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues to progress, awareness about its long-term impacts has been growing. To date, studies on the long-term course of symptoms, factors associated with persistent symptoms, and quality of life after 12 months since recovery from acute COVID-19 have been limited. METHODS: A prospective online survey (First: September 8, 2020-September 10, 2020; Second: May 26, 2021-June 1, 2021) was conducted on recovered patients who were previously diagnosed with COVID-19 between February 13, 2020 and March 13, 2020 at Kyungpook National University Hospital. Responders aged between 17 and 70 years were included in the study. Overall, 900 and 241 responders were followed up at 6 and 12 months after recovery from COVID-19 in the first and second surveys, respectively. Clinical characteristics, self-reported persistent symptoms, and EuroQol-5-dimension (EQ5D) index score were investigated for evaluating quality of life. RESULTS: The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 454 (interquartile range [IQR] 451-458) days. The median age of the responders was 37 (IQR 26.0-51.0) years, and 164 (68.0%) responders were women. Altogether, 11 (4.6%) responders were asymptomatic, and 194 (80.5%), 30 (12.4%), and 6 (2.5%) responders had mild, moderate, and severe illness, respectively. Overall, 127 (52.7%) responders still experienced COVID-19-related persistent symptoms and 12 (5.0%) were receiving outpatient treatment for such symptoms. The main symptoms were difficulty in concentration, cognitive dysfunction, amnesia, depression, fatigue, and anxiety. Considering the EQ5D index scores, only 59.3% of the responders did not have anxiety or depression. Older age, female sex, and disease severity were identified as risk factors for persistent neuropsychiatric symptoms. CONCLUSION: COVID-19-related persistent symptoms improved over time; however, neurological symptoms can last longer than other symptoms. Continuous careful observation of symptom improvement and multidisciplinary integrated research on recovered COVID-19 patients are required.

Beta-Lactam Plus Macrolide for Patients Hospitalized With Community-Acquired Pneumonia: Difference Between Autumn and Spring.

BACKGROUND: The 2017 Korean guideline on community-acquired pneumonia (CAP) recommended beta-lactam plus macrolide combination therapy for patients hospitalized with severe pneumonia, and beta-lactam monotherapy for mild-to-moderate pneumonia. However, antibiotic treatment regimen for mild-to-moderate CAP has never been evaluated for Korean patients. METHODS: In this retrospective cohort study, study patients were selected from three evaluation periods (October 1 to December 31, 2014; April 1 to June 30, 2016; October 1 to December 31, 2017) of the National Quality Assessment Program for CAP management and the National Health Insurance data on the selected patients was extracted from 1 year before the first patient enrollment and 1 year after the last patient enrollment at each evaluation period for the analysis of risk adjustment and outcomes. The survival rates between beta-lactam plus macrolide (BM) groups and beta-lactam monotherapy (B) were compared using a Kaplan-Meier survival analysis after propensity score matching by age, gender, confusion, urea, respiratory rate, blood pressure at age of 65 years or older (CURB-65), and Charlson comorbidity index for risk adjustment. The differences between autumn and spring season were also evaluated. RESULTS: A total of 30,053 patients were enrolled. Mean age and the male-to-female ratio were 64.7 ± 18.4 and 14,197:15,856, respectively. After matching, 2,397 patients in each group were analyzed. The 30-day survival rates did not differ between the BM and B groups (97.3% vs. 96.5%, P = 0.081). In patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.7% vs. 91.0%, P = 0.044). Among patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.3% vs. 88.5%, P = 0.009) during autumn season, which was not observed during spring (94.2% vs. 94.1%, P = 0.986). CONCLUSION: Beta-lactam plus macrolide combination therapy shows potential as an empirical therapy for CAP with CURB-65 ≥ 2, especially in autumn.

Workload of Healthcare Workers During the COVID-19 Outbreak in Korea: A Nationwide Survey.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea. METHODS: A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients. RESULTS: Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4-5] vs. 1.1 [0.8-2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary. CONCLUSION: As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.

Clinical outcomes and healthcare costs of inpatients with tetanus in Korea, 2011-2019.

BACKGROUND: Tetanus is a rare, vaccine-preventable but extremely serious disease. We investigated the recent trend of the clinical outcomes and medical costs for inpatients with tetanus in South Korea over 10 years. METHODS: We conducted a retrospective review to determine the clinical factors and medical costs associated with tetanus at two national university hospitals in South Korea between January 2011 and October 2019. RESULTS: Forty-nine patients were admitted for tetanus (mean age, 67.0 years [range, 53.0-80.0 years]; 32 women [57.1%]). All the patients had generalized tetanus, and 5 (10.2%) died during hospitalization. The median duration from symptom onset to hospital admission was 4 days. Trismus (85.7%) was the most common symptom, and the median hospital stay was 39 days. Thirty-two patients (65.3%) required mechanical ventilation, and 20 (40.8%) developed aspiration pneumonia. The median total healthcare cost per patient was US $18,011. After discharge, 35 patients (71.4%) recovered sufficiently to walk without disability. CONCLUSIONS: Tetanus requires long hospital stays and high medical expenditures in South Korea; however, the vaccination completion rate is low. Medical staff should therefore promote medical advice and policies on the management of tetanus to the general South Korean population.

Trends of Cause of Death among Human Immunodeficiency Virus Patients and the Impact of Low CD4 Counts on Diagnosis to Death: a Retrospective Cohort Study.

BACKGROUND: Monitoring the full spectrum of causes of death among human immunodeficiency virus (HIV) patients has become increasingly important as survival improves because of highly active antiretroviral therapy. However, there are no recently published data regarding the changes in the causes of death among HIV patients based on year of HIV diagnosis, and the impact of low CD4 count at the time of HIV diagnosis on the clinical outcome is still unclear in Korea. METHODS: A retrospective cohort study was conducted with 801 patients with HIV infection who were followed up at a tertiary university hospital and diagnosed with HIV between July 1984 and October 2019. The causes of death were analyzed by descriptive analysis based on CD4 count and the year of HIV diagnosis. Kaplan-Meier and log rank tests were performed to compare the prognosis between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. RESULTS: Among 801 patients, 67 patients were eligible for the death cause analysis. Infection-related death accounted for 44 patients (65.7%) and non-infection related death accounted for 23 patients (32.4%). Pneumocystis pneumonia (29.9%) was the single most common cause of death in both past and present cases, and tuberculosis (19.4%) was the second leading cause of death from infections, but the frequency has declined in recent years. Causes of infection-related death have decreased, whereas non-infection related causes of death have increased remarkably. Malignancy-related death was the most common cause of non-infection related death. Acquired immunodeficiency syndrome (AIDS) non-related malignancy accounted for 11.9%, whereas AIDS-related malignancy accounted for 6.0% of the total death among HIV patients. No significant statistical differences were found in mortality rate (P = 0.228), causes of death (P = 0.771), or survival analysis (P = 0.089) between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. CONCLUSION: Being diagnosed with CD4 < 200 cells/mm³ at the time of HIV diagnosis was not an indicator of greater risk of death compared with the CD4 ≥ 200 cells/mm³ group. Malignant tumors have become an important cause of death in recent years, and an increasing tendency of AIDS-non-related malignancy causes has been observed.

Detection of amyloid ß oligomers toward early diagnosis of Alzheimer's disease.

Amyloid ß (Aß) peptide accumulation in the brain is considered to be one of the hallmarks of Alzheimer's disease. Here, we compare two analytical techniques for detecting neurotoxic Aß1-42 oligomers - Quartz Crystal Microbalance with Dissipation (QCM-D) and Single Molecule Array (Simoa). Both detection methods exploit a feature of the monoclonal antibody bapineuzumab, which targets N-terminal residues 1-5 of Aß with high affinity and use it as both a capture and detection reagent. Assays developed with the two methods allow us to specifically recognize neurotoxic Aß1-42 oligomers and higher aggregates such as fibrils but discriminate against Aß1-42 monomer species. We find that for detection of Aß1-42 oligomers, Simoa was roughly 500 times more sensitive than the QCM-D technique with limits of detection of 0.22 nM and 125 nM, respectively.

A New Scoring System for the Differential Diagnosis between Tuberculous Meningitis and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium < 135 mmol/L in serum (hyponatremia), lactate dehydrogenase > 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0-13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.

From the Cover: Neutralization of terminal differentiation in gliomagenesis.

An immature state of cellular differentiation--characterized by stem cell-like tendencies and impaired differentiation--is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetically targeted in carcinogenesis and whether neutralizing such genes also plays an active role to reinforce the impaired differentiation state and promote malignancy. To that end, we screened 71 genes with known roles in promoting nervous system development that also sustain copy number loss in GBM through antineoplastic assay and identified A2BP1 (ataxin 2 binding protein 1, Rbfox1), an RNA-binding and splicing regulator that is deleted in 10% of GBM cases. Integrated in silico analysis of GBM profiles to elucidate the A2BP1 pathway and its role in glioma identified myelin transcription factor 1-like (Myt1L) as a direct transcriptional regulator of A2BP1. Reintroduction of A2BP1 or Myt1L in GBM cell lines and glioma stem cells profoundly inhibited tumorigenesis in multiple assays, and conversely, shRNA-mediated knockdown of A2BP1 or Myt1L in premalignant neural stem cells compromised neuronal lineage differentiation and promoted orthotopic tumor formation. On the mechanistic level, with the top-represented downstream target TPM1 as an illustrative example, we demonstrated that, among its multiple functions, A2BP1 serves to regulate TPM1's alternative splicing to promote cytoskeletal organization and terminal differentiation and suppress malignancy. Thus, in addition to the activation of self-renewal pathways, the neutralization of genetic programs that drive cells toward terminal differentiation may also promote immature and highly plastic developmental states that contribute to the aggressive malignant properties of GBM.

Expression platforms for producing eukaryotic proteins: a comparison of E. coli cell-based and wheat germ cell-free synthesis, affinity and solubility tags, and cloning strategies.

Vectors designed for protein production in Escherichia coli and by wheat germ cell-free translation were tested using 21 well-characterized eukaryotic proteins chosen to serve as controls within the context of a structural genomics pipeline. The controls were carried through cloning, small-scale expression trials, large-scale growth or synthesis, and purification. Successfully purified proteins were also subjected to either crystallization trials or (1)H-(15)N HSQC NMR analyses. Experiments evaluated: (1) the relative efficacy of restriction/ligation and recombinational cloning systems; (2) the value of maltose-binding protein (MBP) as a solubility enhancement tag; (3) the consequences of in vivo proteolysis of the MBP fusion as an alternative to post-purification proteolysis; (4) the effect of the level of LacI repressor on the yields of protein obtained from E. coli using autoinduction; (5) the consequences of removing the His tag from proteins produced by the cell-free system; and (6) the comparative performance of E. coli cells or wheat germ cell-free translation. Optimal promoter/repressor and fusion tag configurations for each expression system are discussed.

Analysis of microbiological tests in patients withholding or withdrawing life-sustaining treatment at the end stage of life in 2 Korean hospitals.

OBJECTIVE: We evaluated the adequacy of microbiological tests in patients withholding or withdrawing life-sustaining treatment (WLST) at the end stage of life. SETTING: The study was conducted at 2 tertiary-care referral hospitals in Daegu, Republic of Korea. DESIGN: Retrospective cross-sectional study. METHODS: Demographic findings, clinical and epidemiological characteristics, statistics of microbiological tests, and microbial species isolated from patients within 2 weeks before death were collected in 2 tertiary-care referral hospitals from January to December 2018. We also reviewed the antimicrobial treatment that was given within 3 days of microbiological testing in patients on WLST. RESULTS: Of the 1,187 hospitalized patients included, 905 patients (76.2%) had WLST. The number of tests per 1,000 patient days was higher after WLST than before WLST (242.0 vs 202.4). Among the category of microbiological tests, blood cultures were performed most frequently, and their numbers per 1,000 patient days before and after WLST were 95.9 and 99.0, respectively. The positive rates of blood culture before and after WLST were 17.2% and 18.0%, respectively. Candida spp. were the most common microbiological species in sputum (17.4%) and urine (48.2%), and Acinetobacter spp. were the most common in blood culture (17.3%). After WLST determination, 70.5% of microbiological tests did not lead to a change in antibiotic use. CONCLUSIONS: Many unnecessary microbiological tests are being performed in patients with WLST within 2 weeks of death. Microbiological testing should be performed carefully and in accordance with the patient's treatment goals.

Effect of Regdanvimab on Mortality in Patients Infected with SARS-CoV-2 Delta Variants: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Regdanvimab, a monoclonal antibody pharmaceutical, is the first Korean drug approved for treating coronavirus disease 2019 (COVID-19). We analyzed the therapeutic efficacy of regdanvimab in patients with the COVID-19 delta variant infection. METHODS: We retrospectively reviewed the electronic medical records of patients hospitalized at two Korean tertiary COVID-19 hospitals with COVID-19 delta variant infection between May 26, 2021, and January 30, 2022. To analyze the therapeutic efficacy of regdanvimab, the patients were divided into regdanvimab and non-regdanvimab groups and were 1:1 propensity-score (PS)-matched on age, severity at admission, and COVID-19 vaccination history. RESULTS: Of 492 patients, 262 (53.3%) and 230 (46.7%) were in the regdanvimab and non-regdanvimab groups, respectively. After PS matching the groups on age, severity at admission, and COVID-19 vaccination history, each group comprised 189 patients. The 30-day hospital mortality rates (0.0% vs. 1.6%, p = 0.030), proportions of patients with exacerbated conditions to severe/critical/died (9.5% vs. 16.4%, p = 0.047), proportions who received oxygen therapy because of pneumonia exacerbation (7.4% vs. 16.4%, p = 0.007), and proportions with a daily National Early Warning Score ≥ 5 from hospital day 2 were significantly lower in the regdanvimab group. CONCLUSIONS: We showed that regdanvimab reduced the exacerbation rates of conditions and mortality in patients with the COVID-19 delta variant infection. Thus, it is recommended to streamline the drug approval system during epidemics of new variant viruses to improve the availability and usage of therapeutics for patients. To facilitate this, relevant institutional support is required.

Clinical Outcomes of Solid Organ Transplant Recipients Hospitalized with COVID-19: A Propensity Score-Matched Cohort Study.

BACKGROUND: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. MATERIALS AND METHODS: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. RESULTS: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes. CONCLUSION: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Adverse Reactions after BNT162b2 Messenger RNA Vaccination for Coronavirus Disease 2019 in Healthcare Workers Compared with Influenza Vaccination.

This study aimed to compare adverse reactions following BNT162b2 and influenza vaccinations in healthcare workers. This study included healthcare workers who received the BNT162b2 vaccine and/or inactivated influenza vaccine, quadrivalent (IIV4), on 18-29 October 2021 at a tertiary hospital in Korea. IIV4 was administered and BNT162b2 was subsequently administered one week later. The participants responded to a mobile questionnaire regarding adverse events. The overall adverse reaction rates were 90.6% in the BNT162b2 + IIV4 group, 90.4% in the BNT162b2 alone group, and 44.1% in the IIV4 alone group (p < 0.001). Fever occurred in 19.5%, 26.9%, and 3.3% of participants in the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). The most common local and systemic adverse reactions were injection site pain (65.0%) and fatigue (58.6%), respectively. Injection-site pain was experienced by 88.7%, 88.5%, and 37.5% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Fatigue was experienced by 74.8%, 78.8%, and 38.6% of the BNT162b2 + IIV4, BNT162b2 alone, and IIV4 alone groups, respectively (p < 0.001). Adverse reactions occurred at a significantly higher frequency after BNT162b2 than after IIV4. The frequency of adverse reactions one week after vaccination with IIV4 and BNT162b2 was not different from that after vaccination with BNT162b2 alone. Therefore, coadministration of influenza vaccine with BNT162b2 can be expected to be safe.