Serial quantitative chest computed tomography imaging as prognosticators of coronavirus disease 2019 pneumonia.

In 2019, a large outbreak of a novel coronavirus disease (COVID-19) occurred in China. The purpose of this study is to quantitatively analyze the evolution of chest computed tomography (CT) imaging features in COVID-19. Nine patients with positive real-time reverse-transcriptase polymerase chain reaction results were included in this study. Totally 19 CT scans were analyzed. Lesion density, lesion volume, and lesion load were higher in the severe group than in the mild group. A significantly positive correlation was noted between major laboratory prognosticators with lesion volume and load. Lesion load at the first week of disease was significantly higher in severe group (p = 0.03). Our study revealed that several CT features were significantly different between severely and mildly infected forms of COVID-19 pneumonia. The CT lesion load value at the first week of infection may be applied as an outcome predictor of the disease.

Functional Plasmon-Activated Water Increases Akkermansia muciniphila Abundance in Gut Microbiota to Ameliorate Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with dysbiosis and intestinal barrier dysfunction, as indicated by epithelial hyperpermeability and high levels of mucosal-associated bacteria. Changes in gut microbiota may be correlated with IBD pathogenesis. Additionally, microbe-based treatments could mitigate clinical IBD symptoms. Plasmon-activated water (PAW) is known to have an anti-inflammatory potential. In this work, we studied the association between the anti-inflammatory ability of PAW and intestinal microbes, thereby improving IBD treatment. We examined the PAW-induced changes in the colonic immune activity and microbiota of mice by immunohistochemistry and next generation sequencing, determined whether drinking PAW can mitigate IBD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dysbiosis through mice animal models. The effects of specific probiotic species on mice with TNBS-induced IBD were also investigated. Experimental results indicated that PAW could change the local inflammation in the intestinal microenvironment. Moreover, the abundance of Akkermansia spp. was degraded in the TNBS-treated mice but elevated in the PAW-drinking mice. Daily rectal injection of Akkermansia muciniphila, a potential probiotic species in Akkermansia spp., also improved the health of the mice. Correspondingly, both PAW consumption and increasing the intestinal abundance of Akkermansia muciniphila can mitigate IBD in mice. These findings indicate that increasing the abundance of Akkermansia muciniphila in the gut through PAW consumption or other methods may mitigate IBD in mice with clinically significant IBD.

Case report of an unusual hepatic abscess caused by Actinomyces odontolyticus in a patient with human immunodeficiency virus infection.

BACKGROUND: Actinomyces odontolyticus is not commonly recognized as a causative microbe of liver abscess. The detection and identification of A. odontolyticus in laboratories and its recognition as a pathogen in clinical settings can be challenging. However, in the past decades, knowledge on the clinical relevance of A. odontolyticus is gradually increasing. A. odontolyticus is the dominant oropharyngeal flora observed during infancy [Li et al. in Biomed Res Int 2018:3820215, 2018]. Herein we report a case of severe infection caused by A. odontolyticus in an immunocompromised patient with disruption of the gastrointestinal (GI) mucosa. CASE PRESENTATION: We present a unique case of a patient with human immunodeficiency virus infection who was admitted due to liver abscess and was subsequently diagnosed as having coinfection of A. odontolyticus, Streptococcus constellatus, and Candida albicans during the hospital course. The empirical antibiotics metronidazole and ceftriaxone were replaced with the intravenous administration of fluconazole and ampicillin. However, the patient's condition deteriorated, and he died 3 weeks later. CONCLUSION: This report is one of the first to highlight GI tract perforation and its clinical relevance with A. odontolyticus infection. A. odontolyticus infection should be diagnosed early in high-risk patients, and increased attention should be paid to commensal flora infection in immunocompromised individuals.

In vitro activities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and Stenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan.

Objectives: We investigated the in vitro activities of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam and other related drugs against imipenem-resistant Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumannii and Stenotrophomonas maltophilia isolates. Methods: Non-duplicated bacteraemia isolates (n = 300) of imipenem-resistant P. aeruginosa (n = 100), imipenem-resistant A. baumannii (n = 100) and S. maltophilia (n = 100) were evaluated. Imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii isolates were defined as isolates exhibiting imipenem MIC ≥8 mg/L, as determined using the VITEK 2 system. The MICs of 11 other antimicrobial agents for the isolates were determined by the broth microdilution method. Iron-depleted CAMHB was used to determine the MICs of cefiderocol. Results: The rates of colistin resistance of imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii were 5% and 10%, respectively. The MIC90 values of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam, tigecycline and colistin were as follows: imipenem-resistant P. aeruginosa: 1, 4, 16, >4 and 2 mg/L; imipenem-resistant A. baumannii: 8, >64, >64, 4 and 2 mg/L; and S. maltophilia: 0.25, >64, >64, 2 and >8 mg/L, respectively. For imipenem-resistant A. baumannii isolates, the MICs of cefiderocol, ceftolozane/tazobactam and ceftazidime/avibactam were ≤4 mg/L for 88%, 8% and 1% of the isolates, respectively. Cefiderocol MICs were ≤4 mg/L for the five colistin-resistant imipenem-resistant P. aeruginosa isolates and 70% of the 10 colistin-resistant imipenem-resistant A. baumannii isolates. Conclusions: Cefiderocol exhibited more potent in vitro activity than ceftolozane/tazobactam and ceftazidime/avibactam against imipenem-resistant P. aeruginosa, imipenem-resistant A. baumannii and S. maltophilia isolates.

Author Contribution Correction: An Integrated Influenza Surveillance Framework Based on National Influenza-Like Illness Incidence and Multiple Hospital Electronic Medical Records for Early Prediction of Influenza Epidemics: Design and Evaluation.

[This corrects the article DOI: 10.2196/12341.].

An Integrated Influenza Surveillance Framework Based on National Influenza-Like Illness Incidence and Multiple Hospital Electronic Medical Records for Early Prediction of Influenza Epidemics: Design and Evaluation.

BACKGROUND: Influenza is a leading cause of death worldwide and contributes to heavy economic losses to individuals and communities. Therefore, the early prediction of and interventions against influenza epidemics are crucial to reduce mortality and morbidity because of this disease. Similar to other countries, the Taiwan Centers for Disease Control and Prevention (TWCDC) has implemented influenza surveillance and reporting systems, which primarily rely on influenza-like illness (ILI) data reported by health care providers, for the early prediction of influenza epidemics. However, these surveillance and reporting systems show at least a 2-week delay in prediction, indicating the need for improvement. OBJECTIVE: We aimed to integrate the TWCDC ILI data with electronic medical records (EMRs) of multiple hospitals in Taiwan. Our ultimate goal was to develop a national influenza trend prediction and reporting tool more accurate and efficient than the current influenza surveillance and reporting systems. METHODS: First, the influenza expertise team at Taipei Medical University Health Care System (TMUHcS) identified surveillance variables relevant to the prediction of influenza epidemics. Second, we developed a framework for integrating the EMRs of multiple hospitals with the ILI data from the TWCDC website to proactively provide results of influenza epidemic monitoring to hospital infection control practitioners. Third, using the TWCDC ILI data as the gold standard for influenza reporting, we calculated Pearson correlation coefficients to measure the strength of the linear relationship between TMUHcS EMRs and regional and national TWCDC ILI data for 2 weekly time series datasets. Finally, we used the Moving Epidemic Method analyses to evaluate each surveillance variable for its predictive power for influenza epidemics. RESULTS: Using this framework, we collected the EMRs and TWCDC ILI data of the past 3 influenza seasons (October 2014 to September 2017). On the basis of the EMRs of multiple hospitals, 3 surveillance variables, TMUHcS-ILI, TMUHcS-rapid influenza laboratory tests with positive results (RITP), and TMUHcS-influenza medication use (IMU), which reflected patients with ILI, those with positive results from rapid influenza diagnostic tests, and those treated with antiviral drugs, respectively, showed strong correlations with the TWCDC regional and national ILI data (r=.86-.98). The 2 surveillance variables-TMUHcS-RITP and TMUHcS-IMU-showed predictive power for influenza epidemics 3 to 4 weeks before the increase noted in the TWCDC ILI reports. CONCLUSIONS: Our framework periodically integrated and compared surveillance data from multiple hospitals and the TWCDC website to maintain a certain prediction quality and proactively provide monitored results. Our results can be extended to other infectious diseases, mitigating the time and effort required for data collection and analysis. Furthermore, this approach may be developed as a cost-effective electronic surveillance tool for the early and accurate prediction of epidemics of influenza and other infectious diseases in densely populated regions and nations.

Effect of Influenza Vaccination Against Postoperative Pneumonia and Mortality for Geriatric Patients Receiving Major Surgery: A Nationwide Matched Study.

Background: Limited information is available on the association between influenza vaccination and postoperative outcomes. Methods: Using Taiwan's National Health Insurance Research Database reimbursement claims data from 2008-2013, we conducted a matched cohort study of 16903 patients aged >66 years who received influenza vaccinations and later underwent major surgery. Using a propensity score matching procedure adjusted for sociodemographic characteristics, medical condition, surgery type, and anesthesia type, 16903 controls who underwent surgery but were not vaccinated were selected. Logistic regressions were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative pneumonia and in-hospital mortality associated with influenza vaccination. Results: Patients who received preoperative influenza vaccination had a lower risk of postoperative pneumonia (OR, 0.60; 95% CI, .56-.64) and in-hospital mortality (OR, 0.46; 95% CI, .39-.56), compared with unvaccinated patients, in both sexes and every age group. Vaccinated patients who underwent surgery also had a decreased risk of postoperative intensive care unit admission (OR, 0.56; 95% CI, .53-.60), shorter hospital stays (P < .0001), and lower medical expenditures (P < .0001) than nonvaccinated controls. Conclusions: Vaccinated geriatric patients who underwent surgery had lower risks of pneumonia and in-hospital mortality, compared with unvaccinated patients who underwent similar major surgeries. Further studies are needed to explain how preoperative influenza vaccination improves perioperative outcomes.

Impact of active screening for methicillin-resistant Staphylococcus aureus (MRSA) and decolonization on MRSA infections, mortality and medical cost: a quasi-experimental study in surgical intensive care unit.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of healthcare-associated infections in intensive care units (ICUs). Prior studies have shown that decolonization of MRSA carriers is an effective method to reduce MRSA infections in ICU patients. However, there is currently a lack of data on its effect on mortality and medical cost. METHODS: Using a quasi-experimental, interrupted time-series design with re-introduction of intervention, we evaluated the impact of active screening and decolonization on MRSA infections, mortality and medical costs in the surgical ICU of a university hospital in Taiwan. Regression models were used to adjust for effects of confounding variables. RESULTS: MRSA infection rate decreased from 3.58 (baseline) to 0.42‰ (intervention period) (P <0.05), re-surged to 2.21‰ (interruption period) and decreased to 0.18‰ (re-introduction of intervention period) (P <0.05). Patients admitted to the surgical ICU during the intervention periods had a lower in-hospital mortality (13.5% (155 out of 1,147) versus 16.6% (203 out of 1,226), P = 0.038). After adjusting for effects of confounding variables, the active screening and decolonization program was independently associated with a decrease in in-hospital MRSA infections (adjusted odds ratio: 0.3; 95% CI: 0.1 to 0.8) and 90-day mortality (adjusted hazard ratio: 0.8; 95% CI: 0.7 to 0.99). Cost analysis showed that $22 medical costs can be saved for every $1 spent on the intervention. CONCLUSIONS: Active screening for MRSA and decolonization in ICU settings is associated with a decrease in MRSA infections, mortality and medical cost.

The role of vestibular function tests in nontuberculous mycobacterial otomastoiditis: A case report.

BACKGROUND: Nontuberculous mycobacteria (NTM), an extremely rare pathogen causing cervicofacial infections, may result in permanent hearing impairment or intracranial complications. Due to the lack of specific manifestations during the initial onset of NTM otomastoiditis, physicians may misdiagnose it as cholesteatoma or other common bacterial infections. PATIENT CONCERNS: A 44-year-old male who complained of left-sided aural fullness, otalgia, and dizziness for 2 months. DIAGNOSIS: The initial diagnosis was hypothesized to be cholesteatoma based on a whitish mass with mucoid discharge filling the entire outer ear canal on otoscopy and left-sided mixed hearing loss. However, NTM was identified by microbial culture at the 2-month follow-up after surgery. INTERVENTIONS: The patient underwent a left-sided exploratory tympanotomy. Because NTM otomastoiditis was diagnosed, 3 weeks of starting therapies were administered with azithromycin (500 mg/day, oral administration), cefoxitin (3 g/day, intravenous drip), and amikacin (750 mg/day, intravenous drip). The maintenance therapies were azithromycin (500 mg/day, oral administration) and doxycycline (200 mg/day, oral administration) for 7 months. OUTCOMES: The patient's clinical condition improved initially after surgery, but the otomastoiditis gradually worsened, combined with subtle meningitis, 2 months after surgery. The external auditory canal became swollen and obstructed, making it difficult to monitor the treatment efficacy through otoscopy. Thus, we used regular vestibular function tests, including static posturography, cervical vestibular evoked myogenic potentials, and video Head Impulse Test, to assess recovery outcomes. After antibiotic treatment, the infectious symptoms subsided significantly, and there was no evidence of infection recurrence 7 months after treatment. Improvements in static posturography and cervical vestibular evoked myogenic potentials were compatible with the clinical manifestations, but video Head Impulse Test showed an unremarkable correlation. LESSONS: The clinical condition of NTM otomastoiditis may be evaluated using vestibular tests if patients have symptoms of dizziness.

Correlation between antibiotic consumption and resistance of Pseudomonas aeruginosa in a teaching hospital implementing an antimicrobial stewardship program: A longitudinal observational study.

BACKGROUND/PURPOSE: The rapid emergence of Pseudomonas aeruginosa resistance made selecting antibiotics more challenge. Antimicrobial stewardship programs (ASPs) are urging to implant to control the P. aeruginosa resistance. The purpose of this study is to evaluate the relationship between antimicrobial consumption and P. aeruginosa resistance, the impact of ASPs implemented during the 14-year study period. METHODS: A total 14,852 P. aeruginosa isolates were included in our study. The resistant rate and antimicrobial consumption were investigated every six months. Linear regression analysis was conducted to examine the trends in antibiotics consumption and antimicrobial resistance over time. The relationship between P. aeruginosa resistance and antimicrobial consumption were using Pearson correlation coefficient to analysis. The trend of resistance before and after ASPs implanted is evaluated by segment regression analysis. RESULTS: P. aeruginosa resistance to ceftazidime, gentamicin, amikacin, ciprofloxacin and levofloxacin significantly decreased during the study period; piperacillin/tazobactam (PTZ), cefepime, imipenem/cilastatin and meropenem remained stable. The P. aeruginosa resistance to ciprofloxacin and levofloxacin increasing initial then decreased after strictly controlled the use of levofloxacin since 2007. As the first choice antibiotic to treat P. aeruginosa, the consumption and resistance to PTZ increase yearly and resistance became stable since extended-infusion therapy policy implant in 2009. CONCLUSION: Our ASP intervention strategy, which included extended infusion of PTZ and restrict use of levofloxacin, may be used to control antimicrobial resistance of P. aeruginosa in medical practice.

Human diphyllobothriosis in Taiwan: A review of cases and molecular evidence of Dibothriocephalus nihonkaiensis.

Diphyllobothriosis is an infectious disease caused by the consumption of raw freshwater or marine fish containing larvae of broad tapeworms (Diphyllobothriidae). In the present study, we critically reviewed all cases of human diphyllobothriosis reported from Taiwan, including unpublished reports from hospitals in Taipei. Genotyping based on mitochondrial DNA marker (cox1) confirmed that two of the recent cases were caused by Dibothriocephalus nihonkaiensis, which is not native to Taiwan and was probably imported with Pacific salmon infected with larvae of D. nihonkaiensis. The causative species previously reported in Taiwan could not be definitively confirmed. However, considering the distribution of Dibothriocephalus latus, which is not endemic in Taiwan, past cases diagnosed as D. latus are questionable.

Outcomes after surgery in patients with and without recent influenza: a nationwide population-based study.

Background: The influence of recent influenza infection on perioperative outcomes is not completely understood. Method: Using Taiwan's National Health Insurance Research Data from 2008 to 2013, we conducted a surgical cohort study, which included 20,544 matched patients with a recent history of influenza and 10,272 matched patients without. The main outcomes were postoperative complications and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the complications and for mortality in patients with a history of influenza within 1-14 days or 15-30 days compared with non-influenza controls. Results: Compared with patients who had no influenza, patients with influenza within preoperative days 1-7 had increased risks of postoperative pneumonia (OR 2.22, 95% CI 1.81-2.73), septicemia (OR 1.98, 95% CI 1.70-2.31), acute renal failure (OR 2.10, 95% CI 1.47-3.00), and urinary tract infection (OR 1.45, 95% CI 1.23-1.70). An increased risk of intensive care admission, prolonged length of stay, and higher medical expenditure was noted in patients with history of influenza within 1-14 days. Conclusion: We found that there was an association between influenza within 14 days preoperatively and the increased risk of postoperative complications, particularly with the occurrence of influenza within 7 days prior to surgery.

Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan.

OBJECTIVES: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. METHODS: Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to December 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. RESULTS: Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that blaCMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring blaCMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring blaCTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring blaDHA-1 on IncA/C2 plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. CONCLUSION: The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern.

Development of a combination antibiogram for empirical treatments of Pseudomonas aeruginosa at a university-affiliated teaching hospital.

INTRODUCTION: The significantly higher mortality rate in the critical illness patients with Pseudomonas aeruginosa (PA) infection is linked to inappropriate selecting of empirical treatment. Traditional local antibiogram provides clinicians the resistant rate of a single antimicrobial agent to the pathogen in the specific setting. The information is valuable to the clinicians in selecting suitable empirical antibiotic therapy. However, traditional local antibiogram can only provide information for single agent empirical antibiotic not combination regimens. The combination antibiogram should be developed to facilitate the selection of appropriate antibiotics to broader the coverage rate of resistant PA. METHODS: The susceptibility to the ß-lactam antibiotics (piperacillin/tazobactam (PTZ), ceftazidime, cefepime, imipenem, or meropenem) or to those administered in combination with an aminoglycoside (gentamicin or amikacin) or fluoroquinolone (ciprofloxacin or levofloxacin) was calculated. The chi-square test was used to compare the differences of combination coverage rates between non-ICU and ICU isolates. RESULTS: 880 PA isolates were isolated during study period. The susceptibility of single agents ranged from 83.1% to 89.7%. The combination regimens containing amikacin provide the highest cover rate (98.9%-99.1%) and those containing levofloxacin provide less coverage rate (92.3%-93.9%). The susceptibility to five ß-lactam single agents in ICU isolates significantly lower than non-ICU isolates. The non-ICU isolates exhibited significantly higher susceptibility to the PTZ-gentamicin (p = 0.002) and ceftazidime-gentamicin (p = 0.025) than ICU isolates. CONCLUSION: Our results support the use of aminoglycosides instead of fluoroquinolones as additive agents in empirical combination treatments for patients with critical infections caused by PA.

Minimally Invasive Surgical Treatment of Extensive Spinal Epidural Abscess With Unilateral Laminotomy for Bilateral Decompression Using an Ultrasonic Bone Curette: A Technique Note.

BACKGROUND: An extensive spinal epidural abscess is a devasting infection of the multiple-level epidural space. Emergent surgical decompression is required to remove the abscess and decompress the affected spinal cord. This study evaluated the efficacy of unilateral laminotomy for bilateral decompression (ULBD) in the treatment of extensive spinal epidural abscesses. METHODS: Three patients with extensive spinal epidural abscesses (epidural abscess involving more than 5 vertebral levels) were treated with the ULBD technique between September 2019 and August 2020. An ultrasonic curette was used for over-the-top decompression. Surgical drainage of the epidural abscess was performed concurrently with sublaminar drilling on top of the dura sac by using cold saline to automatically maintain the effluent in the ultrasonic curettage device. RESULTS: The 3 patients were men, with a mean age of 65.7 years. Diabetes mellitus, fever, and paraplegia were reported in all 3 patients. Escherichia coli, Staphylococcus aureus, and Streptococcus intermedius were cultured separately. The mean operative time was 163 minutes, and the mean estimated blood loss was 160 mL. All patients fully recovered from neurologic deficits and returned to preinjury levels of functioning at the final follow-up. CONCLUSIONS: As a minimally invasive technique, ULBD is a safe and effective treatment for extensive spinal epidural abscesses in critically ill patients. Moreover, the use of an ultrasonic bone curette not only safely accelerates over-the-top decompression but also flushes the epidural abscess with copious amount of cold saline.

Using anti-malondialdehyde-modified peptide adduct autoantibodies in serum of taiwanese women to diagnose primary Sjogren's syndrome.

BACKGROUND: Sjogren's syndrome (SS) is a systemic autoimmune disease featured with a dry mouth and dry eyes. Several autoantibodies, including anti-SSA, anti-SSB, antinuclear antibodies can be detected in patients with SS. Oxidation-specific epitopes (OSEs) can be formed from malondialdehyde (MDA)-modified protein adducts and trigger chronic inflammation. In this study, our purposes were used serum levels of anti-MDA-modified peptide adducts autoantibodies to evaluate predictive performance by machine learning algorithms in primary Sjögren's syndrome (pSS) and assess the association between pSS and healthy controls. METHODS: Three novel MDA-modified peptide adducts, including immunoglobulin (Ig) gamma heavy chain 1 (IGHG1)102-131, complement factor H (CFAH)1045-1062, and Ig heavy constant alpha 1 (IGHA1)307-327 were identified and validated. Serum levels of protein, MDA-modified protein adducts, MDA, and autoantibodies recognizing unmodified peptides and MDA-modified peptide adducts were measured. Statistically significance in correlations and odds ratios (ORs) were estimated. RESULTS: The random forest classifier utilized autoantibodies combination composed of IgM anti-IGHG1102-131, IgM anti-IGHG1102-131 MDA and IgM anti-IGHA1307-327 achieved predictive performance as an accuracy of 88.0%, a sensitivity of 93.7%, and a specificity of 84.4% which may be as potential diagnostic biomarkers to differentiate patients with pSS from rheumatoid arthritis (RA), and secondary SS in RA and HCs. CONCLUSIONS: Our findings imply that low levels of IgA anti-IGHG1102-131 MDA (OR = 2.646), IgA anti-IGHG1102-131 (OR = 2.408), IgA anti-CFAH1045-1062 (OR = 2.571), and IgA anti-IGHA1307-327 (OR = 2.905) may denote developing risks of pSS, respectively.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers.

Accurately predicting binding affinity constant (K(A)) is highly required to determine the binding energetics of the driving forces in drug-DNA interactions. Recently, PD153035, brominated anilinoquinazoline, has been reported to be not only a highly selective inhibitor of epidermal growth factor receptor but also a DNA intercalator. Here, we use a dual-trap optical tweezers to determining K(A) for PD153035, where K(A) is determined from the changes in B-form contour length (L) of PD153035-DNA complex. Here, L is fitted using a modified wormlike chain model. We found that a noticeable increment in L in 1 mM sodium cacodylate was exhibited. Furthermore, our results showed that K(A)=1.18(±0.09)×10(4) (1/M) at 23±0.5°C and the minimum distance between adjacent bound PD153035≈11 bp. We anticipate that by using this approach we can determine the complete thermodynamic profiles due to the presence of DNA intercalators.

Molecular Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Urine at a Teaching Hospital in Taiwan.

Urinary tract infections (UTIs) are common in clinics and hospitals and are associated with a high economic burden. Enterobacterium Klebsiella pneumoniae is a prevalent agent causing UTIs. A high prevalence of carbapenem-resistant K. pneumoniae (CRKP) has emerged recently and is continuing to increase. Seventeen urinary CRKP isolates collected at a teaching hospital in Taiwan from December 2016 to September 2017 were analyzed to elucidate their drug resistance mechanisms. Two-thirds of the isolates were obtained from outpatients. Antimicrobial susceptibility tests demonstrated multidrug resistance in all the isolates. Multilocus sequence typing analysis showed high diversity among the isolates. PCR analysis demonstrated the presence of carbapenemases in three isolates. All isolates carried at least one other extended-spectrum ß-lactamase, including TEM, DHA, and CTX-M. Fifteen isolates contained mutations in one of the outer membrane porins that were assessed. The expression levels of the acrB and/or oqxB efflux pump genes, as determined by qRT-PCR, were upregulated in 11 isolates. Six isolates might have utilized other efflux pumps or antimicrobial resistance mechanisms. These analyses demonstrated a highly diverse population and the presence of complex resistance mechanisms in urinary isolates of K. pneumoniae.