Performance evaluation of the Panbio COVID-19/Flu A&B Panel for detection of SARS-CoV-2, influenza A, and influenza B antigens using mid-turbinate nasal swabs.

The Panbio COVID-19/Flu A&B Panel (Abbott) is an in vitro diagnostic rapid test designed for the qualitative detection of nucleocapsid proteins SARS-CoV-2 and nucleoprotein influenza A and B antigens in nasal mid-turbinate (NMT) swab specimens from symptomatic individuals meeting COVID-19 and influenza clinical and/or epidemiological criteria. This study, the largest global one to date using fresh samples, aimed to assess the diagnostic sensitivity and specificity of the Panbio COVID-19/Flu A&B Panel in freshly collected NMT swab specimens from individuals suspected of respiratory viral infection consistent with COVID-19 and/or influenza within the first 5 days of symptom onset compared with results obtained with the cobas SARS-CoV-2 and influenza A/B qualitative assay (cobas 6800/8800 systems), which were tested using nasopharyngeal swab samples. A total of 512 evaluable subjects were enrolled in the COVID-19 cohort across 18 sites, and 1,148 evaluable subjects were enrolled in the influenza cohort across 22 sites in the Asia-Pacific, Europe, and the USA. The Panbio COVID-19/Flu A&B Panel demonstrated a sensitivity of 80.4% and a specificity of 99.7% for COVID-19. For influenza A, the sensitivity and specificity rates were 80.6% and 99.3%, respectively. Likewise, for influenza B, the sensitivity and specificity rates were 80.8% and 99.4%, respectively. In conclusion, the Panbio COVID-19/Flu A&B Panel emerges as a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.4% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B. IMPORTANCE: The Panbio COVID-19/Flu A&B Panel is a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.0% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.

Global epidemiology and antimicrobial resistance of Enterobacterales harbouring genes encoding OXA-48-like carbapenemases: insights from the results of the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme 2018-2021.

OBJECTIVES: The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes. METHODS: Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018-2021. Comprehensive antimicrobial susceptibility testing and ß-lactamase gene detection were also conducted, along with statistical analysis of the collected data. RESULTS: Among the 72 244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (P < 0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018-2021. CONCLUSIONS: This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens.

Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study.

BACKGROUND: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). METHODS: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. RESULTS: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1ß, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. CONCLUSION: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Performance assessment of the Bruker Biotyper MALDI-TOF MS for the identification of difficult-to-identify viridans group streptococci.

Differentiating Streptococcus pneumoniae among nonpneumococcal viridans group streptococci (VGS) is challenging in conventional laboratories. Therefore, we aimed to evaluate the performance of the latest Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system in identifying VGS by comparing the results to those of the specific gene sequencing approach. Clinical isolates were initially identified using the BD Phoenix system to identify Streptococcus species. The optochin test was used to distinguish nonpneumococcal VGS from S. pneumoniae. The species of individual reference strains and clinical isolates were determined by comparing the sequences of the 16S rDNA, gyrB, sodA, groESL, or coaE genes with those in the GenBank sequence databases. We evaluated the performance of the Bruker Biotyper MALDI-TOF MS in VGS identification using two different machines with three databases. We collected a total of 103 nonpneumococcal VGS and 29 S. pneumoniae blood isolates at a medical center in northern Taiwan. Among these isolates, only seven could not be identified at the species level by the specific gene sequencing approach. We found that none of the nonpneumococcal VGS isolates were misidentified as pneumococci by the latest Biotyper system, and vice versa. However, certain strains, especially those in the mitis and bovis groups, could still not be correctly identified. The latest Bruker Biotyper 4.1 (DB_10833) showed significant improvement in identifying VGS strains. However, a specific gene sequencing test is still needed to precisely differentiate the species of strains in the mitis and bovis groups.

Emerging infections in vulnerable hosts: Stenotrophomonas maltophilia and Elizabethkingia anophelis.

PURPOSE OF REVIEW: This systematic review aimed to explore the recent trends in the epidemiology, risk factors, and antimicrobial susceptibility of two emerging opportunistic pathogens, Stenotrophomonas maltophilia and Elizabethkingia anophelis . RECENT FINDINGS: Since 2020, numerous outbreaks of S. maltophilia and E. anophelis have been reported worldwide. Most of these outbreaks have been associated with healthcare facilities, although one outbreak caused by E. anophelis in France was considered a community-associated infection. In terms of antimicrobial susceptibility, trimethoprim/sulfamethoxazole (TMP-SMZ), levofloxacin, and minocycline have exhibited good efficacy against S. maltophilia . Additionally, cefiderocol and a combination of aztreonam and avibactam have shown promising results in in vitro susceptibility testing. For E. anophelis , there is currently no consensus on the optimal treatment. Although some studies have reported good efficacy with rifampin, TMP-SMZ, piperacillin/tazobactam, and cefoperazone/sulbactam, minocycline had the most favourable in vitro susceptibility rates. Cefiderocol may serve as an alternative due to its low minimum inhibitory concentration (MIC) against E. anophelis . The role of vancomycin in treatment is still uncertain, although several successful cases with vancomycin treatment, even with high MIC values, have been reported. SUMMARY: Immunocompromised patients are particularly vulnerable to infections caused by S. maltophilia and E. anophelis , but the optimal treatment strategy remains inconclusive. Further research is necessary to determine the most effective use of conventional and novel antimicrobial agents in combatting these multidrug-resistant pathogens.

Molecular epidemiology of bacteraemic vancomycin-resistant Enterococcus faecium isolates and in vitro activities of SC5005 and other comparators against these isolates collected from a medical centre in northern Taiwan, 2019-2020.

OBJECTIVES: The global prevalence of vancomycin-resistant Enterococcus faecium (VREfm) highlights the need for new anti-enterococcal agents. Here, we assessed the molecular epidemiology of clinical VREfm bacteraemic isolates from a medical centre in northern Taiwan in 2019-2020 and to evaluate their susceptibility to last-line antibiotics and a new antimicrobial agent, SC5005. METHODS: The molecular epidemiology of VREfm was investigated using van genotyping, MLST and PFGE. The susceptibilities of VREfm strains to antibiotics and SC5005 were determined using the agar dilution and broth microdilution methods. The capability of E. faecium to develop resistance to antibiotics and SC5005 was evaluated using frequency of resistance and multipassage resistance assays. The mode of action of SC5005 was assessed by time-kill, bacterial membrane integrity and membrane potential assays. RESULTS: All 262 VREfm isolates harboured vanA gene, and the most prevalent sequence type was ST17 (51%, n = 134, 84 pulsotypes), followed by ST78 (25%, n = 65, 54 pulsotypes). Additionally, we identified four new STs (ST2101, ST2102, ST2135 and ST2136) and observed the arrival of multidrug-resistant ST1885 in Taiwan. Moreover, SC5005 was effective against all VREfm isolates, including those non-susceptible to last-line antibiotics. SC5005 can disrupt and depolarize the bacterial membrane to kill E. faecium without detectable resistance. CONCLUSIONS: The findings provide insights into the latest epidemiology and resistance profiles of bacteraemic-causing VREfm in northern Taiwan. Additionally, SC5005 has the potential for development as a new therapeutic to treat VREfm infections.

Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment.

Nirmatrelvir/ritonavir (NMV-r) is an effective anti-SARS-CoV-2 agent and has been recommended in the treatment of nonhospitalized patients with COVID-19. In rare occasions, some patients experience virologic and symptomatic rebound after initial resolution, which we call COVID-19 rebound after NMV-r. Although COVID rebound can also occur after molnupiravir treatment or even no antiviral treatment, we have more serious concern about the rebound after NMV-r, which remains the most effective antiviral. Due to a lack of information about its frequency, mechanism, outcomes, and management, we conducted this review to provide comprehensive and updated information to address these questions. Based on the limited evidence, the incidence of COVID-19 rebound after NMV-r was less than 2%, and most cases developed 5-15 days after initiating NMV-r treatment. Almost all reported cases had mild symptoms, and the clinical condition gradually subsided without additional treatment. Overall, the clinical outcome was favorable, and only a small number of patients required emergency department visits or hospitalization. Regarding virologic rebound, culturable SARS-CoV-2 with possible transmission was observed, so re-isolation may be needed.

Multisystem inflammatory syndrome in adults: Characteristics, treatment, and outcomes.

Following the rapidly increasing number of multisystem inflammatory syndromes in children (MIS-C), a similar clinical scenario has been observed in adult patients. Although its prevalence is low and probably related to underdiagnosis, its development can be associated with high mortality. Multisystem inflammatory syndrome in adults (MIS-A) can develop following both asymptomatic and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and in previously healthy people. Like MIS-C, MIS-A is a multisystem disease that can involve the cardiovascular, respiratory, gastrointestinal, dermatologic, hematologic, and neurologic systems. In addition to the clinical manifestations, the diagnosis of MIS-A requires laboratory evidence of inflammation and SARS-CoV-2 infection. The appropriate treatment for MIS-A remains unclear; anti-inflammatory agents, including intravenous immunoglobulin and corticosteroids, are commonly used. However, there are still many unknowns regarding MIS-A. Further studies are needed to determine the true prevalence, pathogenesis, and effective treatment for MIS-A.

Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.

Risk factors for poor COVID-19 outcomes in patients with psychiatric disorders.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been found to have a greater impact on individuals with pre-existing psychiatric disorders. However, the underlying reasons for this increased risk have yet to be determined. This study aims to investigate the potential factors contributing poor outcomes among COVID-19 patients with psychiatric disorders, including delayed diagnosis of infection, vaccination rates, immune response, and the use of psychotropic medications. METHODS: This retrospective cohort study analyzed medical records of 15,783 adult patients who were diagnosed with COVID-19 infection by positive PCR tests between January and September 2022 at a single medical center. We identified psychiatric diagnoses using ICD-9 diagnostic codes from the preceding 3 years before COVID infection. Primary outcome was in-hospital mortality and secondary outcomes were severe illness requiring intensive care or mechanical ventilation, and hospitalization within 45 days after a positive COVID-19 test. We compared the rates of outcomes, viral load, vaccination status at the time of positive test, psychotropic medications prescription within 90 days prior, antiviral medication use, and blood inflammation markers between patients with and without psychiatric disorders. The Cox proportional hazard model was used to examine the association of psychiatric diagnoses, vaccination status, and psychotropic medication prescription with poor outcomes. RESULTS: Patients with psychiatric disorders demonstrated higher rates of severe illness (10.4% v.s. 7.1%) and hospitalization (16.4% vs. 11.3%), as well as a shorter duration to in-hospital mortality (6 vs. 12.5 days) compared to non-psychiatric patients. Psychiatric patients had higher vaccination rates and lower levels of inflammatory markers than non-psychiatric patients. Antipsychotic medication use was associated with in-hospital mortality (hazard ratio [HR] = 4.79, 95% confidence interval [CI] = 1.23-18.7), while being unvaccinated was associated with hospitalization (HR = 1.81, 95% CI = 1.29 to 2.54) and severe illness (HR = 3.23, 95% CI = 1.95 to 5.34) among patients with psychiatric disorders. Sedatives prescription was associated with all poor outcomes in general patients. CONCLUSION: Considering the narrow time window between a positive COVID-19 test and poor outcomes, healthcare providers should undertake close monitoring of patients with preexisting psychiatric disorders during the initial days after a positive PCR test. Furthermore, caution should be taken when prescribing psychotropic medications, with special attention to antipsychotics.

Detection of serum Aspergillus-specific IgM and IgG antibody levels for the diagnosis of chronic pulmonary aspergillosis developed in patients with tuberculosis.

Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g., weight loss, fatigue, fever), chronic productive cough, chest discomfort, and occasional haemoptysis, which are similar to the manifestations of pulmonary tuberculosis (PTB) and are often misdiagnosed as PTB. Considering the striking similarities between CPA and PTB in clinical manifestations and imaging features, more specific microbiological and serological detections are needed for a definitive diagnosis. This study aimed to explore the clinical characteristics of CPA in TB as well as the diagnostic significance of Aspergillus-specific IgG and Aspergillus-specific IgM.A total of 140 patients diagnosed with TB by culture between December 2017 and February 2019 were included. Enrolled patients were categorized into two groups (CPA group and non-CPA group) according to CPA diagnostic criteria. All collected specimens were subjected to Aspergillus-specific IgG and IgM detection testing.The median concentration of Aspergillus-specific IgG in the CPA group (211.04 AU/ml) was significantly higher than that in the non-CPA group (77.88 AU/ml) (Z value - 6.397, P < 0.001). The sensitivity and specificity of Aspergillus-specific IgG for CPA diagnosis were 81.82% and 72.97%, respectively. In the chronic cavitary pulmonary aspergillosis (CCPA) group, the IgG positivity rate (≥ 120 AU/ml) was 96.2%, which was 21.4% in the non-CCPA patients (P < 0.001).The detection of Aspergillus-specific IgG serological changes is feasible and facilitates reliable differentiation between Aspergillus and Mycobacterium tuberculosis infection. However, Aspergillus-specific IgM has limited diagnostic value, with unsatisfactory sensitivity results.

Value of monocyte distribution width for predicting severe cholecystitis: a retrospective cohort study.

OBJECTIVES: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity. METHODS: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade. RESULTS: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay. CONCLUSIONS: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer.

Bladder cancer is a common cancer with well-established therapeutic strategies. However, recurrence occurs in 50% of patients with non-muscle-invasive bladder cancer, and 20% of patients progress to muscle-invasive bladder cancer. The 5-year survival rate for muscle-invasive bladder cancer patients is disappointingly low, ranging from 36% to 48%. A molecular marker of interest is chitinase 3-like-1 (CHI3L1), which is elevated in various cancers, including bladder cancer. In addition to its role in cancer cells, CHI3L1 also has regulatory abilities in immune cells. Neutrophil infiltration has been shown to positively correlate with overall survival, progression-free survival, and relapse-free survival in bladder cancer patients. However, the relationship between CHI3L1 and neutrophils remain poorly understood. Therefore, this study investigated the relationship between CHI3L1 level and protumor neutrophil infiltration in bladder cancer. We analyzed the GSE128959 dataset and the data of a bladder cancer cohort undergoing chemotherapy. We observed higher expression of CHI3L1 in bladder cancer patients with invasive or chemotherapy-resistance. Our results revealed a positive correlation between CHI3L1 expression and protumor neutrophil infiltration. Elevated CHI3L1 expression was associated with genes which were related to the recruitment and infiltration of neutrophils. Consequently, CHI3L1 may serve as a novel evaluation factor for the degree of neutrophil infiltration in advanced bladder cancer in those scheduled for chemotherapy.

Geographic Patterns of Carbapenem-Resistant Pseudomonas aeruginosa in the Asia-Pacific Region: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) Program, 2015-2019.

Pseudomonas aeruginosa is a common pathogen that is associated with multidrug-resistant (MDR) and carbapenem-resistant (CR) phenotypes; therefore, we investigated its resistance patterns and mechanisms by using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program in the Asia-Pacific region from 2015 to 2019. MICs were determined using the broth microdilution method. Genes encoding major extended-spectrum ß-lactamases and carbapenemases were investigated by multiplex PCR assays. Susceptibility was interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoints. A total of 6,349 P. aeruginosa isolates were collected in the ATLAS program between 2015 and 2019 from 14 countries. According to the CLSI definitions, the numbers (and rates) of CR and MDR P. aeruginosa isolates were 1,198 (18.9%) and 1,303 (20.5%), respectively. For 747 of the CR P. aeruginosa strains that were available for gene screening, 253 ß-lactamase genes were detected in 245 (32.8%) isolates. The most common gene was blaVIM (29.0%, 71/245), followed by blaNDM (24.9%, 61/245) and blaVEB (20.8%, 51/245). The resistance patterns and associated genes varied significantly between the countries in the Asia-Pacific region. India had the highest rates of carbapenem resistance (29.3%, 154/525) and gene detection (17.7%, 93/525). Compared to those harboring either class A or B ß-lactamase genes, the CR P. aeruginosa isolates without detected ß-lactamase genes had lower MICs for most of the antimicrobial agents, including ceftazidime-avibactam and ceftolozane-tazobactam. In conclusion, MDR and CR P. aeruginosa infections pose a major threat, particularly those with detected carbapenemase genes. Continuous surveillance is important for improving antimicrobial stewardship and antibiotic prescriptions.

The implications of the COVID-19 pandemic for long term care facilities.

PURPOSE OF REVIEW: Despite advances in infection prevention and control and breakthroughs in vaccination development, challenges remain for long-term care facilities (LTCFs) as they face a likely future of emerging infectious diseases. To ensure the safety of LTCF residents from the current and future pandemics, we identify lessons learned from the coronavirus disease 2019 (COVID-19) experience for improving future prevention and response efforts. RECENT FINDINGS: In addition to high disease susceptibility among LTCF residents, LTCF vulnerabilities include a lack of pandemic preparedness, a lack of surge capacity in human, material and testing resources, and poorly designed buildings. External sources of vulnerability include staff working in multiple LTCFs and high COVID-19 rates in surrounding communities. Other challenges include poor cooperation between LTCFs and the other components of health systems, inadequately enforced regulations, and the sometimes contradictory interests for-profit LTCFs face between protecting their residents and turning a profit. SUMMARY: These challenges can be addressed in the post-COVID-19 period through systemic reforms. Governments should establish comprehensive health networks that normalize mechanisms for prediction/preparedness and response/recovery from disruptive events including pandemics. In addition, governments should facilitate cooperation among public and private sector health systems and institutions while utilizing advanced digital communication technologies. These steps will greatly reduce the threat to LTCFs posed by emerging infectious diseases in future.