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Peripheral intravenous (i.v.) catheter-related soft tissue infections begin with local skin and soft tissue inflammation, which can progress to cellulitis or even tissue necrosis requiring aggressive surgical treatment. We conducted a matched case-control study to investigate risk factors for peripheral i.v. catheter-related soft tissue infections in hospitalised patients. We retrospectively identified 46 cases that occurred during 2006-2008 in two teaching hospitals. Each case was randomly matched with four control subjects from the same ward and on the same day that the soft tissue infections arose. Risk factors were analysed using conditional logistic regression. Multiple regression analysis identified the following independent risk factors: >24h of continuous i.v. fluid infusion (odds ratio: 5.2, P=0.001), insertion site in lower extremity (8.5, P=0.003), use of an infusion pump (4.6, P=0.023), and hospitalisation due to a neurological or neurosurgical condition (3.6, P=0.018). The population-attributable fractions (the percentage of cases in the study population that could be prevented if the exposure were removed) were 40%, 19%, 24% and 25%, respectively. Minimising unnecessarily prolonged i.v. fluid infusion and avoidance of insertion in the lower extremity may significantly reduce the incidence of peripheral i.v. catheter-related soft tissue infection in the study hospitals. [ABSTRACT FROM AUTHOR]

BACKGROUND: The American Red Cross initiated systemwide bacterial testing of all apheresis platelet (PLT) collections in March 2004, yet continues to receive reports of septic reactions after transfusion of screened components. STUDY DESIGN AND METHODS: The rates of confirmed bacterial contamination of apheresis PLT collections detected by prospective quality control (QC) testing, and by surveillance of reported septic reactions to screened-negative apheresis PLTs, were analyzed according to the technology utilized for collection. RESULTS: Between March 1, 2004, and May 31, 2006, bacterial culture testing was performed on 1,004,206 donations; of these, 186 (1:5,399) had confirmed-positive culture results. Transfusion of all but 1 of the associated 293 components was prevented. A significantly higher rate of confirmed-positive bacterial cultures was seen with products collected utilizing two-arm collection procedures compared to one-arm procedures (22.7 vs. 11.9 per 10(5) donations; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4-2.7). During this period, 20 septic transfusion reactions were reported, including 3 fatalities (1:498,711 fatalities per distributed component), which implicated screened-negative apheresis PLT products. The frequency of septic reactions was 4.7-fold higher for collections utilizing two-arm procedures (1:41,173; 95% CI, 1:25,000-1:66,667) compared to collections from one-arm procedures (1:193,305; 95% CI, 1:52,632-1:500,000; OR, 4.7; 95% CI, 1.2-18.4); most septic reactions (16 of 20) were due to Staphylococcus spp. and occurred on Day 5 (13 of 20) after collection. CONCLUSION: PLT contamination with bacteria that evade detection by QC culture remains a significant residual transfusion risk, in particular for older PLTs and skin-commensal bacteria in components collected by two-arm apheresis procedures during the study period. [ABSTRACT FROM AUTHOR]

Background: Despite intensive vector control efforts, dengue epidemics continue to occur throughout Southeast Asia in multi-annual cycles. Weather is considered an important factor in these cycles, but the extent to which the El Niño-Southern Oscillation (ENSO) is a driving force behind dengue epidemics remains unclear.Methods: We examined the temporal relationship between El Niño and the occurrence of dengue epidemics, and constructed Poisson autoregressive models for incidences of dengue cases. Global ENSO records, dengue surveillance data, and local meteorological data in two geographically diverse regions in Thailand (the tropical southern coastal region and the northern inland mountainous region) were analyzed.Results: The strength of El Niño was consistently a predictor for the occurrence of dengue epidemics throughout time lags from 1 to 11 months in the two selected regions of Thailand. Up to 22% (in 8 northern inland mountainous provinces) and 15% (in 5 southern tropical coastal provinces) of the variation in the monthly incidence of dengue cases were attributable to global ENSO cycles. Province-level predictive models were fitted using 1996-2004 data and validated with out-of-fit data from 2005. The multivariate ENSO index was an independent predictor in 10 of the 13 studied provinces.Conclusion: El Niño is one of the important driving forces for dengue epidemics across the geographically diverse regions of Thailand; however, spatial heterogeneity in the effect exists. The effects of El Niño should be taken into account in future epidemic forecasting for public health preparedness. [ABSTRACT FROM AUTHOR]

Background: Enterovirus is a common pediatric infectious disease, but the epidemiological data in young infants were lacking. This study aims to evaluate the role of enterovirus in febrile young infants and identify risk factors for severe infections., Methods: We enrolled febrile infants younger than 90 days admitted to National Taiwan University Hospital from January 2010 to June 2021. Enterovirus infection was confirmed via viral isolation or pan-enterovirus PCR. Central nervous system involvement was defined by positive culture or PCR in cerebrospinal fluid. Severe complications included sepsis, hepatic failure, myocarditis, shock, encephalitis, acute kidney injury, respiratory failure, and multiorgan failure., Results: Out of 840 febrile infants, 17.4% (n = 146) had enterovirus infection. Among these, 46% (n = 67) presented with meningitis and/or encephalitis. Early-onset enterovirus infection within the first two weeks of life was significantly linked to increased risks of anemia (hemoglobin <9 g/dL), ICU admission, central nervous system involvement, shock, hepatic failure, and mortality. Multivariable logistic regression identified high-risk serotypes (aOR 17.4, [95% CI 1.58, 191.5], p = 0.019) and hemoglobin <9 g/dL (aOR 44.9, [95% CI 5.6, 357.6], p < 0.001) as significant risk factors for severe complications., Conclusions: Enterovirus accounted for 17.4% of the etiology in febrile young infants and the case-fatality rate was 2%. Febrile young infants who had risk factors of enterovirus infection should consider viral culture or PCR examination for confirmation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Despite current guidelines for tuberculosis (TB) control in health care settings, which focused on smear-positive cases, prevention of nosocomial TB transmission continues to be a challenge. Here, we report the results of the first hospital-wide prospective study applying interferon-gamma release assay to investigate the role of smear-negative, culture-positive index cases in nosocomial TB transmission., Methods: We prospectively identified cases of culture-confirmed smear-negative pulmonary TB receiving aerosol-generating procedures (AGPs) and cases of culture-confirmed smear-positive pulmonary TB admitted at a medical center. Nosocomial transmission was evaluated by screening their close contacts for latent TB infection (LTBI) using an interferon-gamma release assay., Results: A total of 93 smear-negative index receiving AGP and 122 smear-positive index were enrolled. Among them, 13 (14.0%) and 43 (35.2%) index cases, respectively, had secondary cases of LTBI (P < .001). Sputum smear negativity (adjusted odds ratio: 0.20 [0.08-0.48]) and AGP (sputum suction; adjusted odds ratio: 3.48 [1.34-9.05]) are independent factors of transmission. A similar proportion in the close contacts of the 2 index groups had LTBI (17 [15.3%] and 63 [16.0%], respectively), and the former index group contributed to 21.3% of the nosocomial transmission., Conclusions: Smear-negative, culture-positive index cases receiving AGPs could be as infectious as smear-positive index cases. Hospital TB control policy should also focus on the former group., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain., Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days., Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98)., Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19., (Copyright © 2024. Published by Elsevier B.V.)

Background: Real-time surveillance of COVID-19 in large-scale community outbreaks presents challenges. Simple counts of the daily confirmed cases can be misleading due to constraints from bottlenecks in access to care or laboratory testing. This study aimed to investigate the role of the SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) in addressing these challenges for real-time COVID-19 surveillance., Methods: This study included the results of 86,933 SARS-CoV-2 Ag-RDT and real-time reverse transcription polymerase chain reaction (RT-PCR) tests. These were conducted at four community testing stations within the Taipei metropolitan area during a community COVID-19 outbreak spanning from May 17, 2021, to August 9, 2021. We examined the correlation between the positive rates of Ag-RDT tests and the epidemic curve of laboratory-confirmed COVID-19 cases by onset date to examine its role in real-time surveillance., Results: During the 85-day study period, the trend of Ag-RDT test positive rates paralleled that of the epidemic curve. The correlation between the Ag-RDT positive rate and the number of cases (Pearson correlation coefficient: 0.968) is comparable to that of the RT-PCR positive rate (Pearson correlation coefficient: 0.964). The Ag-RDT positive rate exhibited a more advanced leading trend, with Ag-RDT leading by 3 days in comparison to the 2-day lead for RT-PCR., Conclusion: The positive rate of SARS-CoV-2 Ag-RDT tests at community testing stations serves as a good surrogate for assessing virus activity within the community and a useful tool for real-time COVID-19 surveillance. It is a robust indicator of the outbreak trend and near-term numbers of cases. This finding may facilitate the management of subsequent outbreaks of emerging infectious diseases., Competing Interests: Conflict of interest disclosure All authors have no competing interest to disclose., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups., Methods: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden., Results: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB., Conclusions: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power., (Copyright © 2024. Published by Elsevier B.V.)

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii , Hysterothylacium aduncum , Hysterothylacium zhoushanense , Hysterothylacium amoyense , and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis , posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zeng, Fang, Wang, Qadeer, Qiu, Hong and Mahmoud.)

The global spread of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b virus since 2021 necessitates a re-evaluation of the role of vaccination in controlling HPAI outbreaks among poultry, which has been controversial because of the concern of silent spread with viral mutation and spillover to human. We systematically reviewed and meta-analyzed all existing data from experimental challenge trials to assess the efficacy of HPAI vaccines against mortality in specific pathogen free (SPF) chickens, with evaluation of the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Out of 223 screened publications, 46 trials met our eligibility criteria. Inactivated vaccines showed an efficacy of 95% (risk ratio [RR] = 5% [95% CI: 1% to 17%], I 2  = 0%, CoE high) against homologous strains and an efficacy of 78% (RR = 22% [95% CI: 14% to 37%], I 2  = 18%, CoE high) against heterologous strains (test for subgroup difference p  = 0.02). Live recombinant vaccines exhibited the highest efficacy at 97% (RR = 3% [95% CI: 1% to 13%], I 2  = 0%, CoE high). Inactivated recombinant vaccines had an overall efficacy of 90% (RR = 10% [95% CI: 6% to 16%], I 2  = 47%, CoE high). Commercial vaccines showed an overall efficacy of 91% (RR = 9% [95% CI: 5% to 17%], I 2  = 23%, CoE high), with 96% efficacy (RR = 4% [95% CI: 1% to 21%], I 2  = 0%, CoE high) against homologous strains and 90% efficacy (RR = 10% [95% CI: 5% to 20%], I 2  = 31%, CoE moderate) against heterologous strains. Our systematic review offers an updated and unbiased assessment of vaccine efficacy against HPAI-related mortality, providing timely and crucial information for re-evaluating the role of vaccination in poultry avian influenza control policy amist the global HPAI outbreak post-2021., Competing Interests: All authors declare that they have no conflicts of interest., (© 2024 The Authors.)

The synthesis and characterization of a linear two-coordinate Cr(II) amido complex, Cr{N( t Bu)Dipp} 2 (Dipp=2,6-diisopropylphenyl), from the reaction of 1 molar equivalent (equiv) of CrCl 2 and 2 equiv. of LiN( t Bu)Dipp is reported. Single-crystal X-ray diffractometry (SC-XRD) analysis revealed that it has a short Cr-N bond distance of 1.8878(9) Å, which could be attributed to the relatively less bulky nature of the amido ligand compared with reported systems. Furthermore, the oxidation reaction of the two-coordinate Cr(II) complex was explored. The oxidation reaction of Cr{N( t Bu)Dipp} 2 with the one-electron oxidants AgOTf and [FeCp 2 ][BAr F 4 ] (BAr F 4 - =[B{C 6 H 3 -3,5-(CF 3 ) 2 } 4 ] - ) afforded the trigonal planar three- and bent two-coordinate Cr(III) complexes Cr{N( t Bu)Dipp} 2 (OTf) and [Cr{N( t Bu)Dipp} 2 ][BAr F 4 ], respectively. The reaction of Cr{N( t Bu)Dipp} 2 with 1 equiv. of the organic azides AdN 3 (Ad=1-adamantyl) and PhN 3 afforded the three-coordinate Cr(IV) imido complexes Cr{N( t Bu)Dipp} 2 (NAd) and Cr{N( t Bu)Dipp} 2 (NPh), respectively. The reaction of Cr{N( t Bu)Dipp} 2 and two equiv. of Me 3 NO afforded the Cr(VI) dioxo complex Cr{N( t Bu)Dipp} 2 (O) 2 . The reaction of Cr{N( t Bu)Dipp} 2 with 1 equiv. of CyN=C=NCy resulted in the insertion of the carbodiimide into the Cr-N bond, with the formation of a three-coordinate Cr(II) complex. Finally, density functional theory (DFT) calculations were used to elucidate the electronic structure of these complexes., (© 2023 Wiley-VCH GmbH.)

Background: Whether early HIV diagnosis is beneficial for HIV patients themselves remains uncertain, given the stigma and social discrimination associated with an HIV diagnosis. This study aimed to measure the impact of early HIV diagnosis on quality-adjusted life expectancy (QALE) in comparison with late HIV diagnosis, from real-world data in Taiwan under universal access to antiretroviral therapy (ART)., Methods: This population-based cohort study included 14,570 men who have sex with men (MSM) in the national HIV registry and a quasi-random sample (n = 127) of MSM patients to measure quality of life using the EQ-5D health utility instrument. We integrated quality of life data into the extrapolated cohort survival curve to estimate the QALE in patients with early versus late HIV diagnosis (≤30 days before AIDS diagnosis). Loss-of-QALE were estimated by comparing the cohort with age-, sex-, and calendar-year-matched referents simulated from vital statistics. Difference-in-differences was estimated to quantify the effect of early HIV diagnosis., Results: Early HIV diagnosis is associated with a loss-of-life expectancy of 3.11 years, with an average health utility of 0.95, in contrast to those diagnosed late (loss-of-life expectancy 8.47 years, with an average health utility of 0.86). After integration of survival and life quality, early HIV diagnosis results in a reduction of loss-of-QALE by 8.28 quality-adjusted life years among MSM living with HIV., Conclusions: Under universal access to ART, early HIV diagnosis is highly beneficial for people living with HIV themselves, with a net gain of 8.28 healthy life years compared with those diagnosed late., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organisations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behaviour changes coincident with high-risk group awareness on the mpox epidemic in the US., Methods: We fitted a deterministic, risk-structured SEIARV model to the epidemic curve of reported mpox cases in the US between May 22, 2022 and December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing., Findings: Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively, with 71.8% of mpox cases estimated from the high-risk population. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%-24.1%) of cases, while behaviour changes due to high-risk group awareness alone could prevent 15.4% (14.3%-20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%-69.0%) of US cases were averted that would have otherwise occurred., Interpretation: Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction., Funding: Taiwan Ministry of Education grant #NTU-112L9004, Taiwan National Science and Technology Council grant #MOST-109-2314-B-002-147-MY3 and grant #NSC-112-2314-B-002-216-MY3. SHV was supported, in part, by US National Institutes of Health grant #P30MH062294., Competing Interests: All authors declare no competing interests., (© 2023 The Author(s).)

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Despite never imposing a lockdown, Taiwan achieved COVID-19 zero, with reporting only 56 local coronavirus disease 2019 (COVID-19) cases after testing 126,987 individuals in 2020, and further contained a large outbreak rapidly and successfully in 2021. At the onset of the COVID-19 pandemic, our infectious disease modeling results indicated that testing and contact tracing alone would fail to contain the pandemic. However, by supplementing this approach with general public surgical mask-wearing, the reproduction number (R0) could be suppressed to less than 1. This would effectively contain the virus's spread within Taiwan, particularly when combined with strict border control measures to prevent the overwhelming influx of imported COVID-19 cases and ensure the capacity of the medical and public health systems remains resilient. These modeling results became the theoretical basis behind the highly successful Taiwan model against COVID-19 during 2020-2021, supporting by negative excess mortality, seroepidemiological surveys, and molecular epidemiological analyses. This is a public health triumph demonstrating that a democratic and humane approach to the COVID-19 pandemic is not only feasible but highly effective. It also highlights the crucial role of infectious disease modeling in assisting the formulation of a successful national pandemic response., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU)., Material and Methods: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed., Results: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period., Conclusion: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB)., Methods: This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease., Results: Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001)., Conclusion: Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now., Case Presentation: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy., Conclusion: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity., Methods: We enrolled 222 parturient (gestational age 34-42 weeks) women aged 20-46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68., Results: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p < 0.001). Geometric mean titers were 3.3 (95% CI 2.9-3.8) for E11, 15.9 (95% CI 12.5-20.3) for CVB3 and 109.9 (95% CI 92.4-131.6) for EVD68. Younger parturient age (33.8 ± 3.6 versus 35.2 ± 4.4, p = 0.04) was related to E11 seropositivity. Neonatal sex, gestational age and birth body weight were not significantly different between the seropositive group and the seronegative group., Conclusion: Cord blood seropositive rate and geometric mean titer of E11 were very low, so a large proportion of newborns are susceptible to E11. The circulation of E11 was low after 2019 in Taiwan. A large cohort of immune naïve newborns existed currently due to lack of protective maternal antibodies. It is imminent to monitor the epidemiology of neonates with enterovirus infections and strengthen the relevant preventive policies., Competing Interests: Declaration of competing interest All authors have no conflicts to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound., Methods: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units)., Results: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 10 9 /L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered., Conclusion: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the prognostic value of reclassified new type III monomicrobial gram-negative necrotizing fasciitis (NF) and the microbial factors associated with an increased risk of mortality., Methods: This study included 235 NF cases treated at National Taiwan University Hospital. We compared the mortality risk of NF caused by different causal microorganisms and examined the bacterial virulence genes profile and antimicrobial susceptibility pattern associated with an increase in mortality risk., Results: Type III NF (n = 68) had a mortality risk two-fold higher than type I (polymicrobial, n = 64) or type II (monomicrobial gram-positive, n = 79) NF (42.6% vs 23.4% or 19.0%, P = 0.019 and 0.002, respectively). Mortality differed by causal microorganism (Escherichia coli [61.5%], Klebsiella pneumoniae [40.0%], Aeromonas hydrophila [37.5%], Vibrio vulnificus [25.0%], polymicrobial [23.4%], group A streptococci [16.7%], and Staphylococcus aureus [16.2%], in decreasing rank, P <0.001). Type III NF caused by E. coli, identified as extraintestinal pathogenic E. coli (ExPEC) via virulence gene analyses, was associated with a particularly high mortality risk (adjusted odds ratio: 6.51, P = 0.003) after adjusting for age and comorbidities. Some (38.5%/7.7%) of the E. coli strains were non-susceptible to third/fourth-generation cephalosporins but remained susceptible to carbapenems., Conclusion: Type III NF, especially cases caused by E. coli or K. pneumoniae, are associated with a comparatively higher mortality risk than type I or type II NF. Wound gram stain-based rapid diagnosis of type III NF may inform empirical antimicrobial therapy to include a carbapenem., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Rationale: Colorectal cancer is the second leading cause of cancer-related deaths in the world. About 50% of patients will have metastases during the course of the disease. The common sites of metastasis are the liver, lung, peritoneum, lymph, etc. Metastatic carcinoma to the testes is uncommon. We found a case of ascending colon cancer metastasized to the testis in the clinic., Patient Concerns: We reported a 50-year-old male patient who was found to have testicular metastases >4 years after intestinal cancer surgery, and multiple metastases in the peritoneum and pelvis were found 1 week later., Diagnoses: After enhanced computed tomography and pathological biopsy, the patient was diagnosed with testicular metastasis of colon cancer., Interventions: Capecitabine combined with bevacizumab is currently undergoing palliative treatment., Outcomes: The patients died of tumor progression on June 28, 2021., Lessons: The testicular metastasis of colorectal cancer is a sign of peritoneum and multiple metastases. When the testicular metastasis occurs in colorectal cancer patients, it usually indicates that the patient has a poor prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tubulin s-palmitoylation involves the thioesterification of a cysteine residue in tubulin with palmitate. The palmitate moiety is produced by the fatty acid synthesis pathway, which is rate-limited by acetyl-CoA carboxylase (ACC). While it is known that ACC is phosphorylated at serine 79 (pSer 79 ) by AMPK and accumulates at the spindle pole (SP) during mitosis, a functional role for tubulin palmitoylation during mitosis has not been identified. In this study, we found that modulating pSer 79 -ACC level at the SP using AMPK agonist and inhibitor induced spindle defects. Loss of ACC function induced spindle abnormalities in cell lines and in germ cells of the Drosophila germarium, and palmitic acid (PA) rescued the spindle defects in the cell line treated transiently with the ACC inhibitor, TOFA. Furthermore, inhibition of protein palmitoylating or depalmitoylating enzymes also induced spindle defects. Together, these data suggested that precisely regulated cellular palmitate level and protein palmitoylation may be required for accurate spindle assembly. We then showed that tubulin was largely palmitoylated in interphase cells but less palmitoylated in mitotic cells. TOFA treatment diminished tubulin palmitoylation at doses that disrupt microtubule (MT) instability and cause spindle defects. Moreover, spindle MTs comprised of α-tubulins mutated at the reported palmitoylation site exhibited disrupted dynamic instability. We also found that TOFA enhanced the MT-targeting drug-induced spindle abnormalities and cytotoxicity. Thus, our study reveals that precise regulation of ACC during mitosis impacts tubulin palmitoylation to delicately control MT dynamic instability and spindle assembly, thereby safeguarding nuclear and cell division., (© 2023. The Author(s).)

Background: Meta-analyses of individual patient data from randomized, controlled trials show that early oseltamivir treatment for influenza cut the risk of pneumonia and hospitalization by 44% and 63%, respectively. However, data on the effectiveness of inhaled zanamivir in preventing hospitalization and death are lacking., Methods: This nationwide, population-based, cohort study included all outpatients treated with inhaled zanamivir or oral oseltamivir within 48 hours after a clinical diagnosis of influenza before and after the rollout of inhaled zanamivir as the first-line antiviral in Taiwan. The main outcome was influenza-related hospitalization or death within 14 days. Those who developed the outcome within 2 days were excluded from analyses. Propensity score stratification was used to control confounding from covariates., Results: A total of 865 032 eligible influenza outpatients were included in the analysis. The risk of developing the main outcome (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], .96 to 1.06) did not differ between the inhaled zanamivir group (n = 595 897, 68.9%, the reference) and the oral oseltamivir group (n = 269 135, 31.1%). Prespecified analysis on high-risk subgroups further showed that inhaled zanamivir is not inferior to oral oseltamivir in either patients aged ≥65 years (aHR, 1.14; 95% CI: 1.05 to 1.25) or patients with chronic lung diseases (aHR, 1.23; 95% CI: 1.08 to 1.41)., Conclusions: Inhaled zanamivir is not inferior to oral oseltamivir as outpatient treatment in preventing influenza-related hospitalization or death for patients whose conditions do not require hospitalization within 2 days., Competing Interests: Potential conflicts of interest. C.-T. F. reports support for the present work from the Taiwan National Health Insurance Agency (NHI Claims Database). K. A. C. reports research grants to the National Taiwan University Hospital outside of the submitted work from Takeda, MSD, Amgen, and Boehringer Ingelheim; consulting fees paid to self from Bayer, Analysis Group, and Atheneum; and writing support for a manuscript from Novartis. The remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy., Case Presentation: A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level., Conclusions: Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD., (© 2022. The Author(s).)

Background: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality., Methods: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512., Findings: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49)., Interpretation: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations., Funding: National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Mistakenly picking and eating poisonous mushrooms can cause acute poisoning. In August 2020, Qingdao Hospital of Traditional Chinese Medicine handled a poisonous mushroom poisoning incident, conducted epidemiological investigation on all poisoned patients, collected suspicious food, clinical manifestations, clinical test results and treatment conditions, and identified the mushrooms as Amanita fuliginea poisoning after morphological identification. In this incident, 6 people ate grey goose paste, of which 4 were sick with a incubation period of 6~12 h. The clinical manifestations were gastrointestinal symptoms such as nausea, vomiting and diarrhea, liver and kidney damage. After symptomatic support treatment, hemoperfusion or continuous hemofiltration treatment, the patients were cured and discharged. It is suggested to strengthen the popular science education on poisonous mushroom poisoning and improve the ability of identification and clinical treatment of poisonous mushrooms in grass-roots medical institutions.

Background: Enterovirus A71 (EV A71) is one of the most important enteroviruses related to morbidity and mortality in children worldwide. This study aimed to analyse the secular trend of EV A71 in Taiwan from 1998 to 2020 and to evaluate the effectiveness of infection control measures., Methods: We collected the epidemiological data of EV A71 from disease surveillance systems in Taiwan. We analysed the association between the secular trend of EV A71 and preventive measures such as hand washing, case isolation, and suspension of classes., Results: The incidence of enterovirus infections with severe complications (EVSC) decreased from 16.25 per 100,000 children under six in 1998 to less than 9.73 per 100,000 children under six after 2012 (P = 0.0022). The mortality rate also decreased significantly, from 3.52 per 100,000 children under six in 1998 to 0 per 100,000 children under six in 2020 (P < 0.0001). The numbers of EVSC and fatalities were significantly higher in the years when EV A71 accounted for more than 10% of the annual predominant serotypes (p < 0.05). After the implementation of many non-pharmaceutical interventions in 2012, the incidence of EVSC and mortality rate decreased significantly (p < 0.001)., Conclusions: After implementing active enterovirus surveillance and preventive measures, we found that the incidence of EVSC and fatalities due to EV A71 in Taiwan decreased significantly from 1998 to 2020. Continuous surveillance and strengthened infection control policies are still needed in the future., (© 2022. The Author(s).)

High-spin, late transition metal imido complexes have attracted significant interest due to their group transfer reactivity and catalytic C-H activation of organic substrates. Reaction of a new two-coordinate iron complex, Fe{N( t Bu)Dipp} 2 (1, Dipp = 2,6-diisopropylphenyl), with mesitylazide (MesN 3 ) afforded a three-coordinate Fe-imidyl complex, Fe{N( t Bu)Dipp} 2 ([double bond, length as m-dash]NMes) (2). X-ray crystallographic characterization of single crystals of 2 showed a long Fe-N distance of 1.761(1) Å. Combined magnetic and spectroscopic (Mössbauer and X-ray absorption near edge structure spectroscopy, XANES) characterization of 2 suggests that it has an S = 2 ground state comprising an S = 5/2 Fe(iii) center antiferromagnetically coupled to an S = 1/2 imidyl ligand. Reaction of 1 and 1-azidoadamantane (AdN 3 ) generated a putative, transient Fe{N( t Bu)Dipp} 2 ([double bond, length as m-dash]NAd) (3') complex that yielded an intramolecular C-H amination product, Fe{N( t Bu)Dipp}{κ 2 - N , N '-&#95;N(CMe 2 CH 2̲ NHAd)Dipp} (3). Quantum mechanical calculations further confirmed the spectroscopic assignment of 2 and 3', as well as the differences in their stability and reactivity. Importantly, imidyl radical delocalization onto the mesityl ring significantly increased the stability of 2 and reduced its reactivity toward potential hydrogen atom transfer (HAT) reagents. In contrast, quantum mechanical calculations of 3' revealed that the radical was solely localized on the imidyl N, leading to a high reactivity toward the proximal C-H bond of the N( t Bu)Dipp - ligand., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Anemia is associated with severe outcomes in adult community-acquired pneumonia (CAP), but few studies investigated its association with pediatric CAP. Hence, we tried to delineate the association of anemia with the clinical outcomes of CAP in children., Methods: This retrospective cohort study was conducted from 2010 to 2019 in a medical center. Inpatients aged 6 months to 17 years who were diagnosed with CAP and without major underlying diseases were included. The subjects' clinical data within 24 h of admission and clinical outcomes were collected. We accessed the rates of adverse outcomes and the adjusted odds ratios (ORs) of these outcomes between anemic and nonanemic patients, as well as among patients with different types of anemia., Results: In this study of 3601 patients, the prevalence of anemia was 11.6% (418/3601). Anemic patients had higher rates of intensive care (16.8% vs. 3.6%; p < 0.001), endotracheal intubation (11.0% vs. 1.3%; p < 0.001), and empyema (8.6% vs. 0.6%; p < 0.001) than nonanemic patients. In addition, anemia was independently associated with intensive care (adjusted OR, 3.00; 95% confidence interval [CI], 2.03-4.42), endotracheal intubation (adjusted OR, 3.79; 95% CI, 2.17-6.63), and empyema (adjusted OR, 4.72; 95% CI, 2.30-9.69). Iron-deficiency anemia (IDA) and normocytic anemia were associated with these adverse outcomes but not with anemia due to thalassemia trait., Conclusion: Anemia is a biomarker associated with poor outcomes in pediatric CAP, and patients with IDA or normocytic anemia should be carefully monitored and managed since they may have higher disease severity., (© 2022 Wiley Periodicals LLC.)

Introduction: Routine HIV testing is expected to facilitate early diagnosis and treatment. Nevertheless, to date, limited data are available on the presumed benefit of early detection with improved outcomes through routine HIV testing., Methods: This study was based on the Taiwan national HIV/AIDS registry, with follow-up data validated through December 31, 2014. Outcomes of people diagnosed with HIV infection through the routine (routinely offered in specific settings, opt-out) versus through nonroutine (individual risk-based) testing were compared. The main outcomes of the study were late diagnosis, HIV-related mortality, and all-cause mortality. Individuals were matched by year of HIV diagnosis and adjusted for age, sex, transmission routes, and SES. Analyses were conducted in 2019-2020., Results: This study included all 28,674 people diagnosed with HIV infection during 1986-2014 (8,431 [29%] by routine testing, 18,305 [64%] by individual risk-based testing) with a mean follow-up time of 6.2 years. Routine testing was associated with an 80% lower likelihood of late HIV diagnosis (AOR=0.20, 95% CI=0.18, 0.23, p<0.001), a 37% lower HIV-related mortality (adjusted hazard ratio=0.63, 95% CI=0.53, 0.75, p<0.001), and a 27% lower all-cause mortality (adjusted hazard ratio=0.73, 95% CI=0.67, 0.79, p<0.001)., Conclusions: Routine HIV testing was associated with highly favorable outcomes, including decreased late diagnosis, lower HIV-related mortality, and lower all-cause mortality, among people diagnosed with HIV infection. Under universal health coverage, expanding routine HIV testing in well-targeted settings may improve both HIV epidemic control for society and clinical outcomes for people living with HIV., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance., Methods: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used., Results: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria., Conclusion: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak., Methods: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors., Results: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05)., Conclusion: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Objective: In Spring 2020, South Korea applied non-lockdown social distancing (avoiding mass gathering and non-essential social engagement, without restricting the movement of people who were not patients or contacts), testing-and-isolation (testing), and tracing-and-quarantine the contacts (contact tracing) to successfully control the first large-scale COVID-19 outbreak outside China. However, the relative contributions of these two interventions remain uncertain., Methods: We constructed an SEIR model of SARS-CoV-2 transmission (disproportionately through superspreading events) and fit the model to outbreak data in Daegu, South Korea, from February to April 2020. We assessed the effect of non-lockdown social distancing (population-wide control measures) and/or testing-contact tracing (individual-specific control measures), alone or combined, in terms of the basic reproductive number (R0) and the trajectory of the epidemic., Results: The point estimate for baseline R0 is 3.6 (sensitivity analyses range: 2.3 to 5.6). Combined interventions of non-lockdown social distancing and testing-contact tracing can suppress R0 to less than one and rapidly contain the epidemic, even under the worst scenario with a high baseline R0 of 5.6. In contrast, either intervention alone will fail to suppress R0. Non-lockdown social distancing alone just postpones the peak of the epidemic, while testing-contact tracing alone only flattens the curve but does not contain the outbreak., Conclusions: To successfully control a large-scale COVID-19 outbreak, both non-lockdown social distancing and testing-contact tracing must be implemented. The two interventions are synergistic., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA., Objective: In a cell model, we studied the effect of different FAs on placental IGF-1 secretion., Methods: This cohort study included pregnant women with term pregnancy and without diabetes or hypertensive disorders in pregnancy. Maternal fasting plasma TGs and FFAs were measured in the second trimester. Cord blood IGF-1, IGF-2, and IGF binding protein-1 and protein-3 were measured at the time of delivery. A human trophoblast cell line, 3A-sub-E, was used to evaluate the effect of different FFAs on placental IGF-1 secretion., Results: We recruited 598 pregnant women-neonate pairs. Maternal plasma TG (180 mg/dL [152.5-185.5 mg/dL] vs 166 mg/dL [133-206 mg/dL], P = .04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs 54.1 ± 22.8 ng/mL, P < .001) were higher in the LGA group and were significantly associated with birth weight z score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) or linoleic acid (LA), were significantly associated with cord blood IGF-1 concentrations. In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced IGF-1 expression and secretion., Conclusion: Certain FFAs can induce placental IGF-1 secretion, which suggests a potential pathophysiology linking maternal plasma lipids and LGA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Type 1 diabetes (T1D) has been linked to enterovirus infection in small population-based epidemiological studies. We investigated the secular relationship of T1D incidence with enterovirus infection and enterovirus species using nationwide population-based analysis., Research Design and Methods: We accessed the National Health Insurance Research Database of Taiwan to identify T1D and enterovirus infection cases from 2001 to 2015. Enterovirus serotype isolation rates were obtained from the nationwide laboratory surveillance systems. Negative binomial regression models assessed the incidence trend, and extended Cox proportional hazards models analyzed the association of enterovirus infection with T1D incidence. Spearman correlation coefficients evaluated the correlation between T1D incidence and circulating enterovirus species., Results: T1D incidence rates in youth younger than 20 years were 6.30 and 5.02 per 100,000 person-years in 2001 and 2015 ( P = 0.287), respectively. T1D incidence increased significantly in children aged 0-6 years ( P < 0.001) but decreased in adolescents aged 13-19 years ( P = 0.011). The T1D risk in children aged 0-6 years with enterovirus infection was significantly higher than that in noninfected subjects (hazard ratio 1.46; 95% CI 1.35-1.58; P < 0.001). Additionally, TID incidence in children aged 0-6 years was significantly correlated with the isolation rates of coxsackievirus A species ( r = 0.60; P = 0.017), but no association was found beyond the age of 7., Conclusions: We demonstrated that T1D incidence increased in children aged 0-6 years but decreased in adolescents aged 13-19 years in Taiwan. Enterovirus-infected subjects younger than 7 years had a higher risk of T1D than noninfected subjects., (© 2021 by the American Diabetes Association.)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Taxol is a first-line chemotherapeutic for numerous cancers, including the highly refractory triple-negative breast cancer (TNBC). However, it is often associated with toxic side effects and chemoresistance in breast cancer patients, which greatly limits the clinical utility of the drug. Hence, compounds that act in concert with taxol to promote cytotoxicity may be useful to improve the efficacy of taxol-based chemotherapy. In this study, we demonstrated that mdivi-1, a putative inhibitor of mitochondrial fission protein Drp1, enhances the anticancer effects of taxol and overcomes taxol resistance in a TNBC cell line (MDA-MB-231). Not only did mdivi-1 induce mitotic spindle abnormalities and mitotic arrest when used alone, but it also enhanced taxol-induced antimitotic effects when applied in combination. In addition, mdivi-1 induced pronounced spindle abnormalities and cytotoxicity in a taxol-resistant cell line, indicating that it can overcome taxol resistance. Notably, the antimitotic effects of mdivi-1 were not accompanied by prominent morphological or functional alterations in mitochondria and were Drp1-independent. Instead, mdivi-1 exhibited affinity to tubulin at μM level, inhibited tubulin polymerization, and immediately disrupted spindle assembly when cells entered mitosis. Together, our results show that mdivi-1 associates with tubulin and impedes tubulin polymerization, actions which may underlie its antimitotic activity and its ability to enhance taxol cytotoxicity and overcome taxol resistance in MDA-MB-231 cells. Furthermore, our data imply a possibility that mdivi-1 could be useful to improve the therapeutic efficacy of taxol in breast cancer.

Objective: Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC)., Methods: We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3., Results: A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: -2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: -2.80, 95% CI: 1.64 to 4.80, P < 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: -1.66, 95% CI: 1.20 to 2.31, P < 0.01), and disease control rate (DCR) (RR: -2.68, 95% CI: 1.41 to 5.06, P < 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone., Conclusion: Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lu-Zhen Li et al.)

The reciprocate scanning scheme of two-dimensional galvanometers is widely used in laser confocal scanning microscopes with high speed. However, the equal interval acquisition of an analog digital acquisition card (AD) and the unequal change of the galvanometer's scanning speed will cause the dislocation of pixels and distortion of the reconstructed image. Meanwhile, the movement properties of the galvanometers in the edge of the scanning area are complex, which will increase the difficulty of segmenting the collected one-dimensional data stream the AD collected into row data of a two-dimensional reconstructed image. Therefore, how to timely and accurately segment the one-dimensional data stream the AD collected into the row data of two-dimensional reconstructed image is not only the key to solve image distortion of a laser confocal scanning microscope with high speed but also the prerequisite to improve the accuracy of row data dislocation correction. A driving mode based on the nonlinear triangular wave and a dislocation-correcting method using a square wave index are proposed. Namely, on the basis of the galvanometer's scanning analysis, the equation of a nonlinear triangular wave driving voltage is established, and the switching frequency of the Y-galvanometer's driving voltage is obtained by calculating the collected switching frequency of the X-galvanometer; thus, the uniformity of the galvanometer's scanning trajectories is secured. Finally, the row segmentation flag pulse is first introduced into the one-dimensional data stream the AD collected, and the square wave index is used to segment the collected data, which means the one-dimensional data stream can be segmented timely and accurately via hardware method. Meanwhile, the pixel dislocation can be corrected. The experimental result shows that, compared with the Nikon A1R+ confocal microscope, the proposed method can effectively correct the pixel dislocation, and the position coincidence error is less than 0.7%. The proposed method will be helpful to improve the image quality of a laser confocal scanning microscope with high speed.

Background: Current knowledge on Rickettsia felis infection in humans is based on sporadic case reports. Here we conducted a retrospective seroepidemiological survey of R. felis infection among febrile patients visiting a medical center in Taipei., Methodology/principal Findings: A total of 122 patients with suspected rickettsioses presenting with fever of unknown origin (FUO) but tested negative for scrub typhus, murine typhus, or Q fever were retrospectively identified during 2009 to 2010. The archived serum samples were examined for the presence of antibodies against R. felis, Rickettsia japonica, and Rickettsia typhi using microimmunofluorescence (MIF) assay. Serological evidence of Rickettsia exposure was found in 23 (19%, 23/122) patients. Eight patients had antibodies reactive to R. felis, including four with current infection (a ≥4-fold increase in IgG titer between acute and convalescent sera). The clinical presentations of these four patients included fever, skin rash, lymphadenopathy, as well as more severe conditions such as pancytopenia, hepatomegaly, elevated liver enzymes/bilirubin, and life-threatening acute respiratory distress syndrome. One of the patients died after doxycycline was stopped after being tested negative for scrub typhus, Q fever, and murine typhus., Conclusions: Rickettsia felis is a neglected flea-borne pathogen in Taiwan, and its infection can be life-threatening. Further prospective studies of the prevalence of R. felis among patients with FUO and compatible clinical manifestations are warranted., Competing Interests: The authors have declared that no competing interests exist.