Search

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of ‘free’ colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

The COVID-19 pandemic places high pressure on everyone, including healthcare workers (HCWs), thus causing them to experience psychological distress. HCWs have priority in receiving the COVID-19 vaccine. However, few studies have identified adverse events (AEs) and psychological distress in the HCWs group. Therefore, we investigated the association between psychological distress and AEs and the determinants of protective behaviors in Taiwanese HCWs. A longitudinal measurement was conducted among HCWs at National Cheng Kung University Hospital (NCKUH), Tainan, Taiwan (n = 483, mean age = 37.55 years). All HCWs completed an online questionnaire on psychological distress, COVID-19 vaccination AEs, and protective behaviors. We used generalized estimating equations (GEE) to analyze the correlation between psychological distress and AEs, and used multivariable logistic regressions to explore the predictors of protective behaviors. Depression and distress and anger were significantly associated with various physical AEs (p = 0.045 to p < 0.001). Suicidal thoughts became a significant independent variable of systemic AEs after COVID-19 vaccination (p = 0.014 to p < 0.001). People of older ages or females engaged more in washing their hands, wearing masks, and reducing their presence in crowded places. Suicidal thoughts were related to the occurrence of systemic AEs among HCWs. Doctors performed better at preventive behaviors compared to nurses and other HCWs. HCWs who experienced anxiety and nervousness tended to avoid crowds.

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.

Cerebrospinal fluid (CSF) hypovolemia is the core of spontaneous intracranial hypotension (SIH). More than 1000 magnetic resonance myelography (MRM) images are required to evaluate each subject. An effective spinal CSF quantification method is needed. In this study, we proposed a cascade artificial intelligence (AI) model to automatically segment spinal CSF. From January 2014 to December 2019, patients with SIH and 12 healthy volunteers (HVs) were recruited. We evaluated the performance of AI models which combined object detection (YOLO v3) and semantic segmentation (U-net or U-net++). The network of performance was evaluated using intersection over union (IoU). The best AI model was used to quantify spinal CSF in patients. We obtained 25,603 slices of MRM images from 13 patients and 12 HVs. We divided the images into training, validation, and test datasets with a ratio of 4:1:5. The IoU of Cascade YOLO v3 plus U-net++ (0.9374) was the highest. Applying YOLO v3 plus U-net++ to another 13 SIH patients showed a significant decrease in the volume of spinal CSF measured (59.32 ± 10.94 mL) at disease onset compared to during their recovery stage (70.61 ± 15.31 mL). The cascade AI model provided a satisfactory performance with regard to the fully automatic segmentation of spinal CSF from MRM images. The spinal CSF volume obtained through its measurements could reflect a patient’s clinical status.

Objectives: Epidural blood patching (EBP) is the mainstay therapy for spontaneous intracranial hypotension (SIH). MRI is used for evaluating spinal CSF leakage. Post-EBP MRI has been. shown to be effective in predicting the efficacy of EBP. However, there are few reports on how post-EBP MRI findings may change with time. The aim of this study was to evaluate the relationship between post-EBP MRI findings at different time points and the corresponding effectiveness of EBP. Methods: We retrospectively reviewed 63 SIH patients who had received target EBP. All patients received an MRI follow-up within 10 days (post-EBP MRI) and at 3 months after EBP (3-month MRI). A sub-group analysis was performed at different post-EBP MRI time points (0–2, 3–6, and 7–10 days). The relationships between the post-EBP MRI findings and the EBP effectiveness were evaluated. Results: Thirty-five (55.56%) patients were assigned to the EBP-effective group, and 28 (44.44%) were assigned to the EBP non-effective group according to the 3-month MRI. Compared to the EBP non-effective group, the EBP-effective group had significantly lower numbers of spinal CSF leakage in the post-EBP MRI (4.49 vs. 11.71; p = 0.000) and greater numbers of leakage improvement (7.66 vs. 2.96; p = 0.003). For patients who received post-EBP MRI during periods of 0–10, 0–2, 3–6, and 7–10 days, the cutoff values of numbers of spinal CSF leakage for predicting EBP failure were 4, 6, 4, and 5, respectively, with an AUC above 0.77. Conclusion: By using post-EBP MRI, which only takes approximately 20 min, predicting EBP efficacy became possible in SIH patients. This study provides cutoff values of numbers of spinal CSF leakage at different follow-up times to serve as clues of if further EBP is needed, which provides the novelty of the current study.

(1) Background: This study aimed to determine the association between the use of efavirenz and depressive disorders among human immunodeficiency virus (HIV)-infected patients. (2) Methods: A retrospective cohort study was conducted using Taiwan’s National Health Insurance Database. We identified patients receiving anti-retroviral therapy (ART) between 2000 and 2009; these patients were followed until 2010 for diagnoses of depressive disorders using the Cox proportional hazard model to estimate hazard ratios. (3) Results: After up to 11 years of follow-up, the incidence of depressive disorders for the efavirenz-treated group was estimated at 12.2/1000 person-years (PYs), and the control group was at 12.5/1000 PY (p = 0.822). The independent risk factors for depressive disorders included an insurance premium of less than NTD 17,820 (New Taiwan Dollars—NTD) (adjusted hazard ratio (aHR) 2.59, 95% confidence interval (CI), 1.79–3.76, p < 0.001), and between NTD 17,821 and NTD 26,400 (aHR 1.55, 95% CI, 1.04–2.31, p = 0.030), living in Southern Taiwan (aHR 1.49, 95% CI, 1.21–1.84, p = 0.002), and with a psychiatric history (excluding depressive disorders) (aHR 4.59, 95% CI, 3.51–6.01, p = 0.030). (4) Conclusions: This study concluded that ART-treated patients with a past history of psychiatric disorders, lower insurance premium, and living in Southern Taiwan have an increased risk of depressive disorders, which are not associated with the use of efavirenz.

The purpose of this study is to develop a tool that can measure the educational well-being of elementary school students and to analyze the fit of the developed instrument. The measurement tool was based on four levels which include: (1) parents’ support, (2) teachers’ care, (3) students’ care in school, and (4) peer cooperation. It also had eight facets which include: (1) basic need, (2) family companionship, (3) happy learning, (4) teacher-student interaction, (5) safety protection, (6) school rules, (7) peer learning, and (8) peer interaction. The participants of this study were grades 5 and 6 students in Taiwan. Pre-testing with 197 grade 6 students was done to assess the validity and reliability of the developed scale. For the formal study, a total of 960 grade 6 students and 834 grades 5 and 6 students were recruited to join. The data collected underwent item analysis, reliability estimation, and confirmatory factor analysis. The results of the analyses were as follows: (1) the confirmatory factor analysis supported the four latent factors of the educational well-being scale; (2) the Cronbach’s alpha ranged from 0.73 to 0.89 for the elementary school students; (3) the cross-validation analysis with split-half samples implies that the study had a well-constructed stability model and that the scale had construct validity; and (4) the average scores of grade 5 students on the 8 facets and their overall score on educational well-being were all significantly higher than that of grade 6 students. Finally, several suggestions were proposed for future studies based on the results obtained.

We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, nontraumatic OHCA adults with bacteremia episodes after achieving sROSC were defined as case patients, and non-OHCA patients with community-onset bacteremia in the emergency department were regarded as control patients. Initially, case patients had a higher bacteremia incidence than non-OHCA visits (231/2171, 10.6% vs. 10,430/314,620, 3.3%; p < 0.001). Compared with the matched control (2288) patients, case (231) patients experienced more bacteremic episodes due to low respiratory tract infections, fewer urosepsis events, fewer Escherichia coli bacteremia, and more streptococcal and anaerobes bacteremia. Antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacteriaceae, were frequently evident in case patients. Notably, each hour delay in AAT administration was associated with an average increase of 10.6% in crude 30-day mortality rates in case patients, 0.7% in critically ill control patients, and 0.3% in less critically ill control patients. Conclusively, the incidence and characteristics of bacteremia differed between the nontraumatic OHCA and non-OHCA patients. The incorporation of blood culture samplings and rapid AAT administration as first-aids is essential for nontraumatic OHCA patients after achieving sROSC.

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

To control the spread of the novel coronavirus disease 2019 (COVID-19), COVID-19 vaccination has been quickly developed. However, the COVID-19 pandemic will not be controlled if the COVID-19 vaccination uptake willingness is low. Therefore, the study aim was to explore the COVID-19 vaccination uptake willingness among the outpatient population and healthcare workers in Taiwan during the worldwide pandemic period without community outbreaks. A cross-sectional survey was conducted among healthcare workers (HCWs; n = 500; mean age = 32.96 years) of National Cheng Kung University Hospital (NCKUH) and outpatients (n = 238; mean age = 34.43 years) arriving at NCKUH. We used an online survey conducted between September 24 and 21 November 2020, for healthcare workers, and between 27 October and 31 December 2020, for the outpatient sample. Information regarding willingness to receive vaccination, willingness to rapid test, fear of COVID-19, risk perception, and preventive behaviors was collected in both samples; information regarding willingness to care for patients was collected in healthcare workers. Willingness to receive vaccination was the main variable in the present study; willingness to rapid test, willingness to care for patients, fear of COVID-19, risk perception, and preventive behaviors were the secondary variables in the study. The factors associated with vaccination willingness were identified through logistic regression analysis. The participants’ willingness to receive vaccination was low for both healthcare workers (23.4%) and the outpatient sample (30.7%). Similarly, their willingness to take rapid tests was low (23.6% for healthcare workers and 28.6% for outpatient sample). Risk perception (crude odds ratio (COR) = 1.29; 95% confidence interval (CI) = 1.03, 1.63), willingness to take rapid test (COR = 9.24; 95% CI = 5.76, 14.83), and preventive COVID-19 infection behaviors (COR = 2.32; 95% CI = 1.52, 3.56) were significant factors explaining the healthcare workers’ willingness to receive vaccination. Willingness to take a rapid test (COR = 8.91; 95% CI = 4.71, 16.87) and preventive COVID-19 infection behaviors (COR = 1.69; 95% CI = 1.09, 2.60) were significant factors explaining the outpatient sample’s willingness to receive vaccination. Willingness to vaccinate against COVID-19 among HCWs and outpatients is low due to the relatively safe status of COVID-19 infection in Taiwan. These findings can help policymakers advocate for the effectiveness of and provide transparent information on COVID-19 vaccination uptake in a country/region with a relatively safe COVID-19 outbreak status.

To compare prognoses and adverse events between bacteraemic patients in the emergency department (ED) who received an early antimicrobial IV-to-PO switch and those treated with late or no IV-to-PO switch, an 8-year multicentre cohort consisting of adults with community-onset bacteraemia was conducted. The clinical characteristics and outcomes were compared in matched cohorts by the closest propensity score calculated based on the independent determinants of 30-day mortality identified by the multivariate regression model. Of the 6664 hospitalised patients who received no or late IV-to-PO switch, 2410 were appropriately matched with 482 patients treated with early IV-to-PO switch and discharged from the ED. There were no significant differences between the two matched groups in their baseline characteristics, including the patient demographics, severity and types of comorbidities, severity and sources of bacteraemia, and the 15- and 30-day mortality rates. Notably, in addition to the shorter lengths of intravenous antimicrobial administration and hospital stay, less phlebitis and lower antimicrobial costs were observed in patients who received an early IV-to-PO switch. Similarity was observed in the clinical failure rates between the two groups. Furthermore, the inappropriate administration of empirical antibiotics and inadequate source control were identified as the only independent determinants of the post-switch 30-day crude mortality in patients who received an early IV-to-PO switch. In conclusion, for less critically ill adults with community-onset bacteraemia who received appropriate empirical antimicrobial therapy and adequate source control, an early IV-to-PO switch might be safe and cost-effective after a short course of intravenous antimicrobial therapy.

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains debated. To assess its efficacy as a definitive agent, the 8-year cohort study consisted of 941 adults with monomicrobial cefazolin-susceptible EKP bacteremia, based on the CLSI criteria issued in 2019, was retrospectively established in a medical center. Based on the definitive antimicrobial prescription, eligible patients were categorized into the cefazolin (399 patients, 42.4%) and broader-spectrum antibiotic (BSA) (542, 57.6%) groups. Initially, fewer proportions of patients with fatal comorbidities (the McCabe classification) and the critical illness (a Pitt bacteremia score ≥4) at the onset and day 3 of the bacteremia episode were found in the cefazolin group, compared to the BSA group. After propensity-score matching, no significant difference of patient proportions between the cefazolin (345 patients) and BSA (345) groups was observed, in terms of the elderly, types and severity of comorbidities, bacteremia severity at the onset and day 3, major bacteremia sources, and the 15-day and 30-day crude mortality. In early outcomes, lengths of time to defervescence, intravenous (IV) antimicrobial administration, and hospitalization were similar in the two matched groups; lower costs of IV antimicrobial administration were observed in the cefazolin group. Notably, for late outcomes, lower proportions of post-treatment infections caused by antimicrobial-resistant pathogens (ARPs) and post-treatment mortality rates were evidenced in the cefazolin group. Conclusively, cefazolin is definitively efficacious and cost-effective for adults with community-onset cefazolin-susceptible EKP bacteremia in this one-center study, compared to BSAs. However, a prospective multicenter study should be conducted for external validation with other communities.

In this study, an organic-inorganic semiconductor gas sensor was fabricated to detect ammonia gas. An inorganic semiconductor was a zinc oxide (ZnO) nanowire array produced by atomic layer deposition (ALD) while an organic material was a p-type semiconductor, poly(3-hexylthiophene) (P3HT). P3HT was suitable for the gas sensing application due to its high hole mobility, good stability, and good electrical conductivity. In this work, P3HT was coated on the zinc oxide nanowires by the spin coating to form an organic-inorganic heterogeneous interface of the gas sensor for detecting ammonia gas. The thicknesses of the P3HT were around 462 nm, 397 nm, and 277 nm when the speeds of the spin coating were 4000 rpm, 5000 rpm, and 6000 rpm, respectively. The electrical properties and sensing characteristics of the gas sensing device at room temperature were evaluated by Hall effect measurement and the sensitivity of detecting ammonia gas. The results of Hall effect measurement for the P3HT-ZnO nanowires semiconductor with 462 nm P3HT film showed that the carrier concentration and the mobility were 2.7 × 1019 cm−3 and 24.7 cm2∙V−1∙s−1 respectively. The gas sensing device prepared by the P3HT-ZnO nanowires semiconductor had better sensitivity than the device composed of the ZnO film and P3HT film. Additionally, this gas sensing device could reach a maximum sensitivity around 11.58 per ppm.