Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Venetoclax Plus Azacitidine as a Bridge Treatment to Allogeneic Stem Cell Transplantation in Unfit Patients with Acute Myeloid Leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. METHODS: This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). RESULT: The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. CONCLUSION: In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

Shared genetic architectures of educational attainment in East Asian and European populations.

Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.

Clinical outcomes, medical costs, and medication usage patterns of different somatic symptom disorders and functional somatic syndromes: a population-based study in Taiwan.

BACKGROUND: Somatic symptom disorders (SSD) and functional somatic syndromes (FSS) are often regarded as similar diagnostic constructs; however, whether they exhibit similar clinical outcomes, medical costs, and medication usage patterns has not been examined in nationwide data. Therefore, this study focused on analyzing SSD and four types of FSS (fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, functional dyspepsia). METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance (NHI) claims database to investigate the impact of SSD/FSS. The study included 2 615 477 newly diagnosed patients with SSD/FSS and matched comparisons from the NHI beneficiary registry. Healthcare utilization, mortality, medical expenditure, and medication usage were assessed as outcome measures. Statistical analysis involved Cox regression models for hazard ratios, generalized linear models for comparing differences, and adjustment for covariates. RESULTS: All SSD/FSS showed significantly higher adjusted hazard ratios for psychiatric hospitalization and all-cause hospitalization compared to the control group. All SSD/FSS exhibited significantly higher adjusted hazard ratios for suicide, and SSD was particularly high. All-cause mortality was significantly higher in all SSD/FSS. Medical costs were significantly higher for all SSD/FSS compared to controls. The usage duration of all psychiatric medications and analgesics was significantly higher in SSD/FSS compared to the control group. CONCLUSION: All SSD/FSS shared similar clinical outcomes and medical costs. The high hazard ratio for suicide in SSD deserves clinical attention.

Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits.

Genome-wide association studies (GWASs) have identified tens of thousands of genetic loci associated with human complex traits. However, the majority of GWASs were conducted in individuals of European ancestries. Failure to capture global genetic diversity has limited genomic discovery and has impeded equitable delivery of genomic knowledge to diverse populations. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia. We identified 968 novel genetic loci, pinpointed novel causal variants through statistical fine-mapping, compared the genetic architecture across TWB, Biobank Japan, and UK Biobank, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores in disease risk prediction. These results demonstrated the potential to advance discovery through diversifying GWAS populations and provided insights into the common genetic basis of human complex traits in East Asia.

Mentalizing in a movie for the assessment of social cognition (MASC): the validation in a taiwanese sample.

BACKGROUND: The present study evaluated the psychometrics properties of a sensitive video-based test used in the evaluation of mentalizing skills, that is, the Movie for the Assessment of Social Cognition-Taiwanese version (MASC-TW). METHODS: We recruited two independent samples of nonclinical participants (N = 167) and adult patients with schizophrenia (N = 41). The MASC-TW and two other social cognition measures, namely the Chinese version of Theory of Mind task (ToM) and the Taiwanese version of the Diagnostic Analysis of Nonverbal Accuracy-2 (DANAV-TW-2), and an executive function measure of the Wisconsin Card Sorting Test (WCST), were administered to both groups. RESULTS: The MASC proved to be a reliable measure of mentalizing capacity, high Cronbach's α value of 0.87. The intraclass correlation coefficient for the MASC-TW total correct scores was 0.85 across three waves of data collection. Across the entire sample, the scores on the MASC-TW were significantly correlated with verbal and nonverbal scores for the ToM task and recognition of facial and prosodic emotion on the DANAV-TW-2. Both executive function and emotion recognition emerged as noteworthy predictors of mentalizing, indicating that these two variables might play crucial roles in the development of mentalizing capacities. Finally, a receiver operating characteristic analysis revealed that in patients with schizophrenia, the MASC was the most accurate discriminator of diagnostic groups, highlighting the validity of the MASC. CONCLUSIONS: Overall, the MASC-TW is an ecologically valid and useful tool for assessing mentalizing abilities in a Taiwanese population.

A National Case-Crossover Study on the Risk of Kidney Injury Requiring Dialysis after Sepsis.

BACKGROUND: Patients with sepsis-associated acute kidney injury (AKI) are at risk of kidney damage, potentially necessitating acute temporary or chronic dialysis. Our study aims to estimate the odds ratio (OR) of preceding sepsis among patients requiring their first dialysis. METHODS: A nationwide population-based case-only study was conducted using claims records from the National Health insurance database of Taiwan. All patients over 20 years of age who underwent their first dialysis between 2004 and 2016 were included in the study. The six months prior to their first dialysis served as a self-control period. RESULTS: The study included 147,201 patients who required acute temporary and 75,031 patients who required chronic dialysis. The odds ratios for patients needing acute temporary dialysis after 1, 2, 3, and 4 weeks of exposure periods were 15.8, 10.7, 9.2, and 8.4, respectively. The ORs for patients requiring chronic dialysis were 7.0, 4.1, 4.2, and 3.7, respectively. CONCLUSIONS: Our findings indicate that sepsis was substantially associated with an increased risk of renal failure. The risk was highest during the first week following sepsis for both acute temporary and chronic dialysis cases.

Genetics of antidepressant response and treatment-resistant depression.

Antidepressant response, the effectiveness of antidepressants in relieving symptoms of depression, is a complex trait influenced by both genetic and environmental factors. However, despite decades of research, the specific genetic variations that contribute to antidepressant response and treatment-resistant depression (TRD) remain largely unknown. In this review, we summarize the current state of knowledge of the genetics of antidepressant response and TRD, including candidate gene association studies, genome-wide association studies (GWAS), polygenic risk score (PRS) analyses, whole genome sequencing studies, research on other genetic and epigenetic changes, and the potential for precision medicine in this field. Although some progress has been made in identifying genetic factors associated with antidepressant response and TRD, much work remains to be done, particularly in terms of larger sample sizes and standardization of outcome measures. Further research in this area has the potential to improve the treatment of depression and increase the chances of successful treatment for individuals with this common and debilitating mental illness.

Causal influence of sleeping phenotypes on the risk of coronary artery disease and sudden cardiac arrest: A Mendelian randomization analysis.

OBJECTIVES: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study. METHODS: We used summary statistics of 5 sleep and circadian traits for genome-wide association studies, including chronotype, sleep duration, long sleep (≥9 h a day), short sleep (<7 h a day), and insomnia (sample size range: 237,622-651,295). Coronary artery disease genome-wide association studies with 60,801 cases and 123,504 controls, sudden cardiac arrest genome-wide association studies with 3939 cases and 25,989 controls, and obesity genome-wide association studies with 806,834 individuals were also used. Multivariable Mendelian randomization was performed to estimate the causality. RESULTS: After adjusting for obesity, genetically predicted short sleep (odds ratio = 1.87 and p = .02), and genetically predicted insomnia (odds ratio = 1.17 and p = .001) were causally associated with increased odds of coronary artery disease. Genetically predicted long sleep (odds ratio = 0.06 and p = .02) and genetically predicted longer sleep duration (odds ratio = 0.36 for per-hour increase in sleep duration and p = .0006) were causally associated with decreased odds of sudden cardiac arrest. CONCLUSIONS: The findings of this Mendelian randomization study indicate that insomnia and short sleep contribute to the development of coronary artery disease, whereas a longer sleep duration protects from sudden cardiac arrest, independent of the influence of obesity. The mechanisms underlying these associations warrant further investigation.

Clinical Use of Intravenous Fosfomycin in Critical Care Patients in Taiwan.

This retrospective study aimed to evaluate the clinical use and side effects of fosfomycin in critically ill patients in Taiwan. Forty-two patients (mean age, 69.9 years; female, 69%) who received fosfomycin were included from a teaching hospital in Taiwan from January 2021 to December 2021. We analyzed the prescription pattern of intravenous fosfomycin and evaluated patient safety profiles, clinical successes, and microbiological cure rates. The main indication was urinary tract infections (35.6%), and the most frequently identified pathogen was Escherichia coli (18.2%). The overall clinical success was 83.4%, with one multidrug-resistant pathogen isolated from eight patients (19.0%). The average dose of fosfomycin given was 11.1 ± 5.2 g/day. The average duration of therapy was 8.7 ± 5.9 days, with a median duration of 8 days, where fosfomycin was mostly (83.3%) given in combination. Fosfomycin was given 12 hourly to a maximum number (47.6%) of cases. The incidence rates of adverse drug reactions (hypernatremia and hypokalemia) were 33.33% (14/42) and 28.57% (12/42), respectively. The overall survival rate was 73.8%. Intravenous fosfomycin may be an effective and safe antibiotic to use in combination with other drugs for empirical broad-spectrum or highly suspected multidrug-resistant infections in critically ill patients.

Better resolving of anti-CD38 antibody interference with blood compatibility testing by using manual polybrene method compared with dithiothreitol-pretreatment indirect antiglobulin test.

BACKGROUND: It is advised to pretreat the reagent erythrocytes with Dithiothreitol (DTT) to denature the surface CD38 to prevent anti-CD38 monoclonal antibodies (MoAb) from interfering with the blood compatibility test. Anti-CD38 has little impact on the Polybrene test, but it is still unknown how sensitive it is to detect irregular antibodies and how effective it is when compared to the standard DTT-based method. METHODS: Twenty-one patients receiving daratumumab (N = 13) and isatuximab (N = 8) had their serum collected. Standard anti-sera (anti-c, D, E, Fyb , Jka , M, Mia ) with serial dilution were added to patients' serum. Antibody screening tests were performed simultaneously using the manual polybrene method (MP) and DTT-pretreated, automatic indirect antiglobulin test (DTT-IAT) to compare the detection sensitivity. These two methods' operating times and costs were also analyzed. RESULTS: Both MP and DTT-IAT can overcome the interference caused by anti-CD38 MoAb. However, MP is more sensitive in detecting anti-M and anti-Mia and is comparable to DTT-IAT in detecting other antibodies. In terms of cost and operating time, MP is also far superior to DTT-IAT. CONCLUSION: MP is a cost-effective alternative to DTT-IAT in resolving anti-CD38 interference and is especially suitable for populations with a high prevalence of anti-M and anti-Mia . However, both methods have a well-known drawback of low detection sensitivity for anti-K, and K-units should be provided to patients to prevent hemolytic transfusion reactions.

Impacts of seafloor characteristics on three-dimensional sound propagation in a submarine canyon.

Three-dimensional (3D) underwater sound propagation in a submarine canyon is investigated with a numerical model and a dataset collected in a towed source experiment. This study emphasizes the impacts of seafloor bathymetry and sediment properties, which may alter the strength of 3D sound reflections from canyon seafloor. Specifically, the numerical model is utilized to analyze the sensitivity of seafloor morphology and sediment types affecting sound propagation in the canyon. The acoustic data reveals a canyon focusing effect, and the numerical model successfully reproduces the location of the focal area and confirms the focusing effect caused by the canyon bathymetry.

Effects of nonlinear internal gravity waves on normal-incident reflection measurements of seafloor sediments.

Sonar data acquired by sub-bottom profilers and echosounder systems are widely used to estimate geoacoustic properties of marine sediments. However, the uncertainty of the seabed property estimates caused by water-column variability may limit the application. In this paper, the acoustic focusing and defocusing effects of nonlinear internal gravity waves on normal-incident acoustic reflection measurements are studied. The experiment data were collected in the South China Sea from two transceiver moorings located at two different sites, one of which contained strong nonlinear internal waves (NIWs), while another site did not. The observed reflection intensity variation at the internal wave site varied up to 10 dB. On the other hand, the bottom reflections at the other site without internal waves were stable, and a seafloor sediment sample collected there was analyzed to validate the sediment type inferred from bottom loss. Numerical simulations using ray-tracing and parabolic equation models confirmed the cause of this intensity fluctuation by the acoustic focusing and defocusing of NIWs. This study eventually showed that NIWs may induce a significant bias for geoacoustic property estimates from seabed reflection coefficients.

Analysis of Immune-Cell Distribution of Bone Marrow in Patients with Myelodysplastic Syndrome.

Myelodysplastic syndrome (MDS) immunity plays an important role in the proliferation and apoptosis of aberrant cells. Immune dysregulation has been studied in various prognostic subgroups. This study analyzed 60 patients with MDS via multidimensional flow cytometry to evaluate the expression of aberrant markers, such as CD7 and cytoplasmic CD3 on lymphocytes. The Revised International Prognostic Scoring System (IPSS-R) scores were used to classify the patients into risk groups. The results showed a significant downregulation of CyCD3- T cells in low-intermediate versus high-risk patients (p = 0.013). This study is the first to show that a significant decrease in cyCD3- T cells in patients with a lower IPSS-R score may indicate microenvironmental changes conducive to transformation in MDS.

Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases.

Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of which have similar statistical significance. While statistical fine-mapping in individuals of European ancestries has made important discoveries, cross-population fine-mapping has the potential to improve power and resolution by capitalizing on the genomic diversity across ancestries. Here we present SuSiEx, an accurate and computationally efficient method for cross-population fine-mapping, which builds on the single-population fine-mapping framework, Sum of Single Effects (SuSiE). SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and LD patterns, accounts for multiple causal variants in a genomic region, and can be applied to GWAS summary statistics. We comprehensively evaluated SuSiEx using simulations, a range of quantitative traits measured in both UK Biobank and Taiwan Biobank, and schizophrenia GWAS across East Asian and European ancestries. In all evaluations, SuSiEx fine-mapped more association signals, produced smaller credible sets and higher posterior inclusion probability (PIP) for putative causal variants, and captured population-specific causal variants.

Case reports of management of aplastic anemia after COVID-19 vaccination: a single institute experience in Taiwan.

Global vaccination against the coronavirus disease 2019 (COVID-19) is thought to be the most effective way to end or at least contain the COVID-19 pandemic. However, despite the good safety profiles and effectiveness of the available COVID-19 vaccines, rare but serious hematological complications have emerged, including thromboembolic outcomes with thrombocytopenia following the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Ad26.COV.2.S (Johnson & Johnson/Janssen) vaccines. Moreover, COVID-19 vaccination may be linked to the development of aplastic anemia (AA). We discuss four cases of AA that arose after COVID-19 vaccination in our hospital and two other such cases identified in our literature review.

Are we of one mind about core competencies of nurse preceptors? A nominal group technique study.

AIM: This paper explored the differences in perspectives on the core competencies of nurse preceptors among postgraduate-year nurses, clinical nursing preceptors and head nurses. DESIGN: Cross-sectional design with nominal group technique (NGT). METHOD: The sample consisted of 32 postgraduate-year nurses, 42 preceptors and 27 head nurses. Two rounds of NGT were used to collect the group opinions. RESULTS: While the rank/level of importance varied, three groups all agreed that teaching traits, clinical nursing profession, communication and collaboration, teaching pedagogy, reaction of contingency and consultation of academic writing were important core competencies for nurse preceptors. The three groups disagreed on critical thinking and reflection, as well as lifelong learning. This study clarifies cognitive differences and expectations among three groups and can assist medical institutes in designing preceptor training courses.

High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a form of cancer that is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells of the hematopoietic system. Patients with acute myeloid leukemia (AML) receiving azacitidine (AZA) alone or in combination with venetoclax (VEN-AZA) are at increased risk for invasive fungal infections (IFIs). We compared the incidence and risk of IFI during these treatment regimens in a single Taiwan hospital. Materials and methods: A total of 61 patients with AML received at least one course of AZA in the hematology ward of China Medical University Hospital (Taichung, Taiwan) between September 2012 and June 2020. Thirty-eight patients (62.3%) received AZA monotherapy; 23 (37.7%) received VEN-AZA. Results: Incidence rates of probable and proven IFI were 18% and 1.6%, respectively, during AZA treatment. One proven case of Fusarium spp. infection was isolated by skin and soft tissue culture. Most (75%) IFI cases occurred during the first cycle of AZA therapy. Half of all IFI cases occurred in patients with prolonged neutropenia. The risk of IFI was significantly higher for the European LeukemiaNet (ELN) nonfavorable-risk group (intermediate- and adverse-risk group) versus the ELN favorable-risk group and for patients with prolonged neutropenia versus those without (P<0.05 for both comparisons). In this study, median OS did not differ significantly between patients with and without IFIs during AZA-containing regimens (14.6 months vs 13.7 months; P=0.59). Conclusion: The incidence of IFI was high in this AML cohort treated with AZA-containing regiments in Taiwan. The majority of IFI cases occurred during the early cycles of AZA (cycles 1-2). Prospective studies are needed to determine the optimal choice of antifungal prophylaxis agent during VEN-AZA therapy for AML.

Causal influence of dietary habits on the risk of major depressive disorder: A diet-wide Mendelian randomization analysis.

BACKGROUND: Extensive observational evidence links diet quality to the risk for major depressive disorder (MDD), while clinical trials show that dietary improvement can improve depressive symptoms. However, due to issues with blinding dietary trials, confirming a causal relationship for diet's influence on MDD requires further research. Thus, we systemically investigated the bi-directional causal relationships between dietary habits and MDD by using two-sample Mendelian randomization (MR). METHODS: We collected publicly available genome-wide association studies' summary statistics for dietary habits from UK Biobank (n = 449,210) and MDD from the Psychiatric Genomics Consortium (n = 142,646). We used a weighted median approach to synthesize MR estimates across genetic instruments. For the robustness of our results, we compared weighted median results with results from the inverse-variance weighted, the weighted mode, and MR-PRESSO. RESULTS: There was moderate evidence that beef intake has a protective effect on MDD. There was weak but detectable evidence that cereal intake has a protective effect on MDD, while non-oily fish intake might increase the risk of MDD. We did not observe any causal effect of MDD on dietary habits. LIMITATIONS: Our study may suffer from the violation of assumptions of MR due to horizontal pleiotropy; therefore, we did several sensitivity analyses to detect and minimize the bias. CONCLUSIONS: In this two-sample MR analysis, we observed that higher beef intake may be protective against MDD. However, MDD did not appear to affect dietary habits. Potential mechanisms need to be further investigated to support our novel findings.

Ceftazidime-avibactam and intrapleural amikacin therapy for extensively drug-resistant Pseudomonas aeruginosa thoracic empyema: A case report.

INTRODUCTION: Thoracic empyema and concomitant bronchopleural fistula are serious complications of pneumonia. The treatment of empyema caused by extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has become increasingly challenging. PATIENTS CONCERNS AND IMPORTANT CLINICAL FINDINGS: A 57-year-old woman with controlled schizophrenia developed hospital-associated bacterial pneumonia secondary to P. aeruginosa on day 13 of hospitalization for brain meningioma surgery. DIAGNOSIS: Chest radiography and computed tomography revealed right-sided necrotizing pneumonia with pneumothorax, a focal soft tissue defect over the right lower chest wall, and a mild right-sided encapsulated pleural effusion with consolidation. XDR-PA was isolated on empyema cultures. INTERVENTIONS: The patient was treated with intrapleural amikacin as a bridge to video-assisted thoracoscopic surgery, followed by novel ceftazidime-avibactam therapy. OUTCOMES: On the 104th day of admission, the patient underwent chest wall debridement and closure. The patient was discharged on day 111. Twenty-eight days after discharge, there were no observable sequelae of empyema. CONCLUSION: Although the minimum inhibitory concentration of ceftazidime-avibactam for XDR-PA is relatively high (8 mg/L), this report emphasizes the efficacy of ceftazidime-avibactam treatment for XDR-PA empyema, as well as the importance of source control.