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Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. Methods: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. Results: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07–1.12], p < 0.001), male sex (1.92 [1.22–3.00], p = 0.004), current smoker (2.31 [1.10–4.87], p = 0.027) and underlying malignancy (1.89 [1.20–2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14–0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5–5778.5 and ≥ 5778.5 mg. Conclusion: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings. [ABSTRACT FROM AUTHOR]

Backgrounds. Acute invasive fungal rhinosinusitis (AIFRS) is a hazardous infectious disease with rapid progression and high mortality and morbidities. Further orbital involvement is commonly seen. This study aims to analyze risk factors, clinical characteristics, and outcomes between patients with or without orbital involvement. Methods. A retrospective review was performed in a single tertiary medical center over a span of 13 years (2005–2018). A total of 21 patients with diagnosis of AIFRS were enrolled. We reviewed the patients' basic characteristics, comorbidities, clinical presentations, image study findings, culture pathogens, and treatment outcomes and analyzed the differences between orbital-involved and orbital sparing disease. Results. The most common comorbidities in AIFRS were diabetes mellitus (DM) and hematological malignancy. Nine the 21 AIFRS patients had orbital-involved disease. Patients with orbital involvement had a higher prevalence of DM (p < 0.05). Image studies revealed significant infection of the ethmoid sinus, sphenoid sinus, and frontal sinus in the group with orbital complication (p < 0.05). Mucor, Rhizopus, and Aspergillus were cultured in both groups. Five patients in the orbital involvement group expired, with all of them having an initial presentation of conscious disturbance (p < 0.01). Rhino-orbital-cerebral fungal infection was noticed in 3 of the 5 expired patients. Conclusion. In AIFRS patients, DM other than hematological malignancy was the main risk factor for orbital-involved disease. Patients with ethmoid, sphenoid, or frontal sinusitis had a higher possibility of orbital complication. Poor consciousness at initial presentation revealed highest possibility of rhino-orbital-cerebral fungal infection and led to death. [ABSTRACT FROM AUTHOR]

Background: It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients.Methods: The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis.Results: We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone.Conclusions: This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity. [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacterial (NTM) infection in immunocompromized patients is currently a growing health concern, and we aimed to examine the relative risk of NTM infection in patients with Sjögren's syndrome (SS) compared with that in non-SS individuals.Methods: We used the 2003-2012 Taiwanese National Health Insurance Research Database to identify 6554 incident SS cases during 2007-2012 and selected 98,310 non-SS controls matched (1:15) for age, gender, and the year of first SS diagnosis date after excluding those who had rheumatoid arthritis or systemic lupus erythematosus.Results: We identified four NTM-infected patients in the SS group (three in the first year) and nine in the non-SS group (three in the first year). SS patients had a higher incidence rate of NTM infection than that in non-SS individuals (IRR, 7.56; 95% CI, 2.33-24.55), especially during the first year (IRR, 16.05; 95% CI, 3.24-79.51). After adjusting for potential confounders, the risk of NTM infection was not increased in SS patients during the entire follow-up period or during the first year, but the risk increased in SS patients treated with immunosuppressants during the entire follow-up period (HR, 17.77; 95% CI, 4.53-69.61), especially during the first year (HR, 33.33; 95% CI, 4.37-254.23).Conclusion: An increased risk of NTM infection was found in SS patients treated with immunosuppressants during the first year after SS diagnosis. [ABSTRACT FROM AUTHOR]

The article examines the taxonomic status of taiwanensis by comparing specimens from China and Taiwan with Myotis adversus from Indonesia using two mitochondrial and two nuclear genes. Findings showed that M. taiwanensis differs from M. adversus in external and dental features. The Myotis bats performed three monophylectic groups for both nuclear and mitochondrial concatenated genes and revealed that M. taiwanensis from Taiwan and China is related to M. pilosus than to M. adversus. The result of phylogenetic analysis supports the hypothesis that the Myotis from Taiwan, Anhui and Shandong are not same as M. adversus.

Objectives: Recent studies highlighted the link of schizophrenia risk with genetic variations in complement, which share the same pathogenesis with systemic lupus erythematosus (SLE). However, the coexistence of SLE and schizophrenia were rarely reported. We aimed to explore the autoantibody profiles, complement levels and prevalence of SLE in chronic schizophrenia patients.Methods: A prospective, cross-sectional study was conducted to recruit 481 long-term hospitalized schizophrenia spectrum disorder patients in Yuli hospital, Taiwan. Severity of schizophrenia was assessed by Positive and Negative Syndrome Scale (PANSS). Immunologic tests of autoantibodies and complement levels were measured. Genome-wide association analysis was conducted to compare genetic variants between schizophrenia with SLE and non-SLE schizophrenia.Results: In total, 47 (9.8%) and 31 (6.4%) participants had positive anti-nuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) antibodies, respectively. After rheumatologic exams, 30 (6.2%) patients were diagnosed schizophrenia with SLE, while 32 (6.7%) subjects were classified as schizophrenia with autoimmune features. Schizophrenia patients with SLE had more arthritis, serositis, homogenous ANA pattern, conceptual disorganization in PANSS and increased salivation due to psychotropics compared with their counterparts. ANA titers and complement levels were significantly correlated with PANSS scores and side effect of psychotropics. No significant genetic variation between schizophrenia with SLE and non-SLE schizophrenia were identified.Conclusion: SLE may coexist in chronic hospitalized schizophrenia. Complement levels could be a potential biomarker in schizophrenia patients. Considering the possible reversibility of psychotic features and adverse effects of antipsychotics, SLE with psychosis should be identified in patients with chronic hospitalized schizophrenia. [ABSTRACT FROM AUTHOR]

• The definition for slowness and weakness were adjusted to the current criteria produced in 2019. • The data about frail population was analyzed in the revised manuscript, as well as the prevalence about the each index of Fried criteria. • The method for multivariate regression analysis was described in detail. • For the relationship about cognitive function, frailty and PF and mortality, more discussion was shown. Both frailty and prefrailty (PF) are related to mortality. However, there is no consensus about the PF subtypes for prediction of the mortality risk. We aimed to compare the 5-year mortality of functionally independent geriatric outpatients with nonfrailty, different PF subtypes and frailty. This was a single-center, retrospective cohort study. Community-dwelling older adults who visited the geriatric outpatient clinic in a healthcare institution in Taiwan were enrolled. PF1 was defined based on exhaustion and/or body weight loss whereas PF2 was defined by one or two of the following criteria: weakness, slowness, and low physical activity. Frailty was defined by three or more above criteria. Demographics and results of comprehensive geriatric assessment were compared and Kaplan–Meier survival analysis was used to determine the 5-year survival among the nonfrail, PF1, PF2 and frail groups. Of the 982 participants, the proportion of PF and frailty was high (PF 45.7% and frailty 24.5%). The cumulative 5-year survival rate of the nonfrail group, PF1, PF2 subgroups and frail group was 98.6%, 95.8%, 89.1% and 81.3% respectively. Age, male sex, PF2 subtype and frailty were significantly associated with 5-year mortality [hazard ratio (95% confidence interval) 1.05 (1.01–1.08), 1.96 (1.08–3.57), 5.18 (1.57–17.09), and 6.87 (2.05–23.04), respectively]. The proportion of PF and frailty was high in old outpatient population with functional independence. PF2 subtypes and frailty could influence the 5-year mortality risk in these participants. Identifying PF2 participants earlier and instituting prompt intervention may be beneficial in older patients. [ABSTRACT FROM AUTHOR]

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape., (© 2024. The Author(s).)

Background: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce., Methods and Results: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G>A and LDLR c.268G>A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD., Conclusions: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

Familial hypercholesterolemia (FH) is a common genetic disorder characterized by a lifelong elevated low-density lipoprotein cholesterol (LDL-C) level. The relationship between FH and ischemic stroke is still controversial. We enrolled ischemic stroke patients prospectively in our neurological ward, and divided them into two groups according to LDL-C levels with a threshold of 130 mg/dl. Targeted sequencing was performed in all stroke patients for LDLR, APOB , and PCSK9 genes. The fifty-eight high-LDL subjects were older, prevalence of previous myocardial infarction/stroke history was lower, and the first stroke age was older compared with values in the sixty-three low-LDL cases. The prevalence of FH in Han-Chinese stroke patients was 5.0%, and was 10.3% in those with a higher LDL-C level. We identified six carriers, who had higher percentages of large vessel stroke subtype (66.7% vs. 15.4%) and transient ischemic attack (33.3% vs. 3.8%), previous myocardial infarction/stroke history (50.0% vs. 11.5%), statin use (50.0% vs. 11.5%), and increased carotid intima-media thickness (IMT) (0.9-1.2mm vs.0.7-9.0mm) compared with the other hypercholesterolemic patients without pathogenic variants. Ischemic stroke patients carrying FH pathogenic variants seemed to have a higher risk for large artery stroke and transient ischemic attack. The IMT exam could be useful to screen for FH in hypercholesterolemic stroke patients.

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival., Competing Interests: The authors have declared that no competing interests exist.

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.

Post-transplant diabetes mellitus (PTDM) is associated with infection, cardiovascular morbidity, and mortality. A retrospective cohort study involving patients who underwent renal transplantation in a transplantation center in Taiwan from January 2000 to December 2018 was conducted to investigate the incidence and risk factors of PTDM and long-term patient and graft survival rates. High age (45-65 vs. <45 years, adjusted odds ratio (aOR) = 2.90, 95% confidence interval (CI) = 1.64-5.13, p < 0.001), high body mass index (>27 vs. <24 kg/m 2 , aOR = 5.35, 95% CI = 2.75-10.42, p < 0.001), and deceased organ donor (cadaveric vs. living, aOR = 2.01, 95% CI = 1.03-3.93, p = 0.04) were the three most important risk factors for the development of PTDM. The cumulative survival rate of patients and allografts was higher in patients without PTDM than in those with PTDM (p = 0.007 and 0.041, respectively). Concurrent use of calcineurin inhibitors and mammalian target of rapamycin inhibitors (mTORis) decreased the risk of PTDM (tacrolimus vs. tacrolimus with mTORi, aOR = 0.28, 95% CI = 0.14-0.55, p < 0.001). Investigating PTDM risk factors before and modifying immunosuppressant regimens after transplantation may effectively prevent PTDM development.