NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2-/- mice were protected from age-related OA development. Taken together, the TLR2-NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.

Prognostic factors for patients with hematologic malignancies admitted to the intensive care unit: is allogeneic transplantation still a risk factor?

The rate of intensive care unit (ICU) mortality in patients with hematologic malignancies is high. The risk factors for this were inconsistent across several previous studies, and there is currently no accepted consensus around risk factors for these patients. We aimed to identify which prognostic factors were associated with ICU mortality in critically ill patients with hematologic malignancies, nearly half of which were allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. In addition, we aimed to compare the characteristics and clinical outcomes of patients with and without allogenic allo-HSCT. In total, 217 patients with hematologic malignancies were enrolled consecutive, 119 (54.8%) of whom underwent HSCT (allo-HSCT: n = 115). All survivors were followed up with until August 1, 2022. The rate of ICU mortality in this cohort was 54.4%: 55.5 and 53.1% for the patients with and without HSCT, respectively (p = 0.724). The probabilities of survival after ICU admission were also comparable between the patients who had allo-HSCT and those who did not. A multivariable analysis revealed that cerebrovascular disease, hyperlactic acidemia on the day of ICU admission, lower platelet count, use of vasoactive drugs, and absence of noninvasive ventilation on the day of ICU admission were independent risk factors for ICU mortality. For patients with three to five of these risk factors, the rate of ICU mortality was as high as 84.6%, which was significantly higher than that of other patients. In this study, the ICU mortality rate in patients with hematologic malignancies was still high, particularly for those with multiple risk factors. However, allo-HSCT was not found to be a risk factor for ICU mortality.

Aberrant Upregulation of Indoleamine 2,3-Dioxygenase 1 Promotes Proliferation and Metastasis of Hepatocellular Carcinoma Cells via Coordinated Activation of AhR and ß-Catenin Signaling.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Chronic liver inflammation due to hepatitis virus infection and other major effectors is a major risk factor of HCC. Indoleamine 2,3-dioxygenase 1 (IDO1), a heme enzyme highly expressed upon stimulation with proinflammatory cytokines such as interferon-γ (IFN-γ), is activated to modulate the tumor microenvironment and potentially crucial in the development of certain cancer types. Earlier studies have majorly reported an immunomodulatory function of IDO1. However, the specific role of IDO1 in cancer cells, particularly HCC, remains to be clarified. Analysis of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) dataset in the current study revealed a significant correlation between IDO1 expression and HCC. We further established inducible IDO1-expressing cell models by coupling lentivirus-mediated knockdown and IFN-γ induction of IDO1 in normal and HCC cells. In functional assays, proliferation and motility-related functions of HCC cells were compromised upon suppression of IDO1, which may partially be rescued by its enzymatic product, kynurenine (KYN), while normal hepatocytes were not affected. Aryl hydrocarbon receptor (AhR), a reported endogenous KYN receptor, is suggested to participate in tumorigenesis. In mechanistic studies, IDO1 activation promoted both AhR and ß-catenin activity and nuclear translocation. Immunofluorescence staining and co-immunoprecipitation assays further disclosed interactions between AhR and ß-catenin. In addition, we identified a Src-PTEN-PI3K/Akt-GSK-3ß axis involved in ß-catenin stabilization and activation following IDO1-mediated AhR activation. IDO1-induced AhR and ß-catenin modulated the expression of proliferation- and EMT-related genes to facilitate growth and metastasis of HCC cells. Our collective findings provide a mechanistic basis for the design of more efficacious IDO1-targeted therapy for HCC.

Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.

Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes.

Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.

A converse 4-1BB and CD40 ligand expression pattern delineates activated regulatory T cells (Treg) and conventional T cells enabling direct isolation of alloantigen-reactive natural Foxp3+ Treg.

Natural regulatory T cells (nTreg) play a central role in the induction and maintenance of immunological tolerance. Experimental transplant models and recent clinical trials demonstrate that nTreg can control alloreactivity. To upgrade Treg-based cell therapies to a selective suppression of undesired immune reactions, only the transfer of Ag-specific nTreg represents the appropriate therapeutic option. However, Ag-specific nTreg are present at extremely low frequencies in the periphery, and so far appropriate surface markers for their precise identification are missing. In this study, we demonstrate that activated nTreg and activated conventional T cells differ in their 4-1BB and CD40 ligand (CD40L) expression signatures, allowing a clear dissection from each other. Based on the expression of 4-1BB and absence of CD40L expression, human alloantigen-reactive Foxp3(+) nTreg can be directly isolated from MLR cultures with high purity. Alloantigen-reactive 4-1BB(+)CD40L(-) nTreg were characterized by a completely demethylated Treg-specific demethylated region and showed alloantigen-specific suppressive properties superior to polyclonal Treg. Importantly, isolated 4-1BB(+)CD40L(-) nTreg maintain the nTreg phenotype and alloantigen-reactivity after in vitro expansion. Our results offer the possibility to simultaneously analyze Ag-specific nTreg and conventional T cells, and to establish cellular therapies with Ag-specific nTreg aiming at a specific inhibition of unwanted immunity.

Interleukin-10-1082A/G and -592C/A polymorphisms with risk of Parkinson's disease: a meta-analysis.

Several studies have been conducted in recent years to evaluate the risk of Parkinson's disease (PD) and polymorphisms of interleukin-10 (IL-10). However, the results were conflicting. Therefore, we performed this meta-analysis of published case-control studies to assess this association. Systematic searches of electronic databases PubMed Web of Science, BIOSIS Previews, Science Direct, Chinese Biomedical Database, WANFANG Database, and Chinese National Knowledge Infrastructure with hand searching of the references of identified articles were conducted. Data were extracted using a standardized form and pooled odd ratios with 95% confidence intervals were calculated to evaluate the strength of the association. A total of seven case-control studies involving 1912 PD cases and 1740 controls were included, concerning two polymorphisms (-1082A/G and -592C/A) of IL-10 gene. No significant associations were found in the overall analysis for both -1082A/G and -592C/A polymorphisms with PD risk. Similar lacking associations were observed in subgroup analysis based on ethnicity and age of onset. In conclusion, there is no enough evidence for association between IL-10 polymorphisms (-1082A/G and -592C/A) and risk of PD at present. Well-designed studies with larger sample size and multi-ethnicity studies are warranted in the future.

Risk factors and predictive model for mortality in patients undergoing allogeneic hematopoietic stem cell transplantation admitted to the intensive care unit.

Hematological malignant tumors represent a group of major diseases carrying a substantial risk to the lives of affected patients. Risk factors for mortality in critically ill patients have garnered substantial attention in recent research endeavors. The present research aimed to identify factors predicting intensive care unit (ICU) mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, the present study analyzed and compared the mortality rate between patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and those undergoing identical sibling donor (ISD) transplantation. A total of 108 patients were included in the present research, 83 (76.9%) of whom underwent Haplo-SCT. ICU mortality was reported in 58 (53.7%) patients, with the values of 55.4 and 48.0% associated with Haplo-SCT and ISD, respectively (P=0.514). The mortality rate of patients undergoing Haplo-SCT was comparable to that of patients undergoing ISD transplantation. The present study found that reduced hemoglobin, elevated total bilirubin, elevated brain natriuretic peptide, elevated fibrinogen degradation products, need for vasoactive drugs at ICU admission, need for invasive mechanical ventilation and elevated APACHE II scores were independent risk factors for ICU mortality. Among patients presenting with 5-7 risk factors, the ICU mortality reached 100%, significantly exceeding that of other patients. The present research revealed that ICU mortality rates remain elevated among patients who underwent allo-HSCT, especially those presenting multiple risk factors. However, the outcome of patients undergoing Haplo-SCT were comparable to those of patients undergoing ISD transplants.

Differential synovial Th1 cell reactivity towards Escherichia coli antigens in patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with clinical and subclinical mucosal inflammation, suggesting that commensal bacteria contribute to the pathogenesis of the disease. METHODS: The frequency of Th1 cells reacting towards conserved Escherichia coli (E coli) proteins and pathogenicity factors in peripheral blood mononuclear cells (PBMNC) and synovial fluid mononuclear cells (SFMNC) of patients with AS and those with rheumatoid arthritis (RA) was determined. PBMNC from healthy individuals were included as controls. RESULTS: Higher frequencies of Th1 cells reacting to conserved E coli proteins were observed in SFMNC and, to a lesser extent, in PBMNC of patients with AS compared with patients with RA (SFMNC, p<0.01; PBMNC, p<0.05). In contrast, the frequencies of cytomegalovirus- and staphylococcal enterotoxin B (SEB)-induced Th1 cells did not differ between patients with AS and those with RA in SFMNC, and SEB-induced Th1 cell frequencies in PBMNCs were even higher in patients with RA than in those with AS (p<0.05). CONCLUSIONS: The high frequency and enrichment of E coli-specific CD4 T cells in the inflamed joints of patients with AS but not those with RA suggests that commensal bacteria are relevant antigens in AS that might trigger the disease.

Exploring the Causal Effect of Constipation on Parkinson's Disease Through Mediation Analysis of Microbial Data.

Background and Aims: Parkinson's disease (PD) is a worldwide neurodegenerative disease with an increasing global burden, while constipation is an important risk factor for PD. The gastrointestinal tract had been proposed as the origin of PD in Braak's gut-brain axis hypothesis, and there is increasing evidence indicating that intestinal microbial alteration has a role in the pathogenesis of PD. In this study, we aim to investigate the role of intestinal microbial alteration in the mechanism of constipation-related PD. Methods: We adapted our data from Hill-Burns et al., in which 324 participants were enrolled in the study. The 16S rRNA gene sequence data were processed, aligned, and categorized using DADA2. Mediation analysis was used to test and quantify the extent by which the intestinal microbial alteration explains the causal effect of constipation on PD incidence. Results: We found 18 bacterial genera and 7 species significantly different between groups of constipated and non-constipated subjects. Among these bacteria, nine genera and four species had a significant mediation effect between constipation and PD. All of them were short-chain fatty acid (SCFA)-producing bacteria that were substantially related to PD. Results from the mediation analysis showed that up to 76.56% of the effect of constipation on PD was mediated through intestinal microbial alteration. Conclusion: Our findings support that gut dysbiosis plays a critical role in the pathogenesis of constipation-related PD, mostly through the decreasing of SCFA-producing bacteria, indicating that probiotics with SCFA-producing bacteria may be promising in the prevention and treatment of constipation-related PD. Limitations: 1) Several potential confounders that should be adjusted were not provided in the original dataset. 2) Our study was conducted based on the assumption of constipation being the etiology of PD; however, constipation and PD may mutually affect each other. 3) Further studies are necessary to explain the remaining 23.44% effect leading to PD by constipation.

A Pilot Study Exploring the Association of Entacapone, Gut Microbiota, and the Subsequent Side Effects in Patients With Parkinson's Disease.

Background and Aims: Entacapone, one of the most common drugs distributed among patients with Parkinson's disease, is a peripherally acting catechol-O-methyltransferase (COMT) inhibitor that is used in addition to levodopa to control symptoms. However, there have been negative effects reported against entacapone, namely, gastrointestinal (GI) problems and drowsiness. In this pilot study, we aim to examine the hypothesis that the discomfort induced by entacapone might be originated from the shift of microbial composition by adjusting the effect of levodopa. Methods: The population in this pilot study consisted of 13 PD patients treated with levodopa only and 11 with both levodopa and entacapone. The 16S rRNA gene sequence data were processed, aligned, and categorized using the DADA2. Alpha diversity indices for Observed, Chao1, Shannon, and Simpson metrics were calculated with Phyloseq 1.32.0. Dissimilarities were calculated using unweighted unique fraction metrics (Unifrac), weighted Unifrac, and Canberra distance. Functional differences were calculated by PICRUSt2 based on the KEGG database. Results: Results of 16S rRNA sequencing analysis showed that while entacapone did not influence the species richness, the composition of the microbial community shifted considerably. Relative abundances of bacteria related to constipation and other GI disorders also altered significantly. Functional enrichment analysis revealed changes in the metabolic activity of alanine, aspartate, and glutamate. These amino acids are related to common side effects of entacapone such as auditory hallucinations, fatigue, and nightmare. Conclusion: Our findings provide testable hypothesis on the cause of unpleasant side effects of entacapone, which in the long run could possibly be reduced through gut microbiota manipulation.

Predicting perineural invasion using histogram analysis of zoomed EPI diffusion-weighted imaging in rectal cancer.

PURPOSE: To investigate the utility of histogram analysis of zoomed EPI diffusion-weighted imaging (DWI) for predicting the perineural invasion (PNI) status of rectal cancer (RC). METHODS: This prospective study evaluated 94 patients diagnosed with histopathologically confirmed RC between July 2020 and July 2021. Patients underwent preoperative rectal magnetic resonance imaging (MRI) examinations, including the zoomed EPI DWI sequence. Ten whole-tumor histogram parameters of each patient were derived from zoomed EPI DWI. Reproducibility was evaluated according to the intra-class correlation coefficient (ICC). The association of the clinico-radiological and histogram features with PNI status was assessed using univariable analysis for trend and multivariable logistic regression analysis with ß value calculation. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance. RESULTS: Forty-two patients exhibited positive PNI. The inter- and intraobserver agreements were excellent for the histogram parameters (all ICCs > 0.80). The maximum (p = 0.001), energy (p = 0.021), entropy (p = 0.021), kurtosis (p < 0.001), and skewness (p < 0.001) were significantly higher in the positive PNI group than in the negative PNI group. Multivariable analysis showed that higher MRI T stage [ß = 2.154, 95% confidence interval (CI) 0.932-3.688; p = 0.002] and skewness (ß = 0.779, 95% CI 0.255-1.382; p = 0.006) were associated with positive PNI. The model combining skewness and MRI T stage had an area under the ROC curve of 0.811 (95% CI 0.724-0.899) for predicting PNI status. CONCLUSION: Histogram parameters in zoomed EPI DWI can help predict the PNI status in RC.

Menstrual blood-derived mesenchymal stromal cells efficiently ameliorate experimental autoimmune encephalomyelitis by inhibiting T cell activation in mice.

BACKGROUND: Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE). METHODS: We assessed the therapeutic effect of MB-MSCs transplanted via either intravenous (i.v.) or intraperitoneal (i.p.) route in EAE in comparison with umbilical cord-derived MSCs (UC-MSCs). We used histology to assess myelin sheath integrity and infiltrated immune cells in CNS and flow cytometry to evaluate EAE-associated inflammatory T cells and antigen-presenting cells in lymphoid organs. RESULTS: We observed disease-ameliorating effects of MB-MSCs when transplanted at various stages of EAE (day - 1, 6, 10, and 19), via either i.v. or i.p. route, with a potency comparable to UC-MSCs. We observed reduced Th1 and Th17 cell responses in mice that had received MB-MSCs via either i.v. or i.p. injection. The repressed Th1 and Th17 cell responses were associated with a reduced frequency of plasmacytoid dendritic cells (pDCs) and a suppressed co-stimulatory capacity of pDCs, cDCs, and B cells. CONCLUSIONS: Our data demonstrate that the readily available MB-MSCs significantly reduced the disease severity of EAE upon transplantation. Thus, they have the potential to be developed as ready-to-use allo-MSCs in MS-related inflammation.

Optimization of chondrocyte isolation from human articular cartilage to preserve the chondrocyte transcriptome.

The isolation of chondrocytes from human articular cartilage for single-cell RNA sequencing requires extensive and prolonged tissue digestion at 37 C. Modulations of the transcriptional activity likely take place during this period such that the transcriptomes of isolated human chondrocytes no longer match their original status in vivo. Here, we optimized the human chondrocyte isolation procedure to maximally preserve the in vivo transcriptome. Cartilage tissues were transferred into a hypoxia chamber (4% O2) immediately after being removed from OA patients and minced finely. Collagenase II at concentrations of 0.02%, 0.1%, 0.25%, 0.5%, 1%, and 2% was applied for 0.5, 1, 2, 4, and 18 h to digest the minced tissue. Actinomycin D (ActD) was added to test its capacity in stabilizing the transcriptome. Cell yield, viability, cell size, and transcriptome were determined using counter chamber, flow cytometry, and RNA sequencing (RNA-seq). Collagenase II at 2% concentration released small chondrocytes from cartilage matrix during the first digestion hour and started to release large cells thereafter, reaching a complete release at 4 h. During 4-h digestions, collagenase II at 2% and 1% but not at lower concentrations yielded maximal release also of the large chondrocyte population. RNA-seq analysis revealed that a 4-h digestion period with 1% or 2% collagenase II plus Actinomycin D optimally preserved the transcriptome. Thus, this study provides an isolation protocol for single chondrocytes from human articular cartilage optimized for transcriptome preservation and RNA-seq analysis.

Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic autoimmune inflammation.

T-helper (Th) cells activated by cytokines in the absence of T-cell receptor ligation are suspected to participate in inflammatory processes by production of interferon-gamma (IFN-gamma). Still, the relevance of such a mechanism has not been addressed in humans. Here we demonstrate that a subset of human effector-memory Th cells expressing functional interleukin-12R (IL-12R), IL-18Ralpha, and CCR5 ex vivo can be induced to secrete IFN-gamma by cytokines signaling via the IL-2R common gamma-chain in combination with IL-12 and IL-18. Cytokine-driven IFN-gamma production depends on JAK3- and p38 mitogen-activated kinase signals and is sensitive to suppression by CD25(++) regulatory T cells. Contrary to IFN-gamma(+) Th cells induced upon antigen-specific stimulation, their cytokine-activated counterparts characteristically lack expression of costimulator 4-1BB (CD137). Strikingly, the majority of Th cells infiltrating inflamed joints of rheumatoid arthritis patients is equipped with receptors prerequisite for cytokine-induced IFN-gamma secretion. Among these cells, we detected a substantial fraction that secretes IFN-gamma directly ex vivo but lacks 4-1BB expression, indicating that cytokine-induced IFN-gamma(+) Th cells operate in autoimmune inflammation. Our data provide a rationale for how human effector-memory Thcells can participate in perpetuating inflammatory processes in autoimmunity even in the absence of T-cell receptor ligation.

Different Trends of Distinct Time Points of AIDS Events Following HIV Diagnosis in Various At-risk Populations: A Retrospective Nationwide Cohort Study in Taiwan.

INTRODUCTION: Acquired immune deficiency syndrome (AIDS) events at distinct time points after human immunodeficiency virus (HIV) diagnosis require various AIDS prevention strategies. However, no nationwide epidemiological surveillance studies have been conducted to explore the trends of distinct AIDS event time points in various at-risk populations. The aim of this study was to explore the issues and characterize the determinants of AIDS status after HIV diagnosis. METHODS: This nationwide cohort study enrolled HIV-positive Taiwanese during 1984-2016. AIDS events were classified into three time points (≤ 3, 4-12, > 12 months) by their occurrence time after HIV diagnosis. The periods of HIV/AIDS diagnosis were divided into six categories according to the calendar year of HIV/AIDS diagnosis: 1984-1991, 1992-1996, 1997-2001, 2002-2006, 2007-2011, and 2012-2016. HIV-positive Taiwanese during 1984-2011 were then selected to determine the factors associated with four AIDS statuses within 5 years after HIV diagnosis (no AIDS, AIDS ≤ 3 months, within 4-12 months, > 12 months) using multinomial logistic regression. RESULTS: Of 33,142 cases, we identified 15,254 (46%) AIDS events. The overall AIDS incidence (events/100 person-years) peaked during 1992-1996 (20.61), then declined, and finally stabilized from 2002 (8.96-9.82). The evolution of the proportion of distinct time points of AIDS events following HIV diagnosis changed significantly in heterosexuals and intravenous drug users (IDUs) during 1984-2016 (decline at ≤ 3 months in IDUs, decline at 4-12 months in IDUs, and increase at > 12 months in heterosexuals and IDUs) but not among men who have sex with men (MSM). Time points at ≤ 3 months remained at > 50% among MSM and at > 55% among heterosexuals. In multinomial logistic regression, IDUs (vs. men who have sex with men; MSM) had a lower risk of all AIDS statuses; heterosexuals (vs. MSM) had a higher risk of AIDS events ≤ 3 months after HIV diagnosis. CONCLUSION: The magnitude of AIDS in Taiwan has been stable since 2002. Enhancing early diagnosis among people with sexual contact and optimizing the HIV care continuum among heterosexuals and IDUs should be priorities for further AIDS prevention strategies.

Changing Pattern of Chemsex Drug Use Among Newly Diagnosed HIV-Positive Taiwanese from 2015 to 2020 in the Era of Treat-All Policy.

Chemsex drug use (CDU) is a frequent, yet neglected issue in the era of treat-all policy. We evaluated the temporal pattern of CDU, factors associated with CDU, and drug-drug interactions (DDIs) between chemsex drugs and initial antiretroviral therapy (ART) by surveying 621 Taiwanese individuals (mean age: 29.7 years; 99.2% men; 92.9% men who have sex with men) diagnosed with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) from 2015 to 2020 [2015 to 2016 (period 1), 2017 to 2018 (period 2), and 2019 to 2020 (period 3)]. CDU was defined as chemsex in the past 1 year before HIV diagnosis. CDU remained prevalent across three periods (34.3-30.5%). Among CDU, methamphetamine (43.4%) was most frequently used, followed by amphetamine (40.0%) and poppers (various alkyl nitrites) (39.5%). We identified significantly increasing amphetamine use (37.0-61.5%) and decreasing ecstasy (methylenedioxy-methamphetamine) use (32.1-17.9%) in CDU across three periods. Besides, polydrug chemsex also significantly increased in CDU across three periods (23.5-43.6%), with amphetamine plus gamma-hydroxybutyrate being the most commonly used combination. CDU was associated with multiple sexual partners and a history of sexually transmitted diseases (STDs). DDIs between chemsex drugs and initial ART remained stable across three periods (10.6-7.8%), with cobicistat/elvitegravir and methamphetamine most common combination. In summary, the magnitude of CDU remained high across 2015-2020 in Taiwan, causing DDIs with initial ART agents. Strategies to reduce the frequency of high-risk sexual practices, STD transmission, and DDIs for newly diagnosed HIV-positive patients engaging in chemsex should be implemented.

High prevalence of unawareness of HCV infection status among both HCV-seronegative and seropositive people living with human immunodeficiency virus in Taiwan.

OBJECTIVES: HCV infection status awareness is crucial in the HCV care continuum for both HCV-seropositive (HCV-positive status awareness) and seronegative (HCV-negative status awareness) populations. However, trends in the unawareness of HCV infection status (UoHCV) remain unknown in HIV-positive patients. This study investigated UoHCV prevalence, the associated factors of UoHCV, and its association with HCV-related knowledge in HIV-positive patients. METHODS: For this cross-sectional, multicenter, questionnaire-based study, 844 HIV-infected participants were recruited from three hospitals in Taiwan from June 2018 to March 2020. Participants were grouped by HCV serostatus (HCV-seronegative [n = 734] and HCV-seropositive [n = 110]) and categorized by their HIV diagnosis date (before 2008, 2008-2013, and 2014-2020). Exploratory factor analysis was used to categorize the 15 items of HCV-related knowledge into three domains: route of HCV transmission, HCV course and complications, and HCV treatment. RESULTS: The prevalence of UoHCV was 58.7%-62.6% and 15.1%-31.3% in the HCV-seronegative and HCV-seropositive groups, respectively, across 3 periods. More participants with UoHCV believed that HCV infection was only contracted by intravenous injection. In the HCV-seropositive group, participants with UoHCV were more likely to have HIV diagnosis before 2008 (vs. 2014-2020), be men who have sex with men (vs. people who inject drugs), and have hepatitis A virus seronegativity. In the HCV-seronegative group, participants with UoHCV were more likely to have a recent history of sexually transmitted diseases, but had a lower education level, had received less information on HCV infection from clinicians, and were less likely to have heard of HCV infection prior to the research. UoHCV was associated with lower scores for three domains of HCV-related knowledge in both groups. CONCLUSIONS: The negative association of UoHCV with HCV-related knowledge suggests that strategies targeting patients according to their HCV serostatus should be implemented to reduce UoHCV and eradicate HCV infection among HIV-positive patients.

Cascade Analysis of Anonymous Voluntary HIV Counseling and Testing Among Patients with HIV Infection in Taiwan.

Despite successful implementation of anonymous voluntary human immunodeficiency virus (HIV) counseling and testing (aVCT) in Taiwan, the trend of late HIV presentation in sexually active populations has remained unchanged in Taiwan over the past decade. We evaluated the effect and acceptance of an aVCT cascade program among Taiwanese individuals by surveying 572 participants (mean age: 29.6 years; 99.3% men; and 79.5% same-sex sexual contact) diagnosed with HIV/acquired immune deficiency syndrome (AIDS) from 2015 to 2019. We designed a five-stage continuum based on acceptance of the program before HIV diagnosis: at high risk of HIV infection (Stage 1), heard of aVCT (Stage 2), wants to receive aVCT (Stage 3), has received aVCT (Stage 4), and regularly receives aVCT (Stage 5). Four domains established from exploratory factor analysis described reasons for inability to reach the next aVCT stage: low perceived HIV risk, fear of testing positive because of discrimination/stigmatization, and structural barriers to aVCT. Regular aVCT (vs. never receiving aVCT) protected against AIDS on diagnosis (p < 0.001). There were no significant differences in program acceptance across 2015-2019. However, uptake reduced markedly across the program; the largest reduction (37.4.0-61.0%) occurred from Stage 4 to Stage 5. Fear of testing positive because of discrimination/stigmatization was the main reason for not proceeding to the next aVCT stage. Although the findings indicate the benefits of regular aVCT for early HIV diagnosis, additional strategies to reduce fear of negative social consequences of HIV infection are prioritized to optimize aVCT in Taiwan.

[Improving the cancer screening model: experience applying an integrated operating system].

BACKGROUND & PROBLEMS: Cancer patient numbers have continued to rise in recent years. In terms of deaths from various cancers, malignancies are involved in 28.9% of cases. Over the course of disease contraction, treatment and aftercare, patients face unease and pressure of various forms and degrees. Patients may abort treatment due to treatment pain and discomfort. The case manager may play a positive role by following up at appropriate moments to understand patient needs and deliver proper resources in order to avoid cancer recrudescence, which may delay treatment progress. PURPOSE: The objective of this study was to improve nursing quality and management performance in cancer patient care. Through the integration of the management information system, A "Cancer Case Screening System" was built using a management information system to shorten the amount of time spent on scanning new cases and to reduce the rate of scanning error. RESOLUTION: Using a decision matrix, the research team proposed the following solution: (1) Define the system infrastructure currently employed in hospitals; (2) Discuss the Cancer Cases Screening System workflow and determine system specifications; (3) Write the Cancer Cases Screening System program to establish an effective management information system. RESULTS: The time spent on scanning case per day dropped from 117.14 to 28.57 minutes. The error rate was also reduced from 34.65% to 8.87%. These results achieved the objective of the project. CONCLUSION: Promoting the developed screening system in the broader medical community can help reduce medical treatment costs and increase treatment continuity. This project may be considered and referenced by managers of relevant medical organizations.