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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Group A Streptococcus Subcutaneous Infection-Induced Central Nervous System Inflammation Is Attenuated by Blocking Peripheral TNF.

Group A streptococcus (GAS) infection causes a strong inflammatory response associated with cytokine storms, leading to multiorgan failure, which is characterized as streptococcal toxic shock syndrome. However, little is known about GAS subcutaneous infection-mediated brain inflammation. Therefore, we used a bioluminescent GAS strain and reporter mice carrying firefly luciferase under transcriptional control of the nuclear factor-kappa B (NF-κB) promoter to concurrently monitor the host immune response and bacterial burden in a single mouse. Notably, in addition to the subcutaneous inoculation locus at the back of mice, we detected strong luminescence signals from NF-κB activation and increased inflammatory cytokine production in the brain, implying the existence of central nervous system inflammation after GAS subcutaneous infection. The inflamed brain exhibited an increased expression of glial fibrillary acidic protein and nicotinamide adenine dinucleotide phosphate oxidase components and greater microglial activation and blood-brain barrier (BBB) disruption. Furthermore, Fluoro-Jade C positive cells increased in the brain, indicating that neurons underwent degeneration. Peripheral tumor necrosis factor (TNF), which contributes to pathology in brain injury, was elevated in the circulation, and the expression of its receptor was also increased in the inflamed brain. Blockage of peripheral TNF effectively reduced brain inflammation and injury, thereby preventing BBB disruption and improving survival. Our study provides new insights into GAS-induced central nervous system inflammation, such as encephalopathy, which can be attenuated by circulating TNF blockage.

Changing Spectrum of Opportunistic Illnesses among HIV-Infected Taiwanese Patients in Response to a 10-Year National Anti-TB Programme.

The current trends and spectrum of acquired immunodeficiency syndrome (AIDS)-related opportunistic illnesses (AOIs) among newly diagnosed human immunodeficiency virus (HIV)-infected patients after the implementation of the 2006⁻2015 national anti-tuberculosis (TB) programmes in Taiwan remain unknown. We retrospectively reviewed 1757 patients at two centres in southern Taiwan between 2001 and 2015. Based on the anti-TB programme, patients were classified into periods 1 (2001⁻2005), 2 (2006⁻2010), and 3 (2011⁻2015). We further analysed factors associated with Mycobacterium tuberculosis (MTB) at presentation and during follow-up. The overall AOI incidence rate (23.6%) remained unchanged across the periods, with 81.4% of AOIs occurring at presentation. Pneumocystis jirovecii pneumonia was the leading AOI across the periods. MTB declined significantly from period 1 to period 3 (39.3% vs. 9.3%). Age and CD4+ cell count <200 cells/µL (vs. ≥501) were the risk factors associated with MTB at presentation, whereas period 2/3 (vs. period 1) was the protective factor. Intravenous drug use (vs. homosexual contact) was the risk factor associated with MTB during follow-up, and period 3 (vs. period 1) was the protective factor. AOI statistics in Taiwan must be closely monitored for fluctuations. Although MTB decreased substantially after implementation of the anti-TB programmes, additional efforts to reduce MTB are required.

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.

[Clinical characteristics and predictors of mortality in patients with candidemia in intensive care unit].

OBJECTIVE: To investigate the clinical characteristics and predictors of mortality in patients with candidemia in intensive care unit (ICU). METHODS: The patients with candidemia admitted to ICU of Peking University People's Hospital from January 2010 to December 2017 were enrolled. The general clinical data, indicators related to Candidia infection and prognosis were collected, and the clinical characteristics, infection characteristics and prognosis of patients with candidiasis were analyzed. Patients were divided into death group and survival group according to hospital survival status. The differences of each index were compared between two groups. The independent risk factors of mortality in patients with candidemia were analyzed by multivariate Logistic regression analysis. RESULTS: A total of 95 patients (55 males) with candidemia were included, with an average age of (69.3±16.5) years, acute physiology and chronic health evaluation II (APACHE II) was 24.7±3.6, sequential organ failure assessment (SOFA) was 6.6±2.7. Candida albicans accounted for the largest proportion of Candida infections (n = 56, 58.9%). Thirty-two (33.7%) patients received inadequate antifungal therapy and 38 (40.0%) patients received inadequate source control. Fifty-five (57.9%) patients were died in hospital. Compared with the survival group, patients in the death group was older (years: 72.5±14.6 vs. 64.9±18.0, P < 0.05), had higher APACHE II and SOFA scores (26.6±2.2 vs. 22.1±3.6, 7.9±2.0 vs. 4.7±2.4, both P < 0.01), higher rate of glucocorticoid treatment (18.2% vs. 10.0%, P < 0.05), and higher proportion of Candida albicans and Candida glabrata (69.1% vs. 45.0%, 10.9% vs. 7.5%, both P < 0.05), the rate of multi-site Candida infection also significantly increased (47.3% vs. 17.5%, P < 0.05). Intra-abdominal infection was the primary infection site and more common in death group (49.1% vs. 35.0%, P < 0.05). The rates of sepsis (87.3% vs. 62.5%), inadequate antifungal therapy (49.1% vs. 10.0%), inadequate source control (60.0% vs. 12.5%) in death group were all higher than those in survival group (all P < 0.01). It was shown by multivariate Logistic regression analysis that APACHE II [odds ratio (OR) = 1.605, P = 0.002, ß = 0.473], SOFA (OR = 1.501, P = 0.029, ß = 0.406), inadequate antifungal therapy (OR = 12.084, P = 0.006, ß = 2.492) and inadequate source control (OR = 7.332, P = 0.024, ß = 1.992) were independent risk factors for mortality in ICU patients with candidemia. CONCLUSIONS: Candidemia patients were severe and had poor prognosis. APACHE II, SOFA, inadequate antifungal therapy and inadequate source control were independent risk factors of mortality.

An explorative study on deep profiling of peripheral leukocytes to identify predictors for responsiveness to anti-tumour necrosis factor alpha therapies in ankylosing spondylitis: natural killer cells in focus.

BACKGROUND: Therapeutic targeting of tumour necrosis factor (TNF)-α is highly effective in ankylosing spondylitis (AS) patients. However, since one-third of anti-TNF-treated AS patients do not show an adequate clinical response there is an urgent need for new biomarkers that would aid clinicians in their decision-making to select appropriate therapeutic options. Thus, the aim of this explorative study was to identify cell-based biomarkers in peripheral blood that could be used for a pre-treatment stratification of AS patients. METHODS: A high-dimensional, multi-parametric flow cytometric approach was applied to identify baseline predictors in 31 AS patients before treatment with the TNF blockers adalimumab (TNF-neutralisation) and etanercept (soluble TNF receptor). RESULTS: As the major result, the frequencies of natural killer (NK) cells, and in particular CD8-positive (CD8+) NK cell subsets, were most predictive for therapeutic outcome in AS patients. While an inverse correlation between classical CD56+/CD16+ NK cells and reduction of disease activity was observed, the CD8+ NK cell subset behaved in the opposite direction. At baseline, responders showed significantly increased frequencies of CD8+ NK cells compared with non-responders. CONCLUSIONS: This is the first study demonstrating that the composition of the NK cell compartment has predictive power for prediction of therapeutic outcome for anti-TNF-α blockers, and we identified CD8+ NK cells as a potential new player in the TNF-α-driven chronic inflammatory immune response of AS.

Effects of a Psychoeducational Intervention in Patients With Breast Cancer Undergoing Chemotherapy.

BACKGROUND: Compelling evidence has yet to be published regarding the positive effect of psychoeducational interventions (PEIs) on psychological distress in patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and quality of life is also unclear. PURPOSE: The aim of this study was to assess the effects of a PEI on anxiety, depression, disease-specific care knowledge, self-efficacy, resilience and quality of life in patients with breast cancer during and after chemotherapy. The intervention was administered before and during five rounds of chemotherapy treatment. METHODS: A randomized controlled trial was conducted. Patients with breast cancer (N = 40) were randomly assigned to either the experimental or control group. The experimental group participated in PEI, a brief and highly structured program consisting of two parts: (a) an educational manual that addressed depression, anxiety, disease-specific care knowledge, self-efficacy, and resilience and (b) a self-assessment of learning. The control group received only traditional pamphlet education. Data were collected at four time points: before the first chemotherapy session (T1), during the third chemotherapy session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after the final chemotherapy session (T4). RESULTS: Anxiety, depression, resilience, and quality of life in the experimental group showed significant differences at T4. Significant differences became apparent at T2 for knowledge and at T3 for self-efficacy. The effects of knowledge, resilience, and quality of life remained significant when group and time interactions were included in the model, showing a positive relationship between PEI and the variables of knowledge, resilience, and quality of life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.

In vivo pre-activation of monocytes in patients with axial spondyloarthritis.

INTRODUCTION: Innate immune responses, including monocyte functions, seem to play an important role in the pathogenesis of axial spondyloarthritis (axSpA). Therefore, we characterized the phenotype and functional state of monocytes of patients with axSpA. METHODS: Fifty-seven patients with axSpA, 11 patients with rheumatoid arthritis (RA), and 29 healthy controls were included in the study. We determined the percentage of classic, intermediate, and non-classic monocytes according to CD14 and CD16 expression and the expression of Toll-like receptor (TLR) 1, 2, and 4 in whole blood by flow cytometry. The percentage of monocytes producing interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNFα), IL-12/23p40, and IL-1 receptor antagonist (IL-1ra) was detected by flow cytometry after stimulation of whole blood without and with different TLR and nucleotide-binding oligomerization domain ligands-i.e., lipopolysaccharide (LPS), fibroblast-stimulating lipopeptid-1, PAM3CSK4, and muramyl dipeptide (MDP)-for 5 h. IL-10 production was measured after 18 h of stimulation in supernatants by enzyme-linked immunosorbent assay. RESULTS: In patients with axSpA but not patients with RA, we found higher frequencies of classic monocytes than in controls (median of 90.4% versus 80.4%, P < 0.05), higher frequencies of monocytes spontaneously producing IL-1beta and IL-1ra (P < 0.05), and a higher percentage of monocytes producing IL-1beta after MDP stimulation (P < 0.05). Elevated cytokine production was confined to axSpA patients under conventional therapy (non-steroidal anti-inflammatory drugs) and not found in patients under TNFα inhibitor treatment. The LPS-induced production of IL-6 and IL-10 was lower in axSpA patients compared with controls (P < 0.05). Monocytic TLR expression was unaffected in patients with axSpA. CONCLUSION: Enhanced spontaneous and MDP-induced cytokine secretion by monocytes suggests in vivo pre-activation of monocytes in axSpA patients under conventional therapy which is reverted under TNF inhibitor treatment.