ObjectiveHospice care could improve the quality of life among advanced HIV patients during end-of-life (EOL) treatment. However, providing hospice care services for people living with HIV (PLWH) is ...challenging due to HIV-related stigma. This nationwide cohort study aims to determine the utilisation of hospice care services among PLWH and HIV-negative individuals during EOL treatment.DesignA retrospective cohort study.SettingFrom 2000 to 2018, we identified adult PLWH from the Taiwan centres for disease control HIV Surveillance System. Individuals who had positive HIV-1 western blots were regarded as HIV-infected. Age-matched and sex-matched controls without HIV infection were selected from the Taiwan National Health Insurance Research Database for comparison. All PLWH and controls were followed until death or 31 December 2018.Participants32 647 PLWH and 326 470 HIV-negative controls were analysed.Primary outcome measuresUtilisation of hospice care services during the last year of life among PLWH and HIV-negative individuals.ResultsA total of 20 413 subjects died during the 3 434 699 person-years of follow-up. Of the deceased patients, 2139 (10.5%) utilised hospice care services during their last year of life, including 328 (5.76%) PLWH and 1811 (12.30%) controls. Adjusting for demographics and comorbidities, PLWH were less likely to receive hospice care services during the last year of life, compared with HIV-negative individuals (adjusted OR: 0.66; 95% CI: 0.57 to 0.75).ConclusionsPLWH had significantly lower utilisation of hospice care services during the last year of life. Our results suggest that future hospice care programmes should particularly target PLWH to increase the optimal utilisation of hospice care services during EOL treatment.
Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering ...receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults.
This prospective, observational study enrolled 100 adults with newly diagnosed and treatment-naïve DLBCL from May 2019 to October 2021. Human circulating M-MDSCs were obtained from freshly isolated peripheral blood, and each patient's surface-TREM2 level on M-MDSCs was normalized via a healthy control at the same performance of flow-cytometry analysis. Murine MDSCs derived from bone marrow (BM-MDSCs) were adopted to assess the link between Trem2 and cytotoxic T lymphocytes.
More circulating M-MDSCs at diagnosis of DLBCL predicted worse progression-free (PFS) and overall survival (OS). Patients with higher IPI scores, bone marrow involvement, or lower absolute counts of CD4
or CD8
T cells in PB had significantly higher normalized TREM2 levels on M-MDSCs. Additionally, normalized TREM2 levels on M-MDSCs could be grouped into low (< 2%), medium (2-44%), or high (> 44%) levels, and a high normalized TREM2 level on M-MDSCs was proven as an independent prognostic factor for both PFS and OS via multivariate Cox regression analysis and associated with worst PFS and OS. Interestingly, normalized levels of surface TREM2 on M-MDSCs were negatively associated with absolute counts of PB CD8
T cells and positively correlated with levels of intracellular arginase 1 (ARG1) within M-MDSCs. Wild-type BM-MDSCs had significantly higher mRNA levels of Arg1 and showed more prominent ability to suppress the proliferation of co-cultured CD8
T cells than BM-MDSCs from Trem2 knockout mice, and the suppressive ability could be impaired by adding Arg1 inhibitors (CB1158) or supplementing L-arginine.
In treatment-naïve DLBCL adults, a high surface-TREM2 level on circulating M-MDSCs is a poor prognostic factor for both PFS and OS and warrants further investigation for its potential as a novel target in immunotherapy.
Abstract Purpose The aim was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of ...in-hospital cardiac arrest (IHCA). Methods We analyzed our extracorporeal membrane oxygenation (ECMO) results for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated. Results In the last 5 years, ECPR was used 230 times for OHCA ( n = 31) and IHCA ( n = 199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4 ± 24.7 min vs. 67.5 ± 30.6 min, p < 0.05). About 50% of each group underwent a further intervention to treat the underlying etiology. ECMO was maintained for a shorter duration in the OHCA patients (61 ± 48 h vs. 94 ± 122 h, p < 0.05). Survival to discharge was similar in the two groups (38.7% for OHCA vs. 31.2% for IHCA, p > 0.05), as was the favorable outcome rate (25.5% for OHCA vs. 25.1% for IHCA, p > 0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 min. Conclusions In addition to having a beneficial effect in IHCA, ECPR can lead to survival and a positive neurological outcome in selected OHCA patients after prolonged resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted.
Hepatocarcinogenesis and distant metastasis pose major challenges for physicians. They are regulated by several genes, such as
,
,
, and
, and their expression activates several important processes ...such as cell proliferation, migration, motility, and interaction in the microenvironment. The leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR-5) is a novel biomarker, particularly in stem cells, and is involved in embryogenesis, tumor development, and tumor cell signal transduction. Here, we investigated LGR-5 expression using immunohistochemistry and analyzed the correlation between clinical features and prognosis in patients with hepatocellular carcinoma (HCC). We found that LGR-5 expression was higher in tumor tissues than in normal liver tissues, and that high LGR-5 expression possibly favored poor outcomes in HCC, especially in well/moderate differentiation grade, hepatitis C virus (HCV)-negative, and hepatitis B virus (HBV)-positive groups. Thus, the LGR-5 marker is suggested to be a routine biomarker for poor prognosis, thereby providing a platform for anti-LGR-5-targeted therapy in the future.
Several studies have indicated the biological role of mitochondrial Ca2+ uptake in cancer pathophysiology; however, its implications in predicting the prognosis of hepatocellular carcinoma (HCC) are ...not yet fully understood. Here, we collected tumor specimens and adjacent normal liver tissues from 354 confirmed HCC patients and analyzed the levels of cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB), mitochondrial calcium uniporter (MCU), mitochondrial calcium uptake 1 and 2 (MICU1, MICU2) using bioinformatics, qRT-PCR, and immunohistochemistry (IHC), and their relationship with clinicopathological characteristics and prognosis. HCC patients with low CREB/MICU1 and high MCU/MICU2 expression exhibited poor survival rate and prognosis in overall survival (OS) and disease-free survival (DFS) analyses. Low CREB/MICU1 and low MICU1 alone indicated poor prognosis in stage I/II and III/IV patients, respectively. In the poor differentiation/undifferentiation group, low expression of MICU1 indicated poor clinical outcomes. Low CREB/MICU1 expression suggested poor outcomes in patients with or without hepatitis B virus (HBV) infection and poor prognosis in the HCV infection group. In the non- hepatitis C virus (HCV) infection group, low MCU1 indicated a poor prognosis. Multivariate analysis demonstrated that CREB and MICU1 expression showed prognostic significance. This study demonstrates the prognostic significance of CREB, MCU, MICU1, and MICU2, in predicting HCC outcomes. Low CREB/MICU1 and high MCU/MICU2 in HCC tissues are associated with poor prognosis, thus offering a novel perspective in the clinical management for HCC patients.
Cancer growth, metastasis and development are regulated by a number of genes, whose expression mediates important processes, including cellular plasticity, motility and internal interactions in the ...tumor microenvironment. The epithelial cell adhesion molecule (EpCAM) serves an important role in cell-cell migration and tumorigenicity, particularly metastasis. The aim of the present study was to measure EpCAM expression using immunohistochemistry and to investigate the association between clinicopathological features and prognosis in hepatocellular carcinoma (HCC). The results revealed that EpCAM expression may be a biomarker for poor prognosis in patients with HCC and may therefore be used to predict clinical outcome. The present study suggests that EpCAM expression in HCC can be considered as a routine biomarker for unfavorable prognosis and may provide a basis for the future development of anti-EpCAM-targeted therapy.
Background: Hospice care involves improving quality of end-of-life (EOL) care and respecting patients’ preferences regarding EOL treatment. However, the impact of hospice care services on the ...utilization of life-sustaining treatments during EOL care in patients with life-limiting diseases has not been extensively studied. Objectives: This nationwide cohort study aimed to determine the impact of hospice care services on the utilization of life-sustaining treatments during the last 3 months of life among people living with HIV/AIDS (PLWHA) in Taiwan. Methods: From 2000 to 2018, we identified adult PLWHA from Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined as positive HIV-1 Western blot. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, and defibrillation. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. Results: Of 5691 PLWHA, 2595 (45.9%) subjects utilized life-sustaining treatments during the last 3 months of life. After adjusting for other covariates, PLWHA with hospice care services were less likely to receive life-sustaining treatments during the last 3 months of life than those without the services (adjusted odds ratio AOR = .50, 95% confidence interval CI: .37-.66). Considering the type of life-sustaining treatments, hospice care services were associated with lower likelihood of receiving cardiopulmonary resuscitation (AOR = .22, 95% CI: .13-.39), endotracheal intubation (AOR = .48, 95% CI: .35-.65), and mechanical ventilation support (AOR = .56, 95% CI: .42-.75). Conclusion: Hospice care services were associated with a lower utilization of life-sustaining treatments during the last 3 months of life among PLWHA.
Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary ...HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristic curves (AUC) and a multivariate generalized additive model (GAM) were applied to predict these outcomes of interest. Urinary HJV differentiated patients with/without AKI, advanced AKI or composite outcome after surgery (p < 0.001, by a generalized estimating equation) in this study. At three hours post-surgery, urinary HJV predicted advanced AKI (p < 0.001) and composite outcome (p < 0.001) with corresponding AUC values of 0.768 and 0.828, respectively. The performance of creatinine-adjusted HJV was also superior to NGAL in predicting advanced AKI (AUC = 0.784 and 0.694; p = 0.037) and composite outcome (AUC = 0.842 and 0.676; p = 0.002). The integration of HJV into the Cleveland Clinic score for advanced AKI led to a significant increase in risk stratification (net reclassification improvement NRI = 0.598; p < 0.001).
Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, ...short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.
This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.
This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).
Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.