Determining the cut-off value for the Minimal Documentation System (MIDOS2) screening tool to initiate specialized palliative care based on patient's subjective need for palliative support and symptom burden in inpatients with advanced cancer.

PURPOSE: The Minimal Documentation System (MIDOS2) is recommended as a systematic screening tool for assessing symptom burden and patient needs in advanced cancer patients. Given the absence of an optimal weighting of individual symptoms and a corresponding cut-off value, this study aims to determine a threshold based on inpatient's subjective need for palliative support. Additionally, we investigate the correlation between symptom burden and subjective need for palliative support collected through a patient-reported outcome measure (PROM) with survival duration of less or more than one year. METHODS: Inpatients diagnosed with advanced solid cancer completed an electronic PROM, which included the MIDOS2 questionnaire among other tools. Differences in symptom burden were analysed between patients expressing subjective need for palliative support and those with survival of less or more than one year using ANOVA, Mann-Whitney-U Test, logistic regression, Pearson and Spearman correlation tests. Cut-off analyses were performed using a ROC curve. Youden-Index, sensitivity, and specificity measures were used as well. RESULTS: Between April 2020 and March 2021, 265 inpatients were included in the study. Using a ROC curve, the MIDOS2 analysis resulted in an Area under the curve (AUC) of 0.732, a corresponding cut-off value of eight points, a sensitivity of 76.36% and a specificity of 62.98% in assessing the subjective need for palliative support. The MIDOS2, with double weighting of the significant symptoms, showed a cut-off value of 14 points, achieving a sensitivity of 78.18% and a specificity of 72.38%. A total of 55 patients (20.8%) expressed a need for support from the palliative care team. This need was independent of the oncological tumour entity and increased among patients with a survival of less than one year. These patients reported significantly poorer physical (p < 0.001) or mental (p < 0.001) condition. Additionally, they reported higher intensities of pain (p = 0.002), depressive symptoms (p < 0.001), weakness (p < 0.001), anxiety (p < 0.001), and tiredness (p < 0.001). CONCLUSION: Using the established MIDOS2 cut-off value with an adjusted double weighting in our study, a large proportion of inpatients may be accurately referred to SPC based on their subjective need for palliative support. Additionally, subjective reports of poor general, mental, and physical condition, as well as pain, depressive symptoms, weakness, anxiety, and tiredness, increase the subjective need for palliative support, particularly in patients with a survival prognosis of less than one year.

Electronic Patient-Reported Outcome Measures (ePROMs) Improve the Assessment of Underrated Physical and Psychological Symptom Burden among Oncological Inpatients.

For advanced cancer inpatients, the established standard for gathering information about symptom burden involves a daily assessment by nursing staff using validated assessments. In contrast, a systematic assessment of patient-reported outcome measures (PROMs) is required, but it is not yet systematically implemented. We hypothesized that current practice results in underrating the severity of patients' symptom burden. To explore this hypothesis, we have established systematic electronic PROMs (ePROMs) using validated instruments at a major German Comprehensive Cancer Center. In this retrospective, non-interventional study, lasting from September 2021 to February 2022, we analyzed collected data from 230 inpatients. Symptom burden obtained by nursing staff was compared to the data acquired by ePROMs. Differences were detected by performing descriptive analyses, Chi-Square tests, Fisher's exact, Phi-correlation, Wilcoxon tests, and Cohen's r. Our analyses pointed out that pain and anxiety especially were significantly underrated by nursing staff. Nursing staff ranked these symptoms as non-existent, whereas patients stated at least mild symptom burden (pain: meanNRS/epaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.46; anxiety: meanepaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.48). In conclusion, supplementing routine symptom assessment used daily by nursing staff with the systematic, e-health-enabled acquisition of PROMs may improve the quality of supportive and palliative care.

Regulation of HIV-1 infection in cells derived from purified CD34+ cells through manipulation of APOBEC3G expression.

The cytidine deaminase APOBEC3G has been identified as an antiviral host factor that combats HIV-1. The protein was found to be present in HIV-1 target cells such as macrophages and dendritic cells. The antiviral state of these cells has been partially attributed to a G→A hypermutation of the HIV genome caused by APOBEC3G during reverse transcription. However, the viral infectivity factor (Vif) counteracts this antiviral mechanism by inducing the inactivation of APOBEC3G. In this study, we tested the effect of APOBEC3G expression on the HIV-1 infection of cells derived from purified CD34+ cells that have been transduced with lentiviral vectors containing APOBEC3G and/or shRNAs directed against APOBEC3G and then have been differentiated before infection with HIV-1. In cell lines, the infection was strongly inhibited after upregulation of APOBEC3G. The infection could then be rescued after transducing these cells with shRNAs targeting APOBEC3G. In cells derived from purified CD34+ cells a strong inhibition of the HIV-1 infection was observed in both a Vif defective HIV-1 virus and the corresponding wild-type HIV-1 virus with Vif. Our data implies that when APOBEC3G is expressed high enough, it can escape the inhibition from Vif, thereby exerting its antiviral activity.

Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages.

In order to identify cellular genes which interfere with HIV-1 replication in monocyte-derived macrophages (MAC), cells were stimulated with interferon (IFN) or lipopolysaccharide (LPS) leading to a pronounced inhibition of HIV-1 infection in these cells, and the resulting gene expression was analyzed. Using the microarray technology we identified a gene named Stimulated Trans-Acting Factor of 50 kDa (Staf50), which is known to repress the activity of the HIV-1 LTR. Analysis of the Staf50 expression by real-time PCR showed an overexpression in IFNalpha (up to 20-fold) and LPS (up to 10-fold)-stimulated MAC as well as in infected cells (up to 3-fold). For stable overexpression, 293 T cells and primary macrophages were transduced with Staf50-IRES-GFP bicistronic pseudotype viruses. After transduction, 293 T CD4/CCR5 and MAC were infected with HIV-1, and virus replication was monitored by p24 ELISA. Overexpression of Staf50 inhibited the HIV-1 infection between 50% and 90% in 293 T CD4/CCR5 as well as in MAC. Our findings suggest that host genetic effects in combination with viral properties determine the susceptibility of an appropriate target cell for HIV-1 infection as well as the replication potential of the virus in the cell resulting in an overall productive infection.