Prevalence of multidrug-resistant organisms on palliative care patients in a university hospital-bound palliative care unit: A prospective cohort analysis.

BACKGROUND: Multidrug-resistant organisms are a growing challenge and burden to patient care. To date, there are only data concerning the prevalence of methicillin-resistant Staphylococcus aureus infections. Thus, numbers of other multidrug-resistant organisms can only be extrapolated and inferred from more or less comparable cohorts. AIM: To evaluate the prevalence of multidrug-resistant organisms on palliative care in-patients. DESIGN: A prospective cohort analysis. SETTING/PARTICIPANTS: A University Hospital-bound palliative care unit, in which all patients admitted to the unit were screened for inclusion. RESULTS: In total, 304 patients were included in this study. The prevalence for methicillin-resistant Staphylococcus aureus of 5.2% (95% confidence interval: 2.9%-8.4%), for vancomycin-resistant Enterococcus faecium of 10.5% (95% confidence interval: 7.2%-14.8%), for Ciprofloxacin-resistant-extended spectrum beta-lactamases isolates of 5.8% (95% confidence interval: 3.4%-9.3%) and Ciprofloxacin-resistant Carbapenem-resistant Gram-negative bacteria of 0.3% (95% confidence interval: 0%-1.3%) was calculated. Except for methicillin-resistant Staphylococcus aureus, patients carrying a multidrug-resistant organism had a significant longer duration of hospitalization. Median length of stay was 12 days (interquartile range: 14.5, no multidrug-resistant organisms), 14.5 days (interquartile range: 15, methicillin-resistant Staphylococcus aureus), 21 days (interquartile range: 16.5, vancomycin-resistant enterococci), 22 days (interquartile range: 20.75, Ciprofloxacin-resistant-extended spectrum beta-lactamases) and 32 days (interquartile range: 22.00) for patients carrying two organisms. CONCLUSION: There is a high prevalence of all multidrug-resistant organisms within the hospitalized palliative care patients. However, the multidrug-resistant organisms do not seem to impact the survival within this cohort. Further studies should evaluate additional end-points, for example, quality of life, which are of special interest in this cohort.

Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis.

New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first-line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first-line treatment including induction therapy, cytotoxic stem cell mobilization and high-dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34(+) HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long-term HSPC proliferation in vitro. We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF-ß signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long-term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF-ß signaling pathway.

Methicillin-resistant Staphylococcus aureus in palliative care: A prospective study of Methicillin-resistant Staphylococcus aureus prevalence in a hospital-based palliative care unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus is a common organism in hospitals worldwide and is associated with morbidity and mortality. However, little is known about the prevalence in palliative care patients. Furthermore, there is no standardized screening protocol or treatment for patients for whom therapy concentrates on symptom control. AIM: Examining the prevalence of methicillin-resistant Staphylococcus aureus in palliative care patients as well as the level of morbidity and mortality. DESIGN: We performed a prospective study where methicillin-resistant Staphylococcus aureus screening was undertaken in 296 consecutive patients within 48 h after admission to our palliative care unit. Medical history was taken, clinical examination was performed, and the Karnofsky Performance Scale and Palliative Prognostic Score were determined. Prevalence of Methicillin-resistant Staphylococcus aureus was compared to data of general hospital patients. RESULTS: In total, 281 patients were included in the study having a mean age of 69.7 years (standard deviation = 12.9 years) and an average Karnofsky Performance Scale between 30% and 40%. The mean length of stay was 9.7 days (standard deviation = 7.6 days). A total of 24 patients were methicillin-resistant Staphylococcus aureus positive on the first swab. Median number of swabs was 2. All patients with a negative methicillin-resistant Staphylococcus aureus swab upon admission remained Methicillin-resistant Staphylococcus aureus negative in all subsequent swabs. CONCLUSION: Our study suggests that the prevalence of Methicillin-resistant Staphylococcus aureus among patients in an in-hospital palliative care unit is much higher than in other patient populations.

Molecular monitoring of minimal residual disease in the peripheral blood of patients with multiple myeloma.

The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma is still an open question. In bone marrow, the level of residual myeloma cells is associated with treatment outcome, but the role of clonotypic cells in the peripheral blood (PB) for the prognosis of patients is not identified yet. In this study, we retrospectively analyzed MRD by quantitative real-time IgH-PCR (IgH-qPCR) in the PB of 42 patients undergoing high-dose therapy followed by autologous PB stem cell transplantation as first-line therapy for multiple myeloma. The MRD level of PB samples was in median 40-fold lower than in bone marrow samples, collected on the same day, with a wide intra- and interindividual variation (range, .4- to 4628-fold). The presence or absence of detectable MRD levels in PB did not correlate with the serological remission status. Still, patients with negative PCR results in PB 3 months after high-dose therapy and PB stem cell transplantation had lower International Staging System stage (P = .01), lower levels of ß2-microglobulin (P = .02), higher hemoglobin levels (P = .01), and a prolonged event-free (median, 15 versus 4 months; P = .004) and overall (median, 52 versus 17 months; P = .03) survival. Importantly, by sequential monitoring of clonotypic cells in PB, in 19 of 29 patients (66%) with progressive disease, an increase of the 2IgH/ß-actin ratio of at least 1 log step could be detected in median 4 months (range, .8 to 13 months) before the relapse was diagnosed on the basis of the European Group for Blood and Marrow Transplantation criteria. These patients with a molecular relapse in PB before a serological relapse had a significantly shorter overall survival than other patients (median, 17 months versus median not reached, P = .02). In conclusion, IgH-qPCR is a sensitive technique for the detection of clonotypic cells in PB, which precede clinical relapse. Future studies are needed to evaluate whether these circulating tumor cells play a role in promoting disease recurrence.

Impact of the COVID-19 pandemic on emergency medical resources : An observational multicenter study including all hospitals in a major urban center of the Rhein-Ruhr metropolitan region.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) outbreak hospitals prepared for increasing numbers of patients without knowing how patient populations were evolving and what resources would be required. The present study aimed to analyze the impact of the local COVID-19 pandemic on emergency resources of all hospitals in a major urban center (Mönchengladbach) in Germany. METHODS: This observational multicenter study involved all acute care hospitals (n = 4). Systemic emergency department (ED) parameters from weeks 4-24 in 2020 were compared to the corresponding period in 2019 for each hospital and in a summative data analysis using a logistic regression model. RESULTS: The first regional COVID-19 patients were detected in week 9 of 2020. The cumulative number of ED visits dropped from 34,659 in 2019 to 28,008 in 2020. Weekly ED visits per hospital decreased from week 8 onwards between 38% and 48% per week and hospital and began to rise again after week 16. The pooled data analysis of ED patients showed significant decreases in outpatient visits (20,152 vs. 16,477, p < 0.001), hospital admissions (14,507 vs. 11,531, p < 0.001), and work-related accidents (2290 vs. 1468, p < 0.001). The decrease in ED to ICU admissions showed no significance (2093 vs. 1566, p = 0.255). The decline in ED cases was equally distributed between the medical specialties. CONCLUSION: The regional COVID-19 outbreak led to significantly reduced ED contacts in a German major urban region after the first COVID-19 cases appeared. Both hospital admissions and the number of ED to ICU admissions decreased, whereas the ratio of emergency outpatients vs. inpatients remained stable. Therefore, it can be assumed that patients with severe medical problems did not seek emergency care. These secondary effects of the pandemic on healthcare and the socioeconomic impact should be analyzed further.

Dysbalance of angiogenic and angiostatic mediators in patients with mixed connective tissue disease.

OBJECTIVE: Vascular disease is common in mixed connective tissue disease (MCTD). The aim of the present study was to investigate, whether dysbalance of angiogenic and angiostatic factors occurs in MCTD. METHODS: In all, 38 patients with MCTD, and 40 patients with systemic sclerosis (SSc) for comparison, were included. Four centres contributed to this cross-sectional analysis. A total of 66 healthy volunteers were used as controls. The serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin were determined by ELISA. For comparisons between controls and patients with MCTD and detection of associations of serum levels with dichotomous clinical parameters in patients with MCTD the Mann-Whitney test was used. RESULTS: Serum levels of the angiogenic factor VEGF were significantly elevated in patients with MCTD and SSc. Significantly increased levels of the angiostatic factor endostatin were also detected in MCTD, but not in SSc. No differences were observed for bFGF. Levels of VEGF were higher in patients with MCTD with pulmonary arterial hypertension (PAH), acrosclerosis and myositis. In multivariate linear regression analysis, an additive model of PAH, myositis and lymphadenopathy accounted for 79% of the variability of the VEGF levels (r=0.889). CONCLUSIONS: Molecular factors modulating angiogenic responses are dysregulated in patients with MCTD and SSc with increases of VEGF in MCTD and SSc and selective upregulation of endostatin in MCTD. Furthermore, high serum levels of VEGF might characterise patients with MCTD with a more severe course of the disease with increased prevalence of PAH and myositis.