scholarly journals Mesenchymal Stem Cells — Their Antimicrobial Effects and Their Promising Future Role as Novel Therapies of Infectious Complications in High Risk Patients

10.5772/60640 ◽  
2015 ◽  
Author(s):  
K.A. Al-Anazi ◽  
A.M. Al-Jasser
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Risk ◽  
Infectious Complications ◽  
Novel Therapies ◽  
Future Role ◽  
Antimicrobial Effects ◽  
High Risk Patients ◽  
Risk Patients

Excellent Stem Cell Mobilization Using Escalated BEACOPP in High-Risk Patients with Hodgkin’s Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4717-4717
Author(s):  
Gabriele Kandler ◽  
Michael Fillitz ◽  
Michaela Moestl ◽  
Ernst Schloegl ◽  
Regina Reisner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
High Risk ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Previous Treatment ◽  
Additional Risk Factor ◽  
High Risk Patients ◽  
Risk Patients ◽  
Cell Mobilization

Abstract Introduction: After intensive treatment regimens have been established, the survival rate for patients with advanced Hodgkin’s disease is approximately 91 % after five years and 13 % of the patients have a relapse or have primary progressive disease (2 %) within the first five years. For patients with relapse after conventional chemotherapy +/− radiotherapy, however, there is a real chance of achieving remission again. Since it is often difficult to harvest autologous stem cells following an intensive pretreatment, our center embarks on the strategy to harvest autologous blood stem cells in high-risk patients, defined according to the risk stratification of the German Hodgkin Study Group, already as part of the initial polychemotherapy. Results: Between 9/2003 and 5/2005, we analyzed the results of the stem cell harvest of 12 consecutive patients with Hodgkin’s disease who were mobilized with the escalated BEACOPP regimen. There were 7 female and 5 male patients. Escalated BEACOPP was the primary therapy in ten patients and a relapse was treated in two patients; the previous treatment was 4 or 6 cycles of the ABVD regime + involved field radiation. The ten patients who did not receive previous treatment were classified as having Ann Arbor stage IIA/2 IIB/5, IIIB/2 and IVB/1 and all of them had a large mediastinal bulk as an additional risk factor. The two patients who did receive a previous treatment were classified as having an initial Ann Arbor stage IIA or IIB, without an additional risk factor. The stem cells were collected in 1 patient from cycle 2, in 8 patients from cycle 3 and in 3 patients from cycle 4 of the escalated BEACOPP regimen. A total of 11 patients received a standard dose of filgrastim, 5μg/kg body weight s.c., from day 8 up to the last apheresis and 1 patient received pegfilgrastim 6mg s.c. All aphereses were performed using an Amicus cell separator® (Baxter, MNC set, closed two-arm). 7 patients required only 1 apheresis and the remaining 5 patients required 2 aphereses. An apheresis result sufficient for a possible reinfusion could be achieved in all patients (4.26 – 14.4 x10e6 CD34 pos. cells/kg/body weight, mean: 7.7). Summary: According to our experience, escalated BEACOPP regimen is very suitable for the harvesting of stem cells in high-risk patients with Hodgkin’s disease even though they are receiving procarbazine. A sufficient quantity of stem cells can also be collected from pretreated patients. The stem cell mobilization can be integrated into the escalated BEACOPP regimen safely and without a delay in treatment and thus creates, already at an early stage, the pre-condition for a high-dose therapy, which might be required in high-risk patients.

scholarly journals Factors associated with unplanned readmissions and costs following resection of brain metastases in the United States

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raees Tonse ◽  
Alexandra Townsend ◽  
Muni Rubens ◽  
Vitaly Siomin ◽  
Michael W. McDermott ◽  
...  
Keyword(s):  
High Risk ◽  
Brain Metastasis ◽  
Readmission Rate ◽  
The United States ◽  
Neurological Complications ◽  
Infectious Complications ◽  
Unplanned Readmission ◽  
Factors Associated ◽  
High Risk Patients ◽  
Risk Patients

AbstractThe purpose of this study was to critically analyze the risk of unplanned readmission following resection of brain metastasis and to identify key risk factors to allow for early intervention strategies in high-risk patients. We analyzed data from the Nationwide Readmissions Database (NRD) from 2010–2014, and included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rate. Secondary outcomes included reasons and costs of readmissions. Hierarchical logistic regression model was used to identify the factors associated with 30-day readmission following craniotomy for brain metastasis. During the study period, 44,846 index hospitalizations occurred for patients who underwent resection of brain metastasis. In this cohort, 17.8% (n = 7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the five-year study period (p-trend = 0.286). The median per-patient cost for 30-day unplanned readmission was $11,109 and this amounted to a total of $26.4 million per year, which extrapolates to a national expenditure of $269.6 million. Increasing age, male sex, insurance status, Elixhauser comorbidity index, length of stay, teaching status of the hospital, neurological complications and infectious complications were associated with 30-day readmission following discharge after an index admission for craniotomy for brain metastasis. Unplanned readmission rates after resection of brain metastasis remain high and involve substantial healthcare expenditures. Developing tools and interventions to prevent avoidable readmissions could focus on the high-risk patients as a future strategy to decrease substantial healthcare expense.

Mesenchymal Stem Cells Preconditioned with Myeloma Cells from High-Risk Patients Support the Growth of Myeloma Cells from Low-Risk Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3304-3304 ◽  
Author(s):  
Syed Mehdi ◽  
Sharmin Khan ◽  
Wen Ling ◽  
Randal S Shelton ◽  
Joshua Epstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Risk ◽  
Cell Growth ◽  
Research Funding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Myeloma Cells ◽  
Risk Patients

Abstract Introduction: Each disease stage in myeloma (MM) is associated with parallel changes in both the MM clone and the bone marrow (BM) microenvironment. Mesenchymal cell lineages derived from mesenchymal stem cells (MSCs), including osteoblasts, adipocytes and pericytes play an important role in MM cell growth mediated by the modification of the MM niche in the BM. The overall goal of the study was to test and identify changes induced in MSCs by high-risk (HR) MM cells that impact MSC function and promote oncogenic pathways capable of supporting low-risk (LR) MM cells. Methods: Normal MSCs were either cultured alone ("unconditioned") or co-cultured with MM cells for 5 days. The cultured and co-cultured cells were trypsinized, replated for 40 min, followed by serial washing to remove MM cells from the adherent MSCs. More than 95% of the remaining adherent cells after co-culture were MSCs ("preconditioned"). The unconditioned and preconditioned MSCs or their 24 hrs conditioned media (CM; 50%) were tested for their ability to support the 5-days growth of CD138+ MM cells from LR (n=4) and HR (n=3) patients. To identify factors altered in MSCs by HR MM cells, the unconditioned and preconditioned MSCs and their serum-free conditioned media (n=4) underwent gene expression profiling and proteomic analysis. Whole bone biopsy gene expression profiles from newly diagnosed patients with MM enrolled in Total Therapy clinical trials were used to correlate the altered expression of factors in preconditioned MSCs with their expression in clinical samples. Results: Growth of all MM cells tested was increased by inclusion of MSCs preconditioned with HR MM cells by 2.2± 0.2 (p<0.0004) and by CM from these MSCs by 9.6±2.0 (p<0.006), compared to culture of MM cells in fresh media. In contrast, CM from unconditioned MSCs increased growth of HR MM cells by 2.6±0.6 (p<0.01) fold but had minor effect on growth of LR MM cells. CM from MSCs preconditioned with HR MM cells increased growth of LR and HR MM cells by 5.7±0.1 (p<0.0002) and 2.6±1.2 (p<0.04), compared to culture of MM cells in CM from unconditioned MSCs, respectively. Growth of LR MM cells was higher by 2.9±0.3 fold using CM from MSCs preconditioned with HR MM cells than by using CM from MSCs preconditioned with LR MM cells (p<0.005). To determine the role of cell-cell contact, we compared the effect of the preconditioned MSCs and their CM on growth of LR and HR MM cells. Growth of LR MM cells (p< 0.003) and HR MM cells (p< 0.005) was higher when cultured in CM than in co-culture with MSCs. These data imply that soluble factors from preconditioned MSCs support MM cell proliferation and that adhesion of MM cells to MSCs may restrain proliferation. Genes overexpressed in preconditioned MSCs included growth factors (e.g. IL6) and receptors (e.g. EDNRA); genes underexpressed include factors associated with activity of osteoblasts (e.g. ITGBL1) and adipocytes (IGFBP2). A proteomic analysis showed a reduced level of the secreted factors IGFBP2 and ITGBL1 and increase level of IL6 in CM from MSCs preconditioned with HR MM cells compared to CM from unconditioned MSCs. IGFBP2 mediates local bioavailability of IGF1 and IGF2 and is also involved in bone formation and angiogenesis independently of the IGF axis. ITGBL1 is involved in osteoblastogenesis whereas EDNRA is known to be expressed by pericytes. Global gene expression profiles from patient material showed that EDNRA and IGFBP2 are not expressed in MM cells but are highly expressed in cultured MSCs compared to hematopoietic cells in buffy coat BM samples. EDNRA is overexpressed (p<0.005) whereas IGFBP2 is underexpressed (p<0.005) in whole BM biopsy samples from MM patients with HR disease compared to patients with LR disease (p<0.005) and in Focal Lesion compared to random BM biopsies taken from the same patients (p<0.0000006 for EDNRA and p<0.02 for IGFBP2). IHC staining of patients' bone biopsies showed higher numbers of EDNRA+ mesenchymal-like cells in MM (n=10) than MGUS/AMM (n=10, p<0.0003) and in HR MM BM than LR MM BM (p<0.03). IHC analysis also revealed that IGFBP2 is highly expressed by immature adipocytes and that its expression in these cells is reduced in HR MM BM. Conclusion: Preconditioning of MSCs is essential for promoting growth of MM cells from LR patients. Factors altered in MSCs by HR MM cells are linked to signaling pathways known to directly stimulate MM cell growth and markers associated with distinct MSC lineages changed in HR MM niche. Disclosures Davies: Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Barlogie:Signal Genetics: Patents & Royalties. Morgan:Janssen: Research Funding; Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria.

Prolonged Febrile Neutropenia in the Pediatric Patient with Cancer

2012 ◽  
pp. 565-569
Author(s):  
Andrew Y. Koh
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Pediatric Patients ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Infectious Complications ◽  
Great Promise ◽  
High Risk Patients ◽  
Patients With Cancer ◽  
Risk Patients

Overview: Infectious diseases continue to be major causes of morbidity and mortality in pediatric patients with cancer. Yet not all pediatric patients with cancer with fever and neutropenia are at equal risk for substantial morbidity or mortality from infection. Patients at highest risk for developing infectious complications are those with severe and prolonged neutropenia, substantial medical comorbidity, and hematologic malignancy, or recipients of stem-cell transplantation. These “high-risk” patients also have concomitant host immune deficits as well: severe mucositis, lymphopenia, hypogammaglobulinemia, and gut microbial dysbiosis. Because bacterial and fungal infections are the most common infectious complications, continuation of empirical antibacterial antibiotics that were initiated at the onset of febrile neutropenia and prompt initiation of empirical antifungal therapy in the setting of prolonged fever and neutropenia continue to be the standard of care. In high-risk patients, antibiotic therapy should be maintained until neutrophil counts have recovered. Adjunctive therapies have been shown to be ineffective (e.g., colony-stimulating factors) or necessitate further study (e.g., granulocyte infusions or keratinocyte growth factor treatment to heal mucositis). Prophylactic use of antibacterial and antifungal antibiotics in high-risk patients has shown promise but the fear of inducing antimicrobial-resistant strains remains a deterrent. Finally, the novel concepts of manipulating the host gut microbiota and/or augmenting GI mucosal immunity to prevent invasive bacterial and fungal infections in pediatric patients with cancer offers great promise, but more definitive studies need to be performed.

scholarly journals Improved Clinical Outcome of Patients with Myelodysplastic Syndrome (MDS) Progressing after Hypomethylating Agent: In the Era of Novel Therapies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3688-3688
Author(s):  
Ahmad Ghorab ◽  
Aref Al-Kali ◽  
Michelle A. Elliot ◽  
Mithun V. Shah ◽  
Jeanne M. Palmer ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Research Funding ◽  
Advisory Board ◽  
Novel Therapies ◽  
High Risk Patients ◽  
Line Therapy ◽  
Duration Of Response ◽  
Risk Patients ◽  
Very High

Abstract Introduction: Historically, clinical outcome of patients with myelodysplastic syndrome (MDS), progressing on hypomethylating agents (HMA; azacitidine or decitabine) has been dismal with median overall survival (OS) of less than 6 months (Jabbour et al. Cancer 2010). With recent approval of venetoclax based combinations for acute myeloid leukemia (AML) and CPX-351 for AML with MDS related changes (primary or secondary), clinical outcome has improved in sub-set of high-risk patients compared to historical cohorts. Hence, we analyzed clinical outcome of MDS patients progressing on HMA, in the current era of novel therapies. Methods: We retrospectively analyzed clinical outcome of 43 MDS patients who progressed on HMA-based therapy and treated at the Mayo Clinic between February 2015 and February 2021. We describe clinical characteristics of these patients, therapies received after progressing on HMA-based therapy, duration of response attained after 1st line therapy post HMA-based therapy and OS from time of HMA failure till death or last follow up. We also performed Cox regression multivariate analysis for OS after progression on HMA-based therapy. Results: Baseline characteristics are summarized in Table 1.The median age of the patients were 69 years (range [R], 48-93). R-IPSS score in this cohort of patients was very low (2[5%]), low (5[12%]), intermediate (5 [12%]), high (11[26%]) and very high (20 [46.5%]). Forty-nine percent of patients had complex cytogenetics. Most commonly occurring mutations (≥ 5%) were TP53 (42%), splicing mutation (SRSF2/SF3B1/ or U2AF1) (16%), ASXL1 (12%), RUNX1 (7%), DNMT3A (5%) and IDH1/ or IDH2 (5%). The HMA-based therapy patients received were azacitidine (40%), decitabine (30%) and HMA plus venetoclax (30%). The median time to progression from time of initiation of HMA-based therapy was 5 months (R= 1-30). Sixty-three percent (n= 27) of patients progressed to AML after HMA-based therapy. The most common 1 st line therapies post HMA was venetoclax-based (12 [28%]), CPX-351 (12 [28%]), and allogeneic stem cell transplantation (SCT) (4 [9%]). Fifteen (45.5%) patients achieved CR/CRi, 17 (51.5%) patients progressed and 1 (3%) patient had stable disease. The percentage of patients received venetoclax with HMA, 1 st and 2 nd line therapy post HMA were 26%, 28% and 10%, respectively. Overall, 11 (25%) patients received SCT in this cohort of patients. The median duration of response after 1 st line therapy post HMA was not reached (NR; 66% progression free at 1 year) (Figure 1A). The median OS after HMA failure was 12.7 months (95% CI: 3.1-22.2) (Figure 1B). In the univariate analysis for OS after HMA failure, SCT at any time point (p = 0.01) and achieving CR/CRi after 1 st line therapy post HMA (p= &lt;0.001) showed favorable significance for OS. Whereas, R-IPSS high/very high (p= 0.35), treatment with CPX-351 on AML progression (p=0.33), venetoclax-based therapy (p= 0.59) did not show statistical significance. Subsequently, in multivariate analysis, only achievement of CR/CRi after 1 st line therapy post HMA retained significance for favorable OS (HR: 0.19, 95% CI: 0.04-0.86, p= 0.03). Conclusions: To the best of our knowledge, this is the first report analyzing outcome of MDS patients progressing on HMA in the recent era. Acknowledging the limitations of retrospective analysis, our report suggests improved outcome of these high-risk patients compared to historical data. Utilizing venetoclax plus HMA combination earlier in patients with high-risk MDS as being evaluated in VERONA trial and consolidation therapy with SCT in eligible patients have potential to improve long term outcome of this group of high-risk patients. Figure 1 Figure 1. Disclosures Al-Kali: Astex: Other: Research support to institution; Novartis: Research Funding. Palmer: PharmaEssentia: Research Funding; Incyte: Research Funding; Protagonist: Consultancy, Research Funding; CTI BioPharma: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding. Murthy: CRISPR Therapeutics: Research Funding. Litzow: Pluristem: Research Funding; Actinium: Research Funding; AbbVie: Research Funding; Omeros: Other: Advisory Board; Jazz: Other: Advisory Board; Amgen: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Foran: pfizer: Honoraria; takeda: Research Funding; trillium: Research Funding; boehringer ingelheim: Research Funding; syros: Honoraria; sanofi aventis: Honoraria; revolution medicine: Honoraria; servier: Honoraria; bms: Honoraria; certara: Honoraria; abbvie: Research Funding; OncLive: Honoraria; gamida: Honoraria; taiho: Honoraria; novartis: Honoraria; aptose: Research Funding; actinium: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees.

Combination of norfloxacin and cisapride in prevention of SBP in high risk patients: A new approach

2001 ◽  
Vol 120 (5) ◽  
pp. A376-A376
Author(s):  
B JEETSANDHU ◽  
R JAIN ◽  
J SINGH ◽  
M JAIN ◽  
J SHARMA ◽  
...  
Keyword(s):  
High Risk ◽  
New Approach ◽  
High Risk Patients ◽  
Risk Patients

1610: High-Risk Patients Undergoing Radical Prostatectomy Today are Less High-Risk than in the Past

2005 ◽  
Vol 173 (4S) ◽  
pp. 436-436
Author(s):  
Christopher J. Kane ◽  
Martha K. Terris ◽  
William J. Aronson ◽  
Joseph C. Presti ◽  
Christopher L. Amling ◽  
...  
Keyword(s):  
High Risk ◽  
Radical Prostatectomy ◽  
High Risk Patients ◽  
The Past ◽  
Risk Patients
Sign in / Sign up

Export Citation Format

Share Document