scholarly journals P270 Mesenchymal stromal cells contribute to the recovery of secondary loss of response to infliximab in patients with ulcerative colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
O Knyazev ◽  
A V Kagramanova ◽  
A Lishchinskaya ◽  
I Li ◽  
T Shkurko ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Clinical Status ◽  
Acquired Drug Resistance ◽  
Laboratory Parameters ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Group 2 ◽  
Group 1

Abstract Background Long-term experience with infliximab (IFХ) shows that within a year, 20–30% of patients with ulcerative colitis (UC) develop acquired drug resistance (secondary inefficiency). Aim To establish the possibility of overcoming the secondary inefficiency of IFX in UC patients using mesenchymal stromal cells (MSC). Methods In the IBD treatment Department, the clinical status of 84 UC patients receiving IFX therapy was evaluated. Secondary loss of response was registered in 28 UC patients, which required optimization of IFX therapy. 12 patients (group 1), in order to overcome the secondary loss of response, were administered MSCS three times every 4 weeks, 16 patients with UC (group 2) received standard optimized IFX therapy. The effectiveness of therapy was evaluated after 12 weeks of therapy (reduction of the Mayo score) and normalization of laboratory parameters (ESR, C-reactive protein (CRP), hemoglobin, fecal calprotectin (FCP). The comparative analysis was carried out using the method of four-field tables using nonparametric statistical criteria. Results In 10 (83.3%) of 12 patients of group 1, a significant positive dynamics was observed after 12 weeks: a decrease in the Mayo index and normalization of laboratory parameters (ESR, CRP, hemoglobin, FCP). In 4 (25.0%) patients with UC from group 2, against the background of optimized IFX therapy, a significant positive dynamics was also observed with a decrease in the meio index and an improvement in ESR, CRP, hemoglobin and FCP levels. However, 12 patients from group 2 were transferred to therapy with other anti-TNF-α drugs and drugs with a different mechanism of action (RR-0.222, 95% CI 0.061–0.812; x2 - 7.146; p=0.00334). Conclusion The use of mesenchymal stromal cells of the bone marrow helps to overcome the secondary loss of response to infliximab in patients with ulcerative colitis.

scholarly journals P005 Overcoming Secondary Loss of Response to Infliximab in Patients With Ulcerative Colitis With the Use of Mesenchymal Stromal Cells

2020 ◽  
Vol 115 (1) ◽  
pp. S2-S2
Author(s):  
Knyazev Oleg ◽  
Lishchinskaya Albina ◽  
Konoplyannikov Anatoliy ◽  
Kagramanova Anna ◽  
Fadeeva Nina ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Secondary Loss ◽  
Loss Of Response

scholarly journals Application of conditioned medium from mesenchymal stromal cells in the protocol for ex vivo production of megakaryocytes and platelets

2021 ◽  
Vol 66 (4) ◽  
pp. 526-538
Author(s):  
D. Yu. Klyuchnikov ◽  
M. Yu. Yazykova ◽  
A. A. Stepanov ◽  
S. E. Volchkov ◽  
O. V. Tyumina
Keyword(s):  
Cord Blood ◽  
Conditioned Medium ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Blood Platelets ◽  
Venous Blood ◽  
Hematopoietic Stem ◽  
Group 2 ◽  
Group 1

Introduction. Of interest is the use of a conditioned medium from mesenchymal stromal cells in order to increase the expansion of CD34+  hematopoietic stem cells (HSCs).Aim — to analyze the effi cacy of two methods of ex vivo production of human megakaryocytes and platelets from CD34+ cord blood HSC using conditioned media from mesenchymal stromal cells and IMDM. Methods. Two cultivation methods that differ from each other by medium composition were compared. As a control of antigen expression of the donor, venous blood platelets were used. CD34+ HSCs were isolated from mononuclear fraction of cord blood using the immunomagnetic selection technique. The resulting cells were introduced at a concentration of 1 × 104  cells/mL into 24-well plates and cultured at 39 °C and 10 % CO2  for the first 7 days, after which the conditions were changed to 37 °C and 5 % CO2  and cultured for 14 days. In Group 1, up to day 7, the culture was performed using conditioned medium from mesenchymal stromal cell containing TPO (30 ng/mL), SCF (2 ng/mL), IL-6 (7.5 ng/mL), IL-9 (13.5 ng/mL), and in Group 2 a IMDM medium with the same cytokine cocktail was used. The cells were calculated using haemocytometer. CD34, CD41a, CD42b expression was evaluated using fl ow cytometry. Statistic data was processed with using R-language. The differences were evaluated as statistically signifi cant at signifi cance level p < 0.05.Results. Megakaryocyte production was observed starting from day 7 of culture. The expression level using conditioned medium from mesenchymal stromal cells (Group 1) according to CD41a was 5.84 ± 0.33 % versus 10.43 ± 1.08 % using IMDM medium (Group 2). On day 13 the ratio increased up to 42.05 ± 1.71 % in Group 1 and 61.78 ± 1.71 % in Group 2. CD41a+ megakaryocytes of Group 1 expressed the CD42b marker at the level of 96.85 ± 1.06 % versus 88.7 ± 0.56 % in Group 2. With the application of MSC conditioned medium the average number of nucleated cells was signifi cantly higher on the day 11 and it was equal 326.016 ± 1.86 × 104  cells/mL vs 197.26 ± 10.55 × 104  cells/mL in IMDM medium. Proplatelet formation was observed with microscopy staring from the day 12. The ratio of CD41a+ /CD42b+  platelets was 59.5 ± 3.85 % in conditioned medium, 65.9 ± 8.72 % in IMDM, and 96.11 ± 0.89 % in control platelets derived from venous blood.Conclusion. It was demonstrated that the use of MSC conditioned medium leads to an increase in the expansion of nucleated cells, however it decreases the rate of differentiation in megakaryocytes. 

scholarly journals Effect of Mother’s Age and Pathology on Functional Behavior of Amniotic Mesenchymal Stromal Cells—Hints for Bone Regeneration

2019 ◽  
Vol 9 (17) ◽  
pp. 3471
Author(s):  
Matteo ◽  
Beccia ◽  
Carbone ◽  
Castellani ◽  
Milillo ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Differentiation Capacity ◽  
Functional Behavior ◽  
Group 3 ◽  
Titanium Surfaces ◽  
Group 2 ◽  
Mother’S Age ◽  
Group 1

Human amnion-derived mesenchymal stromal cells (hAMSCs) are used increasingly in regenerative medicine applications, including dentistry. The aim of this study was to evaluate if hAMSCs from aged and pathological mothers could be affected in their phenotype and functional behavior. hAMSCs were isolated from placentas of women aged younger than 40 years (Group 1, n = 7), older than 40 years (Group 2, n = 6), and with pre-eclampsia (Group 3, n = 5). Cell yield and viability were assessed at isolation (p0). Cell proliferation was evaluated from p0 to p5. Passage 2 was used to determine the phenotype, the differentiation capacity, and the adhesion to machined and sandblasted titanium disks. hAMSCs recovered from Group 3 were fewer than in Group 1. Viability and doubling time were not different among the three groups. Percentages of CD29+ cells were significantly lower in Group 3, while percentages of CD73+ cells were significantly lower in Groups 2 and 3 as compared with Group 1. hAMSCs from Group 2 showed a significant lower differentiation capacity towards chondrogenic and osteogenic lineages. hAMSCs from Group 3 adhered less to titanium surfaces. In conclusion, pathology can affect hAMSCs in phenotype and functional behavior and may alter bone regeneration capacities.

Fertile Potential of Freshly Isolated Adipose Tissue Derived Stromal cells and Bone Marrow Mesenchymal Stromal cells Against Premature Ovarian Failure

2021 ◽  
Vol 17 ◽  
Author(s):  
Tahir Maqbool ◽  
Faheem Hadi ◽  
Sehrish Tahir ◽  
Sadia Naz ◽  
Sajida Shahnawaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Premature Ovarian Failure ◽  
Stromal Cells ◽  
Serum Levels ◽  
Ovarian Failure ◽  
Group 4 ◽  
Group 3 ◽  
Group 2

Background: Failure to attain pregnancy or even miscarriage leads to infertility and premature ovarian failure (POF) is challenging type of infertility, stem cells have the ability to repair ovarian damage adipose tissue derived stromal cells (AT-SCs) and bone marrow mesenchymal stromal cells (BM-MSCs) have demonstrated promising regenerative abilities in several diseases including POF. Methods: Experiments were performed to prove the ability of AT-SCs and BM-MSCs in restoring ovarian functions, a total of 20 rats were randomly assigned to four groups; 5 rats in each group 1st group was untreated, 2nd was cyclophosphamide and busulfan treated group, 3rd was cyclophosphamide and busulfan + AT-SCs, 4th was cyclophosphamide and busulfan + BM-MSCs. Results: Group 3 and group 4 showed restored ovarian functions in the form of increase of weight (including body weight and ovarian weight), and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 and group 4 versus group 2. Increased antioxidant level of glutathione (GSH) and superoxide dismutase (SOD) in group 3 and group 4 compared with group 2, also histochemistry analysis demonstrated normal tissue distribution in 3rd and 4th group compared with 2nd group. Conclusions: We demonstrated the ability of AT-SCs and BM-MSCs to restore ovarian function in female with POF.

Impact of Changing Treatment Strategies on Outcomes in Pediatric Ulcerative Colitis

2019 ◽  
Vol 25 (11) ◽  
pp. 1838-1844 ◽  
Author(s):  
Rishi Bolia ◽  
Jeremy Rajanayagam ◽  
Winita Hardikar ◽  
George Alex
Keyword(s):  
Ulcerative Colitis ◽  
Hospital Admissions ◽  
Treatment Strategies ◽  
Median Number ◽  
Cumulative Probability ◽  
Therapeutic Drug ◽  
Disease Outcomes ◽  
Group 2 ◽  
Group 1 ◽  
Baseline Demographic

Abstract Background In recent years, treatment strategies for ulcerative colitis have evolved with an early step-up approach, the availability of biologicals, and therapeutic drug monitoring. We carried out this study to evaluate the effect of these changes on disease outcomes. Methods In this retrospective review, 2 time periods were defined: Group 1 (2005–2010) and Group 2 (2011–2016). Baseline demographic, endoscopic parameters, and medication use were compared. Overall colectomy rate, number of disease flares per year, and number of hospital admissions per year were compared between the 2 groups. Results Group 1 had 71 children, and in children in Group 2. The use of 5-ASA increased in Group 2 (Group 2, 99.2% vs. Group 1, 84.5%, P = 0.0007). In addition, infliximab and thiopurines were introduced earlier in the disease course. The 2-year cumulative probability of colectomy decreased from 14% to 3% (P = 0.02) between the 2 periods. No change in median number of flares per year [Group 1, 0.41 (IQR 0.6) vs. Group 2, 0.62 (IQR 0.91), P = 0.28] or median number of hospital admissions per year [Group 1, 0.30 (IQR 0.77) vs. Group 2, 0.21 (IQR 0.75), P = 0.52] was seen. Thereafter, we proceeded to identify the changes in treatment strategies that were responsible for the reduction in colectomy and we found that the use of infliximab OR 3.7 (95% CI 1.1–11.7), P = 0.02, was independently associated with it. Conclusions A reduction in 2-year colectomy rates has been observed in patients with pediatric ulcerative colitis since biologics have become available for its treatment. The numbers of disease-flares rates and hospital admissions remain unchanged.

scholarly journals Loss of response and frequency of adverse events in patients with ulcerative colitis and Crohn’s disease when switching from the original infliximab to its biosimilars

2021 ◽  
Vol 93 (2) ◽  
pp. 150-157
Author(s):  
O. V. Knyazev ◽  
M. Yu. Zvyaglova ◽  
A. V. Kagramanova ◽  
I. A. Li ◽  
E. A. Sabelnikova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
The Other ◽  
Induction Treatment ◽  
Tnf Inhibitor ◽  
Crohns Disease ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Trade Name

Aim. To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohns disease (CD), treated with original medicine infliximab (IFX) Remicaide and its biosimilars. Materials and methods. We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar. Results. Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p0.05). Conclusion. Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events.

scholarly journals The Conundrum of Ventricular Dilatations Following Decompressive Craniectomy: Is Ventriculoperitoneal Shunt, The Only Panacea?

2018 ◽  
Vol 09 (02) ◽  
pp. 232-239 ◽  
Author(s):  
Raja K. Kutty ◽  
Sunilkumar Balakrishnan Sreemathyamma ◽  
Jyothish Sivanandapanicker ◽  
Prasanth Asher ◽  
Rajmohan Bhanu Prabhakar ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Ventriculoperitoneal Shunt ◽  
Clinical Status ◽  
Clinical Signs ◽  
Outpatient Basis ◽  
Radiological Criteria ◽  
Shunt Group ◽  
Csf Diversion ◽  
Group 2 ◽  
Group 1

ABSTRACTIntroduction:Ventriculomegaly and hydrocephalus (HCP) are sometimes a bewildering sequela of decompressive craniectomy (DC). The distinguishing criteria between both are less well defined. Majority of the studies quoted in the literature have defined HCP radiologically, rather than considering the clinical status of the patient. Accordingly, these patients have been treated with permanent cerebrospinal fluid (CSF) diversion procedures. We hypothesize that asymptomatic ventriculomegaly following DC should undergo aspiration with cranioplasty and be followed up regularly. Materials and Methods: All patients with post-DC who were scheduled for cranioplasty and satisfied the radiological criteria for HCP were included. These patients were categorized into two groups. Group 1 included ventriculomegaly with clinical signs attributable to HCP and Group 2 constituted ventriculomegaly but no clinical signs attributable to HCP. All patients in Group 1 underwent ventriculoperitoneal shunt followed by cranioplasty, whereas all patients in Group 2 underwent cranioplasty along with simultaneous ventriculostomy and temporary aspiration of the lateral ventricle. All patients were regularly followed as the outpatient basis. Results: There were 21 patients who developed ventriculomegaly following DC. There were 10 patients in Group 1 and 11 patients in Group 2. The average duration of follow-up was from 6 months to 2 years. Two patients in the shunt group - (group 1) had over drainage and required revision. One patient in aspiration group - (group 2) required permanent CSF diversion. Conclusion: Cranioplasty with aspiration is a viable option in selected group of patients in whom there is ventriculomegaly but no signs or symptoms attributable to HCP.

Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels

2021 ◽  
Author(s):  
Xavier Roblin ◽  
Capucine Genin ◽  
Stéphane Nancey ◽  
Nicolas Williet ◽  
Pauline Veyrard ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Group Treatment ◽  
Treatment Discontinuation ◽  
Dose Optimization ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Trough Levels

Abstract Background In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma—either ADA dose optimization or switching to vedolizumab or ustekinumab. Methods Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels &gt; 4.9 μg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. Results Adalimumab was optimized (n = 61 patients, 42 Crohn’s disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn’s disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P &lt; 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (&gt;24 months) than in the optimization group (13.3 months, P &lt; 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin &gt;500 μg/g (HR, 3.53; 95% CI, 1.16–10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (&gt;2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13–0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. Conclusion In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are &gt;4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

Evidence for Selective Benefit of Sequential Treatment with Azanucleosides in Patients with Myelodysplastic Syndromes (MDS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4937-4937 ◽  
Author(s):  
Susmitha Apuri ◽  
Jeffrey E Lancet ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Viet Q. Ho ◽  
...  
Keyword(s):  
Median Time ◽  
Response Rate ◽  
Sequential Treatment ◽  
Overall Response ◽  
Loss Of Response ◽  
Drug Actions ◽  
The Mean ◽  
Group 2 ◽  
Group 1 ◽  
Median Interval

Abstract Abstract 4937 Background: Azanucleosides (AZN) remain the mainstay of therapy in Myelodysplastic syndrome (MDS). Azacitidine (AZA) and decitabine (DAC) have distinct differences in nucleic acid specificity and mechanisms of cellular resistance. The only published experience with sequential treatment described 14 patients, with a 28% response with DAC treatment after failure or lack of response to AZA. The response rate to AZA after DAC is unknown. Sequential use of alternative AZNs is common practice given the limited alternatives. To investigate the potential benefit of this approach, we reviewed cases of sequential AZN treatment. Methods: Patients who received treatment with both AZNs were identified through the Moffitt Cancer Center (MCC) MDS database. Two groups were identified; group one who received DAC after AZA failure, and group 2, who received AZA after DAC failure. AZN failure was defined as lack of response, loss of response or discontinuation due to adverse events or disease progression. The primary objective was to estimate response rates according to the International Working Group (IWG) 2006 criteria. Results: A total of 39 MDS patients were identified. Complete records were available in 31 patients, including 21 patients in group 1 (DAC after AZA), and 10 patients in group 2 (AZA after DAC). Table-1 summarizes baseline characteristics. In Group 1, 21 patients received DAC after AZA, 57% were originally red blood cell transfusion dependent (RBC TD). The median time from diagnosis to AZA treatment was 10 month (0. 2–52). The mean number of AZA treatment cycles was 8 (1–20). IWG responses to AZA treatment were 2 (10%) CR, 4 (20%) marrow CR (mCR), 7 (33%) hematological improvement (HI), 1 (5%) stable disease (SD) and 6 (28%) progressive disease (PD). Reasons for AZA discontinuation were 7(33%) no response, 1 (5%) progression, 9 (43%) lost response, and 4 (19%) toxicity. The median interval between end of AZA and initiation of DAC was 118 days (21–948). The mean number of DAC cycles was 4 (1–18). IWG responses to DAC were 1 (5%) mCR, 3 (14%) HI, 14 (67%) PD, and 3 (14%) unknown. The best overall response was 19%. The median OS from time of DAC initiation was 17. 8 month (95%CI 14–21). The rate of AML transformation was 29%. In Group 2, 10 patients received AZA after DAC, and 70% were originally RBC TD. The median time from diagnosis to DAC treatment was 2. 5 month (0–56). The mean number of DAC cycles was 4. 3 (1–9). IWG responses to DAC treatment were 2 (10%) mCR, 4 (40%) HI, 2 (20%) PD. The reasons for DAC discontinuation were no response (n=1), loss of response (n=3), PD (n=2), toxicity (n=3), and physician choice (n=1). The median interval between end of DAC and initiation of AZA was 179 days (19–448). The mean number of AZA cycles was 6 (2–12). The best responses to AZA were 2 (20%) mCR, 2 (20%) HI, 2 (20%) SD, 4 (40%) PD. The best overall response was 40%. The median OS from time of AZA start was 22 month. The rate of AML transformation was 20%. The median OS for Group 1 from diagnosis was 48 month and for group 2 was100 month (p=0. 7). Table-2 summarizes key differences between the two groups. Conclusions: Sequential use of AZNs after failure of first line may be an effective alternative outside the context of clinical trials. Despite limitations of cohort size and retrospective nature of the analysis, our findings suggest that response rate may be higher in patients who receive AZA after DAC, which could reflect the dual RNA/DNA drug actions. Sequential use of HMA should be considered in context of randomized clinical trial of novel agent as the control arm. Disclosures: List: Celgene: Consultancy. Komrokji:Celgene: Honoraria, Speakers Bureau.

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