scholarly journals Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in Brca1-deficient mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Di Zhang ◽  
Bijay Singh ◽  
Jessica Moerland ◽  
Owen Mitchell ◽  
Lizbeth Lockwood ◽  
...  
Keyword(s):  
High Risk ◽  
Parp Inhibitor ◽  
Tumor Development ◽  
Radical Mastectomy ◽  
Mammary Glands ◽  
Parp Inhibitors ◽  
Control Group ◽  
Emotional Challenges ◽  
Risk Patients ◽  
Deficient Mice

AbstractMutations in BRCA genes are the leading cause of hereditary breast cancer. Current options to prevent cancer in these high-risk patients, such as anti-estrogen drugs and radical mastectomy, are limited by lack of efficacy, undesirable toxicities, or physical and emotional challenges. We have previously shown that PARP inhibitors can significantly delay tumor development in BRCA1-deficient mice. Here, we fabricated the PARP inhibitor talazoparib (TLZ) into spacer implants (InCeT-TLZ) for localized and sustained delivery. We hypothesized that this novel formulation will provide an effective chemopreventive strategy with minimal toxicity. TLZ was released gradually over 30 days as implants degraded. InCeT-TLZ significantly decreased proliferation and increased DNA damage in the mammary glands of BRCA1-deficient mice. Notably, the number of mice that developed hyperplasia in the mammary glands was significantly lower with InCeT-TLZ treatment compared to the control group. Meanwhile, InCeT-TLZ was also better tolerated than oral TLZ, without loss of body weight or anemia. This study provides proof of concept for a novel and safe chemopreventive strategy using localized delivery of a PARP inhibitor for high-risk individuals. Future studies will directly evaluate the effects of InCeT-TLZ for preventing tumor development.

scholarly journals Audio-guided self-hypnosis for reduction of claustrophobia during MR imaging: results of an observational 2-group study

2021 ◽  
Author(s):  
Adriane E. Napp ◽  
Torsten Diekhoff ◽  
Olf Stoiber ◽  
Judith Enders ◽  
Gerd Diederichs ◽  
...  
Keyword(s):  
High Risk ◽  
Mr Imaging ◽  
Odds Ratio ◽  
Control Group ◽  
Waiting Room ◽  
High Risk Patients ◽  
Imaging Results ◽  
Before And After ◽  
Risk Patients ◽  
And Coping

Abstract Objectives To evaluate the influence of audio-guided self-hypnosis on claustrophobia in a high-risk cohort undergoing magnetic resonance (MR) imaging. Methods In this prospective observational 2-group study, 55 patients (69% female, mean age 53.6 ± 13.9) used self-hypnosis directly before imaging. Claustrophobia included premature termination, sedation, and coping actions. The claustrophobia questionnaire (CLQ) was completed before self-hypnosis and after MR imaging. Results were compared to a control cohort of 89 patients examined on the same open MR scanner using logistic regression for multivariate analysis. Furthermore, patients were asked about their preferences for future imaging. Results There was significantly fewer claustrophobia in the self-hypnosis group (16%; 9/55), compared with the control group (43%; 38/89; odds ratio .14; p = .001). Self-hypnosis patients also needed less sedation (2% vs 16%; 1/55 vs 14/89; odds ratio .1; p = .008) and non-sedation coping actions (13% vs 28%; 7/55 vs 25/89; odds ratio .3; p = .02). Self-hypnosis did not influence the CLQ results measured before and after MR imaging (p = .79). Self-hypnosis reduced the frequency of claustrophobia in the subgroup of patients above an established CLQ cut-off of .33 from 47% (37/78) to 18% (9/49; p = .002). In the subgroup below the CLQ cut-off of 0.33, there were no significant differences (0% vs 9%, 0/6 vs 1/11; p = 1.0). Most patients (67%; 35/52) preferred self-hypnosis for future MR examinations. Conclusions Self-hypnosis reduced claustrophobia in high-risk patients undergoing imaging in an open MR scanner and might reduce the need for sedation and non-sedation coping actions. Key Points • Forty percent of the patients at high risk for claustrophobia may also experience a claustrophobic event in an open MR scanner. • Self-hypnosis while listening to an audio in the waiting room before the examination may reduce claustrophobic events in over 50% of patients with high risk for claustrophobia. • Self-hypnosis may also reduce the need for sedation and other time-consuming non-sedation coping actions and is preferred by high-risk patients for future examinations.

scholarly journals COVID-19: step-by-step treatment strategies

2021 ◽  
pp. 155-162
Author(s):  
D. P. Salivonchik
Keyword(s):  
World War Ii ◽  
Survival Rate ◽  
High Risk ◽  
Oxygen Therapy ◽  
Treatment Strategies ◽  
Pulse Therapy ◽  
Adverse Outcomes ◽  
Control Group ◽  
Clinical Hospital ◽  
Risk Patients

Objective: to evaluate the effectiveness and safety of anticoagulant and glucocorticosteroid therapy in patients with COVID-19, to determine step-by-step solutions in the prescription of drug therapy at the inpatient stage.Materials and methods. We performed two randomized continuous prospective comparative studies including 1,801 patients diagnosed with COVID-19 pneumonia who were undergoing inpatient treatment in November-December 2020 (1,004 patients) in Gomel Regional Clinical Hospital for the Disabled of World War II and in February 2021 (797 patients) in Gomel City Clinical Hospital No. 3.Results. The step-by-step strategy for treating patients with pneumonia associated with COVID-19 is to divide the patients into groups of high and moderate risks of adverse outcomes (based on the developed predictors) on the first day of hospitalization. In moderate-risk patients, the “protocol” therapy stabilizes the condition; in high-risk patients, it is not effective. Early preemptive anticoagulant therapy (ACT) and individual hormone therapy (prior to pulse therapy) may stabilize the condition of the patients, increase the survival rate from 82.1 % to 96.8 %, p = 0.0001. The additional steps are: targeted use of tocilizumab in the Somatic Department before the Intensive Care Department (70 % survival, p = 0.031), oxygen therapy, pronposition, catheterization of patients, use of the domestic hepatoprotector, membrane-stabilizing antiischemic drug “Thiotriazoline” in patients with high blood lactate levels (lactate dehydrogenase (LDH)), which stabilizes metabolic processes in the affected organs (in dynamics by 342.7 ± 92.8 units/l for 5 days compared to the control group, p=0.0001). When the patient’s condition gets stabilized, the use of respiratory and physical rehabilitation are the final steps of the recovery strategy at the inpatient stage.Conclusion. Therapeutic anticoagulant and individual glucocorticosteroid therapy in combination with oxygen therapy, the use of thiotriazoline in some COVID-19 patients being at a high risk of adverse outcomes have led to an increased survival rate — from 82.1 % to 96.8 % at the hospital stage, p = 0.0001.

Abstract 2471: Contemporary Results of Isolated Aortic Valve Replacement in High-Risk Patients in the Context of Emerging Percutaneous Approaches

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Pierre Voisine ◽  
Siamak Mohammadi ◽  
Josep Rodés-Cabau ◽  
Patrick Mathieu ◽  
Jean Perron ◽  
...  
Keyword(s):  
High Risk ◽  
Aortic Valve ◽  
Survival Benefit ◽  
Control Group ◽  
Perioperative Mortality ◽  
High Risk Patients ◽  
All Cause Mortality ◽  
Risk Patients ◽  
Related Mortality ◽  
Parsonnet Score

Percutaneous aortic valve replacement (AVR) is emerging as an alternative therapeutic approach for high-risk surgical patients, but criteria for patient selection are not clearly established. We sought to evaluate the perioperative and mid-term outcomes in a contemporary cohort of high-risk patients undergoing isolated AVR. Between 1997 and 2006, 855 consecutive patients underwent isolated AVR at our institution. High-risk patients (n=162, 19%) were defined by a preoperative Parsonnet score ≥ 30 or Euroscore ≥ 9. The remaining 693 patients (81%) composed the control group for comparison of perioperative mortality and mid-term freedom from all-cause and cardiac-related mortality. Mean follow up was 2.9±2.1 years. Perioperative mortality was 8.6% in the high-risk and 2.9% in the control group (p=0.0007), lower than that predicted by both scores (p<0.05). Freedom from all-cause mortality at 1 and 5 years were 94% and 82% for the control group and 87% and 65% for high-risk patients (p<0.0001). Freedom from cardiac-related mortality was also higher in the control (96% at 1 year, 91% at 5 years) than the high-risk (89% and 82%, p=0.0003) group. When considering patients who survived the 3-month perioperative period (537 in control, 114 in high-risk group), freedom from all-cause mortality was still higher in the former group at 1 and 5 years (99% vs 99% and 85% vs 75%, respectively, p=0.005), but freedom from cardiac-related mortality was not different (99% vs 100% and 94% vs 92%, respectively, p=0.3). By multivariate analysis, chronic renal failure, emergent procedures and reoperations were identified as independent predictors of mortality in high-risk patients. Contemporary perioperative mortality for isolated AVR in high-risk patients is lower than predicted by the Parsonnet score and Euroscore. Five-year survival in these patients is acceptable, and survivors of the operation experience the same cardiac-related survival benefit as those with standard perioperative risk. The perioperative survival benefit of percutaneous approaches for high-risk patients undergoing AVR remains to be demonstrated and, if present, should be weighed against mid-term outcome benefits of conventional surgical AVR.

scholarly journals Polysaccharide hemostatic powder to prevent bleeding after endoscopic submucosal dissection in high risk patients: A randomized controlled trial

Endoscopy ◽  
2020 ◽  
Author(s):  
Da Hyun Jung ◽  
Chan Hyuk Park ◽  
Hee Seok Moon ◽  
Jun Chul Park
Keyword(s):  
High Risk ◽  
Endoscopic Submucosal Dissection ◽  
Controlled Trial ◽  
Gastric Neoplasms ◽  
Control Group ◽  
High Risk Patients ◽  
Randomized Controlled ◽  
Submucosal Dissection ◽  
Risk Patients ◽  
Hemostatic Powder

Background and aims: Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Several methods to prevent post-ESD bleeding (PEB) have been introduced; however, they have not been widely used because of technical difficulties. We aimed to investigate whether polysaccharide hemostatic powder (PHP), which is very easy to apply, can prevent early PEB, especially in patients with high risk of PEB. Methods: This was a prospective, multicenter, randomized, open-label, controlled trial. Patients with a high risk for PEB were enrolled. Patients with gastric neoplasms in whom the resected specimen size was expected to be >40 mm and those who were regularly taking antithrombotic agents were defined as high-risk patients. Patients were randomly assigned to the PHP or control group. Results: Between May 2017 and September 2018, 143 patients were enrolled (PHP group: 73, control group: 70). The total PEB rate was 6.3% (PHP group: 5% vs. control group: 7.1%, P=0.742). There was no bleeding within 7 days after ESD in the PHP group. Continued antithrombotic use was an independent risk factor of PEB. In subgroup analysis excluding patients who continued to take antithrombotics (n=129) during ESD, the rate of PEB was tended to be lower in the PHP group than in the control group (0% vs. 6.3%, P=0.058). Conclusion: PHP did not demonstrate a significant effect on the prevention of PEB in this study. Further larger-scale, randomized controlled trials are needed to confirm this.(ClinicalTrials.gov 03169569)

scholarly journals Prophylactic Application of an Intra-Aortic Balloon Pump in High-Risk Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

Cardiology ◽  
2015 ◽  
Vol 131 (2) ◽  
pp. 109-115 ◽  
Author(s):  
WenJun Ding ◽  
Qiang Ji ◽  
Qiang Wei ◽  
YunQing Shi ◽  
RunHua Ma ◽  
...  
Keyword(s):  
High Risk ◽  
Artery Bypass ◽  
Control Group ◽  
Bypass Grafting ◽  
Surgical Mortality ◽  
Low Cardiac Output ◽  
Off Pump ◽  
High Risk Patients ◽  
Risk Patients ◽  
Pump Coronary Artery Bypass

Background: An intra-aortic balloon pump (IABP) is the most commonly used circulatory assist device in cardiac surgery. We hypothesized that prophylactic application of an IABP improves early clinical outcome of high-risk patients undergoing scheduled off-pump coronary artery bypass grafting (OPCABG). Methods: From January 2010 to December 2013, hemodynamically stable, high-risk patients undergoing scheduled OPCABG with preincision use of an IABP were recruited to the IABP group. Using the propensity score-matching method, every patient in the IABP group was matched with another patient (the control group) with a similar propensity score who received an IABP on an as-needed basis during or after OPCABG. Surgical mortality and major morbidity rates were compared between groups. Results: A total of 116 patient pairs were included in this study. In patients in the IABP group, postoperative low cardiac output and respiratory as well as renal failure were less frequent, intensive care unit stay was shorter, and surgical mortality was lower compared to patients in the control group. In multivariate logistic regression, timing of IABP implantation, as an independent risk factor, was associated with postoperative low cardiac output (OR = 2.02, 95% CI 1.28-5.76), respiratory failure (OR = 1.86, 95% CI 1.19-4.27), renal failure (OR = 2.96, 95% CI 1.51-6.63) and surgical mortality (OR = 2.45, 95% CI 1.42-6.07). Conclusions: Prophylactic application of an IABP improves postoperative cardiac performance, reduces respiratory and renal complications, and consequently lowers surgical mortality in high-risk patients undergoing scheduled OPCABG.

Intensified Conditioning for Children Undergoing BMT for First Bone Marrow Relapse of Acute Lymphoblastic Leukaemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5169-5169
Author(s):  
John Moppett ◽  
Jerry Hancock ◽  
Christopher J.C. Knechtli ◽  
Anthony Oakhill ◽  
Nicholas J. Goulden
Keyword(s):  
High Risk ◽  
Treatment Failure ◽  
Risk Group ◽  
Control Group ◽  
Childhood All ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients ◽  
High Level ◽  
Risk Of Treatment

Abstract BMT remains the treatment of choice for early BM relapse of childhood ALL. We reasoned that further intensification of cytoreductive therapy pre-BMT may further improve survival amongst those with the highest risk of treatment failure, early BM relapse (BFM groups S3/4) and high level MRD pre-BMT. A cohort of 32 patients transplanted at a single institution (1996–1999) provided an historical control. 8 high risk patients transplanted 1999–2000 received additional fludarabine cytoreduction therapy at the time of transplant (FLA group). MRD analysis and time to relapse were used in a subsequent cohort of 22 patients (BMT 2000–2002) to allocate those at highest risk of treatment failure to receive a further cytoreductive block, FLX, pre-BMT. Method. All patients were conditioned with cyclophosphamide (60mg/m2 x2) and TBI (14.4 Gy). UD and haplo-BMT were T-cell depleted with Campth-1M in vitro and Campath-1G day -9 to -5 (Control and FLA group), and by Miltenyi CD34+ cell depletion (FLX group). GvHD prophylaxis - CSA + MTX for matched related, CSA for Campath treated grafts and none for Miltenyi grafts. The FLA group received fludarabine 25mg/m2 from d −12 to d −10. Patients with on treatment relapse (S4) or high level MRD pre-BMT (MRD++) in the FLX group received DaunoXome 100mg/m2, fludarabine 30mg/m2 x 5d and cytosine 2g/m2 x 5d 3 weeks prior to BMT. Patients and donors. Control group: 28 precursor-B ALL 4 T-ALL; donors - 7 matched related, 13 matched unrelated (MUD) and 12 mismatched unrelated (MMUD); 14 S2, 18 S3/4. FLA group: 5 presursor-B ALL and 3 T-ALL; donors - 2 SIB, 4 MUD, 1 MMUD and 2 haplo; all S4. FLX group: 21 precursor-B and 1 T-ALL; donors - 6 SIB, 7 MUD, 5 MMUD and 4 haplo;13 S2, 9 S4. 7 patients received FLX intensified conditioning (6 S4, 5 high level MRD ++). 3 high risk patients violated protocol and did not receive FLX (1 age &lt;1yr on treatment relapse, 2 S2 MRD ++). Results. Considering those in the high-risk S3/4 group, there was no significant difference in OS between the 3 groups. Survival by study and risk group Study S2 S3/4 Overall Control 10/14 (71%) 3/18 (17%) 13/32 (41%) FLA 2/8 (25%) 2/8 (25%) FLX 11/13 (85%) 3/9 (33%) 14/22 (64%) No excess cardiac events were seen. The TRM is higher in the FLX group than in the control. Outcome data Study TRM Relapse Alive Total Control 3 16 13 32 S2 2 2 10 14 S3/4 1 14 3 18 FLA 3 3 6 12 S2 - - - - S3/4 3 3 3 9 FLX 6 2 14 22 S2 2 0 11 13 S3/4 4 2 3 9 Total 12 21 33 66 2 of 7 patients treated with FLX are in CCR, 2 relapsed and 3 died of TRM. The 3 high risk patients in the FLX study, but who did not receive FLX, are also in CCR. Survival in those in the S2 group (late BM relapse) has been good throughout the study period. Conclusion. In this study the addition of intensive pre-BMT conditioning has not improved survival amongst high risk (S3/4 or MRD ++ pre-BMT) relapses. The number of post-BMT relapses has fallen but this is not clearly related to the use of FLX. The use of more haploidentical donors, more immunosupressive BMT regimes and additional cytoreductive chemotherapy may have contributed to the increased TRM seen. Time and site of relapse remain the clearest predictor of outcome. Further novel strategies are required to improve survival for the S4 risk group. The good OS for children receiving BMT in the S2 group should be noted.

A GITIL Prospective Randomized Multicenter Phase III Study of High Dose Sequential Chemotherapy with Rituximab (R-HDS) and Autologous Transplantation (ASCT) of Peripheral Blood Stem Cells Versus CHOP and Rituximab Delivered Every 14 Days (R-CHOP-14) in High-Risk Patients with Diffuse Large B-Cell Lymphomas (DLBCL): Interim Analysis on Feasibility and Toxicity (Protocol R-HDS 0305).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1898-1898
Author(s):  
Sergio Cortelazzo ◽  
Atto Billio ◽  
Alessandro Rambaldi ◽  
Corrado Tarella ◽  
Ingnazio Majolino ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Ecog Ps

Abstract R-HDS 0305 (Clinical Trials. gov. number NCT00355199) is a multi-centre, unblinded, randomized controlled phase III trial involving 240 patients in 3 years from 16 Italian Cancer Centres, with DLBCL without CNS involvement, advanced stage (stage ≥IIB, bulk), age from 18 to 60 years with ECOG-PS=0–3 and aaIPI=2–3 or age from 61 to 65 years with ECOG-PS=0–2 and IPI 3–5. The control group received R-CHOP-14, which comprised 8 courses of chemotherapy every 14 days, supported by GCSF (day 7–11)±IFRT, if they achieved at least a PR after 4 cycles. Cases refractory to R-CHOP-14 were given R-HDS as salvage therapy. Experimental arm consisted in a R-HDS program, including a debulking phase of 3 courses of doxorubicin-containing chemotherapy (APO), followed by high-dose (HD)-cyclophosphamide (CTX) 7g/sqm, HD-Ara-C (2 g/sqm every 12 hours for 6 days), HD-etoposide 2g/sqm+Cisplatin 100 mg/sqm. After HDS chemotherapy, HD-mitoxantrone plus melphalan (60 and 180 mg/sqm) or a BEAM (BCNU 300 mg/sqm, etoposide 200 mg/sqm, Ara-C 4000 mg/sqm, L-PAM 140 mg/sqm) conditioning regimen with ASCT±IFRT was planned. Rituximab (375 mg/sqm) is given for a total of 6 doses, twice after HD-CTX and HD-Ara-C, as in vivo purging before CD34+ cells harvest, and twice after ASCT. The primary outcomes of the study are complete remission and disease-free survival, overall survival, event-free survival and toxicity. From July 2005 to July 2007, 89 patients were enrolled in the study (R-CHOP-14=43; R-HDS=46). The median age was 51 (range 19–65 years), 11 (12%) had ≥60 years and the M/F was 1.3. Patients presented with adverse features such as advanced stage (88%), BM infiltration (28%), bulky disease (71%), elevated LDH (84%), poor ECOG-PS (55%) and &gt;1 extranodal sites (59%). Until now only 3 patients (3.4%) were refractory to planned treatment: 1/43 (2%) patients belonging to R-CHOP-14 arm shifted to R-HDS salvage treatment and other 2 patients died from lymphoma progression. The main G 3–4 WHO toxicity was haematological: anemia, granulocytopenia and thrombocytopenia occurred in 8%, 18% and 13% of patients, respectively. Grade 2–3 gastrointestinal toxicity and infectious episodes were recorded in 6% and 9% of patients, respectively. Two patients recovered from acute respiratory distress and 2 died of treatment-related toxicity (2.2%). In conclusion, if the R-HDS trial confirms earlier results, preliminary data show that intensive programs such as dose-dense chemo-immunotherapy and R-HDS with ASCT are feasible until 65 years with an acceptable toxic profile, also on the multi-centre basis. At completion of the trial we will assess the role of R-HDS and ASCT on the outcome of high-risk patients with DLBCL.

Platelet Functions and Risk Prognosis in Myelodysplastic Syndromes,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3806-3806
Author(s):  
Nora V. Butta ◽  
Mónica Martín Salces ◽  
Raquel de Paz ◽  
Elena G. Arias Salgado ◽  
Ihosvany Fernández Bello ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Surface Expression ◽  
Low Risk ◽  
Control Group ◽  
Platelet Surface ◽  
High Risk Patients ◽  
Fibrinogen Receptor ◽  
Risk Patients

Abstract Abstract 3806 The myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders with peripheral cytopenias and increased incidence of leukemic transformation. The prognosis of MDS is determined by several factors, including the presence of specific cytogenetic abnormalities, the percentage of blastoid cells in bone marrow and peripheral blood, the number of affected cell lineages, and transfusion dependency. The most commonly used risk stratification system is the International Prognostic Scoring System (IPSS). This score divides patients into a lower risk subset (low and intermediate-1) and a higher risk subset (intermediate-2 and high). Patients with MDS may have hemorrhagic complications with serious outcomes that are among the major causes of death in this population. These bleeding episodes that are often related to thrombocytopenia also occur in MDS patients with normal platelet count. The aim of this work was to study functional characteristics of platelets in MDS patients and their relationship to risk evaluated as indicated by IPSS. Eighty diagnosed MDS patients risk-stratified according to IPSS were included: 40 with low-risk, 29 with intermediate-1-risk (I-1), 8 with intermediate-2-risk (I-2) and 3 with high-risk. Eighty healthy donors were included as control group. Platelet-related primary haemostasis was evaluated with an automated platelet function analyzer (PFA-100®, Siemens Healthcare Diagnostics). Samples of citrated blood were aspirated under a shear rate of 4,000–5,000/s through a 150-μm aperture cut into a collagen-ADP (COL-ADP) or collagen-epinephrine (COL-EPI) coated membrane. The platelet haemostatic capacity is indicated by the time required for the platelet plug to occlude the aperture (closure time, CT), which is expressed in seconds. Platelet activation was determined through FITC-PAC-1 (a mAb that recognizes activated conformation of fibrinogen receptor) and FITC-P-selectin mAb binding to quiescent and 100 μM TRAP activated platelets by flow cytometry. Surface expression of fibrinogen receptor (αIIb and β3 subunits) was determined by flow cytometry with specific mAbs. Apoptosis was determined by flow cytometry analysis through FITC-annexin V binding to platelet membrane phosphatidylserine (PS) exposed in basal conditions. I-2 and high-risk patients were gathered together in a high-risk group in order to analyze experimental results. Statistical analysis was performed with one-way ANOVA and Tukey test. CTs obtained with COL-EPI and COL-ADP cartridges in controls and low risk patients were similar and significantly shorter than CTs observed in I-1-risk and high-risk MDS patients (p<0.05). Platelets from all MDS patients showed a reduced capability for being activated by 100 μM TRAP. This impairment was more evident in I-1-risk and high-risk patients: PAC-1 binding, in arbitrary units (AU), was 11368±1017 in controls; 7849±789 in low-risk MDS (p<0.05); 4161±591 in I-1-risk MDS (p<0.01 versus control and p<0.05 versus low-risk) and 492±184 in high-risk MDS (p<0.01 versus control and p<0.05 versus low-risk). The platelet surface expression of P-selectin induced by 100 μM TRAP was also reduced: 5102±340 AU in controls, 3318±400 AU in low-risk MDS (p<0.05); 1880 ±197 AU in I-1-risk MDS (p<0.05 versus control and versus low-risk), and 1211±130 AU in high-risk MDS (p<0.05 versus control and versus low-risk). Diminished responses to TRAP were not due to a reduction in surface expression of fibrinogen receptor in platelets from MDS patients. Platelets from MDS patients expressed more PS than controls under basal conditions. Mean fluorescence values for FITC-annexin binding were: 383±16 in controls; 444±21 in low-risk (p<0.05); 575±52 in I-1-risk MDS (p<0.05 versus control and versus low-risk); 611±17 in high-risk MDS (p<0.05 versus control and versus low-risk). Our results indicated that platelets from MDS patients had less ability to be activated and were more apoptotic than control ones. These dysfunctions were more pronounced when the risk of the disease was higher according to IPSS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The PARP Inhibitors, Veliparib and Olaparib, Are Effective Chemopreventive Agents for Delaying Mammary Tumor Development in BRCA1-deficient Mice

2014 ◽  
Vol 7 (7) ◽  
pp. 698-707 ◽  
Author(s):  
Ciric To ◽  
Eun-Hee Kim ◽  
Darlene B. Royce ◽  
Charlotte R. Williams ◽  
Ryan M. Collins ◽  
...  
Keyword(s):  
Mammary Tumor ◽  
Tumor Development ◽  
Parp Inhibitors ◽  
Chemopreventive Agents ◽  
Deficient Mice

scholarly journals Elastography and Metalloproteinases in Patients at High Risk of Preterm Labor

2021 ◽  
Vol 10 (17) ◽  
pp. 3886
Author(s):  
Izabela Dymanowska-Dyjak ◽  
Aleksandra Stupak ◽  
Adrianna Kondracka ◽  
Tomasz Gęca ◽  
Arkadiusz Krzyżanowski ◽  
...  
Keyword(s):  
High Risk ◽  
Preterm Delivery ◽  
Plasma Concentrations ◽  
Cervical Length ◽  
Control Group ◽  
Study Group ◽  
Median Length ◽  
High Risk Patients ◽  
Ultrasound Evaluation ◽  
Risk Patients

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Its etiopathology is multifactorial; therefore, many of the tests contain the assessment of the biochemical factors and ultrasound evaluation of the cervix in patients at risk of preterm delivery. The study aimed at evaluating the socioeconomic data, ultrasound examinations with elastography, plasma concentrations of MMP-8 and MMP-9 metalloproteinases, and vaginal secretions in the control group as well as patients with threatened preterm delivery (high-risk patients). The study included 88 patients hospitalized in the Department of Obstetrics and Pregnancy Pathology, SPSK 1, in Lublin. Patients were qualified to the study group (50) with a transvaginal ultrasonography of cervical length (CL) ≤ 25 mm. The control group (38) were patients with a physiological course of pregnancy with CL > 25 mm. In the study group, the median length of the cervix was 17.49 mm. Elastographic parameters: strain and ratio were 0.20 and 0.83. In the control group, the median length of the cervix was 34.73 mm, while the strain and ratio were 0.20 and 1.23. In the study group, the concentration of MMP-8 in the serum and secretions of the cervix was on average 74.17 and 155.46 ng/mL, but in the control group, it was significantly lower, on average 58.49 and 94.19 ng/mL. The concentration of MMP-9 in both groups was on the same level. Evaluation of the cervical length and measurement of MMP-8 concentration are the methods of predicting preterm delivery in high-risk patients. The use of static elastography did not meet the criteria of a PTB marker.

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