The Story of Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Author(s):  
Joseph P. Broderick ◽  
James C. Grotta ◽  
Andrew M. Naidech ◽  
Thorsten Steiner ◽  
Nikola Sprigg ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Factor Viia ◽  
Phase Iii ◽  
Hemostatic Agents ◽  
The Past ◽  
End Point ◽  
Clot Removal ◽  
Modifiable Factors ◽  
Large Phase

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.

Intraperitoneal Chemotherapy for Ovarian Cancer: Overview and Perspective

2007 ◽  
Vol 25 (20) ◽  
pp. 2867-2872 ◽  
Author(s):  
Gautam Rao ◽  
Marta Crispens ◽  
Mace L. Rothenberg
Keyword(s):  
Ovarian Cancer ◽  
Abdominal Cavity ◽  
Drug Distribution ◽  
The United States ◽  
Phase Iii ◽  
Systemic Absorption ◽  
Current Interest ◽  
The Past ◽  
Phase Iii Trials ◽  
Large Phase

Intraperitoneal (IP) chemotherapy has theoretical, pharmacologic, and clinical advantages over intravenous (IV) chemotherapy in women with optimally debulked epithelial ovarian cancer confined to the abdominal cavity. Consistent, statistically significant improvements in both progression-free and overall survival have been demonstrated in three large phase III trials conducted in the United States during the past 10 years. Nevertheless, concerns over IP drug distribution and systemic absorption, technical challenges of IP catheter placement and the incidence of IP catheter-related complications, and the clinical relevance of these studies have limited the adoption of IP therapy in ovarian cancer. Current interest in the evaluation of molecularly targeted therapies should build on the progress that has been made through the use of IP chemotherapy in women with optimally debulked ovarian cancer.

scholarly journals Thrombolysis for Evacuation of Intracerebral and Intraventricular Hemorrhage: A Guide to Surgical Protocols With Practical Lessons Learned From the MISTIE and CLEAR Trials

2020 ◽  
Vol 20 (1) ◽  
pp. 98-108 ◽  
Author(s):  
Sean P Polster ◽  
Julián Carrión-Penagos ◽  
Seán B Lyne ◽  
Fernando D Goldenberg ◽  
Ali Mansour ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Intraventricular Hemorrhage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Lessons Learned ◽  
Catheter Placement ◽  
Phase Iii ◽  
Surgical Performance ◽  
Hematoma Evacuation ◽  
Functional Benefit ◽  
Modifiable Factors

Abstract BACKGROUND Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. OBJECTIVE To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. METHODS We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. RESULTS Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. CONCLUSIONS Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.

Two decades of therapy in metastatic colorectal cancer (mCRC): An analysis to discern the contribution and progress made by chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14064-e14064
Author(s):  
Irfan Jawed ◽  
Julia Wilkerson ◽  
Austin G. Duffy ◽  
Antonio Tito Fojo
Keyword(s):  
Supportive Care ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Phase Ii Trials ◽  
First Line ◽  
The Past ◽  
Large Phase ◽  
And Control ◽  
Over Time

e14064 Background: The past 20 years have seen progress in mCRC with more effective agents and better medical, surgical and supportive care. Methods: Systematic review of 101 phase III and large phase II trials in mCRC to quantify benefit over time with first-line and subsequent therapies. Outcomes in the experimental (EA) and control arms (CA) included progression-free survival (PFS), overall response rate (ORR), stable disease (SD), and overall survival (OS). Data were analyzed according to dates of publication and median enrollment. Results: Significant outcomes are reported; most had R2 values > 0.6. OS of EA improved 0.83 mos/yr. Importantly OS of CA improved 0.58 mos/yr likely reflecting subsequent use of experimental regimens in CA and improvement in mCRC care over time. Chemotherapy has contributed only partly to gains in OS since (1) only modest improvements of PFS (0.33 [EA] and 0.26 [CA] mos/yr) and we have shown OS gains are proportional to PFS gains indicating other factors are as or more important than chemotherapy; and (2) lack of OS improvement in 14 second/subsequent line trials. Furthermore, to assess the contribution of each drug/drug class to improvement in OS we performed linear regression with OS the dependent variable versus time publication. We found oxaliplatin, irinotecan and bevacizumab have contributed to progress; but not cetuximab/panitumumab likely explained by inclusion of pts with tumors harboring mutant ras in studies. Not surprisingly, capecitabine in place of 5-fluorouracil had no impact on progress made. As expected PFS correlates highly with OS, but importantly ORR had very high correlations with both PFS and OS. SD was an “adverse” outcome, OS decreasing as SD rates increase. Conclusions: OS of mCRC patients has improved gradually over the past two decades, with gains from chemotherapy and importantly gains from other factors, including lead-time bias, better loco-regional approaches and supportive care. Gains from first line therapies have been modest but consistent; gains from second line therapies have been disappointing. We believe future progress will be more fruitful if emphasis is given to improving second line therapies.

Intracerebral Hemorrhage

2018 ◽  
pp. 37-44
Author(s):  
Opeolu Adeoye
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Intracerebral Hemorrhage ◽  
Surgical Management ◽  
Clinical Management ◽  
Intraventricular Hemorrhage ◽  
Severe Form ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Future Directions ◽  
The Past

Spontaneous intracerebral hemorrhage (ICH) is a severe form of stroke with no proven treatments to date. However, multiple clinical trials in the past decade have contributed to the growing knowledge in the field, and ongoing trials will further inform clinical management. Completed and ongoing trials have informed blood pressure management, surgical management, hemostasis, treatment of coagulopathy, treatment of intraventricular hemorrhage, and neuroprotection, among others. This chapter discusses recent advancements in ICH, how those advancements have informed clinical management, and future directions for innovative research that may lead to proven interventions for ICH.

Atopic dermatitis: new horizons of therapy

2019 ◽  
Vol 1 (7) ◽  
pp. 29-32 ◽  
Author(s):  
L. S. Kruglova ◽  
E. M. Gensler
Keyword(s):  
Blood Pressure ◽  
Immune Response ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Targeted Therapy ◽  
Inflammatory Response ◽  
Bronchial Asthma ◽  
New Horizons ◽  
The Past

Over the past decades, the first breakthrough milestone in the treatment of severe forms of atopic dermatitis (AD) has been targeted therapy aimed at inhibiting IL-4 and IL-13. This was made possible thanks to advances in the understanding of the pathogenesis of AD, the driver of which is the Th2-type immune response, which also underlies such manifestations of atopy as bronchial asthma, allergic rhinitis, and polynosis. In the case of the Th2-type immune response, cytokines IL-4 and IL-13 are secreted, which are the main promoters of the inflammatory response in AD. Inhibition of IL-4 and IL-13 leads to the prevention of inflammation and is an effective approach to therapy. The use of therapy aimed at inhibition of cytokines allows you to effectively cope with the manifestations of severe and moderately severe blood pressure.

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