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Oncotarget Jun 2017The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM).
RESULTS
Based on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0.001, I2 = 96.3%), suggesting the overall response rate (ORR) of 66% attained from CFZ/DEX dual combination seemed to be higher than that of 28% from carfilzomib single-agent. And, the same trend favoring CFZ/DEX dual combination was found in ≥VGPR and CBR analysis. The ORR of 31% attained from POM/DEX dual combination was superior to that of 19% from pomalidomide single-agent(P < 0.001, I2 = 94.4%). And, the same trend favoring POM/DEX dual combination was found in ≥VGPR and CBR analysis. However, the ORR of 83% attained from POM/BOR/DEX triplet combination was superior to that of 31% from POM/DEX dual combination(P < 0.001, I2 = 99.1%). And, the same trend favoring POM/BOR/DEX triplet combination was found in ≥VGPR analysis.
METHODS
We searched published reports including carfilzomib and (or) pomalidomide therapy for RRMM who had received bortezomib and (or) lenalidomide.
CONCLUSION
Pomalidomide/Carfilzomib plus dexamethasone seemed to attain a superior response rate compared with pomalidomide/carfilzomib single-agent. Furthermore, the combination of pomalidomide, bortezomib and dexamethasone resulted in a much higher response rate compared with pomalidomide plus dexamethasone regimen. These results needed more validation in future trials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease Management; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Prospective Studies; Salvage Therapy; Thalidomide
PubMed: 27458170
DOI: 10.18632/oncotarget.10768 -
International Journal of Gynecological... Jun 2022Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to...
OBJECTIVE
Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol.
METHODS
All patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction.
RESULTS
A total of 186 eligible patients were included. Median age was 59.5 years (range 26-87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325-360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease.
CONCLUSIONS
Our outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.
PubMed: 35675969
DOI: 10.1136/ijgc-2022-003466 -
EuroIntervention : Journal of EuroPCR... Feb 2022Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using... (Review)
Review
BACKGROUND
Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking.
AIMS
In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT.
METHODS
For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness.
RESULTS
Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique).
CONCLUSIONS
This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.
Topics: Angina Pectoris; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Heart; Humans; Vasomotor System
PubMed: 34278990
DOI: 10.4244/EIJ-D-21-00402 -
European Review For Medical and... May 2019Despite the improvements reached by microsurgeons in the last 30 years, postoperative complications still occur and most of them are the result of venous thrombosis at... (Review)
Review
OBJECTIVE
Despite the improvements reached by microsurgeons in the last 30 years, postoperative complications still occur and most of them are the result of venous thrombosis at the pedicle anastomosis. Primary prevention of thrombosis is mandatory and anticoagulant therapy in the preoperative and postoperative period is widely used. Still, there is a lack of consensus in the literature about the best postoperative protocol for microsurgical reconstruction. The authors aimed to review the postoperative antithrombotic regimens described in literature focusing on their effects and risks, and moreover, share their experience.
MATERIALS AND METHODS
The authors performed a literature review of postsurgical antithrombotic protocols applied in reconstructive microsurgery. Research on PubMed server was performed typing the terms "antithrombotic", "postoperative", "microsurgery", "free flap pedicle", "anticlotting", "anticoagulant".
RESULTS
The authors described the postoperative standardized pro-weight pharmacological protocol applied in their unit: a combination of dextran and heparin. They inhibit more than one pattern of coagulation in order to stop platelet aggregation and thrombin action and, in the meantime, contending fluid loss with plasma expansion.
CONCLUSIONS
Nowadays, a non-standardized practice, based on experience, is applied by microsurgeons in postsurgical care; the authors performed a review of the combined antithrombotic therapies described in the literature. A standardized pro-weight pharmacological protocol is proposed; it allows to increase blood flow by volume expander action (Dextran) and thrombin inhibition (Heparin). Still, coagulation cascade and platelet function have a wide variability among humans, as well as the effect of drugs. Achieving an optimal antithrombotic effect and minimizing adverse reactions meantime remains a challenge.
Topics: Fibrinolytic Agents; Humans; Microsurgery; Postoperative Care; Postoperative Complications
PubMed: 31173322
DOI: 10.26355/eurrev_201905_17955 -
The Cochrane Database of Systematic... Jan 2017The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge.
OBJECTIVES
To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions.
SELECTION CRITERIA
Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy.
DATA COLLECTION AND ANALYSIS
Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI).
MAIN RESULTS
Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2. modern chemotherapy (FOLFOX (5-fluorouracil plus leucovorin plus oxaliplatin), irinotecan) is more effective than outdated chemotherapy (5-fluorouracil) (HR for PFS: 0.59, 95% CI 0.49 to 0.73; 2 RCTs; high-quality evidence) (HR for OS: 0.69, 95% CI 0.51 to 0.94; 1 RCT; moderate-quality evidence); 3. irinotecan-based combinations were more effective than irinotecan alone (HR for PFS: 0.68, 95% CI 0.60 to 0.76; 6 RCTs; moderate-quality evidence); 4. targeted agents improved the efficacy of conventional chemotherapy both when considered together (HR for OS: 0.84, 95% CI 0.77 to 0.91; 6 RCTs; high-quality evidence) and when bevacizumab was used alone (HR for PFS: 0.67, 95% CI 0.60 to 0.75; 4 RCTs; high-quality evidence).With regard to secondary endpoints, tumour response rates generally paralleled the survival results; moreover, higher anticancer efficacy was generally associated with worse treatment-related toxicity, with the important exception of bevacizumab-containing regimens, where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of SAE. Finally, we found that oral (instead of intravenous) fluoropyrimidines significantly reduced the incidence of adverse effects (without compromising efficacy) in people treated with oxaliplatin-based regimens.We could not draw any conclusions on other debated aspects in this field of oncology, such as ranking of treatments (not all possible comparisons have been tested and many comparisons were based on single trials enrolling a small number of participants) and quality of life (virtually no data available).
AUTHORS' CONCLUSIONS
Systemic therapy offers a survival benefit to people with metastatic CRC who did not respond to first-line treatment, especially when targeted agents are combined with conventional chemotherapeutic drugs. Further research is needed to define the optimal regimen and to identify people who most benefit from each treatment.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Organoplatinum Compounds; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 28128439
DOI: 10.1002/14651858.CD006875.pub3 -
PeerJ. Computer Science 2023The aim of this article is to identify a range of changes and challenges that present-day technologies often present to contemporary societies, particularly in the...
The aim of this article is to identify a range of changes and challenges that present-day technologies often present to contemporary societies, particularly in the context of smart city logistics, especially during crises. For example, the long-term consequences of the COVID-19 pandemic, such as life losses, economic damages, and privacy and security violations, demonstrate the extent to which the existing designs and deployments of technological means are inadequate. The article proposes a privacy-preserving, decentralized, secure protocol to safeguard individual boundaries and supply governments and public health organizations with cost-effective information, particularly regarding vaccination. The contribution of this article is threefold: (i) conducting a systematic review of most of the privacy-preserving apps and their protocols created during pandemics, and we found that most apps pose security and privacy violations. (ii) Proposing an agent-based, decentralized private set intersection (PSI) protocol for securely sharing individual digital personal and health passport information. The proposed scheme is called secure mobile digital passport agent (SMDPA). (iii) Providing a simulation measurement of the proposed protocol to assess performance. The performance result proves that SMDPA is a practical solution and better than the proposed active data bundles using secure multi-party computation (ADB-SMC), as the average CPU load for SMDPA is approximately 775 milliseconds (ms) compared to about 900 ms for ADB-SMC.
PubMed: 37547404
DOI: 10.7717/peerj-cs.1458 -
Journal of Veterinary Internal Medicine Mar 2023Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
BACKGROUND
Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
HYPOTHESIS/OBJECTIVES
Investigate the efficacy of various drugs in na-IMHA.
ANIMALS
Two hundred forty-two dogs.
METHODS
Multi-institutional retrospective study (2015-2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression.
RESULTS
Use of corticosteroids vs a multi-agent protocol had no effect on time to PCV stabilization (P = .55), duration of hospitalization (P = .13), or case fatality (P = .06). A higher rate of relapse (P = .04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06-14.8) was detected in dogs receiving corticosteroids (11.3%) during follow-up (median: 28.5 days, range: 0-1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0-1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P = .31), relapse (P = .44), or case fatality (P = .08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39-3.28 days), for the corticosteroid with mycophenolate mofetil group (P = .01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36).
CONCLUSIONS AND CLINICAL IMPORTANCE
Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.
Topics: Animals; Dogs; Adrenal Cortex Hormones; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Dog Diseases; Immunosuppressive Agents; Recurrence; Retrospective Studies
PubMed: 36809664
DOI: 10.1111/jvim.16652 -
Formal Methods in System Design 2021Population protocols are a well established model of computation by anonymous, identical finite-state agents. A protocol is well-specified if from every initial...
Population protocols are a well established model of computation by anonymous, identical finite-state agents. A protocol is well-specified if from every initial configuration, all fair executions of the protocol reach a common consensus. The central verification question for population protocols is the : deciding if a given protocol is well-specified. Esparza et al. have recently shown that this problem is decidable, but with very high complexity: it is at least as hard as the Petri net reachability problem, which is TOWER-hard, and for which only algorithms of non-primitive recursive complexity are currently known. In this paper we introduce the class of well-specified strongly-silent protocols and we prove that it is suitable for automatic verification. More precisely, we show that has the same computational power as general well-specified protocols, and captures standard protocols from the literature. Moreover, we show that the membership and correctness problems for reduce to solving boolean combinations of linear constraints over . This allowed us to develop the first software able to automatically prove correctness for of the infinitely many possible inputs.
PubMed: 34866798
DOI: 10.1007/s10703-021-00367-3 -
Allergy & Rhinology (Providence, R.I.) 2020Interleukin-1 (IL-1) antagonists have been successful in the management of monogenic auto-inflammatory diseases, notably classic hereditary fever syndromes, such as...
INTRODUCTION
Interleukin-1 (IL-1) antagonists have been successful in the management of monogenic auto-inflammatory diseases, notably classic hereditary fever syndromes, such as Familial Mediterranean Fever (FMF). Anakinra (Kineret®), a human recombinant IL-1 receptor antagonist (IL-1Ra), has been clinically effective in the management of persistent auto-inflammation, such as FMF. Few studies report anaphylaxis in response to anakinra, which were resolved with an anakinra desensitization or the anti-IL-1β monoclonal antibody canakinumab (ILARIS®). We describe the first reported desensitization protocol to canakinumab.
CASE REPORT
A 51-year-old man with a prior history of FMF presented with history of failed colchicine, nonsteroidal anti-inflammatory drug, and anakinra trials. Anakinra desensitization and canakinumab intradermal testing (IDT) resulted in anaphylactic and allergic symptoms, respectively. Expedited desensitization to canakinumab was successfully performed with 15-minute intervals between 13 doses of incremental increase to 150 mg.
DISCUSSION
Biological agents are immune modulators that may evoke unanticipated hypersensitivity reactions, including anaphylaxis. These anaphylactic reactions to biologics have been infrequently reported, but the expanding market may increase the risk of IgE-mediated hypersensitivities and subsequent need for desensitization protocols. The current, expedited desensitization evaluated several published protocols involving anakinra desensitization to determine appropriate dosing for canakinumab.
CONCLUSION
We report the gastrointestinal intolerance and continued FMF flares on colchicine, followed by anaphylactic responses to anakinra and allergic reaction to IDT of canakinumab, in the present case of FMF. Our novel, expedited canakinumab desensitization protocol serves as an effective and alternative therapy in cases when other appropriate biologic agents are not tolerated.
PubMed: 32612876
DOI: 10.1177/2152656720937694 -
Blood Cancer Journal Jul 2016The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the... (Review)
Review
The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the treatment of MM in 2015. As a result of improved diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade, probably more than any other malignancy. Numerous agents continue to be studied in preclinical models and in clinical trials, with many demonstrating clinical efficacy that appears promising enough to have a trajectory for regulatory approval. The purpose of this article is to summarize the current data and provide perspective on new investigational agents with promising single-agent activity in MM. The agents reviewed include Isatuximab, an anti-CD38 monoclonal antibody; marizomib, a new proteasome inhibitor; oprozomib, an oral proteasome inhibitor; filanesib (ARRY-520), a kinesin spindle protein inhibitor; dinaciclib, a cyclin-dependent kinase inhibitor; venetoclax (ABT-199), a selective BCL-2 inhibitor; and LGH-447, pan PIM kinase inhibitor.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drugs, Investigational; Humans; Molecular Targeted Therapy; Multiple Myeloma; Treatment Outcome
PubMed: 27471867
DOI: 10.1038/bcj.2016.53