-
Leukemia & Lymphoma May 2017The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a... (Review)
Review
The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a significant advancement, HMA lead to responses in less than half of patients and for those that respond most will relapse. As such, there is a crucial need to improve frontline therapy approaches. One promising strategy involves combining azacitidine or decitabine with investigational or existing therapies with the goal of achieving synergistic activity and better patient outcomes. The purpose of this paper is to critically review the efficacy and safety of reported HMA-based combination regimens in patients with higher-risk MDS.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; DNA Methylation; Histone Deacetylase Inhibitors; Humans; Lenalidomide; Molecular Targeted Therapy; Myelodysplastic Syndromes; Protein Kinase Inhibitors; Thalidomide; Treatment Outcome
PubMed: 27654579
DOI: 10.1080/10428194.2016.1228927 -
Journal of Andrology 1990Techniques for freezing bull sperm developed over the past 40 years have not yielded protocols for preserving sperm from other species. Recent advances in our... (Review)
Review
Techniques for freezing bull sperm developed over the past 40 years have not yielded protocols for preserving sperm from other species. Recent advances in our understanding of cell membrane structure function and metabolism now permit alternative modes of investigation. These data will allow development of unique studies which should have a higher probability of yielding successful protocols for sperm from other species. In this review the authors will: (1) provide a general overview of cryopreservation; (2) review emerging concepts of membrane structure and the relationship of membrane composition to water and cryoprotectant movement; (3) emphasize how these parameters affect cell volume and surface areas; (4) focus attention on the concept that cryoprotectants will alter membrane structure and function in addition to their well-recognized effects on bulk solvent; and (5) emphasize the effect of the processing protocol on metabolic balance. These concepts are reintroduced in the context of the established and successful protocol for freezing bull sperm to illustrate the molecular responses that may be necessary to survive a freeze-thaw cycle.
Topics: Animals; Cattle; Cell Survival; Cryopreservation; Cryoprotective Agents; Male; Spermatozoa
PubMed: 2179184
DOI: No ID Found -
International Journal of Molecular... Nov 2021Corneal cryopreservation can partially solve the worldwide concern regarding donor cornea shortage for keratoplasties. In this study, human corneas were cryopreserved...
Corneal cryopreservation can partially solve the worldwide concern regarding donor cornea shortage for keratoplasties. In this study, human corneas were cryopreserved using two standard cryopreservation protocols that are employed in the Tissue Bank of the Teresa Herrera Hospital (Spain) to store corneas for tectonic keratoplasties (TK protocol) and aortic valves (AV protocol), and two vitrification protocols, VS55 and DP6. Endothelial viability and general corneal state were evaluated to determine the protocol that provides the best results. The potential corneal cryopreservation protocol was studied in detail taking into consideration some cryopreservation-related variables and the endothelial integrity and stroma arrangement of the resulting cryopreserved corneas. TK corneas showed mostly viable endothelial cells, while the others showed few (AV) or none (DP6 and VS55). The corneal structure was well maintained in TK and AV corneas. TK corneas showed endothelial acellular areas surrounded by injured cells and a normal-like stromal fiber arrangement. Cryoprotectant solutions of the TK protocol presented an increasing osmolality and a physiological pH value. Cooling temperature rate of TK protocol was of 1 °C/min to -40 °C and 3 °C/min to -120 °C, and almost all of dimethyl sulfoxide left the tissue after washing. Future studies should be done changing cryopreservation-related variables of the TK protocol to store corneas of optical grade.
Topics: Cold Temperature; Cornea; Corneal Transplantation; Cryopreservation; Dimethyl Sulfoxide; Endothelium, Corneal; Humans; Microscopy, Electron, Scanning; Spain; Tissue Banks
PubMed: 34830446
DOI: 10.3390/ijms222212564 -
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 -
BMC Geriatrics Apr 2022To manage the rapidly growing incidence of, and related medical burden resulting from hip fractures in older adults in an aging society, studies involving orthogeriatric...
BACKGROUND
To manage the rapidly growing incidence of, and related medical burden resulting from hip fractures in older adults in an aging society, studies involving orthogeriatric co-management treatment models have reported improved outcomes, including reduced medical costs. The treatment gap for osteoporosis was however seldom emphasized in the published treatment protocols. Aiming to improve the existing orthogeriatric protocol, we have established a patient-centered protocol for elderly patient hip fractures, which simultaneously focuses on fracture care and anti-osteoporosis agent prescription in regarding to healthcare quality and medical expense.
METHODS
This was a retrospective study comparing patients who enrolled in the multidisciplinary co-managed protocol for geriatric hip fractures and those who did not. The inclusion criteria for this study were: (a) single-sided hip fractures treated from 1 to 2018 to 30 June 2020, (b) patients who were 60-years or older (c) trauma treated within 3 days from time of injury, and (d) minimal follow-up period of 12 months after surgery.
RESULTS
From 1 to 2018 to 30 June 2020, 578 patients were included (267 patients in the protocol group vs. 331 patients in the conventional group). The protocol group was associated with significantly reduced lengths of hospital stay (p = 0.041), medical expenditures (p = 0.006), and mortality (p = 0.029) during their acute in-hospital admission period. Early osteoporosis diagnosis and anti-osteoporosis agent prescription were achieved in the protocol group, with a significantly wider coverage for BMD assessment (p < 0.001) and prescriptions for anti-osteoporosis medication (p < 0.001). Yet, there was no significant decline in the one-year refracture rate in the protocol group.
CONCLUSIONS
The implementation of a multidisciplinary co-managed care protocol for geriatric proximal femur fractures successfully improved patient outcomes with significantly reduced lengths of stay, medical expenditures, and mortality during the acute in-hospital admission period. The high prescription rate of anti-osteoporosis medication after hip fractures in the protocol group was not associated with a significantly lower re-fracture rate in the 12-month follow-up. However, the association between early anti-osteoporosis agent prescription and reduced long-term medical expenses in this group of patients has provided a direction for future research.
Topics: Aged; Femoral Fractures; Femur; Hip Fractures; Humans; Osteoporosis; Retrospective Studies
PubMed: 35410173
DOI: 10.1186/s12877-022-03014-6 -
Scientific Reports Jun 2023Agent-Based Models (ABMs) are used in several fields to study the evolution of complex systems from micro-level assumptions. However, a significant drawback of ABMs is...
Agent-Based Models (ABMs) are used in several fields to study the evolution of complex systems from micro-level assumptions. However, a significant drawback of ABMs is their inability to estimate agent-specific (or "micro") variables, which hinders their ability to make accurate predictions using micro-level data. In this paper, we propose a protocol to learn the latent micro-variables of an ABM from data. We begin by translating an ABM into a probabilistic model characterized by a computationally tractable likelihood. Next, we use a gradient-based expectation maximization algorithm to maximize the likelihood of the latent variables. We showcase the efficacy of our protocol on an ABM of the housing market, where agents with different incomes bid higher prices to live in high-income neighborhoods. Our protocol produces accurate estimates of the latent variables while preserving the general behavior of the ABM. Moreover, our estimates substantially improve the out-of-sample forecasting capabilities of the ABM compared to simpler heuristics. Our protocol encourages modelers to articulate assumptions, consider the inferential process, and spot potential identification problems, thus making it a useful alternative to black-box data assimilation methods.
PubMed: 37286576
DOI: 10.1038/s41598-023-35536-3 -
Medicine Feb 2016The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC).A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0).Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78-0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72-0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27-1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups.In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens.
Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Middle Aged; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Treatment Outcome
PubMed: 26937908
DOI: 10.1097/MD.0000000000002792 -
American Journal of Hypertension Jul 2022To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
Differences in Hypertension and Stage II Hypertension by Demographic and Risk Factors, Obtained by Two Different Protocols in US Adults: National Health and Nutrition Examination Survey, 2017-2018.
BACKGROUND
To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
METHODS
Participants aged 18 years and older (n = 4,689) in the National Health and Nutrition Examination Survey (NHANES 2017-2018) had their BP measured following 2 protocols: the legacy auscultation protocol (AP) and oscillometric protocol (OP). The order of protocols was randomly assigned. Prevalence estimates for hypertension (BP ≥130/80 mm Hg or use of medication for hypertension) and stage II hypertension (BP ≥140/90 mm Hg) were determined overall, by demographics, and by risk factors for each protocol. Ratios (OP% ÷ AP%) and kappa statistics were calculated.
RESULTS
Age-adjusted hypertension prevalence was 44.5% (95% confidence interval [CI]: 41.1%-48.0%) using OP and 45.1% (95% CI: 41.5%-48.7%) using AP, prevalence ratio = 0.99 (95% CI = 0.94-1.04). Age-adjusted stage II hypertension prevalence was 15.8% (95% CI: 13.6%-18.2%) using AP and 17.1% (95% CI: 14.7%-19.7%) using OP, prevalence ratio = 0.92 (95% CI = 0.81-1.04). For both hypertension and stage II hypertension, the prevalence ratios by demographics and by risk factors all included unity in their 95% CI, except for stage II hypertension in adults 60+ years (ratio: 0.88 [95% CI: 0.78-0.98]). Kappa for agreement between protocols for hypertension and stage II hypertension was 0.75 (95% CI = 0.71-0.79) and 0.67 (95% CI = 0.61-0.72), respectively.
CONCLUSIONS
In adults and for nearly all subcategories there were no significant differences in prevalence of hypertension and stage II hypertension between protocols, indicating that protocol change may not affect the national prevalence estimates of hypertension and stage II hypertension.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Nutrition Surveys; Prevalence; Risk Factors; United States
PubMed: 35333925
DOI: 10.1093/ajh/hpac042 -
Journal of Traditional Chinese Medicine... Feb 2022To evaluate the anti-oxidant, enzyme inhibition, anti-pyretic, anti-inflammatory and anti-diabetic activities of Iris albicans.
OBJECTIVE
To evaluate the anti-oxidant, enzyme inhibition, anti-pyretic, anti-inflammatory and anti-diabetic activities of Iris albicans.
METHODS
Anti-oxidant assay was evaluated using DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging and ABTS (2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) inhibitory protocol while enzyme inhibitory assay was evaluated by lipoxygenase and cyclooxygenase-2 inhibitory protocol respectively. Antipyretic, anti-inflammatory and anti-diabetic potential was evaluated using brewer's yeast induced pyrexia, carrageenan induced paw edema and streptozocin induced diabetes protocols respectively. Serum biochemical parameters were monitored for the period of study.
RESULTS
The anti-oxidant activity of chloroform fraction of Iris albicans showed the highest scavenging potential against DPPH and ABTS while the maximum inhibitory action recorded against lipo-oxygenase and cyclooxygenase-2 enzymes was shown by n-hexane and chloroform fractions respectively. The anti-pyretic potential of the crude methanolic extract showed dose dependent activity in reducing pyrexia, thereby when the dose was increased the anti-pyretic effect was also enhanced. The anti-inflammatory action of the crude methanolic extract administered at the dose of 300 mg/kg was significant at 1 h after its administration, which was found maintained up to 5 h. Similarly the anti-diabetic effect of the crude methanolic extract administered at the dose of 200 and 300 mg/kg was noted highly significant at day 6 and was found well maintained throughout the study time period up to 10 days. Significant (P < 0.001) improvement appeared in hemoglobin, protein, cholesterol, triglycerides, urea, creatinine, HDL and LDL of extract treated diabetic mice.
CONCLUSION
From this data it could be concluded that Iris albicans have significant anti-oxidant, enzyme inhibition, ant-pyretic, anti-inflammatory and anti-diabetic potential.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chloroform; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Fever; Humans; Iris Plant; Methanol; Mice; Plant Extracts
PubMed: 35322627
DOI: 10.19852/j.cnki.jtcm.2022.01.001 -
Journal of Oral Science 2020The purpose of this study was to evaluate the influence of various polishing protocols on the surface roughness of polyetheretherketone (PEEK) and identify an effective...
The purpose of this study was to evaluate the influence of various polishing protocols on the surface roughness of polyetheretherketone (PEEK) and identify an effective polishing method of dental prostheses at the chairside. The PEEK specimens were assigned to seven groups with different protocols: no additional polishing (NT); polishing using a rubber point (C); polishing using "silky shine" (S); polishing using "aqua blue paste" (A); protocol C followed by protocol S (CS); protocol C followed by protocol A (CA); and protocol C followed by protocols S and A (CSA). The surface roughness (Sa and Ra) of the polished surfaces was measured. The surface roughness decreased in the following order of groups: NT, C, S, CS, CSA, CA, and A. In Groups C and S, wide deep pits formed by abrasive grains of SiC paper were observed, whereas only fine linear structures were observed on the surface in other groups. With respect to the polishing protocol of PEEK, clinically acceptable surface roughness was obtained using a soft polishing brush and agent for more than 3 min.
Topics: Benzophenones; Dental Polishing; Ketones; Materials Testing; Polyethylene Glycols; Polymers; Surface Properties
PubMed: 31996521
DOI: 10.2334/josnusd.18-0473