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The Lancet. Haematology Nov 2020The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful... (Review)
Review
The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful modification of this backbone regimen, which has endured now for almost 20 years. Countless attempts to redefine R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) have migrated from a focus on dose-intense and dose-dense regimens, to the use of maintenance therapies, and most recently the addition of novel agents. To date, none have changed the basic formula. Although there are many reasons for the absence of success, the incredible molecular heterogeneity of DLBCL is likely to be a major complicating factor. It is clear that as the scientific field's understanding of the genetic heterogeneity of DLBCL deepens, a precision medicine approach should be accounted for and might be one of several paths that could lead to improved outcomes. The rapid identification of poor prognostic groups within the evolving diverse molecular landscape of DLBCL will create new opportunities to produce the next generation of studies with targeted agents against specific pathological drivers. It is conceivable that targeting these driver pathways will require more than one agent, and of course, splitting the pool of patients with DLBCL into smaller groups on the basis of molecular characteristics, will reduce the number of eligible patients for clinical trial investigation. The integration of immunological agents might afford new opportunities to develop treatments agnostic to the complex molecular diversity, while adding minimal toxicity to the regimen. With each of these iterations, the hope is to ultimately shift away from a one-size-fits-all chemotherapy mentality to one predicated on an individualised approach, whether that be through the use of a targeted small molecule or a biological drug. In this Viewpoint, we explore the history of the collective efforts to improve upon R-CHOP, and underscore those lessons that might help to reshape our future plans.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Genetic Heterogeneity; Humans; Lenalidomide; Lymphoma, Large B-Cell, Diffuse; Precision Medicine; Prednisone; Prognosis; Rituximab; Vincristine
PubMed: 33091357
DOI: 10.1016/S2352-3026(20)30222-2 -
International Journal of Clinical... Sep 2023Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature...
BACKGROUND
Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent.
METHODS
Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage.
RESULTS
A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev.
CONCLUSIONS
This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.
Topics: Humans; Female; Ovarian Neoplasms; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Bevacizumab; Doxorubicin; Gemcitabine; Irinotecan; Polyethylene Glycols; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37347381
DOI: 10.1007/s10147-023-02367-1 -
Cryobiology Feb 2020Vitrification is a cryopreservation technique for the long-term storage of viable tissue, but the success of this technique relies on multiple factors. In 2012, our... (Comparative Study)
Comparative Study
Vitrification is a cryopreservation technique for the long-term storage of viable tissue, but the success of this technique relies on multiple factors. In 2012, our group published a working vitrification protocol for intact human articular cartilage and reported promising chondrocyte recovery after using a four-step multi-cryoprotectant (CPA) loading method that required 570 min. However, this protocol requires further optimization for clinical practice. Herein, we compared three multi-step CPA loading protocols to investigate their impact on chondrocyte recovery after vitrification of porcine articular cartilage on a bone base, including our previous four-step protocol (original: 570 min), and two shorter three-step protocols (optimized: 420 min, and minimally vitrifiable: 310 min). Four different CPAs were used including glycerol, dimethyl sulfoxide, ethylene glycol and propylene glycol. As vitrification containers, two conical tubes (50 ml and 15 ml) were evaluated for their heat transfer impact on chondrocyte recovery after vitrification. Osteochondral dowels were cored into two diameters of 10.0 mm and 6.9 mm with an approximately 10-mm thick bone base, and then allocated into the twelve experimental groups based on CPA loading protocol, osteochondral dowel size, and vitrification container size. After vitrification at -196 °C and tissue warming and CPA removal, samples in all groups were assessed for both chondrocyte viability and metabolic activity. The optimized protocol proposed based on mathematical modelling resulted in similar chondrocyte recovery to our original protocol and it was 150 min shorter. Furthermore, this study illustrated the role of CPA permeation (dowel size) and heat transfer (container size) on vitrification protocol outcome.
Topics: Animals; Cartilage, Articular; Chondrocytes; Cryopreservation; Cryoprotective Agents; Dimethyl Sulfoxide; Ethylene Glycol; Female; Glycerol; Humans; Models, Theoretical; Propylene Glycol; Swine; Vitrification
PubMed: 31917159
DOI: 10.1016/j.cryobiol.2020.01.001 -
Hematology. American Society of... Dec 2023The routine use of next-generation sequencing methods has underscored the genetic and clonal heterogeneity of acute myeloid leukemia (AML), subsequently ushering in an...
The routine use of next-generation sequencing methods has underscored the genetic and clonal heterogeneity of acute myeloid leukemia (AML), subsequently ushering in an era of precision medicine-based targeted therapies exemplified by the small-molecule inhibitors of FLT3, IDH1/IDH2, and BCL2. This advent of targeted drugs in AML has broadened the spectrum of antileukemic therapies, and the approval of venetoclax in combination with a hypomethylating agent has been a welcome addition to our AML patients unable to tolerate intensive chemotherapy. Mounting evidence demonstrates that molecularly targeted agents combined with epigenetic therapies exhibit synergistic augmented leukemic cell kill compared to single-agent therapy. With such great power comes greater responsibility in determining the appropriate frontline AML treatment regimen in a molecularly defined subset and identifying safe and effective combination therapies with different mechanisms of action to outmaneuver primary and secondary resistance mechanisms in AML.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Myeloid, Acute; Antineoplastic Agents; Combined Modality Therapy
PubMed: 38066868
DOI: 10.1182/hematology.2023000429 -
STAR Protocols Dec 2023Agent-based models are composed of individual agents coded for traits, such as cooperation and cheating, that interact in a virtual world based on defined rules. Here,...
Agent-based models are composed of individual agents coded for traits, such as cooperation and cheating, that interact in a virtual world based on defined rules. Here, we describe the use of an agent-based model of homologous recombination in bacteria playing a public goods game. We describe steps for software installation, setting model parameters, running and testing models, and visualization and statistical analysis. This protocol is useful in analyses of horizontal gene transfer, bacterial sociobiology, and game theory. For complete details on the use and execution of this protocol, please refer to Lee et al..
Topics: Game Theory; Bacteria
PubMed: 37980566
DOI: 10.1016/j.xpro.2023.102733 -
European Radiology Nov 2023Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [F]FDG PET/MRI to...
OBJECTIVES
Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [F]FDG PET/MRI to avoid adverse effects and save time and costs during examination.
METHODS
A total of 105 [F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests.
RESULTS
In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2.
CONCLUSIONS
The use of MRI contrast agents in [F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients.
CLINICAL RELEVANCE STATEMENT
This study gives a scientific baseline switching to a contrast agent-free [F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients.
KEY POINTS
• No additional diagnostic benefit of MRI contrast agents at [F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [F]FDG PET/MRI.
Topics: Humans; Child; Fluorodeoxyglucose F18; Contrast Media; Neoplasm Staging; Magnetic Resonance Imaging; Lymphoma; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 37338559
DOI: 10.1007/s00330-023-09840-5 -
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 -
Respiratory Physiology & Neurobiology Oct 2021Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in...
Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in this study. The harmonic distortion index (k) was used to assess the respiratory system nonlinearity. The analysis of variance showed difference between groups (OVA vs control) and among doses for both protocols. Bolus protocol posttest: there was a difference between OVA and control at 0.3 and 1 mg/kg doses (p<0.0001 and p<0.001) for R. Infusion: there was a difference between OVA and control at 192 μg.kg.min dose for R, G and H, (p<0.01; p<0.001; p<0.001). An increment was found in k values near to the observed peak values in bolus protocol. The bolus protocol could better differentiate inflamed and non-inflamed airway resistance, whereas the differences between OVA and control in continuous infusion protocol were associated to airway- and, mainly, parenchyma-related parameters. Moreover, the bolus protocol presented a higher nonlinear degree compared to the infusion protocol.
Topics: Animals; Asthma; Bronchoconstrictor Agents; Disease Models, Animal; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Models, Theoretical; Respiratory Mechanics
PubMed: 34062282
DOI: 10.1016/j.resp.2021.103705 -
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 -
Dermatology Online Journal Jul 2021Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries...
Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.
Topics: Acitretin; Administration, Oral; Adult; Anti-Bacterial Agents; Clobetasol; Glucocorticoids; Granuloma, Pyogenic; Humans; Keratoderma, Palmoplantar; Keratolytic Agents; Male; Mupirocin; Nail Diseases
PubMed: 34391333
DOI: 10.5070/D327754369