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Methods in Molecular Biology (Clifton,... 2020The advancement toward a clinical application for porcine islets to cure diabetes in humans must include reproducible long-term successes in non-human primate (NHP)...
The advancement toward a clinical application for porcine islets to cure diabetes in humans must include reproducible long-term successes in non-human primate (NHP) models. Many dedicated researchers around the world are continuing to work toward this goal. In this chapter, we describe procedures for islet isolation of pancreatic islets from adult and neonatal/fetal pigs. We further include procedures for the induction of diabetes in non-human primates and subsequent insulin therapy, islet transplantation, immunosuppression, and also the daily maintenance of xenotransplanted NHPs. The procedures that we outline in this chapter are ones that we have successfully utilized in pig-to-NHP islet transplantation models. However, where appropriate, alternative methods will also be identified.
Topics: Animals; Animals, Newborn; Biomarkers; Cell Separation; Diabetes Mellitus, Experimental; Graft Rejection; Graft Survival; Heterografts; Humans; Immunosuppression Therapy; Islets of Langerhans Transplantation; Macaca; Models, Animal; Swine; Transplantation Tolerance; Transplantation, Heterologous
PubMed: 32002916
DOI: 10.1007/978-1-0716-0255-3_19 -
Der Anaesthesist Jul 2019Surgical interventions and invasive procedures can trigger an inflammatory reaction in patients. This inflammatory reaction is an inherent response by the body and can... (Review)
Review
BACKGROUND
Surgical interventions and invasive procedures can trigger an inflammatory reaction in patients. This inflammatory reaction is an inherent response by the body and can be triggered by different stimuli, including the surgical tissue trauma itself and also by the administration of drugs commonly used for the induction and maintenance of general anesthesia.
OBJECTIVE
Immune system activation is mostly beneficial for the host defense against various exogenous pathogens during infectious disorders; however, if uncontrolled and overshooting or in the case of excessive immune system activation as a consequence of sterile inflammation, the inflammatory host response may also carry the risk for tissue and organ damage, which might severely threaten the patient. The aim of this article is to identify the causal factors of a perioperative immune reaction and to present interventional options.
MATERIAL AND METHODS
An extensive MEDLINE search was carried out on the perioperative and postoperative inflammatory response in the field of clinical and basic research.
RESULTS
Current publications provide essential information on how surgical patients may be affected by overshooting inflammatory responses. Thus, the choice of administered anesthetic agent and the surgical trauma itself in addition to a supportive therapy may modulate perioperative inflammation in the perioperative phase. The effects on the patient can be multifarious.
CONCLUSION
This article discusses the causes and effects of inflammatory processes in the perioperative phase. Additionally, it highlights the immunomodulatory effects of perioperatively administered therapeutics and anesthetics. Knowledge of this topic enables the reader to make qualified decisions in the perioperative setting to improve the individual patient outcome.
Topics: Anesthesia, General; Anesthetics; Humans; Inflammation; Intraoperative Complications; Perioperative Care
PubMed: 31076810
DOI: 10.1007/s00101-019-0596-9 -
Critical Care Nursing Clinics of North... Dec 2022Volume overload is a common complication of a multitude of disease states, as well as a complication of many medical therapies. For the critically ill patient in the... (Review)
Review
Volume overload is a common complication of a multitude of disease states, as well as a complication of many medical therapies. For the critically ill patient in the intensive care unit, volume overload is especially concerning when persistent past the first few days of admission. In the setting of chronic kidney disease, the maintenance of fluid balance presents additional challenges. This article focuses on the causes of volume overload as well as treatment options of the critically ill patient, including the nuances of the kidney patient, and ends with outpatient guidelines and recommendations to avoid recurrence.
Topics: Humans; Critical Illness; Acute Kidney Injury; Intensive Care Units; Water-Electrolyte Balance; Fluid Therapy
PubMed: 36336431
DOI: 10.1016/j.cnc.2022.07.001 -
Critical Reviews in Oncology/hematology Sep 2020MCL is a well-characterized generally aggressive lymphoma with a poor prognosis. However, patients with a more indolent disease have been reported in whom the initiation... (Review)
Review
MCL is a well-characterized generally aggressive lymphoma with a poor prognosis. However, patients with a more indolent disease have been reported in whom the initiation of therapy can be delayed without any consequence for the survival. In 2017 the World Health Organization updated the classification of MCL describing two main subtypes with specific molecular characteristics and clinical features, classical and indolent leukaemic nonnodal MCL. Recent research results suggested an improving outcome of this neoplasm. The addition of rituximab to conventional chemotherapy has increased overall response rates, but it did not improve overall survival compared to chemotherapy alone. The use of intensive frontline therapies including rituximab and consolidation with autologous stem cell transplantation ameliorated response rate and prolonged progression-free survival in young fit patients, but any impact on survival remains to be proven. Furthermore, the optimal timing, cytoreductive regimen and conditioning regimen, and the clinical implications of achieving a disease remission even at molecular level remain to be elucidated. The development of targeted therapies as the consequence of better understanding of pathogenetic pathways in MCL might improve the outcome of conventional chemotherapy and spare the toxicity of intense therapy in most patients. Cases not eligible for intensive regimens, may be considered for less demanding therapies, such as the combination of rituximab either with CHOP or with purine analogues, or bendamustine. Allogeneic SCT can be an effective option for relapsed disease in patients who are fit enough and have a compatible donor. Maintenance rituximab may be considered after response to immunochemotherapy as the first-line strategy in a wide range of patients. Finally, since the optimal approach to the management of MCL is still evolving, it is critical that these patients are enrolled in clinical trials to identify the better treatment options.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Mantle-Cell; Neoplasm Recurrence, Local; Prognosis; Rituximab; Transplantation, Autologous
PubMed: 32739830
DOI: 10.1016/j.critrevonc.2020.103038 -
Current Opinion in Oncology Jul 2024There is an unmet need to improve outcomes for patients for Ewing sarcoma, a rare, aggressive sarcoma with a peak incidence in adolescents and young adults (AYA).... (Review)
Review
PURPOSE OF REVIEW
There is an unmet need to improve outcomes for patients for Ewing sarcoma, a rare, aggressive sarcoma with a peak incidence in adolescents and young adults (AYA). Current therapy at diagnosis involves multiagent chemotherapy and local therapy, but despite intensification of treatment, those with metastases at diagnosis and recurrent disease have poor outcomes.
RECENT FINDINGS
Improved understanding of Ewing sarcoma biology has identified novel targets with promising activity in Ewing sarcoma patients, including tyrosine kinase inhibitors that are now undergoing evaluation as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1::FLI1 fusion oncoprotein, and act on DNA damage, cell cycle and apoptotic pathways. Immunotherapeutic approaches, particularly CAR-T-cell therapy directed at GD2, also hold promise. Recent collaborative clinical trials that have defined an international standard of care for patients with newly diagnosed Ewing sarcoma and novel platform studies with adaptive designs offer unique opportunities to investigate these therapies inclusive of all ages.
SUMMARY
Close international collaboration between clinicians and biologists will allow us to prioritize promising emerging therapies and develop biomarkers to facilitate their incorporation into standard of care and more rapidly translate into benefit for Ewing sarcoma patients.
Topics: Humans; Sarcoma, Ewing; Bone Neoplasms; Oncogene Proteins, Fusion; Molecular Targeted Therapy; Immunotherapy, Adoptive
PubMed: 38775200
DOI: 10.1097/CCO.0000000000001048 -
Hematology/oncology Clinics of North... Apr 2024Consolidation therapy consists of short-term therapy after stem cell transplant in multiple myeloma. Key consolidation trials have shown mixed results on whether... (Review)
Review
Consolidation therapy consists of short-term therapy after stem cell transplant in multiple myeloma. Key consolidation trials have shown mixed results on whether consolidation should be included after transplant, leading to varied clinical practice. Maintenance therapy consists of long-term, typically fixed-duration or indefinite, therapy. Standard-risk patients typically receive single-agent therapy, whereas high-risk may benefit from doublet therapy and beyond. Adverse events and quality of life concerns should be considered, as optimal duration of maintenance therapy continues to be studied.
Topics: Humans; Quality of Life; Multiple Myeloma; Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols; Transplantation, Autologous; Maintenance Chemotherapy; Hematopoietic Stem Cell Transplantation; Consolidation Chemotherapy
PubMed: 38262780
DOI: 10.1016/j.hoc.2023.12.006 -
Hematology/oncology Clinics of North... Aug 2020Because patients with follicular lymphoma (FL) usually experience repeated disease recurrences, maintenance treatment is an attractive option to prolong remission after... (Meta-Analysis)
Meta-Analysis Review
Because patients with follicular lymphoma (FL) usually experience repeated disease recurrences, maintenance treatment is an attractive option to prolong remission after induction therapy. Rituximab maintenance therapy has been shown in multiple randomized studies to significantly improve progression-free survival in FL with both low and high tumor burden after induction therapy, independently of patient and disease characteristics. Several questions regarding the use of antibody directed against CD20 (anti-CD20) maintenance remain open, including the optimal antibody administration schedule and duration, the risk/benefit ratio of maintenance in the context of previous bendamustine administration, and its cost-effectiveness.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Follicular; Maintenance Chemotherapy; Molecular Targeted Therapy; Neoplasm Grading; Neoplasm Staging; Retreatment; Treatment Outcome
PubMed: 32586574
DOI: 10.1016/j.hoc.2020.02.005 -
Current Pharmaceutical Design 2020Long term survival and quality of life after lung transplantation are still affected by the development of chronic lung graft dysfunction (CLAD). CLAD is the number one... (Review)
Review
Long term survival and quality of life after lung transplantation are still affected by the development of chronic lung graft dysfunction (CLAD). CLAD is the number one cause of death one year after transplant; and there is no effective therapy available to date. Transplant centers' approaches include perioperative immunosuppression, maintenance immunosuppression, and the treatment of eventual rejection. This review will focus on maintenance immunosuppression and the available data that support these strategies, as well as a brief description of our desensitization protocol and immunologic risk stratification. Optimization of immunosuppression is key to increase survival and graft function in transplant recipients, mostly through the combination of drugs. Since the therapeutic options to manage CLAD are still very limited, more studies are necessary to test new therapies and to clarify the potential role of new agents.
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Quality of Life
PubMed: 32600225
DOI: 10.2174/1381612826666200628023150 -
Annals of Allergy, Asthma & Immunology... Jul 2023To review the safety and efficacy of anti-immunoglobulin E (IgE) monotherapy or as an adjunct to oral immunotherapy (OIT) in the treatment of IgE-mediated food allergy. (Review)
Review
OBJECTIVE
To review the safety and efficacy of anti-immunoglobulin E (IgE) monotherapy or as an adjunct to oral immunotherapy (OIT) in the treatment of IgE-mediated food allergy.
DATA SOURCES
Literature searches were performed using the Excerpta Medica dataBASE, Medline, Scopus, and PubMed Central to identify articles in English related to food allergy and anti-IgE therapies, including omalizumab and ligelizemab.
STUDY SELECTIONS
Original research articles reviewed include interventional studies, retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews. Data were reviewed and summarized.
RESULTS
Here, we discuss the current anti-IgE therapies being studied as a potential treatment option for food allergy. We also review trial design, safety, and efficacy data on the use of anti-IgE therapies as monotherapy or in combination with OIT for food allergies. Finally, we discuss clinical trials in progress using omalizumab and ligelizumab and highlight important clinical considerations.
CONCLUSION
Over the past 20 years, substantial progress has been made in understanding the potential role of anti-IgE therapies for food allergy. Anti-IgE therapies seem to be a promising option that may increase reaction dose thresholds and decrease time to reach OIT maintenance and OIT dosing-related reactions. Two phase 3 trials are currently in progress studying anti-IgE potential monotherapy for the treatment of peanut and multifood allergies. It is important for clinicians to be aware of these emerging treatment options.
Topics: Humans; Omalizumab; Immunoglobulin E; Desensitization, Immunologic; Retrospective Studies; Administration, Oral; Food Hypersensitivity; Allergens; Observational Studies as Topic
PubMed: 37031775
DOI: 10.1016/j.anai.2023.03.030 -
Blood Reviews Sep 2021Relapse in acute myeloid leukemia (AML) is common, especially in older patients, and there is currently no standard of care maintenance therapy for those who achieve... (Review)
Review
Relapse in acute myeloid leukemia (AML) is common, especially in older patients, and there is currently no standard of care maintenance therapy for those who achieve complete remission. Finding effective, tolerable maintenance therapy to prolong remission has been a goal for decades, but early clinical trials testing a variety of agents demonstrated disappointing results with no overall survival benefit. CC-486, an oral hypomethylating agent, was recently approved in the United States for maintenance treatment in patients with AML in first remission following chemotherapy. A number of ongoing studies are assessing various therapeutics in the maintenance setting, including other hypomethylating agents, targeted small-molecule inhibitors, monoclonal antibodies, and immunomodulators. New strategies are needed to identify patients most likely to benefit from maintenance therapy, including those for whom a preemptive approach reliant on monitoring of measurable residual disease would be advantageous.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Maintenance Chemotherapy; Remission Induction; Survival Analysis
PubMed: 33832807
DOI: 10.1016/j.blre.2021.100829