The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Verena Staedtke - One of the best experts on this subject based on the ideXlab platform.
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disruption of a self amplifying catecholamine loop reduces cytokine release syndrome
Nature, 2018Co-Authors: Verena Staedtke, Renyuan Bai, Kibem Kim, Martin Darvas, Marco L Davila, Gregory J Riggins, Paul B Rothman, Nickolas Papadopoulos, Kenneth W KinzlerAbstract:Cytokine release syndrome (CRS) is a life-threatening complication of several new immunotherapies used to treat cancers and autoimmune diseases1–5. Here we report that atrial natriuretic peptide can protect mice from CRS induced by such agents by reducing the levels of circulating catecholamines. Catecholamines were found to orchestrate an immunodysregulation resulting from oncolytic bacteria and lipopolysaccharide through a self-amplifying loop in macrophages. Myeloid-specific deletion of tyrosine hydroxylase inhibited this circuit. Cytokine release induced by T-cell-activating therapeutic agents was also accompanied by a catecholamine surge and inhibition of catecholamine synthesis reduced cytokine release in vitro and in mice. Pharmacologic catecholamine blockade with metyrosine protected mice from lethal complications of CRS resulting from infections and various biotherapeutic agents including oncolytic bacteria, T-cell-targeting antibodies and CAR-T cells. Our study identifies catecholamines as an essential component of the cytokine release that can be modulated by specific blockers without impairing the therapeutic response. Atrial natriuretic peptide, an anti-inflammatory protein, can protect against cytokine release syndrome induced by therapeutic agents such as tumour-targeting bacteria and CAR-T cells by blocking catecholamine synthesis by macrophages.
M F M James - One of the best experts on this subject based on the ideXlab platform.
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the impact of changes in drug availability for hemodynamic management in pheochromocytoma pret a porter or tailor made
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2015Co-Authors: M F M JamesAbstract:Many aspects of the perioperative management of pheochromocytomas and paragangliomas remain contentious, largely because randomized-controlled trials of various therapeutic options are simply not possible in these relatively rare conditions. The situation is rendered even less amenable to scientific endeavour by the fact that the presentation of these tumours may vary greatly. No tumour or disease process is capable of causing a more diversified constellation of manifestations than pheochromocytoma and its associated pathologic entities. Much of this heterogeneity is due to wide-ranging variations in the types and relative amounts of catecholamines produced. The best approach we can foresee is to rely on case reports and case series in which various therapeutic options have been tried and use these as precedents to guide management. Careful preoperative evaluation and management of these patients are regarded as substantial contributors to the remarkable reduction in perioperative mortality that has been achieved in the last 60 years. From being a very high-risk procedure, the surgical mortality associated with catecholamine-secreting tumours is now of the order of 0-3%. Our experience of over 120 cases suggests that mortality is more associated with inoperable tumours rather than hemodynamic catastrophes, although morbidity may be associated to some degree with hemodynamic disturbances as well as technical surgical difficulties. One of the factors to which this marked improvement has been attributed is preoperative alpha-adrenergic blockade which has been the mainstay of preoperative preparation. Indeed, this treatment has a long track record of safe use, providing preoperative blood pressure control and the potential for plasma volume expansion prior to surgery that may lead to better control of post-excision hypotension. Nevertheless, these approaches have not been conclusively shown to alter outcomes. Phenoxybenzamine has been the standard drug used on the basis of its non-competitive alpha-blocking abilities that limit the risk of breakthrough hypertensive episodes during surges of catecholamine release. Unfortunately, this agent has almost no other current clinical application and is therefore gradually disappearing from the marketplace throughout the world. In South Africa, phenoxybenzamine has not been available for the last 20 years. Recently, phenoxybenzamine has also become unavailable in Canada, and its absence has raised the issue of alternative approaches to the preoperative and intraoperative management of pheochromocytoma patients. In this edition of the Journal, Thanapaalasingham et al. report the use of metyrosine as an alternative to phenoxybenzamine for the preoperative preparation of a patient with an adrenal pheochromocytoma. In order to examine the comparative efficacy of metyrosine against phenoxybenzamine as a single agent, they withdrew the existing alpha blockade prior to establishing treatment with metyrosine. Labetalol was briefly introduced in the 24 hr prior to surgery. Blood pressure control during the preoperative period and intraoperative hemodynamic stability were regarded as less than satisfactory, and the authors concluded that metyrosine was not a suitable singular agent for preoperative preparation of these patients. Metyrosine is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. As M. James, MBChB, PhD (&) Department of Anaesthesia, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa e-mail: mike.james@uct.ac.za
Er Kulik - One of the best experts on this subject based on the ideXlab platform.
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PERIOPERATIVE MANAGEMENT_____________________________________________________ Coronary Bypass Surgery in the Presence of Metastatic
2016Co-Authors: Kristen Seery, Burak Ilsin, Er Kulik, Lynn HeartAbstract:ABSTRACT The hemodynamic management of a patient with a pheochromocytoma presents special challenges due to the episodic release of catecholamines from the tumor, which threatens to provoke a hypertensive crisis. We present a patient with metastatic pheochromocytoma (bone, lung, lymph nodes) who underwent successful coronary artery bypass graft (CABG) surgery following premedication with phenoxybenzamine andmetyrosine aswell as the useof intraoperative phentolamine for themanagement of a hypertensive crisis in the operating room. doi: 10.1111/jocs.12533 (J Card Surg 2015;XX:1–2) Pheochromocytoma is a rare catecholamine-secret-ing neuroendocrine tumor of the adrenal medulla or sympathetic ganglia.1 If the tumor is removed in its entirety, surgery may be curative; otherwise medical management consists of a combination of adrenergic and calcium channel blockers to control blood pressure and prevent tachycardia, as well as metyrosine to reduce catecholamine synthesis.2 Surgery for a patient with a pheochromocytoma is particularly high risk due to the provocation of catecholamine release by the physical stresses of anesthetic induction, endotracheal intubation, skin incision, and potential tumor manipula-tion. Precautions must be taken to ensure safe surgical management and prevention of a hypertensive crisis. We present the management of a patient with metastatic pheochromocytoma in need of coronary artery bypass graft (CABG) surgery
Burak Ilsin - One of the best experts on this subject based on the ideXlab platform.
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PERIOPERATIVE MANAGEMENT_____________________________________________________ Coronary Bypass Surgery in the Presence of Metastatic
2016Co-Authors: Kristen Seery, Burak Ilsin, Er Kulik, Lynn HeartAbstract:ABSTRACT The hemodynamic management of a patient with a pheochromocytoma presents special challenges due to the episodic release of catecholamines from the tumor, which threatens to provoke a hypertensive crisis. We present a patient with metastatic pheochromocytoma (bone, lung, lymph nodes) who underwent successful coronary artery bypass graft (CABG) surgery following premedication with phenoxybenzamine andmetyrosine aswell as the useof intraoperative phentolamine for themanagement of a hypertensive crisis in the operating room. doi: 10.1111/jocs.12533 (J Card Surg 2015;XX:1–2) Pheochromocytoma is a rare catecholamine-secret-ing neuroendocrine tumor of the adrenal medulla or sympathetic ganglia.1 If the tumor is removed in its entirety, surgery may be curative; otherwise medical management consists of a combination of adrenergic and calcium channel blockers to control blood pressure and prevent tachycardia, as well as metyrosine to reduce catecholamine synthesis.2 Surgery for a patient with a pheochromocytoma is particularly high risk due to the provocation of catecholamine release by the physical stresses of anesthetic induction, endotracheal intubation, skin incision, and potential tumor manipula-tion. Precautions must be taken to ensure safe surgical management and prevention of a hypertensive crisis. We present the management of a patient with metastatic pheochromocytoma in need of coronary artery bypass graft (CABG) surgery
Kristen Seery - One of the best experts on this subject based on the ideXlab platform.
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PERIOPERATIVE MANAGEMENT_____________________________________________________ Coronary Bypass Surgery in the Presence of Metastatic
2016Co-Authors: Kristen Seery, Burak Ilsin, Er Kulik, Lynn HeartAbstract:ABSTRACT The hemodynamic management of a patient with a pheochromocytoma presents special challenges due to the episodic release of catecholamines from the tumor, which threatens to provoke a hypertensive crisis. We present a patient with metastatic pheochromocytoma (bone, lung, lymph nodes) who underwent successful coronary artery bypass graft (CABG) surgery following premedication with phenoxybenzamine andmetyrosine aswell as the useof intraoperative phentolamine for themanagement of a hypertensive crisis in the operating room. doi: 10.1111/jocs.12533 (J Card Surg 2015;XX:1–2) Pheochromocytoma is a rare catecholamine-secret-ing neuroendocrine tumor of the adrenal medulla or sympathetic ganglia.1 If the tumor is removed in its entirety, surgery may be curative; otherwise medical management consists of a combination of adrenergic and calcium channel blockers to control blood pressure and prevent tachycardia, as well as metyrosine to reduce catecholamine synthesis.2 Surgery for a patient with a pheochromocytoma is particularly high risk due to the provocation of catecholamine release by the physical stresses of anesthetic induction, endotracheal intubation, skin incision, and potential tumor manipula-tion. Precautions must be taken to ensure safe surgical management and prevention of a hypertensive crisis. We present the management of a patient with metastatic pheochromocytoma in need of coronary artery bypass graft (CABG) surgery