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The Journal of Clinical Endocrinology... Dec 2023Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear.
CONTEXT
Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear.
OBJECTIVE
We aimed to assess the proportion and clinical, biochemical, radiological, genetic, histopathological, and follow-up characteristics of incidental pheochromocytomas.
METHODS
A retrospective review was conducted of patients with pheochromocytoma seen between January 2010 and October 2022 at a large UK tertiary care center. The diagnosis was confirmed histologically or by the combined presence of increased plasma and/or urinary metanephrines (MN), indeterminate adrenal mass on cross-sectional imaging, and metaiodobenzylguanidine avidity.
RESULTS
We identified 167 patients with pheochromocytoma; 144 (86.2%) underwent adrenalectomy, for 23 (13.8%) surgery was either awaited, deemed unsuitable due to frailty or other metastatic malignancy, or declined by the patients. Excluding pheochromocytomas diagnosed via screening genetically predisposed individuals (N = 20), 37 of 132 (28.0%) presented with adrenergic symptoms and/or uncontrolled hypertension, while 91 of 132 (69.0%) patients presented with an incidentally detected adrenal mass. Incidentally detected patients were older (median age 62 years) than those detected due to clinical suspicion (aged 42 years) or after genetic screening (aged 33 years) (all P < .05). Incidentally detected pheochromocytomas were smaller (median 42 mm) than tumors detected due to adrenergic symptoms/uncontrolled hypertension (60 mm), but larger than tumors identified by genetic screening (30 mm) (all P < .05). Increased MN excretion showed a similar pattern (symptomatic/uncontrolled hypertension > incidental > genetic screening) (all P < .05). Hereditary predisposition was detected in 20.4% of patients (incidental, 15.3%; symptomatic/uncontrolled hypertension, 42.9%).
CONCLUSION
The majority of pheochromocytomas are diagnosed incidentally and have distinct clinical, radiological, biochemical, and genetic features. Their detection at older age but smaller size may point to a different underlying tumor biology.
Topics: Humans; Middle Aged; Adrenal Gland Neoplasms; Pheochromocytoma; Hypertension; Adrenergic Agents; Genetic Predisposition to Disease
PubMed: 37417693
DOI: 10.1210/clinem/dgad401 -
Annals of Surgery Oct 2023Propranolol, a nonselective beta-receptor blocker, improves outcomes of severely burned patients. While the clinical and physiological benefits of beta-blockade are well... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE AND BACKGROUND
Propranolol, a nonselective beta-receptor blocker, improves outcomes of severely burned patients. While the clinical and physiological benefits of beta-blockade are well characterized, the underlying metabolic mechanisms are less well defined. We hypothesized that propranolol improves outcomes after burn injury by profoundly modulating metabolic pathways.
METHODS
In this phase II randomized controlled trial, patients with burns ≥20% of total body surface area were randomly assigned to control or propranolol (dose given to decrease heart rate <100 bpm). Outcomes included clinical markers, inflammatory and lipidomic profiles, untargeted metabolomics, and molecular pathways.
RESULTS
Fifty-two severely burned patients were enrolled in this trial (propranolol, n=23 and controls, n=29). There were no significant differences in demographics or injury severity between groups. Metabolomic pathway analyses of the adipose tissue showed that propranolol substantially alters several essential metabolic pathways involved in energy and nucleotide metabolism, as well as catecholamine degradation ( P <0.05). Lipidomic analysis revealed that propranolol-treated patients had lower levels of proinflammatory palmitic acid ( P <0.05) and saturated fatty acids ( P <0.05) with an increased ratio of polyunsaturated fatty acids ( P <0.05), thus shifting the lipidomic profile towards an anti-inflammatory phenotype after burn ( P <0.05). These metabolic effects were mediated by decreased activation of hormone-sensitive lipase at serine 660 ( P <0.05) and significantly reduced endoplasmic reticulum stress by decreasing phospho-JNK ( P <0.05).
CONCLUSION
Propranolol's ability to mitigate pathophysiological changes to essential metabolic pathways results in significantly improved stress responses.
Topics: Humans; Propranolol; Adrenergic beta-Antagonists; Burns; Metabolomics; Adipose Tissue
PubMed: 37389480
DOI: 10.1097/SLA.0000000000005973 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and...
BACKGROUND
Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype.
METHODS
We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines.
RESULTS
According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; =0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; =0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis.
CONCLUSIONS
We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
Topics: Humans; Pheochromocytoma; Retrospective Studies; Paraganglioma; Catecholamines; Metanephrine; Myocardial Infarction; Adrenal Gland Neoplasms; Adrenergic Agents; Phenotype; Atherosclerosis; Cardiomyopathies
PubMed: 38152977
DOI: 10.1161/HYPERTENSIONAHA.123.21902 -
Science (New York, N.Y.) Dec 2023Advancing drug discovery requires increasingly integrative structural biology approaches.
Advancing drug discovery requires increasingly integrative structural biology approaches.
Topics: Drug Discovery; Ligands; Receptors, Adrenergic, beta-1; Bioluminescence Resonance Energy Transfer Techniques; Protein Conformation; Adrenergic beta-1 Receptor Agonists; Humans; Protein Binding; Binding Sites
PubMed: 38127769
DOI: 10.1126/science.adm8393 -
Veterinary Immunology and... Jun 2024Polymorphonuclear cells (PMN) provide a rapid response to infection and tissue damage and stress can modify these critical innate immune defences. The study of...
Polymorphonuclear cells (PMN) provide a rapid response to infection and tissue damage and stress can modify these critical innate immune defences. The study of adrenergic receptor (AR) expression and function in bovine PMNs is limited but both neutrophils and eosinophils express numerous AR genes but differ significantly in their expression of individual AR genes. A flow cytometric technique was developed to differentiate between bovine neutrophils and eosinophils so both neutrophil and eosinophil responses to adrenergic agonists could be analysed. Neutrophils and eosinophils displayed significantly different changes in CD11b, L-selectin, and CD44 expression when activated by bovine serum opsonized zymosan and recombinant bovine interferon gamma. The responses of activated and resting neutrophils and eosinophils were then compared following stimulation with endogenous adrenergic agonists, epinephrine (E) norepinephrine (NE), and synthetic agonists targeting α1-, α2-, or β-ARs. Both resting and activated neutrophils and eosinophils displayed differences in iROS, CD44, and L-selectin expression following stimulation with E and NE. Resting neutrophils displayed pro-inflammatory responses to both E and NE, while resting eosinophils displayed a pro-inflammatory response to only NE. No single synthetic adrenergic agonist fully recapitulated responses observed with either E or NE and responses to adrenergic agonists were dose-dependent. In conclusion, bovine eosinophils and neutrophils responded to multiple adrenergic agonists by altering expression of proteins involved in immune surveillance and pro-inflammatory responses. Significant differences in neutrophil and eosinophil responses to adrenergic agonists are consistent with their differences in AR gene expression. This highlights the importance of analysing separately these two PMN subpopulations when investigating the effects of either endogenous or synthetic AR agonists.
Topics: Animals; Cattle; Neutrophils; Eosinophils; L-Selectin; Norepinephrine; Epinephrine; Adrenergic Agonists; Hyaluronan Receptors; Flow Cytometry; CD11b Antigen; Neutrophil Activation; Receptors, Adrenergic
PubMed: 38669937
DOI: 10.1016/j.vetimm.2024.110758 -
The Clinical Respiratory Journal Oct 2023Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can significantly and safely treat adults with cough variant asthma (CVA) remains inconclusive.
AIMS
This meta-analysis systematically evaluated the efficacy and safety of montelukast as an adjuvant treatment for adults with CVA.
MATERIALS AND METHODS
Randomized controlled trials (RCTs) on montelukast combined with inhaled corticosteroids (ICS) and long-acting β2 agonists (LABAs) to treat CVA in adults, from inception to March 6, 2023, were retrieved from the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science databases and Clinical Trials website. Review Manager (version 5.4) and Stata (version 15.0) were used to conduct the meta-analysis.
RESULTS
A total of 15 RCTs were ultimately included in the meta-analysis. It was established that montelukast as adjuvant therapy raised the total effective rate (RR = 1.20, 95% confidence interval [CI] [1.13, 1.27], P < 0.01) and improved the FEV1% (SMD = 0.91, 95% CI [0.40, 1.41], P < 0.01), PEF% (SMD = 0.63, 95% CI [0.38, 0.88], P < 0.01), FEV1 (SMD = 1.15, 95% CI [0.53, 1.77], P < 0.01), PEF (SMD = 0.64, 95% CI [0.42, 0.86], P < 0.01), and FEV1/FVC% (SMD = 0.76, 95% CI [0.51, 1.01], P < 0.01) and reduced the recurrence rate (RR = 0.28, 95% CI [0.15, 0.53], P < 0.01). The incidence of adverse reactions was higher in the montelukast auxiliary group compared to the control group but with no statistical difference (RR = 1.32, 95% CI [0.89, 1.96], P = 0.17).
CONCLUSION
Existing evidence indicated that the use of montelukast as an adjuvant therapy had therapeutic efficacy superior to ICS + LABA alone for the treatment of adult patients with CVA. However, further research is needed, especially a combination of high-quality long-term prospective studies and carefully designed RCTs.
Topics: Adult; Humans; Anti-Asthmatic Agents; Cough; Adrenergic beta-Agonists; Drug Therapy, Combination; Asthma; Adrenal Cortex Hormones
PubMed: 37218346
DOI: 10.1111/crj.13629 -
Kyobu Geka. the Japanese Journal of... Sep 2023The number of elderly patients in thoracic surgery is increasing. The percentage of patients over the age of 80 in surgical cases of malignant diseases such as lung...
The number of elderly patients in thoracic surgery is increasing. The percentage of patients over the age of 80 in surgical cases of malignant diseases such as lung cancer and mediastinal tumors is increasing every year. It is also true that the indications for surgery have been expanding as surgery itself has become less invasive, such as thoracoscopic and robotic surgery. However, it is not uncommon for patients over 80 years of age to have some organ dysfunction and many comorbidities. Therefore, when performing surgery for lung cancer and other diseases, it is important to assess the patient's ability to tolerate surgery, including respiratory and cardiac functions, and to perform risk management. To prevent postoperative complications and improve the accuracy of perioperative management, respiratory rehabilitation should be conducted before and after surgery, and not only smoking cessation instruction but also inhalation training using incentive spirometry( IS), breathing exercises, and the use of inhalers such as long-acting β2 agonist (LABA)/long-acting muscaring antagonist (LAMA) for patients with chronic obstructive pulmonary disease( COPD) are useful.
Topics: Humans; Aged, 80 and over; Aged; Muscarinic Antagonists; Adrenergic beta-2 Receptor Agonists; Administration, Inhalation; Respiratory Therapy; Pulmonary Disease, Chronic Obstructive; Lung Neoplasms; Drug Therapy, Combination
PubMed: 38056855
DOI: No ID Found -
Breast Cancer Research and Treatment Aug 2024Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR).
METHODS
Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger's regression tests.
RESULTS
Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes.
CONCLUSION
In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.
Topics: Humans; Breast Neoplasms; Female; Adrenergic beta-Antagonists; Neoplasm Recurrence, Local
PubMed: 38837086
DOI: 10.1007/s10549-024-07263-4 -
Current Problems in Cardiology Oct 2023Heart failure (HF), a type of cardiovascular disease (CVD), is a major cause of death globally and significantly burdens patients and the healthcare systems. Therefore,... (Review)
Review
Heart failure (HF), a type of cardiovascular disease (CVD), is a major cause of death globally and significantly burdens patients and the healthcare systems. Therefore, an improved treatment strategy is a necessity to reduce the mortality and morbidity rates and reduce its associated costs. Continuous updates in guidelines for the treatment of heart failure, especially for heart failure with reduced ejection fraction (HFrEF), have become evident in the last 5 years. An extensive literature search was conducted and the most recently published guideline recommendations for managing HFrEF in China, Canada, Europe, Portugal, Russia, and the United States were extracted. The differences in the treatment recommendations and the associated burdens, including mortality and morbidity rates and associated costs were analyzed. The HFrEF management guidelines recommended the clinical use of medicines belonging to 4 classes: an angiotensin II-receptor blocker plus neprilysin inhibitor (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium/glucose cotransporter-2 inhibitors (SGLT2i). Several differences in the management guidelines from resulted in significant variability in the disease burden in each country. The annual cost was the lowest in Russia, however, it showed the highest prevalence and incidence rates. In China, disease prevalence and incidence rates were the lowest and the annual cost was also comparatively low. The annual cost was highest in Canada, but it was associated with low prevalence. The annual cost was low in Portugal, but the prevalence was high. There were no significant differences in the prevalence and incidence rates as well as the annual costs between the United States and Europe. The global 5-year mortality rate of heart failure (HF) ranged between 50% and 70%. The research articles from the United States were cited the most (35.8%) in the guidelines. The results indicate differences between HFrEF management guidelines from different countries and their association with increased global disease burden. This study suggests that a unified global collaborative effort between countries is imperative to improve the guidelines for managing HFrEF to lower the associated burden for both the patients and the healthcare systems.
Topics: Humans; United States; Heart Failure; Stroke Volume; Angiotensin Receptor Antagonists; Adrenergic beta-Antagonists; Mineralocorticoid Receptor Antagonists
PubMed: 37302645
DOI: 10.1016/j.cpcardiol.2023.101867 -
Journal of Clinical Pharmacology Oct 2023The purpose of this article is to review the effects of different types of pharmacotherapy on symptoms that affect the quality of a patient's life after stent insertion.... (Review)
Review
The purpose of this article is to review the effects of different types of pharmacotherapy on symptoms that affect the quality of a patient's life after stent insertion. A thorough Medline/PubMed nonsystematic review was conducted from 1987 to January 2023, using the terms: "pigtail" OR "ureteral stents" AND "lower urinary tracts symptoms" OR "LUTS" AND "pharmacotherapy" OR "drugs". Relevant studies conducted in humans and reported in English language were included. The available reviews and articles associating the use of drugs with stent-related symptoms (SRS) provide conflicting results. Most of them show a clear benefit of alpha blockers, particularly alfuzosin, on treating urinary SRS, and hence there is a strong recommendation for the use of alpha blockers for the treatment of SRS in the guidelines of the European Association of Urology. Anticholinergics and mirabegron have shown a significant benefit in dealing with irritative bladder symptoms. In contrast, the findings for combination therapies are contradictory, with some studies showing that combination therapy is no superior to monotherapy with regards to most of the subsets of the Ureteral Stent Symptom Questionnaire (USSQ), whereas others present a clear benefit of combination therapies, specifically silodosin and solifenacin, in treating stent-associated lower urinary tract symptoms (LUTS), in comparison with any other type of monotherapy or combination therapy. Many studies suggest that some categories of pharmacotherapy, such as alpha blockers, can alleviate SRS. However, there is conflicting evidence concerning most other types of medical treatment. Randomized trials with the largest number of patients are needed to investigate the effectiveness of novel approaches on SRS.
Topics: Humans; Drug Therapy, Combination; Solifenacin Succinate; Adrenergic alpha-Antagonists; Urinary Bladder, Overactive; Stents
PubMed: 37476926
DOI: 10.1002/jcph.2314