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Handbook of Experimental Pharmacology Jun 2024β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β-AR, β-AR, β-AR are localized to the...
β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β-AR, β-AR, β-AR are localized to the human heart. Activation of β-AR and β-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of β-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of β-AR is critical in the pathogenesis of cardiac arrhythmias while activation of β-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of β-AR in cardiovascular disease, particularly arrhythmia generation. All β-blockers used therapeutically to treat cardiovascular disease block β-AR with variable blockade of β-AR depending on relative affinity for β-AR vs β-AR. Since the introduction of β-blockers into clinical practice in 1965, β-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. β-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. β-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The β-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other β-blockers and is used successfully in the treatment of heart failure. The discovery of β-AR in human heart created interest in the role of β-AR in heart failure but has not resulted in therapeutics at this stage.
PubMed: 38844580
DOI: 10.1007/164_2024_720 -
Journal of Clinical Imaging Science 2024Glomus tumors (or paragangliomas) are rare, benign tumors of neuroendocrine origin that appear in tissues of paraganglionic origin. This clinical entity poses a...
Glomus tumors (or paragangliomas) are rare, benign tumors of neuroendocrine origin that appear in tissues of paraganglionic origin. This clinical entity poses a significant treatment challenge due to its proximity to critical neurovascular structures, thus the potential of morbid functional damage caused by disease progression and/or treatment approach. While surgery remains the standard of care for such cases, there has been an increasing trend toward management with radiotherapy or close observation. Here, we present a case of a large and irregularly shaped glomus jugulotympanicum tumor that was treated with volumetric arc radiotherapy. Given the risk of cranial neuropathy with surgery, radiation was the preferred treatment modality. This case demonstrated the safety and efficacy of volumetric arc radiotherapy in the management of a large glomus tumor with a complex shape.
PubMed: 38841310
DOI: 10.25259/JCIS_17_2024 -
Journal of Endocrinological... Jun 2024There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which...
BACKGROUND
There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment.
METHODS
This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment.
RESULTS
62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ.
CONCLUSIONS
This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application.
PubMed: 38837102
DOI: 10.1007/s40618-024-02398-z -
HNO Jun 2024Paragangliomas represent a heterogeneous group of rare neuroendocrine tumors with marked variability in symptoms and disease course. Due to the close proximity to...
Paragangliomas represent a heterogeneous group of rare neuroendocrine tumors with marked variability in symptoms and disease course. Due to the close proximity to neurovascular structures, paragangliomas of the head and neck region can cause a variety of symptoms. To this day, there are no reliable prognostic factors that can predict a potentially malignant course. All patients with newly diagnosed paragangliomas should undergo an early diagnostic workup and regular follow-up examinations in specialized centers. While radical resection was previously regarded as standard treatment for paragangliomas, radiotherapy and active surveillance (watch-and-scan strategy) have become equally important over the years. Low-threshold techniques for molecular pathology analysis of the mutation-specific behavior of paragangliomas are nowadays available.
PubMed: 38834894
DOI: 10.1007/s00106-024-01480-5 -
Clinical Case Reports Jun 2024Patients presenting with abdominal pain and retroperitoneal mass in radiographic images may be in the early stages of primary adrenal mantle cell lymphoma, which...
KEY CLINICAL MESSAGE
Patients presenting with abdominal pain and retroperitoneal mass in radiographic images may be in the early stages of primary adrenal mantle cell lymphoma, which requires histological studies for a definite diagnosis.
ABSTRACT
This report presents a 37-year-old woman complaining of ambiguous abdominal pain, with imaging findings revealing a retroperitoneal abdominal mass on the left side of the aorta, and a possible diagnosis of non-functional retroperitoneal paraganglioma. Total laparoscopic excision was performed. Surprisingly, histological examinations revealed features in favor of mantle cell lymphoma.
PubMed: 38831984
DOI: 10.1002/ccr3.8887 -
European Journal of Nuclear Medicine... Jun 2024
PubMed: 38829375
DOI: 10.1007/s00259-024-06776-w -
Neuroendocrinology Jun 2024Aims of the study were to assess the differences in the diagnostic efficacy of 68Ga-somatostatin receptor analogs (68Ga-SSAs) and 18F-fluorodeoxyglucose (18F-FDG)...
INTRODUCTION
Aims of the study were to assess the differences in the diagnostic efficacy of 68Ga-somatostatin receptor analogs (68Ga-SSAs) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting bone metastases in neuroendocrine neoplasm (NEN) and to analyze the correlation between imaging features and clinical features of BMs.
METHODS
We retrospectively analyzed the clinical and imaging data of 213 NEN patients who underwent 68Ga-SSA PET/CT and were finally diagnosed as BMs by pathology or follow-up. Of those, 103 patients underwent 18F-FDG PET/CT within 7 days after 68Ga-SSA PET/CT.
RESULT
The BM detection rate of 68Ga-SSA PET/CT was higher than 18F-FDG PET/CT (86.4% vs. 66.0%, p = 0.02) in 103 patients with dual scanning. Meanwhile, the number of positive lesions in 68Ga-SSA PET/CT was significantly more than in 18F-FDG PET/CT (3.37 ± 1.95 vs. 2.23 ± 2.16, t = 4.137, p < 0.001). Most bone metastasis lesions presented as osteogenic change in CT (55.4%, 118/213). Concerning the primary tumor, the most frequent were of pancreatic origin (26.3%, 56/213), followed by rectal origin (22.5%, 48/213), thymic origin in 33 cases (15.5%), pulmonary origin in 29 cases (13.6%), paraganglioma in 20 cases (9.4%). The efficiency of 68Ga-SSA PET/CT to detect BMs was significantly correlated with the primary site (p = 0.02), with thymic carcinoid BMs being the most difficult to detect, and the positive rate was only 60.6% (20/33). However, 18F-FDG PET/CT positive rate was 76.92% (10/13) in thymic carcinoid BMs. In addition, the BMs of 7 patients in this study were detected by 68Ga-SSA PET earlier than CT for 4.57 months (range: 2-10 months).
CONCLUSION
68Ga-SSA PET/CT has higher sensitivity for detecting the BMs of NEN than 18F-FDG and detects the BM earlier than CT. Moreover, 18F-FDG PET/CT should be a complement for diagnosing the BMs of thymic carcinoids.
PubMed: 38824926
DOI: 10.1159/000539572 -
Blood Pressure Dec 2024Von Hippel-Lindau disease (e.g. VHL) is an autosomal dominant multi-organ cancer syndrome caused by a mutation in the tumour suppressor gene. In this study, we...
Discovering a novel genetic variant in 11 family members who had isolated pheochromocytoma linked to von Hippel-Lindau (VHL) syndrome, aligning with the type 2c phenotype.
INTRODUCTION
Von Hippel-Lindau disease (e.g. VHL) is an autosomal dominant multi-organ cancer syndrome caused by a mutation in the tumour suppressor gene. In this study, we introduce a novel genetic variant found in 11 family members diagnosed initially with isolated Pheochromocytoma. Subsequent findings revealed its association with VHL syndrome and corresponds to the Type 2 C phenotype.
METHODS
The gene was amplified through the utilisation of the polymerase chain reaction (PCR). PCR fragments were sequenced using bidirectional Sanger sequencing, using BigDye™ Terminator v3.1 Cycle Sequencing Kit, running on the 3500 genetic analyser. Results were assembled and analysed Using Software SeqA and chromas pro.
RESULTS
A heterozygous in-frame duplication of three nucleotides, specifically ATG, c.377_379dup; p.Asp126dup in exon 2, was identified in all the patients tested within the pedigree.
CONCLUSION
In this study, we disclose the identification of a novel genetic variant in a Jordanian family, affecting eleven family members with pheochromocytoma associated with VHL disease. This finding underscores the importance of screening family members and contemplating genetic testing for individuals newly diagnosed with pheochromocytoma and could enhance our comprehension of the potential adverse consequences associated with VHL germline mutations.
Topics: Humans; Pheochromocytoma; von Hippel-Lindau Disease; Female; Male; Pedigree; Von Hippel-Lindau Tumor Suppressor Protein; Adult; Phenotype; Adrenal Gland Neoplasms; Middle Aged; Genetic Variation
PubMed: 38824681
DOI: 10.1080/08037051.2024.2355268 -
Revista Espanola de Medicina Nuclear E... May 2024
PubMed: 38821408
DOI: 10.1016/j.remnie.2024.500018 -
Journal of Neurosurgery May 2024Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical...
OBJECTIVE
Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors.
METHODS
This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients' medical and surgical records as well as radiological and pathological findings were analyzed.
RESULTS
During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner's syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome.
CONCLUSIONS
RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.
PubMed: 38820608
DOI: 10.3171/2024.3.JNS232860