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Key Clinical Message: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, paragangliomas, and syringomyelia are uncommon diseases. Furthermore, in the absence of any genetic link and with less than five reported adult patients surviving unrepaired rare form of Tetralogy of Fallot, our case shows noteworthiness. The possibility of definitive treatment of these conditions is rendered unsafe due to this persistent defect. Thus, management and ongoing survival of this patient remains complex and challenging. [ABSTRACT FROM AUTHOR]

In this review, we explore the inconsistencies in the data and gaps in our knowledge that exist in what is currently known regarding gill chemosensors which drive the cardiorespiratory reflexes in fish. Although putative serotonergic neuroepithelial cells (NEC) dominate the literature, it is clear that other neurotransmitters are involved (adrenaline, noradrenaline, acetylcholine, purines, and dopamine). And although we assume that these agents act on neurons synapsing with the NECs or in the afferent or efferent limbs of the paths between chemosensors and central integration sites, this process remains elusive and may explain current discrepancies or species differences in the literature. To date it has been impossible to link the distribution of NECs to species sensitivity to different stimuli or fish lifestyles and while the gills have been shown to be the primary sensing site for respiratory gases, the location (gills, oro-branchial cavity or elsewhere) and orientation (external/water or internal/blood sensing) of the NECs are highly variable between species of water and air breathing fish. Much of what has been described so far comes from studies of hypoxic responses in fish, however, changes in CO2, ammonia and lactate have all been shown to elicit cardio-respiratory responses and all have been suggested to arise from stimulation of gill NECs. Our view of the role of NECs is broadening as we begin to understand the polymodal nature of these cells. We begin by presenting the fundamental picture of gill chemosensing that has developed, followed by some key unanswered questions about gill chemosensing in general. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the efficacy and safety of preoperative embolization, used 48 hours before surgery to reduce tumor size and surgical complications in carotid body paragangliomas. This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane Handbook. A comprehensive literature search was performed in Medline, Embase, Web of Science, and Cochrane databases. The inclusion criteria were: 1) observational studies, 2) reporting on diagnosed carotid body paragangliomas, 3) undergoing preoperative embolization procedures, and 4) with ethylene-vinyl alcohol as an embolic agent. The study analyzed 106 patients, aged 18–79, using primarily Onyx 18 for embolization, with treatment intervals ranging from 24 hours to 2 weeks. Efficacy outcomes showed near-total devascularization in 67% of cases (95% confidence interval [CI]: 0.47–0.87; I² = 74%), subtotal devascularization in 33% (95% CI: 0.12–0.54; I² = 43%), and total devascularization in 97% (95% CI: 0.88–1.00; I² = 41%), indicating significant heterogeneity across outcomes. The mean estimated blood loss was 184.46 ml (95% CI: 116.72–252.20 ml). Postembolization complication rate was exceptionally low at 1% (95% CI: 0.00–0.06; I² = 0%). In conclusion, preoperative embolization of carotid body tumors achieved high rates of devascularization with minimal blood loss and a very low incidence of complications, highlighting its effectiveness and safety as a treatment strategy. [ABSTRACT FROM AUTHOR]

Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes (T2D) and the contribution of the peripheral chemoreceptors to resting cardiovascular and metabolic control. We hypothesized that: (1) adults with T2D exhibit exaggerated peripheral chemoreflex sensitivity; (2) the peripheral chemoreceptors contribute to cardiovascular dysfunction in T2D; and (3) attenuation of peripheral chemoreceptor activity improves glucose tolerance in T2D. Seventeen adults with diagnosed T2D [six males/11 females; aged 54 ± 11 years; glycated haemoglobin (HbA1c) 7.6 ± 1.5%] and 20 controls without T2D (9 males/11 females; aged 49 ± 13 years, HbA1c 5.2 ± 0.4%) participated in the study. The hypoxic ventilatory response (HVR) was assessed as an index of peripheral chemosensitivity. Resting heart rate, blood pressure and minute ventilation were measured when breathing normoxic followed by hyperoxic air (1.0FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) to acutely attenuate peripheral chemoreceptor activity. A subset of participants (n = 9 per group) completed two additional visits [normoxia (0.21FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$), hyperoxia (1.0FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$)] where glucose and insulin were measured for 2 h following an oral glucose challenge. HVR was augmented in adults with T2D (–0.84 ± 0.49 L min–1/%) vs. control (–0.48 ± 0.40 L min–1/%, P = 0.021). Attenuation of peripheral chemoreceptor activity decreased heart rate (P < 0.001), mean blood pressure (P = 0.009) and minute ventilation (P = 0.002); any effect of hyperoxia did not differ between groups. There was no effect of hyperoxia on the glucose (control, P = 0.864; T2D, P = 0.982), nor insulin (control, P = 0.763; T2D, P = 0.189) response to the oral glucose challenge. Peripheral chemoreflex sensitivity is elevated in adults with T2D; however, acute attenuation of peripheral chemoreflex activity with hyperoxia does not restore cardiometabolic function. Key points: Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes and the contribution of the peripheral chemoreceptors to resting cardiovascular control and glucose tolerance. We observed elevated peripheral chemoreflex sensitivity in adults with diabetes which was associated with glycaemic control (i.e. glycated haemoglobin). Notably, acute attenuation of peripheral chemoreflex activity with hyperoxia did not restore cardiometabolic function in the individuals studied. [ABSTRACT FROM AUTHOR]

Schwannomas are rare neoplasms that originate from the nervous system. We describe a case of schwannoma of the ansa-cervicalis in a patient where preoperative imaging is suggestive of glomus caroticum tumor. A 44-year-old man presented to the surgical oncology department with a recurrent anterior triangle neck swelling. Magnatic resonance ımaging (MRI) demonstrated right enhancing soft tissue mass at the carotid bifurcation consistent with glomus tumor. Intraoperatively, the lesion was found abuting the bifurcatuion and arising from the right ansa-cervicalis. Histopathology evaluation revealed schwannoma. Schwannoma of the ansa-cervicalis is extremely rare. Very few cases have been reported in the literature. Making the preoperative diagnosis is difficult. Preoperative imaging is necessary to rule out other causes of neck masses such as thyroid lesions, lymphadenopathy, and carotid body tumor. Verocay bodies were noted on histology. Schwannoma of cervical region can have origin from any nerve. Any Neurologic post-operative deficit depends on the nerve of origin and the precision of the surgery performed. [ABSTRACT FROM AUTHOR]

The carotid body (CB) senses changes in arterial O2 partial pressure (pO2) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO2 through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)‐induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 μmol/mg protein in control rats to 1.45 ± 0.31 μmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione‐reducing stress. [ABSTRACT FROM AUTHOR]

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia-inducible transcription factor (HIF), HIF-2α, as having a nonredundant role in the development and function of that organ. Here, we show that activation of HIF-2α, including isolated overexpression of HIF-2α but not HIF-1α, is sufficient to induce oxygen chemosensitivity in adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues resembling the fetal organ of Zuckerkandl, which also manifests oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of gene classes that are ordinarily characteristic of the carotid body, including G protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2α acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking 2 major oxygen-sensing systems. [ABSTRACT FROM AUTHOR]

Paragangliomas are rare tumors originating from the paraventricular bodies of the autonomic nervous system located in the adrenal glands, chest, abdomen, pelvis and head and neck. Tumors of this type account for 0.5% of head and neck cancers, 0.03% of all cancers and their incidence is estimated at 1–30/100,000 per year. Head and Neck Paragangliomas (HNPGL) are localized in carotid body, tympanic cavity or jugular foramen. It is established that HNPGL may be associated with mutations of the SDH complex, with SDHD being the most prevalent. However, SDHB, SDHC and SDHAF are also potential causes. The aforementioned mutations are influenced by various risk factors, including young age, a positive family history of paraganglioma, the presence of metastases and gender The purpose of this study is to summarize the results of genetic testing performed on patients with head and neck paraganglioma and to create an up-to-date genetic diagnosis algorithm for patients with HNPGL based on previous studies published in the literature that can be used in daily practice. Several papers observed that among SDHD mutation carriers, most or all of those studied had HNPGL, and SDHB mutations were more frequently found in the presence of metastasis. Based on the results, it was concluded that there is no basis for genetic testing for VHL in patients without a positive family history. In each algorithm proposed by different authors, proposals for rational genetic diagnosis were analyzed based on the studies cited by the author and the analyses included in our paper. For the analysis of the treatment algorithms, the following were included: Martin, Mannelli, Neumann, Gupta. Subsequently, publications related to the genetic diagnosis of HNPGL were analyzed to verify the proposed algorithms in light of the latest genetic studies and to establish an updated diagnostic management scheme. [ABSTRACT FROM AUTHOR]

Endothelin‐1 (ET‐1) and its receptors are linked to increases in sensitivity of the chemoreceptors to hypoxic stress and the development of hypertension in preclinical models. We hypothesized ET receptor antagonism would lower resting blood pressure (BP) as well as the acute BP response to chemoreflex stress. Twenty‐four men (31 ± 5 years, 26 ± 3 kg/m2) completed two study visits (control, bosentan). On each visit, BP was assessed under three conditions: (1) normoxia (FiO2 0.21), (2) chemoreflex excitation via hypoxia (FiO2 0.05–0.21), (3) chemoreflex inhibition via hyperoxia (FiO2 1.00). Bosentan increased plasma ET‐1 (0.94 ± 0.90 to 1.27 ± 0.62 pg/mL, p = 0.004), supporting receptor blockade. Resting diastolic (73 ± 5 to 69 ± 7 mmHg, p = 0.007) and mean (93 ± 7 to 88 ± 7 mmHg, p = 0.005) BP were reduced following bosentan compared to control with no change in systolic BP (p = 0.507). The mean BP response to both acute hypoxia (−0.48 ± 0.38 to −0.25 ± 0.31 mmHg/%, p = 0.004) and hyperoxia (area under the curve −93 ± 108 to −27 ± 66 AU, p = 0.018) were attenuated following bosentan. Acute ET receptor inhibition attenuates the rise in BP during chemoreflex excitation as well as the fall in BP during chemoreflex inhibition in healthy young men. These data support a role for ET‐1 in control of resting BP, possibly through a chemoreceptor‐mediated mechanism. [ABSTRACT FROM AUTHOR]

Context: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow‐growing tumours arising from neural crest‐derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined. Objective: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities. Methods: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023. Results: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17–91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5–6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p =.04), tumour size exceeding 2 cm (p =.03), positive SDHx variants (p =.01), and vagal and jugular tumours (p =.04). Conclusion: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD) is a transmissible and fatal prion disease that affects cervids. While both oral and nasal routes of exposure to prions cause disease, the spatial and temporal details of how prions enter the central nervous system (CNS) are unknown. Carotid bodies (CBs) are structures that are exposed to blood-borne prions and are densely innervated by nerves that are directly connected to brainstem nuclei, known to be early sites of prion neuroinvasion. All CBs examined contained mast cells expressing the prion protein which is consistent with these cells playing a role in neuroinvasion following prionemia.

Silent hypoxemia, or "happy hypoxia," is a puzzling phenomenon in which patients who have contracted COVID-19 exhibit very low oxygen saturation ( SaO 2 < 80%) but do not experience discomfort in breathing. The mechanism by which this blunted response to hypoxia occurs is unknown. We have previously shown that a computational model of the respiratory neural network (Diekman et al. in J Neurophysiol 118(4):2194–2215, 2017) can be used to test hypotheses focused on changes in chemosensory inputs to the central pattern generator (CPG). We hypothesize that altered chemosensory function at the level of the carotid bodies and/or the nucleus tractus solitarii are responsible for the blunted response to hypoxia. Here, we use our model to explore this hypothesis by altering the properties of the gain function representing oxygen sensing inputs to the CPG. We then vary other parameters in the model and show that oxygen carrying capacity is the most salient factor for producing silent hypoxemia. We call for clinicians to measure hematocrit as a clinical index of altered physiology in response to COVID-19 infection. [ABSTRACT FROM AUTHOR]

Dopamine and histamine receptors D2R and H3R are G protein-coupled receptors (GPCRs) which can establish physical receptor–receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D2R and H3R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D2R and H3R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D2R and H3R antagonistic functional implications. The CBs of both Sprague–Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D2R and H3R was performed; thereafter, in situ proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D2R and H3R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D2R and H3R RRIs. Additionally, D2R and H3R heterodimers were mainly detected in type I cells (βIII-tubulin-positive cells), but type II cells’ involvement cannot be excluded. RRIs may play a role in functional modulation of CB cells; investigating RRIs in the CB may guide toward the comprehension of its plastic changes and fine regulatory role while also unveiling their possible clinical implications. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima–media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH. [ABSTRACT FROM AUTHOR]

Background: Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH‐mutated HNPs. Methods: Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta‐regression was performed. Cochran's Q test and I2 test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias. Results: Forty‐two studies with 8849 patients were included. Meta‐regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH‐related mutations. Conclusion: Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH‐related mutations has the potential to influence the management approach to such HNPs. [ABSTRACT FROM AUTHOR]

The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure. [ABSTRACT FROM AUTHOR]

Background: Carotid body tumors (CBTs) are rare benign tumors that arise from the chemoreceptor tissue located at the carotid bifurcation that require excision if symptomatic. Depending on the size and location of the tumor, the carotid artery may need to be repaired after resection. This study aims to assess whether CBT excision with artery resection had higher rates of 30-day postoperative outcomes compared with CBT excision without artery resection. Methods: This is a retrospective cohort study. Patients were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry from 2005 to 2017. They were divided into two groups, based on Current Procedural Terminology (CPT®) codes: group A had CBT excision without carotid artery excision (CPT code 60600) and group B with carotid artery excision (CPT code 60605). Patient demographic characteristics, co-morbidities, and 30-days postoperative outcomes were compared between the two groups. Categorical data were analyzed using Pearson's X2 or Fisher exact tests and presented as proportions (percentages). Continuous data were analyzed using parametric or non-parametric tests as appropriate. Statistical significance was defined as p < 0.05. Statistical analysis was performed using the SPSS statistical software package. Results: A total of 463 patients were identified, 410 (88.4%) in group A and 53 (11.4%) in group B. Overall, there were 291 (62.9%) women. A higher proportion of women underwent CBT excision only, compared to men (91.1% [265/291] vs. 84.3% [145/172], p < 0.0001). Demographics and comorbidities were similar between groups. There was no significant difference in the 30-day postoperative outcomes. The reoperation rate was higher in group B (3.8% vs. 1.5%, p = 0.334), while the readmission rate was higher in group A (3.2% vs. 0% p = 0.269), and both were not significantly different. Overall morbidity and serious morbidity were higher in group B (7.5% vs. 5.9%, p = 0.626) and lower in group A (5.7% vs. 3.9%, p = 0.544), respectively, but were not significantly different. Operative time (mean, SD) was higher in group B (187 ± 107 vs. 138 ± 66 min, p < 0.001). However, the median (IQR) of hospital length of stay (LOS) was similar (2 [1, 4] vs. 2 [1, 3] days, p = 0.134). Conclusions: Overall, no difference was noted in the 30-day postoperative outcome between the two surgical approaches of CBT. However, operative time was longer when artery resection was performed. Further research to determine the factors predicting the need for carotid artery resection among patient gender is needed. [ABSTRACT FROM AUTHOR]

Introduction: Carotid body tumors are rare neoplasms with malignant potential. We aim to follow up on our initial experience published in 2015 and compare the occurrence of complications and postoperative outcomes with the use of retrocarotid dissection (RCD) against the standard caudocranial (SCCD) technique. Methods: This was an observational, case–control study in which we analyzed all of the carotid body tumor resections performed from 1986 to 2022. Parametric and nonparametric tests were used accordingly. Statistical analysis was performed on Stata 17. Results: A total of 181 surgical procedures were included, mean age was 56 years (± 13.63), and 168 (93%) were performed in women. The mean medio-lateral diameter was larger in the RCD group (2.85 ± 1.57 cm vs 1.93 ±1.85 cm; p = 0.002) and presurgical embolization was more frequently performed in the SCCD group (27.5% vs 0.7%; p < 0.001). A total of 40 (22.09%) resections were performed using the SCCD technique. In contrast, in 141 (77.91%) procedures the RCD technique was used. The mean surgical time in the RCD group was lower (197.37 ± 70.56 min vs 232 ± 98.34 min; p = 0.01). No statistically significant difference was found between SCCD and RCD in terms of vascular lesions (n = 20 [11.04%], 15% vs 9%, respectively; p = 0.36), transient or permanent nerve injuries (25% vs 33%, respectively; p = 0.31), or mean intraoperative bleeding (SCCD: 689.95 ± 680.05 mL vs RCD: 619.64 ± 837.94 mL; p > 0.05). Conclusions: RCD appears to be a safe and equivalent alternative to the standard caudocranial approach in terms of intraoperative bleeding or vascular lesions, with a sustained, significant decrease in surgical time. [ABSTRACT FROM AUTHOR]

Carotid body tumors (CBTs) are neoplasms that occur at the bifurcation of the carotid artery and are pathologically classified as paragangliomas. In the 4th edition of the WHO classification, paragangliomas are categorized as neoplasms with malignant potential. Clinically, about 5% of CBTs present with malignant features such as metastasis. Currently, it is challenging to distinguish between tumors with benign courses and those that present malignantly. Recent advances in genetic testing have elucidated the genetic characteristics of paragangliomas, including carotid body tumors. Over 20 genes have been identified as being involved in tumor development. Particularly in head and neck paragangliomas, abnormalities in genes related to succinate dehydrogenase are frequently observed. Research is ongoing to understand the mechanisms by which these genes contribute to tumor development. The definitive treatment for CBTs is surgical resection. These tumors are prone to bleeding and often adhere firmly to the carotid artery, making intraoperative bleeding control challenging. The risk of lower cranial nerve paralysis is relatively high, and there is a risk of stroke because of manipulation of the carotid artery. Preoperative evaluation with angiography is essential, and a multi-disciplinary surgical team approach is necessary. In cases where the tumor is difficult to resect or has metastasized, radiation therapy or chemotherapy are employed. Clinical trials involving targeted molecular therapies and radiopharmaceuticals have recently been conducted, with some applied clinically. The development of various new treatments is anticipated, providing hope for therapeutic options in refractory cases. [ABSTRACT FROM AUTHOR]

The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature. [ABSTRACT FROM AUTHOR]

Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100,000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as 18F-FDA and 18F-FDG PET/CT, 18F-DOPA PET, 123I-MIBG, and 68Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate. [ABSTRACT FROM AUTHOR]

Abstract The carotid body (CB) senses changes in arterial O2 partial pressure (pO2) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO2 through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)‐induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 μmol/mg protein in control rats to 1.45 ± 0.31 μmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione‐reducing stress.

Abstract Endothelin‐1 (ET‐1) and its receptors are linked to increases in sensitivity of the chemoreceptors to hypoxic stress and the development of hypertension in preclinical models. We hypothesized ET receptor antagonism would lower resting blood pressure (BP) as well as the acute BP response to chemoreflex stress. Twenty‐four men (31 ± 5 years, 26 ± 3 kg/m2) completed two study visits (control, bosentan). On each visit, BP was assessed under three conditions: (1) normoxia (FiO2 0.21), (2) chemoreflex excitation via hypoxia (FiO2 0.05–0.21), (3) chemoreflex inhibition via hyperoxia (FiO2 1.00). Bosentan increased plasma ET‐1 (0.94 ± 0.90 to 1.27 ± 0.62 pg/mL, p = 0.004), supporting receptor blockade. Resting diastolic (73 ± 5 to 69 ± 7 mmHg, p = 0.007) and mean (93 ± 7 to 88 ± 7 mmHg, p = 0.005) BP were reduced following bosentan compared to control with no change in systolic BP (p = 0.507). The mean BP response to both acute hypoxia (−0.48 ± 0.38 to −0.25 ± 0.31 mmHg/%, p = 0.004) and hyperoxia (area under the curve −93 ± 108 to −27 ± 66 AU, p = 0.018) were attenuated following bosentan. Acute ET receptor inhibition attenuates the rise in BP during chemoreflex excitation as well as the fall in BP during chemoreflex inhibition in healthy young men. These data support a role for ET‐1 in control of resting BP, possibly through a chemoreceptor‐mediated mechanism.

The article discusses the presence of α-Synuclein pathology in the carotid body, a chemosensory organ that plays a role in respiratory control. The study found evidence of α-Synuclein deposition in the carotid body and carotid sinus nerve in Parkinson's disease patients, suggesting a potential link to respiratory dysfunction in the disease. The findings highlight the need for further research on the role of the carotid body in respiratory control in Parkinson's disease and its implications for patient care. [Extracted from the article]

The article delves into the impact of disrupting the peripheral chemoreflex on brachial blood flow in individuals with treated hypertension. Researchers discovered that blocking the chemoreflex with low-dose dopamine led to increased blood flow and vascular conductance during exercise. The study suggests that those with hypertension may have heightened chemoreflex sensitivity affecting blood flow to muscles during exercise. Future research should address limitations like the absence of a healthy control group and the narrow focus on handgrip exercise to enhance the findings' generalizability. The article also discusses the effects of exercise pressor reflex and isocapnic hypoxia on brachial blood flow in individuals with hypertension, as well as the use of low-dose dopamine and rhythmic handgrip contraction to regulate blood flow. Additional information can be found in the online Supporting Information section of the article. [Extracted from the article]

This article discusses the use of positron emission tomography/computed tomography (PET/CT) in the management of head and neck paragangliomas (HNPGL). It highlights the importance of PET/CT in assessing the locoregional extension and screening for multifocality or metastasis in HNPGL patients. The article specifically focuses on differentiating between vagal and carotid paragangliomas on unenhanced PET/CT. It introduces a characteristic imaging feature called the "sweet potato" shape with a nipple, which is frequently seen in large vagus nerve paragangliomas but not in carotid body paragangliomas. The authors suggest that this feature can aid in distinguishing between the two types of paragangliomas, but recommend confirming the findings with contrast-enhanced morphological imaging. [Extracted from the article]

Abstract An adequate supply of O2 is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O2 availability or associated with diseases, or a combination of both. Exposure to hypoxia triggers adjustments in multiple physiological systems in the body to generate appropriate homeostatic responses. However, with significant reductions in the arterial partial pressure of O2, hypoxia can be life‐threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O2 availability on cellular activity, O2 chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O2, triggering orchestrated responses of increased ventilation and cardiac output, blood flow redistribution and metabolic adjustments. In mammals, the peripheral chemoreceptors of the carotid body are considered to be the main hypoxic sensors and the primary source of excitatory feedback driving respiratory, cardiovascular and autonomic responses. However, current evidence indicates that the CNS contains specialized brainstem and spinal cord regions that can also sense hypoxia and stimulate brain networks independently of the carotid body inputs. In this manuscript, we review the discoveries about the functioning of the O2 chemoreceptors and their contribution to the monitoring of O2 levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O2 homeostasis. We also discuss the implications of the chemoreflex‐related mechanisms in paediatric and adult pathologies.

The Olfr78 gene encodes a G-protein-coupled olfactory receptor that is expressed in several ectopic sites. Olfr78 is one of the most abundant mRNA species in carotid body (CB) glomus cells. These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in constitutive Olfr78 knockout mice. In another study, constitutive Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. To further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for maturation of glomus cells. Graphical Abstract [ABSTRACT FROM AUTHOR]

Molecular oxygen suffices the ATP production required for the survival of us aerobic organisms. But it is also true that oxygen acts as a source of reactive oxygen species that elicit a spectrum of damages in living organisms. To cope with such intrinsic ambiguity of biological activity oxygen exerts, aerobic mechanisms are equipped with an exquisite adaptive system, which sensitively detects partial pressure of oxygen within the body and controls appropriate oxygen supply to the tissues. Physiological responses to hypoxia are comprised of the acute and chronic phases, in the former of which the oxygen-sensing remains controversial particularly from mechanistic points of view. Recently, we have revealed that the prominently redox-sensitive cation channel TRPA1 plays key roles in oxygen-sensing mechanisms identified in the peripheral tissues and the central nervous system. In this review, we summarize recent development of researches on oxygen-sensing mechanisms including that in the carotid body, which has been recognized as the oxygen receptor organ central to acute oxygen-sensing. We also discuss how ubiquitously the TRPA1 contributes to the mechanisms underlying the acute phase of adaptation to hypoxia. [ABSTRACT FROM AUTHOR]

The carotid body paraganglioma is a rare benign neoplasm arising from the chemoreceptor cells of the carotid bulb. The carotid body has the largest collection of paraganglia in the head and neck with 60–70% of head and neck paraganglioma. Paraganglia are clusters of cells originating from the neural crest with histological and cytochemical characteristics of neuroendocrine cells. It is mostly asymptomatic in early presentation but become symptomatic and difficult to manage when the tumor is large. We present a case of a 26-year-old male who presented with a painless, pulsatile, progressively increasing left lateral neck swelling of 5 years duration with Shamblin IIIa. The diagnosis of the tumor was confirmed based on clinical features, histology, and radiological findings. We had difficult surgical dissection of the tumor with neurovascular damage. [ABSTRACT FROM AUTHOR]

Background: Carotid body paraganglioma (CBP) is a rare, highly vascularized, and slow-growing neuroendocrine tumor. Surgical resection is the definitive treatment for CBP, however, it remains challenging due to the tumor's proximity to critical blood vessels and cervical cranial nerves. This study aimed to document the characteristics of CBP and examine the clinical outcomes of patients following surgical extirpation of CBP. Methods: This is a single-center retrospective review analyzed patients who underwent CBP extirpation. We examined the patient demographics, preoperative clinical features, tumor characteristics, levels of catecholamines and their metabolites in the serum and urine. Surgeries were performed by one vascular surgeon with follow-ups at 1,3,6 months and yearly thereafter. Logistic regression analysis was conducted to identify risk factors associated with the occurrence of either permanent or temporary cervival cranial nerve palsy (CNP). Results: From September 2020 to February 2023, this study examined 21 cases of CBP removal surgeries that were carried out in 19 patients. The mean age of the patients was 38.9 ± 10.9 years and the percentage of males was 57.1% (n = 12). The most common preoperative clinical feature was painless neck mass (n = 12; 57.1%). Complete resection was achieved in 20 cases; excluding one case with pathologically proven sclerosing paraganglioma. Vascular procedures were performed in four cases (ECA resection, n = 2; primary repair of ICA tear without carotid shunting, n = 1; and ICA patch angioplasty with carotid shunting, n = 1). Temporary cranial neurologic complications, specifically aspiration and hoarseness occurred in four (19.0%), and three (14.3%) cases, respectively. Hoarseness associated with permanent CNP persisted for more than 6 months in two cases (9.5%). No recurrence or mortality was observed during the follow-up period. Conclusions: Surgical resection is the primay treatment approach for CBP; however, it poses risks of vascular or cervical CNP. The intraoperative estimated blood loss was the only identified risk factor for CNP. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. SDHx mutations currently account for the vast majority of mutations identified in HNPGLs, and SDHB and SDHD are the two most common types. Surgery remains the definitive treatment, while radiation therapy is being increasingly used as an adjuvant or primary treatment for surgically challenging or inoperable cases. Our study provided clinical and outcome data on a large cohort of patients with HNPGLs and the results can help provide guidance on improving the care and outcomes of patients with HNPGL. Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs. [ABSTRACT FROM AUTHOR]

Bioelectronic medicine are an emerging class of treatments aiming to modulate body nervous activity to correct pathological conditions and restore health. Recently, it was shown that the high frequency electrical neuromodulation of the carotid sinus nerve (CSN), a small branch of the glossopharyngeal nerve that connects the carotid body (CB) to the brain, restores metabolic function in type 2 diabetes (T2D) animal models highlighting its potential as a new therapeutic modality to treat metabolic diseases in humans. In this manuscript, we review the current knowledge supporting the use of neuromodulation of the CSN to treat T2D and discuss the future perspectives for its clinical application. Firstly, we review in a concise manner the role of CB chemoreceptors and of CSN in the pathogenesis of metabolic diseases. Secondly, we describe the findings supporting the potential therapeutic use of the neuromodulation of CSN to treat T2D, as well as the feasibility and reversibility of this approach. A third section is devoted to point up the advances in the neural decoding of CSN activity, in particular in metabolic disease states, that will allow the development of closedloop approaches to deliver personalized and adjustable treatments with minimal side effects. And finally, we discuss the findings supporting the assessment of CB activity in metabolic disease patients to screen the individuals that will benefit therapeutically from this bioelectronic approach in the future. [ABSTRACT FROM AUTHOR]

Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single‐cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single‐cell RNA sequencing (scRNA‐seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia‐inducible factor‐1 (HIF‐1) and as well as an early EPCs cell‐like population expressing CD14 and vascular endothelial growth factor. In addition to HIF‐1‐related transcriptional protein expression, macrophages1 also display a neovasculogenesis‐promoting phenotype. SMCs included three populations showing platelet‐derived growth factor receptor beta and vimentin expression, indicative of a cancer‐associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA‐seq profiles, providing novel insights into the mechanisms underlying its formation. [ABSTRACT FROM AUTHOR]

This study provides a single-center experience involving intracapsular dissection for Shamblin II carotid body tumors (CBTs) and compares the outcomes with the classic technique of subadventitial resection. Based on the preliminary results, it seems that the enucleation technique facilitates the dissection of carotid body tumors, offering protection to cranial nerves and the internal/external/common carotid artery by utilizing the capsule as a barrier. The classic subadventitial resection approach and the enucleation technique have comparable postoperative complications. However, it is crucial to continue following the patients who underwent these resection techniques to determine the long-term outcomes. Moreover, the enucleation technique significantly reduces surgery duration and intraoperative blood loss. [ABSTRACT FROM AUTHOR]

An adequate supply of O2 is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O2 availability or associated with diseases, or a combination of both. Exposure to hypoxia triggers adjustments in multiple physiological systems in the body to generate appropriate homeostatic responses. However, with significant reductions in the arterial partial pressure of O2, hypoxia can be life‐threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O2 availability on cellular activity, O2 chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O2, triggering orchestrated responses of increased ventilation and cardiac output, blood flow redistribution and metabolic adjustments. In mammals, the peripheral chemoreceptors of the carotid body are considered to be the main hypoxic sensors and the primary source of excitatory feedback driving respiratory, cardiovascular and autonomic responses. However, current evidence indicates that the CNS contains specialized brainstem and spinal cord regions that can also sense hypoxia and stimulate brain networks independently of the carotid body inputs. In this manuscript, we review the discoveries about the functioning of the O2 chemoreceptors and their contribution to the monitoring of O2 levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O2 homeostasis. We also discuss the implications of the chemoreflex‐related mechanisms in paediatric and adult pathologies. What is the topic of this review?Hypoxia is a life‐threatening condition. Specialized sensory mechanisms in the periphery and CNS respond to reduced O2 levels, triggering ventilatory and haemodynamic responses to enhance O2 uptake and delivery to the tissues.What advances does it highlight?Although anatomically distinct, both peripheral and central mechanisms should be considered when examining the homeostatic responses to hypoxia. Herein, we review past and current research on O2 monitoring in the periphery and CNS, discussing how their sensing mechanisms, pathways and interactions modify respiratory and sympathetic activities. [ABSTRACT FROM AUTHOR]

The global impact of severe acute respiratory syndrome COVID-19 has extended beyond physical health, significantly affecting mental well-being worldwide. Amid the pandemic's initial wave, COVID-19 patients exhibited symptoms of post-traumatic stress disorder and notably depressive symptoms. Alongside manifestations like delirium, confusion, agitation, and altered consciousness, prevalent mental health issues during the pandemic encompassed depression, anxiety, and insomnia. Individuals recovering from COVID-19 may face enduring psychiatric challenges post-hospital discharge, potentially linked to dopamine. Dopaminergic receptors might heighten the susceptibility of certain viruses to bind with the central nervous system, instigating viral encephalitis in the virus's early infection stages. Dopamine could also disrupt the human basal carotid body's respiratory response to hypoxia. Additionally, the virus could manipulate the immune system by elevating dopamine levels, facilitating viral entry. These findings emphasize the significance of considering dopamine's role in the diagnosis, treatment, and care of COVID-19 patients and those with diagnosed psychosis. Tailored interventions are crucial for individuals exhibiting distinctive features. Another intriguing aspect worthy of investigation is whether dopamine confers protection against COVID-19. This review article aims to elucidate the intricate relationship between the impactful COVID-19 pandemic and dopamine, shedding light on its potential implications and avenues for further exploration. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea (OSA) and components of metabolic syndrome (MetS) are inextricably connected. Considering the increasing burden of MetS and OSA, in the present review, we aimed to collate and summarise the potential pathophysiological mechanisms linking these pathologies. In short, obesity appears to promote OSA development via multiple pathways, some of which are not directly related to mass but rather to metabolic complications of obesity. Simultaneously, OSA promotes weight gain through central mechanisms. On the other hand, diabetes mellitus contributes to OSA pathophysiology mainly through effects on peripheral nerves and carotid body desensitization, while intermittent hypoxia and sleep fragmentation are the principal culprits in OSA-mediated diabetes. Apart from a bidirectional pathophysiological relationship, obesity and diabetes mellitus together additively increase cardiovascular risk in OSA patients. Additionally, the emergence of new drugs targeting obesity and unequivocal results of the available studies underscore the need for further exploration of the mechanisms linking MetS and OSA, all with the aim of improving outcomes in these patients. [ABSTRACT FROM AUTHOR]

This article examines the use of computed tomography (CT) imaging in diagnosing and characterizing neck paragangliomas. The study analyzed CT scans of 87 patients with confirmed neck paragangliomas and found consistent features such as well-defined hyper-vascular masses with strong contrast enhancement, typically located at the carotid bifurcation or along the carotid sheath. The study also identified calcifications and encasement of nearby structures as common in advanced stage paragangliomas. The findings demonstrate the importance of CT imaging in accurately diagnosing and planning treatment for neck paragangliomas. The study suggests that CT imaging can replace other imaging methods like MRI and provides valuable insights into the characteristics of these tumors, potentially guiding personalized treatment approaches. [Extracted from the article]

The carotid body (CB), located bilaterally at the carotid artery bifurcations, is the primary sensory organ for monitoring arterial blood O2 levels. Carotid bodies are immature at birth, exhibiting low sensitivity to hypoxia, and become more sensitive with maturation during the first few weeks of neonatal life. To understand the molecular basis for the postnatal developmental hypoxic responses of CB, we isolated CBs from 5-day and 21-day-old Sprague–Dawley rats and performed RNA sequencing, which allows comprehensive analysis of gene expression. Differentially expressed genes (DEGs) were generated using Edge R, while functional enrichment analysis was performed using gene-set enrichment analysis (GSEA). Analysis of RNA-Seq data showed 2604 DEGs of the total 12,696 genes shared between neonates and adults. Of the 2604 DEGs, 924 genes were upregulated, and 1680 genes were downregulated. Further analysis showed that genes related to oxidative phosphorylation (Ox/phos) and hypoxia-signaling pathways were significantly upregulated in neonatal CBs compared to adult CBs, suggesting a possible link to differential developmental hypoxic responses seen in CB. Genes related to cytokine signaling (INFγ and TNFα) and transcription factors (CREB and NFΚB) mediated pathways were enriched in adult CBs, suggesting that expression of these pathways may be linked to developmental regulation. The RNA-Seq results were verified by analyzing mRNA changes in selected genes by qRT-PCR. Our results of enrichment analysis of biological pathways offer valuable insight into CB hypoxic sensing responses related to the development process. [ABSTRACT FROM AUTHOR]

Introduction. Carotid body paragangliomas are rare, representing 0.6% of head and neck tumors, with average age of presentation in the fifth decade of life. The objective of this article is to describe a clinical case of carotid body paraganglioma in an adolescent. Clinical case. Review and analysis of the clinical case, reviewing its clinical history, study tests, surgical technique used and its corresponding evolution. Information obtained from the clinical record prior authorization by consent of the patient's parents. Results. Adolescent patient with paraganglioma of the right carotid body, 5x3x3 cm, Shamblin III. With complete surgical resection and inverted saphenous vein graft, favorable evolution, with complete permeability of the vascular bridge, without sequelae. Conclusion. This case could correspond to a tumor of familiar etiology, given its early age of presentation. It is necessary to complement the study with images and to objectively determine the associated vascular involvement for surgical planning. In these patients, the complexity of their location and vascular involvement of the tumor requires a multidisciplinary team with head and neck and vascular surgeons for a successful outcome. [ABSTRACT FROM AUTHOR]

Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta‐Analysis (MA) guided the articles search from 2000 to 2023 on PubMed, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II–III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case‐by‐case basis. [ABSTRACT FROM AUTHOR]

Dopamine and histamine receptors D2R and H3R are G protein-coupled receptors (GPCRs) which can establish physical receptor–receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D2R and H3R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D2R and H3R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D2R–H3R antagonistic functional implications. The CBs of both Sprague–Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D2R and H3R was performed; thereafter, in situ proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D2R/H3R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D2R–H3R RRIs. Additionally, D2R–H3R heterodimers were mainly detected in type I cells (βIII-tubulin-positive cells), but type II cells’ involvement cannot be excluded. RRIs may play a role in functional modulation of CB cells; investigating RRIs in the CB may guide toward the comprehension of its plastic changes and fine regulatory role while also unveiling their possible clinical implications.

The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.

Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors.

On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels, but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review, we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.

ABSTRACTPrion diseases are fatal neurologic disorders that can be transmitted by blood transfusion. The route for neuroinvasion following exposure to infected blood is not known. Carotid bodies (CBs) are specialized chemosensitive structures that detect the concentration of blood gasses and provide feedback for the neural control of respiration. Sensory cells of the CB are highly perfused and densely innervated by nerves that are synaptically connected to the brainstem and thoracic spinal cord, known to be areas of early prion deposition following oral infection. Given their direct exposure to blood and neural connections to central nervous system (CNS) areas involved in prion neuroinvasion, we sought to determine if there were cells in the human CB that express the cellular prion protein (PrPC), a characteristic that would support CBs serving as a route for prion neuroinvasion. We collected CBs from cadaver donor bodies and determined that mast cells located in the carotid bodies express PrPC and that these cells are in close proximity to blood vessels, nerves, and nerve terminals that are synaptically connected to the brainstem and spinal cord.