Access to Sudden Sensorineural Hearing Loss Care at Private Equity-Owned Otolaryngology Clinics.

OBJECTIVE: Characterizing access to sudden sensorineural hearing loss (SSNHL) care at private practice otolaryngology clinics of varying ownership models. STUDY DESIGN: Cross-sectional prospective review. SETTING: Private practice otolaryngology clinics. METHODS: We employed a Secret Shopper study design with private equity (PE) owned and non-PE-owned clinics within 15 miles of one another. Using a standardized script, researchers randomly called 50% of each clinic type between October 2021 and January 2022 requesting an appointment on behalf of a family member enrolled in either Medicaid or private insurance (PI) experiencing SSNHL. Access to timely care was assessed between clinic ownership and insurance type. RESULTS: Seventy-eight total PE-owned otolaryngology clinics were identified across the United States. Only 40 non-PE clinics could be matched to the PE clinics; 39 PE and 28 non-PE clinics were called as Medicaid patients; 39 PE and 25 non-PE clinics were called as PI patients; 48.7% of PE and 28.6% of non-PE clinics accepted Medicaid. The mean wait time to new appointment ranged between 9.55 and 13.21 days for all insurance and ownership types but did not vary significantly (P > .480). Telehealth was significantly more likely to be offered for new Medicaid patients at non-PE clinics compared to PE clinics (31.8% vs 0.0%, P = .001). The mean cost for an appointment was significantly greater at PE clinics than at non-PE clinics ($291.18 vs $203.75, P = .004). CONCLUSIONS: Patients seeking SSNHL care at PE-owned otolaryngology clinics are likely to face long wait times prior to obtaining an initial appointment and reduced telehealth options.

The multifaceted functions of ß-arrestins and their therapeutic potential in neurodegenerative diseases.

Arrestins are multifunctional proteins that regulate G-protein-coupled receptor (GPCR) desensitization, signaling, and internalization. The arrestin family consists of four subtypes: visual arrestin1, ß-arrestin1, ß-arrestin2, and visual arrestin-4. Recent studies have revealed the multifunctional roles of ß-arrestins beyond GPCR signaling, including scaffolding and adapter functions, and physically interacting with non-GPCR receptors. Increasing evidence suggests that ß-arrestins are involved in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). ß-arrestins physically interact with γ-secretase, leading to increased production and accumulation of amyloid-beta in AD. Furthermore, ß-arrestin oligomers inhibit the autophagy cargo receptor p62/SQSTM1, resulting in tau accumulation and aggregation in FTD. In PD, ß-arrestins are upregulated in postmortem brain tissue and an MPTP model, and the ß2AR regulates SNCA gene expression. In this review, we aim to provide an overview of ß-arrestin1 and ß-arrestin2, and describe their physiological functions and roles in neurodegenerative diseases. The multifaceted roles of ß-arrestins and their involvement in neurodegenerative diseases suggest that they may serve as promising therapeutic targets.

Synthetic peptides of IL-1Ra and HSP70 have anti-inflammatory activity on human primary monocytes and macrophages: Potential treatments for inflammatory diseases.

Chronic inflammatory diseases are increasing in developed societies, thus new anti-inflammatory approaches are needed in the clinic. Synthetic peptides complexes can be designed to mimic the activity of anti-inflammatory mediators, in order to alleviate inflammation. Here, we evaluated the anti-inflammatory efficacy of tethered peptides mimicking the interleukin-1 receptor antagonist (IL-1Ra) and the heat-shock protein 70 (HSP70). We tested their biocompatibility and anti-inflammatory activity in vitro in primary human monocytes and differentiated macrophages activated with two different stimuli: the TLR agonists (LPS + IFN-γ) or Pam3CSK4. Our results demonstrate that IL-1Ra and HSP70 synthetic peptides present a satisfactory biocompatible profile and significantly inhibit the secretion of several pro-inflammatory cytokines (IL-6, IL-8, IL-1ß and TNFα). We further confirmed their anti-inflammatory activity when peptides were coated on a biocompatible material commonly employed in surgical implants. Overall, our findings support the potential use of IL-1Ra and HSP70 synthetic peptides for the treatment of inflammatory conditions.

Carriers of autosomal recessive conditions: are they really 'unaffected?'

Mendel's Law of Dominance suggests that recessive disease expression requires the inheritance of two mutated alleles as the dominant, wildtype allele suppresses disease presentation leading to the expression of physiological normal phenotypes. However, there is existing evidence that challenges this school of thought. Here, we summarise existing literature evaluating metabolic and health impacts among carriers of autosomal recessive conditions, focusing on phenylketonuria (PKU), classical homocystinuria, galactosemia and Usher syndrome as examples. Our findings suggest that carriers, often described as 'unaffected', may actually display attenuated symptoms for the recessive disease they are carrying. For instance, PKU is an inborn error of metabolism characterised by the build-up of plasma phenylalanine attributed to the deficiency of the phenylalanine hydroxylase (PAH) enzyme. While less severe, PKU carriers also exhibit this impaired enzymatic activity, leading to elevated plasma phenylalanine levels, especially after phenylalanine consumption. Related to these metabolic alterations in the PAH pathway, there is early evidence to suggest that PKU carriers may have compromised cognitive and mental health outcomes. Overall, research on the health and metabolic impacts of PKU carriers is sparse, with most studies conducted several decades ago. However, early evidence suggests that intermediate phenotypes among carriers of autosomal recessive conditions are plausible. The illustrated possible intermediate phenotypes observed among carriers necessitates future research to determine possible clinical implications among this population.

Understanding the chronic pain journey and coping strategies that patients use to manage their chronic pain: a qualitative, patient-led, Canadian study.

OBJECTIVE: To gain an insight into coping strategies that people living with chronic pain use to self-manage their pain. DESIGN: This qualitative Patient-oriented Research study used the Patient and Community Engagement Research approach. It was conducted by people with chronic pain lived experience, ensuring that patient perspective and needs were considered and addressed throughout the research cycle. Purposeful sampling was used for recruiting individuals living with chronic pain. A focus group and one-on-one semi-structured interviews were conducted via videoconference. The data were analysed iteratively using inductive thematic analysis and narrative story analysis. SETTING: Calgary, Alberta, Canada. PARTICIPANTS: Eleven adult participants, between the ages of 18 and 65, who self-identified as living with chronic pain for greater than 2 years. RESULTS: Three main themes emerged from the data: (1) the elements of chronic pain, (2) the chronic pain journey to acceptance and (3) daily coping strategies for chronic pain. Participants thought it was important to discuss these three themes because the daily coping strategies that they employed at any given time (theme 3) depended on the factors discussed in themes 1 and 2. Overlaying all of this is also a grieving process that people living with chronic pain may have to go through more than once. Participants also identified recommendations for healthcare professionals to support people living with chronic pain. CONCLUSIONS: Dealing with chronic pain affects all aspects of a person's life and involves a grieving process. When treating patients with chronic pain, it is important for healthcare professionals to understand the journey that people living with chronic pain go through, not just coping strategies. Diagnosis is critical for a patient's acceptance and in helping them find their new normal where they can employ daily coping strategies to manage their pain.

International Multi-Institutional Experience with Presentation and Management of Aortic Arch Laterality in Aberrant Subclavian Artery and Kommerell's Diverticulum.

BACKGROUND: Aberrant subclavian artery (ASA) with or without Kommerell's diverticulum (KD) is a rare anatomic aortic arch anomaly that can cause dysphagia and/or life-threatening rupture. The objective of this study is to compare outcomes of ASA/KD repair in patients with a left versus right aortic arch. METHODS: Using the Vascular Low Frequency Disease Consortium methodology, a retrospective review was performed of patients ≥18 years old with surgical treatment of ASA/KD from 2000 to 2020 at 20 institutions. RESULTS: 288 patients with ASA with or without KD were identified; 222 left-sided aortic arch (LAA), and 66 right-sided aortic arch (RAA). Mean age at repair was younger in LAA 54 vs. 58 years (P = 0.06). Patients in RAA were more likely to undergo repair due to symptoms (72.7% vs. 55.9%, P = 0.01), and more likely to present with dysphagia (57.6% vs. 39.1%, P < 0.01). The hybrid open/endovascular approach was the most common repair type in both groups. Rates of intraoperative complications, death within 30 days, return to the operating room, symptom relief and endoleaks were not significantly different. For patients with symptom status follow-up data, in LAA, 61.7% had complete relief, 34.0% had partial relief and 4.3% had no change. In RAA, 60.7% had complete relief, 34.4% had partial relief and 4.9% had no change. CONCLUSIONS: In patients with ASA/KD, RAA patients were less common than LAA, presented more frequently with dysphagia, had symptoms as an indication for intervention, and underwent treatment at a younger age. Open, endovascular and hybrid repair approaches appear equally effective, regardless of arch laterality.

Ventricular Septal Defect Exposure by Tricuspid Valve Chordal Detachment-A Retrospective Matched Study.

Background: Transatrial approach is the standard method in repairing ventricular septal defects (VSD) in the pediatric population. However, the tricuspid valve (TV) apparatus might obscure the inferior border of the VSD risking the adequacy of repair by leaving residual VSD or heart block. Detachment of the TV chordae has been described as an alternative technique to TV leaflet detachment. The aim of this study is to investigate the safety of such a technique. Methods: Retrospective review of patients who underwent VSD repair between 2015 and 2018. Group A (n = 25) had VSD repair with TV chordae detachment were matched for age and weight to group B (n = 25) without tricuspid chordal or leaflet detachment. Electrocardiogram (ECG) and echocardiogram at discharge and at 3 years of follow-up were reviewed to identify new ECG changes, residual VSD, and TV regurgitation. Results: Median ages in groups A and B were 6.13 (IQR 4.33-7.91) and 6.33 (4.77-7.2) months. New onset right bundle branch block (RBBB) was diagnosed at discharge in 28% (n = 7) of group A versus 56% (n = 14) in group B (P = .044), while the incidence dropped to 16% (n = 4) in group A versus 40% (n = 10) in group B (P = .059) in the 3 years follow-up ECG. Echocardiogram at discharge showed moderate tricuspid regurgitation in 16% (n = 4) in group A and 12% (n = 3) in group B (P = .867). Three years of follow-up echocardiography revealed no moderate or severe tricuspid regurgitation and no significant residual VSD in either group. Conclusion: No significant difference in operative time was observed between the two techniques. TV chordal detachment technique reduces the incidence of postoperative RBBB without increasing the incidence of TV regurgitation at discharge.

Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum.

OBJECTIVE: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset. METHODS: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak. RESULTS: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms. CONCLUSIONS: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.

Characterization of Secondary Interventions After Fenestrated-branched Endovascular Repair of Complex Aortic Aneurysms and Its Effect on Quality of Life and Patient Survival.

OBJECTIVE: To assess the impact of secondary intervention (SI) on health-related quality of life (HR-QOL) after fenestrated-branched endovascular aortic repair (FB-EVAR) for complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. BACKGROUND: The effect of SI after FB-EVAR on physical and mental HR-QOL has not been described. METHODS: A cohort of 430 consecutive patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR (2013-2020) was assessed with 1325 short-form 36 HR-QOL questionnaires preoperatively and during follow-up visits. SIs were classified as major or minor procedures. Endpoints included patient survival, freedom from aortic-related mortality (ARM), freedom from SIs, and changes in HR-QOL physical component score (PCS) and mental component score. RESULTS: There were 302 male with mean age 74±8 years treated by FB-EVAR for 133 complex abdominal aortic aneurysms and 297 thoracoabdominal aortic aneurysms. After a mean follow up of 26±20 months, 97 patients (23%) required 137 SIs. At 5 years, freedom from any SI was 64%±4%, including freedom from minor SIs of 77%±4% and major SIs of 87%±3%. There was no difference in patient survival and freedom from ARM at same interval. On adjusted analysis, minor SIs correlated with improved survival. SIs had a negative correlation with PCS ( r =-0.8). There were no significant changes in mental component score with SIs. Predictors for SIs were fluoroscopy time, graft design, and aneurysm sac change. CONCLUSION: SIs were needed in nearly 1 out of 4 patients treated by FB-EVAR with no effect on patient survival or ARM. SI resulted in decline in PCS.

Device Occlusion of Native Pulmonary Blood Flow After Cavopulmonary Anastomosis With Persistent Pleural Effusions.

Native pulmonary tract flow after a cavopulmonary anastomosis may promote pulmonary artery growth but can lead to undesirable consequences. We report the case of a 17-month child with prolonged pleural effusions after cavopulmonary anastomosis in whom a ventricular septal defect occluder device was placed in the native right ventricular outflow tract. (Level of Difficulty: Advanced.).

Maternal Factors in Pregnancy and Ethnicity Influence Childhood Adiposity, Cardiac Structure, and Function.

Importance: The links between maternal and offspring adiposity and metabolic status are well established. There is much less evidence for the impact of these relationships combined with ethnic background on cardiac structure and function in childhood. Objective: To test the hypothesis that ethnicity, maternal adiposity and glycemic status, and child adiposity affect cardiac structure and function. Design: A prospective cohort study. Setting: A single-center mother-child cohort study. The cohort is a subset of the international multi-center Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. Participants: This study included 101 healthy pre-pubertal British-born children [56 White Europeans (WEs) and 45 South Asians (SAs)] with a median age of 9.1 years, range 6.0-12.2 years, at the time of the investigation. Main Outcomes and Measures: Anthropometric and echocardiographic measurements were made on the cohort. Maternal pregnancy and birth data were available. Relationships between maternal parameters (BMI and glucose status), child adiposity, and echo measures were assessed. Results: Despite no ethnic difference in BMI SDS at a median age of 9.1 years, SA children exhibited higher levels of body fat than WE children (whole body, right arm, and truncal fat all p < 0.001). SA children also exhibited greater changes in weight and height SDS but not BMI SDS from birth than WE children. As expected, maternal BMI correlated with child BMI (r = 0.28; p = 0.006), and body fat measures (e.g., whole body fat r = 0.25; p = 0.03). Maternal fasting glucose levels were associated with child body fat measures (r = 0.22-0.28; p = 0.02-0.05). Left ventricular (LV) indices were not different between SA and WE children, but E/A and E'/A' (measures of diastolic function) were lower in SA when compared with WE children. LV indices correlated positively to BMI SDS and body fat markers only in SA children. Maternal fasting and 2-h glucose were negatively correlated with E'/A' in SA children (r = -0.53, p = 0.015, and r = -0.49, p = 0.023, respectively) but not in WE children. Conclusion and Relevance: SA and WE children exhibit differences in adiposity and diastolic function at a median age of 9.1 years. Novel relationships between maternal glycemia, child adiposity, and cardiac structure and function, present only in SA children, were identified.

Pathological characterization of a novel mouse model expressing the PD-linked CHCHD2-T61I mutation.

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies, with the CHCHD2-T61I mutation being the most widely studied. However, at present, only CHCHD2 knockout or CHCHD2/CHCHD10 double knockout mouse models have been investigated. They do not recapitulate the pathology seen in patients with CHCHD2 mutations. We generated the first transgenic mouse model expressing the human PD-linked CHCHD2-T61I mutation driven by the mPrP promoter. We show that CHCHD2-T61I Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, is also observed along with α-synuclein pathology. Significant motor dysfunction is seen with no changes in learning and memory at 1 year of age. A minor proportion of the CHCHD2-T61I Tg mice (~10%) show a severe motor phenotype consistent with human Pisa Syndrome, an atypical PD phenotype. Unbiased proteomics analysis reveals surprising increases in many insoluble proteins predominantly originating from mitochondria and perturbing multiple canonical biological pathways as assessed by ingenuity pathway analysis, including neurodegenerative disease-associated proteins such as tau, cofilin, SOD1 and DJ-1. Overall, CHCHD2-T61I Tg mice exhibit pathological and motor changes associated with LBDs, indicating that this model successfully captures phenotypes seen in human LBD patients with CHCHD2 mutations and demonstrates changes in neurodegenerative disease-associated proteins, which delineates relevant pathological pathways for further investigation.

Access to Urological Care for Medicaid-Insured Patients at Urology Practices Acquired by Private Equity Firms.

OBJECTIVE: To characterize appointment access for Medicaid-insured patients seeking care at urology practices affiliated with private equity firms in light of the recent national trends in practice consolidation. METHODS: We identified 214 urology offices affiliated with private equity firms that were geographically matched with 231 non-private equity affiliated urology offices. Using a standardized script, researchers posed as an adult patient with either Medicaid or commercial insurance in the clinical setting of new onset, painless hematuria. The primary outcome was whether the patient's insurance was accepted for an appointment. The secondary outcome was appointment wait time. RESULTS: We conducted 815 appointment inquiry calls to 214 private equity (PE) and 231 non-PE-affiliated urology offices across 12 states. Appointment availability was higher for commercially-insured patients (99.0%; 95% CI: 98.1%-99.9%) vs Medicaid-insured patients (59.8%; 95% confidence interval [CI]: 55.0%-64.6%) (P < .0001). Medicaid acceptance was higher at non-PE affiliated (66.8%; CI 60.4%-73.2%) than PE-affiliated practices (52.1%; 95% CI 45.0%-59.2%) (P = .003). On multivariable logistic regression analysis, state Medicaid expansion status (odds ratio [OR] 2.20; CI 1.14-4.28; P = .020) was independently associated with Medicaid appointment availability, whereas PE-affiliation (OR 0.55; CI 0.37-0.83; P = .004) was independently associated with lower Medicaid access. Appointment wait times did not differ significantly for commercially-insured vs Medicaid patients (19.2 vs 20.1 days; p = .59), but PE-affiliated practices offered shorter mean wait times than non-PE offices (17.5 vs 21.4 days; P = .017). CONCLUSION: Access disparities for urologic evaluation in patients with Medicaid insurance at urology practices and were more pronounced at private equity acquired practices.

Initial experience and early outcomes of the management of acute pulmonary embolism using the FlowTriever mechanical thrombectomy device.

BACKGROUND: Submassive and massive pulmonary embolism is associated with a high risk of complications. We aimed to evaluate our initial experience with a mechanical thrombectomy device in the management of these patients. METHODS: A single-center, retrospective study was performed in patients with acute submassive and massive pulmonary embolism treated with the FlowTriever device (Inari Medical, Irvine, CA, USA) between June 2019 and November 2020. Clinical and technical parameters were analyzed during the hospitalization and at 30- and 180-days after the procedure. RESULTS: Fourteen patients were evaluated with a median (IQR) age of 60 (50-69) years and 64% were male. All had right heart strain as the main indication for thrombectomy. The procedure duration and fluoroscopic time was 52 (37-89) and 13 (9-24) minutes, respectively. There was 100% technical success, and the pulmonary arterial pressure went from 60 (48-65) mmHg to 40 (34-47) mmHg. Thrombolysis was used in two patients and nine patients required intensive care. 100% experienced improvement in symptoms at the time of discharge. There were no device-related complications, major bleeding events, myocardial infarctions, or deaths. Preprocedural hemoglobin was 13 (12-15) g/dL, and predischarge was 12 (10-13) g/dL. Overall postprocedural length of stay was three (2-6) days. All the patients were discharged with oral anticoagulation. There were no device-related complications or recurrence of embolism at 30 and 180 days. CONCLUSIONS: The mechanical thrombectomy device for submassive and massive pulmonary embolism is promising and appears a safe and effective procedure with 100% technical success, no complications, short intensive care requirement/stay, and good early clinical outcomes.

Incorporation of Celiomesenteric Trunk With Double Kissing Directional Branches During Fenestrated-Branched Endovascular Aortic Repair.

PURPOSE: Common celiomesenteric trunk (CMT) is a rare anatomical variation that occurs in 0.5% to 3.4% of the general population. Its presence may complicate planning and implantation of fenestrated and branched stent-grafts because the wide diameter and short length of the CMT to its bifurcation does not allow sufficient sealing for placement of bridging stents. CASE REPORT: We report a patient with thoracoabdominal aortic aneurysm (TAAA) and CMT treated by fenestrated-branched endovascular aortic repair (FB-EVAR) using double kissing directional branches to incorporate the celiac axis and superior mesenteric artery. Pitfalls of stent design and implantation are outlined. CONCLUSION: Double kissing directional branches should be considered as an alternative to incorporate vessels with early bifurcation such as a CMT.

Aneurysmal Fibrous Histiocytoma: A Large Soft Tissue Tumor with Metastases Treated with Palliative Radiation Therapy and Targeted Therapy.

Aneurysmal fibrous histiocytoma (AFH) is a rare variant of cutaneous fibrous histiocytoma, with low malignant potential and infrequent metastatic progression. We present the case of a 19-year-old female with a large AFH of the neck metastatic to soft tissue and treated with radiation therapy and molecularly targeted therapy. To our knowledge, this is the first report describing either radiation therapy and palliation or the use of targeted therapy in this uncommon malignancy and can provide insight into future therapeutic strategies.

Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2.

Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine cancer that accounts for 1-2% of thyroid cancers in the United States (U.S.). While most cases are sporadic, 25% of MTC cases are hereditary. These hereditary cases occur in the setting of Multiple Endocrine Neoplasia Type 2A (MEN2A) or 2B (MEN2B) driven by mutations in the Rearranged during Transfection RET proto-oncogene. This article discusses hereditary MTC in the setting of MEN2 and the treatment options available for it. The first line treatment for this disease is typically a total thyroidectomy and tyrosine kinase inhibitors. Two tyrosine kinase inhibitors, vandetanib and cabozantinib, have been approved for treatment of advanced MTC, but options beyond those are limited. However, several promising treatments are being studied, which are discussed in this review.