Comprehensive linear and nonlinear heart rate variability normative data in children.

BACKGROUND: The autonomic nervous system (ANS) is critical in regulating involuntary bodily functions, including heart rate. Heart rate variability (HRV) reflects the complex interplay between the ANS and humoral factors, making it a valuable noninvasive tool for assessing autonomic function. While HRV has been extensively studied in adults, normative data for HRV in children, primarily based on long-term rhythm recordings, are limited. OBJECTIVE: This study aimed to establish comprehensive normative data for HRV in children. METHODS: In this retrospective study, we examined 24-h Holter monitors of children aged 1 day to 18 years, divided into six age groups, at Nemours Children's Health in Orlando, Florida, spanning the years 2013-2023. HRV analysis encompassed time-domain, frequency-domain, and nonlinear indices. RESULTS: Holter data for a total of 247 patients in six age groups were included. An age-related uptrend was observed in all time- and frequency-domain variables except the normalized unit of low-frequency power. Entropy analysis revealed contradictory results among different entropy techniques. Sample and approximate entropy analyses were consistent and showed less complexity and more predictability of HRV with decreasing heart rate, while Shannon entropy analysis showed the opposite. Fractal detrended fluctuation analysis exhibited significant decreases across the age groups, suggestive of diminishing self-similarity of HRV patterns. CONCLUSION: Control of heart rate and HRV is a highly complex process and requires further study for a better understanding. It seems that no single parameter can fully elucidate the entire process. A combination of time-domain, frequency-domain, and nonlinear indices may be necessary to explain HRV behavior in the growing body.

Sex Differences in Predicting Difficult Laryngeal Exposure: Validation and Modification of Predictive Models.

OBJECTIVES/HYPOTHESIS: To determine the presence of sex differences in difficult laryngeal exposure and the Laryngoscore, validate the Laryngoscore, mini-Laryngoscore, and Clarysse's model for predicting difficult laryngeal exposure, and modify the Laryngoscore for improved prediction accuracy. STUDY DESIGN: Retrospective study. METHODS: This study included 153 patients who underwent laryngeal microsurgery at a tertiary laryngology center and university hospital. Patients were evaluated using the 11 items of the Laryngoscore, mini-Laryngoscore, and Clarysse's model to predict difficult laryngeal exposure. Difficult laryngeal exposure was defined as the inability to view the anterior commissure through a rigid laryngoscope under counterpressure to the anterior neck. Descriptive statistics and receiver-operating characteristic curve analysis were used to assess the diagnostic performance of the predictive models and variables, including sex. RESULTS: The prevalence of difficult laryngeal exposure was significantly higher in men than in women, despite higher Laryngoscore values in females. The Laryngoscore, mini-Laryngoscore, and Clarysse's model demonstrated good diagnostic performance with C-indexes of 0.751, 0.727, and 0.783, respectively. Based on these findings, we proposed a modified Laryngoscore, including treatment history, interincisors gap, upper jaw dental status, thyro-mental distance, degree of neck flexion-extension, and sex, achieving a C-index of 0.835. CONCLUSIONS: Inclusion of sex in the Laryngoscore and related predictive models enhances the accuracy of predicting difficult laryngeal exposure. These findings support the inclusion of sex as a factor in future modifications of these models to improve their predictive performance.

A Rare Case of Fungal Granuloma Confined to the Nasal Septum.

Granulomatous lesions in the nasal sinuses are associated with a variety of diseases, including immune disorders such as sarcoidosis, vasculitis, immunoglobulin G4 (IgG4)-related diseases, malignant lymphomas, and microbial infections. Here, we report a rare case of fungal granuloma that occurred exclusively within the nasal septum. The patient presented to the Department of Surgery with the chief complaint of nasal obstruction associated with nasal septal deviation. A bulge was found below the right nasal septum. Initially, it was diagnosed as mucosal swelling associated with rhinitis, and surgery was performed. A granulomatous lesion with bone destruction was found under the mucosa of the nasal septum, which led to the diagnosis of fungal granulation based on postoperative pathology. Though bacterial and fungal infections of the nasal septum are occasionally observed, this is the first reported instance of a fungal granuloma confined to the nasal septum. Infection within the nasal septum, although rare, should also be considered as a differential diagnosis for morphological abnormalities of the nasal septum.

An observational study on the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma.

BACKGROUND: Pulmonary sarcomatoid carcinoma is a rare tumor that is resistant to cytotoxic agents. This observational study aimed to evaluate the detection rate of driver gene alteration and the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma. METHODS: We established a database of patients with pulmonary sarcomatoid carcinoma and their clinical information, including EGFR mutation, ALK fusion gene, ROS1 fusion gene, BRAF mutation, and MET exon 14 skipping mutation. The present study retrieved and analyzed the data of patients with pulmonary sarcomatoid carcinoma in whom driver gene alterations were evaluated, and the survival duration after the initiation of treatment with targeted therapy was examined. RESULTS: A total of 44 patients were included in the present study. The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in 2/43 patients (4.7%), 2/34 patients (5.9%), and 2/16 patients (12.5%), respectively. The ROS1 fusion gene (0/18 patients) and BRAF mutation (0/15 patients) were not detected. Female patients (P = 0.063, Fisher's exact test) and patients without smoking history (P = 0.025, Fisher's exact test) were the dominant groups in which any driver mutation was detected. Five patients with driver gene alterations were treated with targeted therapy. Progression-free survival (PFS) was 1.3 months and 1.6 months in 2 of the patients treated with gefitinib. Two patients with the ALK fusion gene showed 2.1 and 14.0 months of PFS from the initiation of treatment with crizotinib, and a patient with the MET exon 14 skipping mutation showed 9.7 months of PFS from the initiation of treatment with tepotinib. CONCLUSION: The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in patients with pulmonary sarcomatoid carcinoma in clinical practice, and some patients achieved long survival times after receiving targeted therapy. Further investigation is necessary to evaluate the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma.

Beneficial Effects of Exercise on Hypertension-Induced Cardiac Hypertrophy in Adolescents and Young Adults.

PURPOSE OF REVIEW: Hypertension-induced cardiac hypertrophy is widely known as a major risk factor for increased cardiovascular morbidity and mortality. Although exercise is proven to exert overall beneficial effects on hypertension and hypertension-induced cardiac hypertrophy, there are some concerns among providers about potential adverse effects induced by intense exercise, especially in hypertensive athletes. We will overview the underlying mechanisms of physiological and pathological hypertrophy and delineate the beneficial effects of exercise in young people with hypertension and consequent hypertrophy. RECENT FINDINGS: Multiple studies have demonstrated that exercise training, both endurance and resistance types, reduces blood pressure and ameliorates hypertrophy in hypertensives, but certain precautions are required for hypertensive athletes when allowing competitive sports: Elevated blood pressure should be controlled before allowing them to participate in high-intensity exercise. Non-vigorous and recreational exercise are always recommended to promote cardiovascular health. Exercise-induced cardiac adaptation is a benign and favorable response that reverses or attenuates pathological cardiovascular remodeling induced by persistent hypertension. Exercise is the most effective nonpharmacological treatment for hypertensive individuals. Distinction between recreational-level exercise and competitive sports should be recognized by medical providers when allowing sports participation for adolescents and young adults.

A Case of Pott's Puffy Tumor in a Patient With Eosinophilic Chronic Rhinosinusitis.

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory type 2 inflammation-based airway allergic disease that is prone to complications such as bronchial asthma. Pott's puffy tumor (PPT) is a rare clinical entity characterized by osteomyelitis of the frontal bone accompanied by a subperiosteal abscess. A 56-year-old female with a history of cranial surgery and bronchial asthma presented to an otolaryngology clinic with nasal obstruction and loss of smell, later developing swelling and redness on her forehead. She was diagnosed and treated for ECRS and was thought to have developed PPT during her course. Nasal endoscopy reveals bilateral polyp formation originating from the middle meatus. Paranasal computed tomography (CT) indicates substantial swelling extending from the opening of the frontal sinus to the adjacent subcutaneous tissue, accompanied by a defect in the frontal bone and osteolysis at the base of the frontal skull. Her management included conservative antibiotic therapy adjusted due to a drug eruption and, subsequently, endoscopic sinus surgery (ESS). The case was complicated by the patient's medical history and the absence of detailed surgical records, which limited the use of enhanced imaging techniques. This underscores the complexity of diagnosing and managing PPT in adults, particularly those with prior surgeries, emphasizing the need for a tailored diagnostic and therapeutic approach that integrates detailed patient history with current clinical indicators to effectively guide treatment. This case contributes to the limited literature on adult PPT and underscores the critical need for careful patient monitoring and detailed surgical history.

Efficacy and Safety of First-line Pembrolizumab Plus Platinum and Pemetrexed in Elderly Patients with Non-squamous Non-small-cell Lung Cancer.

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

Aberrant Subclavian Artery in Interrupted Aortic Arch with Severe Aortic Outlet Obstruction: Cerebral Blood Flow as a Possible Determinant of Embryonic Cardiovascular Development?

Aberrant subclavian artery (ASCA) is frequently observed in interrupted aortic arch (IAA) with aortic/subaortic obstruction. Developmental significance of ASCA in IAA in utero remains elusive. Newborns with prenatally diagnosed isolated IAA under continuous prostaglandin E1 infusion were studied. Cross-sectional areas of aortic valve opening (AVOCSA) and patent ductus arteriosus (PDACSA) were represented by echocardiographic measurement of (diameter)2 indexed by body surface area (m2). Types of IAA and presence of ASCA were examined in relation to sizes of AVOCSA and PDACSA. Twenty-four newborns with IAA (six type A and 18 type B) were reviewed. Male dominance was seen in type B (male 72%). Twenty-three patients had left aortic arch. No type A patients had ASCA, but 50% of type B had ASCA; AVOCSA was significantly smaller in type B than in type A (p = 0.003). In type B, PDACSA was significantly larger in those with ASCA than without (p = 0.003), but AVOCSA exhibited no significant size difference between these two subgroups. Chromosome 22q11 deletion was only seen in type B (56%) and showed no significant correlation with the presence of ASCA. In type B IAA, the presence of ASCA was associated with larger PDACSA, suggesting an adaptive enlargement of the ductus arteriosus and ASCA in response to reduced antegrade flow across small AVOCSA, which may be augmenting cerebral blood flow. Preservation of cerebral blood flow may be another important determinant affecting embryonic cardiovascular development.

Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

Combination of T cell-redirecting strategies with a bispecific antibody blocking TGF-ß and PD-L1 enhances antitumor responses.

T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-ß play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-ß inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-ß, termed AxF (scFv)2, under the premise that combination with T cell redirecting strategies would improve clinical benefit. The AxF (scFv)2 antibody was well expressed in mammalian and yeast cells, bound both targets and inhibited dose-dependently the corresponding signaling pathways in luminescence-based cellular reporter systems. Moreover, combined treatment with trispecific T-cell engagers (TriTE) or CAR-T cells significantly boosted T cell activation status and cytotoxic response in breast, lung and colorectal (CRC) cancer models. Importantly, the combination of an EpCAMxCD3×EGFR TriTE with the AxF (scFv)2 delayed CRC tumor growth in vivo and significantly enhanced survival compared to monotherapy with the trispecific antibody. In summary, we demonstrated the feasibility of concomitant blockade of PD-L1 and TGF-ß by a single molecule, as well as its therapeutic potential in combination with different T cell redirecting agents to overcome tumor microenvironment-mediated immunosuppression.

Coronary microvascular dysfunction in childhood: An emerging pathological entity and its clinical implications.

Coronary microvascular dysfunction (CMD) encompasses a spectrum of structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without obstruction in epicardial coronary artery. The pathogenesis of CMD is complex involving both functional and structural alteration in the coronary microcirculation. In adults, CMD is predominantly discussed in context with anginal chest pain or existing ischemic heart disease and its risk factors. The presence of CMD suggests increased risk of adverse cardiovascular events independent of coronary atherosclerosis. Coronary microvascular dysfunction is also known in children but is rarely recognized due to paucity of concommitent coronary artery disease. Thus, its clinical presentation, underlying mechanism of impaired microcirculation, and prognostic significance are poorly understood. In this review article, we will overview variable CMD reported in children and delineate its emerging clinical significance.

Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer.

Immune checkpoint inhibitors (ICIs) are indicated for a diverse range of cancer types, and characterizing the tumor immune microenvironment is critical for optimizing therapeutic strategies, including ICIs. T cell infiltration and activation status in the tumor microenvironment greatly affects the efficacy of ICIs. Here, we show that semaphorin 6D (Sema6D) forward signaling, which is reportedly involved in coordinating the orientation of cell development and migration as a guidance factor, impaired the infiltration and activation of tumor-specific CD8+ T cells in murine oral tumors. Sema6D expressed by nonhematopoietic cells was responsible for this phenotype. Plexin-A4, a receptor for Sema6D, inhibited T cell infiltration and partially suppressed CD8+ T cell activation and proliferation induced by Sema6D stimulation. Moreover, mouse oral tumors, which are resistant to PD-1-blocking treatment in wild-type mice, showed a response to the treatment in Sema6d-KO mice. Finally, analyses of public data sets of human head and neck squamous cell carcinoma, pan-cancer cohorts, and a retrospective cohort study showed that SEMA6D was mainly expressed by nonhematopoietic cells such as cancer cells, and SEMA6D expression was significantly negatively correlated with CD8A, PDCD1, IFNG, and GZMB expression. Thus, targeting Sema6D forward signaling is a promising option for increasing ICI efficacy.

Diverse Cardiac Phenotype of Becker Muscular Dystrophy: Under-Recognized Subclinical Cardiomyopathy Due to Partial Dystrophin Deficiency in a Contemporary Era.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder responsible for mild skeletal muscle involvement and variable degree of cardiomyopathy. The characteristics of cardiac phenotype of BMD in childhood remain elusive. Clinical manifestations, genotype, serum biomarkers, and echocardiogram were retrospectively reviewed in BMD patients. Cardiac phenotype was classified into acute progressive (AP), chronic persistent (CP), and latent (L) groups based upon symptoms and echocardiographic findings. Twenty-five BMD patients were studied over 9.5 ± 2.5 years. Sixteen patients presented initially with variable degree of muscle weakness whereas 9 were asymptomatic. Three patients developed medically refractory heart failure by age 18 with progressive dilated cardiomyopathy (DCM) (AP). Six patients developed mild to moderate left ventricular (LV) systolic dysfunction with LV dilatation but remained asymptomatic (CP). Although 16 patients continued to show normal LV function (L), they demonstrated variable degrees of skeletal muscle involvement. The AP groups presented with significantly larger LV size and LV mass index (LVMI) at the initial encounter than groups CP or L, suggesting early myocardial remodeling predicts rapid disease progression. None presented with atrophic myocardial phenotype commonly observed in Duchenne muscular dystrophy (DMD). Wide availability of genetic testing has changed the scope of clinical presentation of BMD. Cardiomyopathy in BMD presents with a diverse clinical spectrum with variable progression of DCM where larger LV dimension and mass at the time of diagnosis may predict the progressiveness of cardiomyopathy.

The current findings in eosinophilic chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a persistent inflammatory disease of the nasal cavity and paranasal sinuses. Traditional classification is denoted by the presence (CRSwNP) or absence of nasal polyps (CRSsNP). Particularly, CRSwNP is distinguished by the presence of infiltrating cells and inflammatory markers in the nasal mucosa. Patients with CRSwNP in Western countries predominantly display a type 2 endotype, whereas those in Asian regions display a mixed type 2 endotype. Nevertheless, recent transcriptome analyses have revealed two types of nasal polyps - type 2 and non-type 2 polyps, suggesting that geographical differences in endotypes likely resulted from the different proportions of each endotype. Moreover, various endotypes of CRSsNP have been identified, making phenotype a crucial factor for predicting treatment efficacy. Type 2 endotypes, designated as eosinophilic CRS (ECRS) in Japan, are characterized by severe eosinophilic infiltration into the paranasal sinus tissue and are particularly refractory. In this review, we discuss the latest developments in ECRS. We also provide recent findings on the involvement of nasal epithelial cells in pathogenesis.

Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel.

INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.

Efficacy and safety of coronary computed tomography angiography in diagnosing coronary lesions in children.

INTRODUCTION: Identification of paediatric coronary artery abnormalities is challenging. We studied whether coronary artery CT angiography can be performed safely and reliably in children. MATERIALS: Retrospective analysis of consecutive coronary CT angiography scans was performed for image quality and estimated radiation dose. Both factors were assessed for correlation with electrocardiographic-gating technique that was protocoled on a case-by-case basis, radiation exposure parameters, image noise artefact parameters, heart rate, and heart rate variability. RESULTS: Sixty scans were evaluated, of which 96.5% were diagnostic for main left and right coronaries and 91.3% were considered diagnostic for complete coronary arteries. Subjective image quality correlated significantly with lower heart rate, increasing patient age, and higher signal-to-noise ratio. Estimated radiation dose only correlated significantly with choice of electrocardiographic-gating technique with median doses as follows: 2.42 mSv for electrocardiographic-gating triggered high-pitch spiral technique, 5.37 mSv for prospectively triggered axial sequential technique, 3.92 mSv for retrospectively gated technique, and 5.64 mSv for studies which required multiple runs. Two scans were excluded for injection failure and one for protocol outside the study scope. Five non-diagnostic cases were attributed to breathing motion, scanning prior to peak contrast enhancement, or scan acquisition during the incorrect portion of the R-R interval. CONCLUSIONS: Diagnostic-quality coronary CT angiography can be performed reliably with a low estimated radiation exposure by tailoring each scan protocol to the patient's body habitus and heart rate. We propose coronary CT angiography is a safe and effective diagnostic modality for coronary artery abnormalities in children.

Understanding hereditary hemorrhagic telangiectasia: From genetic anomalies to systemic manifestations, quality of life, and epistaxis management-Exploring the otolaryngologist's integral role.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a rare autosomal dominant disorder characterized by vascular malformations. This comprehensive review aimed to provide an overview and summarize various aspects of HHT, including the genetic abnormalities, complications associated with visceral arteriovenous malformations (AVMs), prognosis of HHT, quality of life (QOL), and treatment of epistaxis. In addition, this review highlights the challenges in diagnosing HHT and emphasizes the critical role of otolaryngologists in the early detection of HHT. Otolaryngologists can refer patients with refractory epistaxis for AVM screening to expedite intervention. Mutation of the genes involved in the transforming growth factor-ß signaling pathway leads to the incidence of HHT, resulting in the formation of abnormal blood vessel formation. These vascular malformations commonly manifest as telangiectasia on the skin and mucous membranes; however, epistaxis remains the hallmark symptom of HHT. The impact of HHT goes beyond the visible symptoms and often includes the formation of life-threatening visceral AVMs in the lungs, liver, and brain. The prognosis of patients with HHT is closely related to the development of these complications, necessitating timely diagnosis and intervention. Refractory epistaxis diminishes the QOL of patients with HHT. The management of epistaxis ranges from conservative measures to advanced interventions such as prevention, conservative treatments, ablation, surgical procedures, and the administration of anti-angiogenic agents. However, effective management requires a multidisciplinary approach. The diagnosis of HHT remains challenging due to its variable presentation and lack of awareness among physicians. This review highlights the importance of reducing the duration between symptom onset and diagnosis. Otolaryngologists who are experienced in the management of refractory epistaxis can aid in identifying potential cases of HHT. They can facilitate the initiation of screening for visceral AVMs via prompt recognition of the signs and symptoms of HHT, contributing to improved patient outcomes. Early detection and intervention through screening can extend the life expectancy of patients with HHT to levels comparable with that of the general population. In conclusion, this review provides insight into various aspects of HHT and emphasizes the importance of timely diagnosis and intervention in the mitigation of the potentially life-threatening complications associated with this disorder. Otolaryngologists play a critical role in this process, serving as gatekeepers to the identification of cases of HHT and implementation of appropriate screening and management pathways, thereby improving the life expectancy and QOL of patients.

An Unusual Case of Eosinophilic Chronic Rhinosinusitis With Concurrent Eosinophilic Otitis Media: Limited Responsiveness to Multiple Antibody Therapies and Subsequent Cochlear Implantation.

Eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) are debilitating inflammatory conditions that affect the paranasal sinuses and middle ear, respectively, and are characterized by eosinophilic infiltration. This study describes a rare and intricate case of a 65-year-old male patient concurrently afflicted with ECRS, EOM, and bronchial asthma. Despite the systematic administration of corticosteroids and various antibody drugs, the patient's condition remained unimproved, necessitating a cochlear implant for EOM, which is seldom an aggressive intervention. The patient had a history of symptoms dating back to 2005, with notable exacerbations and treatment resistance over the years. Multiple antibody drugs, including anti-IgE, anti-IL-5, and anti-IL-4α antibodies, failed to ameliorate the patient's condition, presenting a significant clinical challenge. Pathological examination revealed marked eosinophilic infiltration and severe fibrosis, suggesting a possible mechanism underlying the poor response to antibody therapy. Cochlear implantation significantly enhanced the patient's communicative abilities. This case highlights the limitations of the current antibody drugs in managing severely intertwined cases of ECRS, EOM, and bronchial asthma, highlighting the need for novel therapeutic strategies. This case also propounds cochlear implantation as an efficacious intervention for refractory EOM with severe sensorineural hearing impairment, extending the spectrum of treatment modalities for such challenging scenarios. This singular case contributes to the growing body of evidence regarding the management of ECRS and EOM, especially against the backdrop of treatment resistance, and can aid clinicians in identifying and navigating similar complex cases in clinical practice.