Joker Sign After Drooling Radioactive Saliva.

ABSTRACT: A 28-year-old man underwent high-dose radioactive iodine therapy after total thyroidectomy due to papillary thyroid carcinomas. After 2 weeks, a linear reddish line was observed extending from the right corner of the mouth to the cheek, resembling the appearance of the Joker. Through a detailed interview, it was determined that the patient had developed radiation dermatitis because of radioactive saliva drooling while sleeping on one side. Although this is expected to be infrequent, educating patients on avoiding saliva contact with the skin during and after radioactive iodine therapy is crucial due to the potential skin damage and cancer risk.

Isolated recurrent metastatic pulmonary nodule from the kidney: An extraordinarily long interval.

Our case highlights the importance of follow-up. Previous meta-analysis has shown that patients with sub-centimetre nodules may have extended follow-up intervals before requiring intervention, unlike those with larger nodules exceeding 1 cm. However, referring to our case, we can see the importance of regular and dense follow-up.

Calcifying fibrous tumour of the pleura without gross calcification.

Calcifying fibrous tumours of the pleura (CFTP) typically appear as calcified, non-enhancing lesions on chest CT scans. However, enhancing pleural lesions can mimic malignancy like mesothelioma. We report a rare case that enhancing pleural thickening, confirmed as CFTP through pathological examination, despite the absence of visible calcification on radiological imaging.

Deep-learning-based gas identification by time-variant illumination of a single micro-LED-embedded gas sensor.

Electronic nose (e-nose) technology for selectively identifying a target gas through chemoresistive sensors has gained much attention for various applications, such as smart factory and personal health monitoring. To overcome the cross-reactivity problem of chemoresistive sensors to various gas species, herein, we propose a novel sensing strategy based on a single micro-LED (µLED)-embedded photoactivated (µLP) gas sensor, utilizing the time-variant illumination for identifying the species and concentrations of various target gases. A fast-changing pseudorandom voltage input is applied to the µLED to generate forced transient sensor responses. A deep neural network is employed to analyze the obtained complex transient signals for gas detection and concentration estimation. The proposed sensor system achieves high classification (~96.99%) and quantification (mean absolute percentage error ~ 31.99%) accuracies for various toxic gases (methanol, ethanol, acetone, and nitrogen dioxide) with a single gas sensor consuming 0.53 mW. The proposed method may significantly improve the efficiency of e-nose technology in terms of cost, space, and power consumption.

NecroX Improves Polyhexamethylene Guanidine-induced Lung Injury by Regulating Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress.

Various environmental compounds are inducers of lung injury. Mitochondria are crucial organelles that can be affected by many lung diseases. NecroX is an indole-derived antioxidant that specifically targets mitochondria. We aimed to evaluate the therapeutic potential and related molecular mechanisms of NecroX in preclinical models of fatal lung injury. We investigated the therapeutic effects of NecroX on two different experimental models of lung injury induced by polyhexamethylene guanidine (PHMG) and bleomycin, respectively. We also performed transcriptome analysis of lung tissues from PHMG-exposed mice and compared the expression profiles with those from dozens of bleomycin-induced fibrosis public data sets. Respiratory exposure to PHMG and bleomycin led to fatal lung injury manifesting extensive inflammation followed by fibrosis. These specifically affected mitochondria regarding biogenesis, mitochondrial DNA integrity, and the generation of mitochondrial reactive oxygen species in various cell types. NecroX significantly improved the pathobiologic features of the PHMG- and bleomycin-induced lung injuries through regulation of mitochondrial oxidative stress. Endoplasmic reticulum stress was also implicated in PHMG-associated lung injuries of mice and humans, and NecroX alleviated PHMG-induced lung injury and the subsequent fibrosis, in part, via regulation of endoplasmic reticulum stress in mice. Gene expression profiles of PHMG-exposed mice were highly consistent with public data sets of bleomycin-induced lung injury models. Pathways related to mitochondrial activities, including oxidative stress, oxidative phosphorylation, and mitochondrial translation, were upregulated, and these patterns were significantly reversed by NecroX. These findings demonstrate that NecroX possesses therapeutic potential for fatal lung injury in humans.

A Rare Case of Familial Schwannomatosis Showing Intrafamilial Variability with Identification of a Shared Novel Germline SMARCB1 Mutation.

Schwannomatosis is characterized by the presence of multiple schwannomas without landmarks of NF2. It is considered the rarest form of neurofibromatosis (NF). Here, we report the first case of familial schwannomatosis with regard to the segmental/generalized phenotype, in which the proband and the daughter present a distinct phenotype in this classification. The proband presents a generalized, painless, extradural type of schwannomatosis, while the daughter shows a segmental, painful, intradural type of schwannomatosis. Whole-exome sequencing of the affected individuals revealed a shared novel SMARCB1 gene mutation (c.92A > G, p.Glu31Gly) despite the clinical variability. We thus suggest two points in the diagnosis of familial schwannomatosis: The identified novel germline SMARCB1 variant can be reflective of a phenotypical progression from a segmental to a generalized type of schwannomatosis, or an intrafamilial variability in inherited schwannomatosis, which was not reported in previous literature. The specific combination of somatic NF2 mutations may be a major factor in regulating the severity and scope of the resulting phenotype in schwannomatosis.

Prevalence and comorbidities of bronchiolitis in adults: A population-based study in South Korea.

ABSTRACT: Bronchiolitis generally refers to inflammation and/or fibrosis of the non-cartilaginous small airways located approximately from the 8th airway generation down to the terminal and respiratory bronchioles. In contrast to young children, the frequency of small airway infection in adult bronchiolitis appears less frequent and a number of other pathophysiological conditions have been implicated in adult bronchiolitis. However, little information is available on the exact medical burden of bronchiolitis such as its prevalence and comorbidities in the adult population. The aim of this study is to elucidate the prevalence and comorbidities of bronchiolitis. We used the Korea National Health Insurance Service-National Sample Cohort, which provides data for 1,000,000 individuals out of the entire population by 2% stratified random sampling according to age, sex, residential area, and level of household income. We defined the cause of bronchiolitis other than acute infection as a patient with diagnostic code J448 or J684 and over 20 years of age who visited a clinic or hospital in South Korea. Then, 1:1 propensity score matching was performed to define a non-bronchiolitis (control) group to compare the comorbidities and mortality in the 2 groups. The overall prevalence of bronchiolitis was 688 cases/1,000,000 population during the study period (95% confidence interval, 625-751). The most common comorbid clinical condition in adults with bronchiolitis was rhinitis (52.3%), followed by bronchial asthma (52.23%), hypertension (43.69%), gastroesophageal reflux disease (30.56%), sinusitis (28.72%), diabetes (22.77%), and osteoporosis (17.85%). Other common bronchiolitis-associated comorbidities were cerebrovascular disease (16.86%), angina (14.37%), peripheral vascular disease (13.42%), congestive heart failure (11.9%), and malignancy in any organ (10.6%). Healthcare costs for bronchiolitis increased steeply during the same period. Malignancy in any organ was the leading cause of mortality in the patient group, followed by bronchiolitis itself. Further larger prospective multiethnic cohort studies should be carried out in the near future.

COPD is a risk factor for COVID-19, but does not confer increased severity of the disease.

Epidemiologic studies suggest that COPD is associated with an increased risk of poor outcome in patients with COVID-19, although they failed to demonstrate COPD as a risk factor for acquiring COVID-19. However, most data have come from a limited global population. In this nationwide cohort study based on the Korean national health insurance claims-based database, COPD is associated with increased risk for COVID-19 and having COPD does not seem to confer substantial risk for severe COVID-19 and mortality. These findings indicate that heterogeneity in the populations across many countries may complicate the net effects of COPD on the COVID-19-related outcomes.

Phosphoinositide 3-kinase-delta could be a biomarker for eosinophilic nasal polyps.

Nasal polyps (NP) cause diverse clinical symptoms of chronic rhinosinusitis (CRS). Chronic inflammation of sinonasal mucosa is known to be crucial in NP formation. We aimed to define the implications of phosphoinositide 3-kinase (PI3K)-δ in nasal inflammation associated with NP by analyzing NP tissue obtained from CRS patients. Results showed that expression of p110δ, a regulatory subunit of PI3K-δ, in NP tissue was increased compared to control tissue. Increased p110δ expression was closely correlated with more severe CRS features. Interestingly, p110δ expression was increased in eosinophilic NP, which are closely related to more complicated clinical courses of the disease. Furthermore, CRS patients possessing NP with higher p110δ expression displayed more eosinophils in NP tissue and blood, higher levels of IL-5 in NP tissue, and more severe features of the disease. Therefore, PI3K-δ may contribute to the formation of NP, especially eosinophilic NP associated with more severe clinical presentations and radiological features.

Airway epithelial phosphoinositide 3-kinase-δ contributes to the modulation of fungi-induced innate immune response.

BACKGROUND: Respiratory fungal exposure is known to be associated with severe allergic lung inflammation. Airway epithelium is an essential controller of allergic inflammation. An innate immune recognition receptor, nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome, and phosphoinositide 3 kinase (PI3K)-δ in airway epithelium are involved in various inflammatory processes. OBJECTIVES: We investigated the role of NLRP3 inflammasome in fungi-induced allergic lung inflammation and examined the regulatory mechanism of NLRP3 inflammasome, focusing on PI3K-δ in airway epithelium. METHODS: We used two in vivo models induced by exposure to Aspergillus fumigatus (Af) and Alternaria alternata (Aa), as well as an Af-exposed in vitro system. We also checked NLRP3 expression in lung tissues from patients with allergic bronchopulmonary aspergillosis (ABPA). RESULTS: Assembly/activation of NLRP3 inflammasome was increased in the lung of Af-exposed mice. Elevation of NLRP3 inflammasome assembly/activation was observed in Af-stimulated murine and human epithelial cells. Similarly, pulmonary expression of NLRP3 in patients with ABPA was increased. Importantly, neutralisation of NLRP3 inflammasome derived IL-1ß alleviated pathophysiological features of Af-induced allergic inflammation. Furthermore, PI3K-δ blockade improved Af-induced allergic inflammation through modulation of NLRP3 inflammasome, especially in epithelial cells. This modulatory role of PI3K-δ was mediated through the regulation of mitochondrial reactive oxygen species (mtROS) generation. NLRP3 inflammasome was also implicated in Aa-induced eosinophilic allergic inflammation, which was improved by PI3K-δ blockade. CONCLUSION: These findings demonstrate that fungi-induced assembly/activation of NLRP3 inflammasome in airway epithelium may be modulated by PI3K-δ, which is mediated partly through the regulation of mtROS generation. Inhibition of PI3K-δ may have potential for treating fungi-induced severe allergic lung inflammation.

Small cell carcinoma of the pyriform sinus successfully treated with concurrent chemo-radiotherapy: A case report.

BACKGROUND: Primary small cell carcinomas (SCCs) are uncommon in extrapulmonary sites and account for only 2.5% to 5.0% of all SCCs. SCCs in the pyriform sinus are rare and there is little information regarding this disease, especially on therapeutics. Herein, we present a case of successfully treated SCC in the right pyriform sinus that occurred in a patient with small cell lung carcinoma (SCLC) that completely resolved 4 years prior. METHODS: A 1.5 × 1.5-cm mass in the right pyriform sinus was detected on imaging studies in a 71-year-old male at a regular check-up visit after being in remission from SCLC. RESULTS: Based on histologic examination and immunohistochemistry, the tumor in the right pyriform sinus was diagnosed as an extrapulmonary SCC. Chemo-radiotherapy was applied to the SCC of the pyriform sinus with a regimen of etoposide and cisplatin. The patient exhibited complete response to treatment and has been disease free for 11 months. CONCLUSION: This interesting case shows that chemotherapy with concurrent radiation may be an effective therapeutic modality for localized extrapulmonary SCC similar to localized SCLC, which is treated with concurrent chemo-radiotherapy as the standard therapeutic option.

Phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress.

BACKGROUND: Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-δ and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-δ and its relationship with ER stress in fungus-induced allergic lung inflammation. METHODS: Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-δ regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis. RESULTS: Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose-regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K-δ inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-δ inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K-δ. CONCLUSIONS: These findings suggest that PI3K-δ regulates Af-induced steroid-resistant eosinophilic allergic lung inflammation through ER stress.

Mediastinal Desmoid Tumor With Remarkably Rapid Growth: A Case Report.

Desmoid tumors (DTs) are a group of rare and benign soft tissue tumors that result from monoclonal proliferation of well-differentiated fibroblasts. Since DTs tend to infiltrate and compress adjacent structures, the location of DTs is one of the most crucial factors for determining the severity of the disease. Furthermore, DTs can further complicate the clinical course of patients when the growth is remarkably rapid, especially for DTs occurring in anatomically critical compartments, including the thoracic cavity.The authors report a case of a 71-year-old man with a known mediastinal mass incidentally detected 4 months ago, presenting dyspnea with right-sided atelectasis and massive pleural effusion. Imaging studies revealed a 16.4 × 9.4-cm fibrous mass with high glucose metabolism in the anterior mediastinum. The mass infiltrated into the chest wall and also displaced the mediastinum contralaterally. Interestingly, the tumor had an extremely rapid doubling time of 31.3 days.En bloc resection of the tumor was performed as a curative as well as a diagnostic measure. Histopathologic examination showed spindle cells with low cellularity and high collagen deposition in the stroma. Immunohistochemical staining was positive for nuclear ß-catenin. Based on these pathologic findings, the mass was diagnosed as DT. After surgery, there has been no evidence of recurrence of disease in the patient.This patient presents a mediastinal DT with extremely rapid growth. Notably, the doubling time of DT in our case was the shortest among reported cases of DT. Our experience also highlights the benefits of early interventional strategy, especially for rapidly growing DTs in the thoracic cavity.

Blockade of Interplay between IL-17A and Endoplasmic Reticulum Stress Attenuates LPS-Induced Lung Injury.

IL-17 is a cytokine mainly from IL-17-producing T cells, which are one of subsets of CD4+ T cells and play a role in adaptive immune system. Recent studies have demonstrated that IL-17A can act rapidly as an innate immune responder during infection before the onset of its classic adaptive immune response. This role of IL-17A in innate immune response is implicated in lipopolysaccharide (LPS)-induced lung inflammation. Very recently, we have reported that endoplasmic reticulum (ER) stress is involved in LPS-induced lung inflammation in vivo and in vitro. This study aimed to elucidate the role of IL-17A in LPS-induced lung injury, focusing on the link with ER stress. We treated a murine model of LPS-induced lung injury with IL-17A neutralizing antibody and 4-phenylbutyrate (4-PBA), a representative ER stress inhibitor. In addition, we evaluated the effects of IL-17A on ER stress in LPS-stimulated bronchial epithelial cells. Our results showed that inhibition of IL-17A decreased LPS-induced pulmonary neutrophilia, vascular leakage, nuclear translocation of nuclear factor-κB (NF-κB), infiltration of dendritic cells, increased expression of Toll-like receptor 4 (TLR4), activation of NLRP3 inflammasome, and increased ER stress in the lung. 4-PBA or TAK-242, a TLR4 inhibitor attenuated expression of IL-17A thereby improving LPS-induced lung inflammation. Intriguingly, we observed that stimulation with LPS increased expression of IL-17A in airway epithelial cells and co-stimulation with IL-17A further increased ER stress and NF-κB activation. This study indicates that the interrelationship between IL-17A and ER stress plays an important role in LPS-induced injury showing a positive feedback in airway epithelial cells and suggests that targeting their interaction can be a potential therapeutic approach to overcome one of severe refractory pulmonary disorders.

A Case of Primary Pulmonary Lymphoepithelioma-like Carcinoma Misdiagnosed as Adenocarcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with a more favorable prognosis compared with that of other types of non-small cell lung cancers. Herein, we describe an interesting case of primary pulmonary LELC confirmed postoperatively, which had been initially diagnosed as poorly differentiated adenocarcinoma. We suggest that despite the rarity of pulmonary LELC, it should be included as one of the differential diagnoses for lung malignancies. Physicians should consider taking a larger biopsy, especially when histologic examination shows undifferentiated nature.