Association between specific human leukocyte antigen alleles and development of thyroid immune-related adverse event.

Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE. Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared. Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively). Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.

Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.

Flowchart for selecting an appropriate surgical airway in neurologically impaired pediatric intubated patients: a case series

Abstract Objective: Medical advances have resulted in increased survival rates of neurologically impaired children who may require mechanical ventilation and subsequent tracheostomy as a surgical airway. However, at present, there is no definite consensus regarding the timing and methods for placement of a surgical airway in a neurologically impaired intubated child who needs to be cared for over a long-term period. We therefore created a flowchart for the selection of a surgical airway for Neurologically Impaired Pediatric Patients (NIPPs). Methods: The flowchart includes information on the patients' backgrounds, such as intubation period, prognosis related to reversibility, and history of aspiration pneumonia. To evaluate the importance of the flowchart, first we conducted a survey of pediatricians regarding selection of a surgical airway, and we also evaluated the appropriateness of the flowchart among pediatricians and caregivers through questionnaire surveys which include satisfaction with the decision-making process, and postoperative course after discharge. Results: A total of 21 NIPPs with intubation underwent surgery and a total of 24 participants (14 pediatricians and 10 caregivers) completed the survey. The answers regarding the importance of the flowchart showed that eleven pediatricians had experience selecting of surgical airways, nine of whom had had experiences in which they had to make a difficult decision. The answers regarding the appropriateness of the flowchart revealed that all pediatricians and caregivers were satisfied with the decision-making process and postoperative course after discharge using the flowchart. Conclusions: The present study demonstrated the effectiveness of our flowchart for selecting an appropriate surgical airway in NIPP. By referring to our flowchart, pediatricians and caregivers are likely to be able to select an appropriate surgical airway, leading to increased satisfaction with the decision-making process and postoperative course. Level of Evidence: 4.

Approach for Elucidating the Molecular Mechanism of Epithelial to Mesenchymal Transition in Fibrosis of Asthmatic Airway Remodeling Focusing on Cl- Channels.

Airway remodeling caused by asthma is characterized by structural changes of subepithelial fibrosis, goblet cell metaplasia, submucosal gland hyperplasia, smooth muscle cell hyperplasia, and angiogenesis, leading to symptoms such as dyspnea, which cause marked quality of life deterioration. In particular, fibrosis exacerbated by asthma progression is reportedly mediated by epithelial-mesenchymal transition (EMT). It is well known that the molecular mechanism of EMT in fibrosis of asthmatic airway remodeling is closely associated with several signaling pathways, including the TGF-ß1/Smad, TGF-ß1/non-Smad, and Wnt/ß-catenin signaling pathways. However, the molecular mechanism of EMT in fibrosis of asthmatic airway remodeling has not yet been fully clarified. Given that Cl- transport through Cl- channels causes passive water flow and consequent changes in cell volume, these channels may be considered to play a key role in EMT, which is characterized by significant morphological changes. In the present article, we highlight how EMT, which causes fibrosis and carcinogenesis in various tissues, is strongly associated with activation or inactivation of Cl- channels and discuss whether Cl- channels can lead to elucidation of the molecular mechanism of EMT in fibrosis of asthmatic airway remodeling.

Cone beam computed tomography with oral contrast for accurate diagnosis and surgical planning of pharyngeal leakage and fistula: a case series

Abstract Objective: Pharyngocutaneous fistula is one of the severe complications related to head and neck surgeries. Detecting the accurate three-dimensional location of both the fistula and leakage is essential for surgical treatment. Videofluoroscopy is usually used for locating these; however, its imaging is two-dimensional. We evaluated pharyngeal leakage and fistulae using Cone Beam Computed Tomography (CBCT), known for its three-dimensional high spatial resolution imaging, taken in a sitting position, with oral contrast (contrast CBCT). Methods: Pharyngeal leakage and fistulae were evaluated in a total of 31 subjects by sequentially performing videofluoroscopy and contrast CBCT. The detection accuracy of videofluoroscopy and contrast CBCT for leakage and fistula, as well as the ability to determine the extent and depth for surgical planning, were investigated and compared. Results: Videofluoroscopy and contrast CBCT showed suspicious leakage and/or fistula in six and three of the 31 subjects, respectively. Surgical findings revealed the presence of leakage and/or fistula in three of the 31 subjects. The positive predictive values of videofluoroscopy and contrast CBCT were 50% (3/6) and 100% (3/3), respectively. Contrast CBCT provided more precise images, showing the extent and depth of leakage and fistula in three-dimensions. Conclusion: The present study's results indicate the usefulness of contrast CBCT in terms of accurate diagnosis of leakage and fistula, due to its three-dimensional imaging being performed with the patient in a sitting position. Level of evidence: 4.