Potentiating Lung Mucosal Immunity Through Intranasal Vaccination

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches. Here, we consider the route of immunization as a critical factor in eliciting tissue resident memory (Trm) populations that are not a target of current licensed intramuscular vaccines. Intranasal vaccination has the potential to boost tissue resident B and T cell populations that reside within specific niches of the upper and lower respiratory tract. Within these niches, Trm cells are poised to respond rapidly to pathogen re-encounter by nature of their anatomic localization and their ability to rapidly deliver anti-pathogen effector functions. Unique features of mucosal immunity in the upper and lower respiratory tracts suggest that antigen localized to these regions is required for the elicitation of protective B and T cell immunity at these sites and will need to be considered as an important attribute of a rationally designed intranasal vaccine. Finally, we discuss outstanding questions and areas of future inquiry in the field of lung mucosal immunity.

Inpatient Diagnosis and Management of Neuromuscular Disorders

Although many neuromuscular conditions are evaluated on an outpatient basis owing to their chronic or progressive nature, more urgent evaluation and management is often required for the inpatient presenting with acute to subacute focal or generalized numbness or weakness. This review focuses on clinical pattern recognition and basic anatomic localization principles to aid in the identification of common, as well as some less frequently encountered, neuromuscular disorders in hospitalized patients. The characteristic clinical and diagnostic features, associated complications, and recommended treatments of key neuromuscular conditions with acute and subacute manifestations are discussed. These conditions can be life-threatening in some cases, such as in Guillain–Barré syndrome, owing to associated oropharyngeal weakness, respiratory failure, or marked dysautonomia. Prompt recognition of the clinical and pathologic features is therefore necessary to reduce associated morbidity and mortality.

Identifying the Location of an Accessory Pathway in Pre-Excitation Syndromes Using an Artificial Intelligence-Based Algorithm

(1) Background: The exact anatomic localization of the accessory pathway (AP) in patients with Wolff–Parkinson–White (WPW) syndrome still relies on an invasive electrophysiologic study, which has its own inherent risks. Determining the AP localization using a 12-lead ECG circumvents this risk but is of limited diagnostic accuracy. We developed and validated an artificial intelligence-based algorithm (location of accessory pathway artificial intelligence (locAP AI)) using a neural network to identify the AP location in WPW syndrome patients based on the delta-wave polarity in the 12-lead ECG. (2) Methods: The study included 357 consecutive WPW syndrome patients who underwent successful catheter ablation at our institution. Delta-wave polarity was assessed by four independent electrophysiologists, unaware of the site of successful catheter ablation. LocAP AI was trained and internally validated in 357 patients to identify the correct AP location among 14 possible locations. The AP location was also determined using three established tree-based, ECG-based algorithms (Arruda, Milstein, and Fitzpatrick), which provide limited resolutions of 10, 5, and 8 AP locations, respectively. (3) Results: LocAP AI identified the correct AP location with an accuracy of 85.7% (95% CI 79.6–90.5, p < 0.0001). The algorithms by Arruda, Milstein, and Fitzpatrick yielded a predictive accuracy of 53.2%, 65.6%, and 44.7%, respectively. At comparable resolutions, the locAP AI achieved a predictive accuracy of 95.0%, 94.9%, and 95.6%, respectively (p < 0.001 for differences). (4) Conclusions: Our AI-based algorithm provided excellent accuracy in predicting the correct AP location. Remarkably, this accuracy is achieved at an even higher resolution of possible anatomical locations compared to established tree-based algorithms.

Endoscopic Endonasal Odontoidectomy with Nasopharyngeal Flap Reconstruction

Objective This study aimed to demonstrate the nuances in preoperative management, surgical technique, and reconstruction for an endoscopic endonasal odontoidectomy. Design Assembly of an operative video demonstrating technique for endoscopic endonasal odontoidectomy. Setting this study is a comprehensive skull base team at a tertiary care center. Participant The patient is a 53-year-old male, with basilar invagination and myelopathy, who underwent cervical fusion, 6 years back, without ventral decompression at an outside hospital. He presented to our clinic with persistent myelopathy and generalized weakness, thus an endoscopic endonasal odontoidectomy for brainstem decompression was recommended. Main Outcome Measures Preoperative computed tomography (CT) angiography and intraoperative CT navigation demonstrated normal carotid artery anatomic localization. An inverted U-shaped mucosal flap was reflected inferiorly and preserved. The C1 arch was identified and resected with a high speed drill. The resultant diseased soft tissue arising from retropulsion of the odontoid process was then removed and the odontoid process identified. This bone was removed centrally until a thin cap remained. After removal of the cap, the underlying ligamentous tissue was removed until dural pulsations were appreciated and brainstem decompression achieved. Hemostasis was attained and the mucosal flap mobilized into position. Results Postoperative CT imaging demonstrated resolution of basilar invagination and brainstem decompression (Fig. 1). The patient improved both in arm dexterity and ambulation after surgery and the reconstruction demonstrated appropriate healing on nasal endoscopy 2 months postoperatively. Conclusions This operative video demonstrates nuances in endoscopic endonasal odontoidectomy. This case also demonstrates that ventral decompression after long-term cervical fusion can improve myelopathy and that fusion in the setting of bony ventral compression, rather than rheumatoid panus, may not reduce over time with fusion only.The link to the video can be found at: https://youtu.be/370FFuBA89Y.

Radiographic Reference Points Do Not Ensure Anatomic Femoral Fixation Sites in Medial Patellofemoral Ligament Reconstruction: A Quantified Anatomic Localization Method Based on the Saddle Sulcus

Background: Medial patellofemoral ligament (MPFL) reconstruction is one of the main treatments for lateral patellar translation. Based on intraoperative true lateral radiographs, the accepted methods for femoral MPFL tunnel location are potentially inaccurate. Direct assessment of anatomic characteristics during surgery through palpation of the anatomic landmarks involving the saddle sulcus might help eliminate tunnel malposition. Hypothesis: The saddle sulcus is a reliable osseous landmark where the MPFL attaches for tunnel placement. Study Design: Descriptive laboratory study. Methods: A total of 9 fresh-frozen unpaired human cadaveric knees were dissected; MPFL insertion point and relative osseous structures were marked. Three-dimensional images and transformed true lateral radiographs were obtained for analysis; 3 previously reported radiographic reference points for MPFL femoral tunnel placement were determined on all images and compared with the anatomic insertion. Results: A saddle sulcus consistently existed where the MPFL was attached, located at 11.7 ± 5.9 mm from the apex of the adductor tubercle (AT) to the medial epicondyle (ME), 62.8% of the average distance between the apexes of the AT and ME, and 5.6 ± 2.8 mm perpendicular-posterior to the border connecting the AT and ME. The reported radiographic reference points were located at average distances of 6.2 ± 3.2 mm (Schöttle method), 5.9 ± 2.3 mm (Redfern method), and 7.3 ± 6.6 mm (Fujino method) from the saddle sulcus center on the true lateral radiographs. Conclusion: The saddle sulcus was a reliable landmark where the MPFL was anatomically attached, located approximately 12 mm from the AT to the ME (approximately 60% along a line from the AT to the ME) and 6 mm perpendicular-posterior to the border connecting the apexes of the AT and ME. Additionally, the saddle sulcus position presented variability on the femoral aspect of different knees. All of the average direct distances from the sulcus to the reference radiographic points exceeded 5 mm, and tunnel localizations on a true lateral radiograph were inaccurate. Clinical Relevance: This study demonstrates the potential precise position of the saddle sulcus, according to the ME and AT, as a reliable anatomic landmark for MPFL femoral tunnel location. Radiographic reference points were not accurate during MPFL reconstruction. Direct palpation of the landmarks might be effective for femoral MPFL tunnel placement.

hMAGEA2 Promotes Cell Growth and Tumorigenicity in Melanoma

Background: Melanoma is one of the most malignant skin cancers, and its incidence continues to rise worldwide, especially in fair-skinned populations. A clinical challenge with melanoma is that it has no unique or specific clinical presentation. The clinical presentation of melanoma varies with the anatomic localization, type of growth, and histopathology. Proteins belonging to the melanoma-associated antigen (MAGEA) gene family are typically expressed in germline cells but differentially expressed in a variety of human cancers, particularly melanoma. Melanoma-associated antigen 2 (MAGEA2) is such a protein. In this study, we investigated whether the expression of human MAGEA2 (hMAGEA2) is associated with melanoma. Methods: SK-MEL-5 and SK-MEL-28 cell lines were used to explore the cellular and molecular mechanisms underlying the progression and invasiveness of melanoma. A melanoma human tissue array was used to examine the correlation between the progression of melanoma and expression of hMAGEA2Results: hMAGEA2 is overexpressed in human melanoma tissues, including metastatic tissues. In SK-MEL-5 and SK-MEL-28 cells, overexpression of hMAGEA2 increased cellular proliferation and colony formation, whereas hMAEGA2 knockdown suppressed cellular proliferation, colony formation, and migration. Conclusion: These results show that the hMAGEA2 protein plays a role in the growth and invasiveness of melanoma cells, and it is correlated with melanoma metastasis. Therefore, hMAGEA2 contributes to the progression of melanoma and may be a diagnostic and novel therapeutic target for the treatment of melanoma metastasis patients.

Trastorno psiquiátrico asociado a una conducta reiterada de ingesta de cuerpos extraños. Pautas de manejo

Introduction. Foreign body ingestion (FBI) usually occurs accidentally. The 70-80% of the cases occur in children with ages between 6 months and 3 years. Cases. The aim of this original article is present a case series of 4 patients with history of psychiatric disorders, all of whom are residents of the same institution, and who repeatedly perform FBI with self-injurious purposes. The treatment was different according to the episodes, from expectant management with radiological control in most of the cases, and upper digestive endoscopy until the finally surgical treatment. Discussion. Most of the objects use to be small inorganic objects such as piles, buttons, coins and pieces of toys. In adult patients, the objects are usually organics like bones, fish bones or food bowls. The most fragile are usually the elderly with dental prostheses ingestion. There is a special group, those patients who ingest voluntarily for different purposes. In one hand patients who have an intellectual disability, mental illness and / or substance abuse disorder, on the other hand, those who do it with economic purposes, also so-called «mules». The symptoms, complications and management depend on the object itself, evolution and anatomic localization. Conclusion. The clinical performance is difficult because there is no protocoled management established currently to prevent, treat and most important, avoiding new episodes.

The comparison of wall thickness of esophagus and gastroesophageal junction using computed tomography with endoscopy and biopsy results

Background: This study aims to establish a cut-off value for increases in the esophageal wall thickness measured using computed tomography to differentiate between benign and malignant pathologies. Methods: A total of 144 patients (61 males, 83 females; mean age 57.2±12.4 years; range, 24 to 86 years) who underwent thoracic and/or abdominal computed tomography in the radiology clinic between January 2015 and June 2018 for any reason and who were found to have a thickening of the esophageal wall or gastroesophageal junction were retrospectively analyzed. Tomography images were examined by two radiologists who reached consensus on the wall morphology and thickness, anatomic localization, and any accompanying findings regardless of the endoscopy results. Benign and malignant patients were identified from the endoscopy and/or biopsy results. The receiver operating characteristic analysis was carried out to establish a cut-off value for the lesion wall thickness to differentiate between benign and malignant pathologies and to determine a cut-off value for the lesion-level thickness-normal segment thickness ratio. Results: A statistically significant difference was found in the wall thicknesses of patients with esophageal cancer and those with benign lesions. According to a cut-off value for wall thickness of 13.5 mm, sensitivity and specificity were found to be 94.3% and 100%, respectively. The lesion-level thickness-normal segment thickness ratio was found to be statistically significant in malignant-benign differentiation, and a significant correlation was found between the asymmetric thickening and malignancy. Conclusion: Increases in the esophageal wall thickness and asymmetry detected on computed tomography can contribute to the early diagnosis of esophageal cancers, particularly in regions endemic to esophageal cancer as in Van province in eastern anatolia region of Turkey. Asymmetric wall thicknesses over 13.5 mm would be highly significant in terms of malignancy in tomographic examinations.