The NEU1-selective sialidase inhibitor, C9- butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-Nacetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to eukaryotic sialidases, C9-BA-DANA exerted far less inhibitory activity for three selected bacterial neuraminidases (IC50 \u3e 800 µM). Structural modeling of the four human sialidases and three bacterial neuraminidases revealed a loop between the seventh and eighth strands of the β-propeller fold, that in NEU1, was substantially shorter than that seen in the six other enzymes. Predicted steric hindrance between this loop and C9-BA-DANA could explain its selectivity for NEU1. Finally, pretreatment of mice with C9-BA-DANA completely protected against flagellin-induced increases in lung sialidase activity. Our combined data indicate that C9- BA-DANA inhibits endogenous and ectopically expressed sialidase activity and established NEU1-mediated bioactivities in human airway epithelia, lung microvascular endothelia, and fibroblasts in vitro and murine lungs in vivo

Carcinoid tumor causing ileoceccal intussusception in an adult patient

Introduction: Little is known about adult intussusception, but current evidence suggests that malignancy, polyps, and diverticula are usual etiologies. We present a case of adult ileoceccal intussusception secondary to carcinoid tumor. Case Presentation: A 53-year-old African American male presented with hematochezia and non-radiating constant left upper quadrant pain accompanied by nausea and vomiting. CT of the pelvis demonstrated a pathognomic ‘target’ sign, consistent with ileoceccal intussusception and early small bowel obstruction. Two years prior to this current presentation, the patient had experienced an episode of hematochezia for which he underwent colonoscopy and polypectomy, with subsequent pathology results negative for colon cancer. He denies diarrhea, constipation, weight loss, decreased appetite or skin flushing. Due to persistent symptoms of bowel obstruction, he underwent exploratory laparotomy. During the surgery a white-colored, chalky mass indicative of penetrating tumor was noted 13 cm proximal to the ileocecal valve. An extended right hemi-colectomy followed the discovery of the mass. Pathology showed a well-differentiated neuroendocrine tumor consistent with carcinoid tumor. Evaluation for metastatic disease using 5-HIAA and chromogranin A was unremarkable, and the resection of the right colon carcinoid tumor was felt to be curative. Conclusion: It is uncommon for adults to present with intussusception; in such cases, malignancy should be ruled out as an underlying cause. Carcinoid should be listed among the other secondary causes, which include inflammatory bowel disease, diverticulitis, polyps, scar tissue, adhesions, and lipomas. Abbreviation: CT (Computer tomography), 5-HIAA (5-hydroxyindole acetic acid), NCCN (National Comprehensive Cancer Network

Implications of an Incidental Pulmonary Arteriovenous Malformation

Introduction. Pulmonary arteriovenous malformations (PAVMs) have been associated with life-threatening complications, such as stroke and massive hemoptysis, thus posing significant morbidity if left untreated. We report a case of an incidental finding of a PAVM in a trauma patient newly recognized to have suspected hereditary hemorrhagic telangiectasia (HHT). Case Description. A 34-year-old man with a history of recurrent epistaxis presented with a sudden fall associated with seizure-like activity. Trauma imaging showed a large subdural hematoma and, incidentally, a serpiginous focus within the right upper lobe with a prominent feeding artery consistent with a PAVM. The patient was diagnosed with a simple PAVM related to possible or suspected HHT, an autosomal dominant trait with age-related penetrance. He underwent a pulmonary arteriography of the right upper and lower lobe with the use of a microcatheter system; however, the PAVM could not be visualized. Thus, he was managed medically. The patient was educated on the need for prophylactic antibiotics prior to dental procedures and surveillance imaging. Discussion. Our case highlights the importance of obtaining a complete past medical and family history in young patients with a history of recurrent epistaxis to elicit features of HHT. The diagnosis can be made clinically and directly affects family members, who would otherwise not receive appropriate screening

Guillain‐Barre syndrome secondary to COVID‐19 infection: A case report

Abstract Guillain‐Barre syndrome (GBS) is a rare autoimmune disease that often manifests as a post‐viral complication. However, its association with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is unclear. We present a rare case of GBS secondary to COVID‐19 infection complicated by rapidly progressive sensorimotor deterioration resistant to plasma exchange therapy

Hypoxic Respiratory Failure Further Complicated During Airway Exchange Catheter Placement

An airway exchange catheter is a hollow-lumen tube able to deliver oxygen and maintain access to a difficult endotracheal airway. This case report demonstrates an undocumented complication associated with an airway exchange catheter and jet ventilation, particularly in a patient with reduced airway diameter due to thick endotracheal secretions. Due to the frequent use of airway exchange catheters in the intensive care unit, this report highlights an adverse event of bilateral pneumothoraces that can be encountered by clinicians

Assessment of local health worker attitudes toward international medical volunteers in low- And middle-income countries: A global survey

© 2020 The Authors. Background: International Medical Volunteers (IMVs) positively and negatively impact host countries, and the goals of their trips may not always align with the interests of the hosts in Low- and Middle-Income Countries (LMICs). We sought to better understand local physicians’ interest of hosting IMVs and what type of support they desired. Methods: This study was a convenience sample survey-based needs assessment. The surveys were distributed to local physicians by 28 professional society groups in LMICs. Findings: A total of 102 physicians from 51 countries completed the survey. Despite 61.8% participants having no experience with IMVs, 75% were interested in hosting them. Host physicians most desired clinical education (39%), research collaboration (18%), and Systems Development (11%). The most requested specialties were obstetrics and gynecology (25%) and emergency medicine (11%). Respondents considered public hospitals (62%) to be the most helpful clinical setting in which IMVs could work, and 3 months (47%) as the ideal length of stay. Respondents expressed interest in advertising the specific needs of the host country to potential IMVs (80%). Qualitative analyses suggested hosts wanted more training opportunities, inclusion of all stakeholders, culturally competent volunteers, and aid focused on subspecialty education, health policy, public health, and research. Conclusion: Hosts desire more bidirectional clinical education and research capacity building than just direct clinical care. Importantly, cultural competence is key to a successful host partnership, potentially improved through IMV preparation. Finally, respondents want IMVs to ensure that they stay within their scope of practice and training

A case of fatal disseminated adenovirus and drug‐resistant Pneumocystis pneumonia in a patient who received chemotherapy for mantle cell lymphoma

Abstract Adenovirus (ADV) may cause severe complications in hematopoietic stem cell transplant recipients, but disseminated ADV infections in patients who received chemotherapy alone for hematological malignancies are poorly understood due to the rarity of cases. Concomitant infection with Pneumocystis (PCP) is extremely rare. Despite being diagnostically challenging, a more specific workup needs to be initiated with a low threshold in patients who are exposed to agents with the potential to suppress T cells. We report a fatal case of disseminated ADV and drug‐resistant PCP pneumonia in a patient with mantle cell lymphoma who had only received combination chemotherapy. A 75‐year‐old man who was diagnosed with mantle cell lymphoma 10 months prior was admitted for mild hypoxic respiratory failure. Bendamustine, Rituximab, Cytarabine regimen had resulted in complete remission of his lymphoma, with the last cycle of chemotherapy administered 3 months prior to admission. CT of the chest revealed ground‐glass opacities concerning pneumonia. Initial laboratory tests were remarkable for mild leukopenia. The respiratory viral panel was only positive for ADV. He did not respond to empiric antibiotics for community‐acquired pneumonia and Trimethoprim / Sulfamethoxazole given later for positive Beta D Glucan (BDG) suggestive of Pneumocystis pneumonia. Then, he developed hemorrhagic cystitis, followed by liver and renal function derangement that prompted checking serum ADV viral load by polymerase chain reaction (PCR). This test took 1 week to return, with a viral load of 50, 000 copies/mL suggesting disseminated ADV infection. Despite initiation of Cidofovir, multi‐organ failure continued to progress, and the follow‐up viral load had doubled on Day 2. The patient passed away the same day shortly after transition to comfort care. T cell suppression seems to be a risk factor for disseminated ADV disease. Clinicians may need to maintain a low threshold to send serum quantitative ADV PCR when symptoms are not improved by antimicrobial treatment for more conventional infections in patients who received agents that are known to suppress T cells, such as Bendamustine