Paraneoplastic pemphigus associated with nonhuman papillomavirus-related tonsillar squamous cell carcinoma: A case report.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare, life-threatening autoimmune bullous disease. Among the ≈500 reported cases of PNP, only 1 case has been associated with tonsillar cancer, specifically, human papillomavirus (HPV)-positive squamous carcinoma. However, the occurrence of PNP in non-HPV-related tonsillar cancer is exceptionally rare and has not been reported to date. METHODS: We present a 58-year-old male with a history of smoking, who experienced recurrent oral ulcers, right neck swelling, and hoarseness for 5 months. Diagnosis of right tonsillar squamous cell carcinoma (cT1N3bM0) was confirmed through computed tomography/magnetic resonance imaging and pathology, not associated with HPV. Histological and immunohistochemical findings indicated PNP. RESULTS: The patient underwent primary tumor resection and ipsilateral neck dissection. Topical steroids and antifungal agents were administered to manage oral lesions and prevent secondary infections. Adjuvant concurrent chemoradiotherapy with cisplatin proceeded smoothly. Postconcurrent chemoradiotherapy follow-up at 3, 6, and 9 months, utilizing computed tomography/magnetic resonance imaging and nasopharyngoscopy, revealed no signs of recurrent cancer or PNP. CONCLUSION: Early indicators, such as oral mucosal ulcers and skin blisters, prompt consideration of underlying oral cancer in PNP. Comprehensive examination is crucial for diagnosing PNP and identifying concurrent internal neoplasms. Effective management includes occult malignancy treatment, postoperative steroid therapy, and infection prevention.

The role of vestibular function tests in nontuberculous mycobacterial otomastoiditis: A case report.

BACKGROUND: Nontuberculous mycobacteria (NTM), an extremely rare pathogen causing cervicofacial infections, may result in permanent hearing impairment or intracranial complications. Due to the lack of specific manifestations during the initial onset of NTM otomastoiditis, physicians may misdiagnose it as cholesteatoma or other common bacterial infections. PATIENT CONCERNS: A 44-year-old male who complained of left-sided aural fullness, otalgia, and dizziness for 2 months. DIAGNOSIS: The initial diagnosis was hypothesized to be cholesteatoma based on a whitish mass with mucoid discharge filling the entire outer ear canal on otoscopy and left-sided mixed hearing loss. However, NTM was identified by microbial culture at the 2-month follow-up after surgery. INTERVENTIONS: The patient underwent a left-sided exploratory tympanotomy. Because NTM otomastoiditis was diagnosed, 3 weeks of starting therapies were administered with azithromycin (500 mg/day, oral administration), cefoxitin (3 g/day, intravenous drip), and amikacin (750 mg/day, intravenous drip). The maintenance therapies were azithromycin (500 mg/day, oral administration) and doxycycline (200 mg/day, oral administration) for 7 months. OUTCOMES: The patient's clinical condition improved initially after surgery, but the otomastoiditis gradually worsened, combined with subtle meningitis, 2 months after surgery. The external auditory canal became swollen and obstructed, making it difficult to monitor the treatment efficacy through otoscopy. Thus, we used regular vestibular function tests, including static posturography, cervical vestibular evoked myogenic potentials, and video Head Impulse Test, to assess recovery outcomes. After antibiotic treatment, the infectious symptoms subsided significantly, and there was no evidence of infection recurrence 7 months after treatment. Improvements in static posturography and cervical vestibular evoked myogenic potentials were compatible with the clinical manifestations, but video Head Impulse Test showed an unremarkable correlation. LESSONS: The clinical condition of NTM otomastoiditis may be evaluated using vestibular tests if patients have symptoms of dizziness.

Antimicrobial Peptides with Enhanced Salt Resistance and Antiendotoxin Properties.

A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.

Ultrashort Antimicrobial Peptides with Antiendotoxin Properties.

Release of lipopolysaccharide (LPS) (endotoxin) from bacteria into the bloodstream may cause serious unwanted stimulation of the host immune system. Some but not all antimicrobial peptides can neutralize LPS-stimulated proinflammatory responses. Salt resistance and serum stability of short antimicrobial peptides can be boosted by adding ß-naphthylalanine to their termini. Herein, significant antiendotoxin effects were observed in vitro and in vivo with the ß-naphthylalanine end-tagged variants of the short antimicrobial peptides S1 and KWWK.

Novel antimicrobial peptides with high anticancer activity and selectivity.

We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid ß-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

Correlations between membrane immersion depth, orientation, and salt-resistance of tryptophan-rich antimicrobial peptides.

The efficacies of many antimicrobial peptides are greatly reduced in the presence of high salt concentrations therefore limiting their development as pharmaceutical compounds. PEM-2-W5K/A9W, a short Trp-rich antimicrobial peptide developed based on the structural studies of PEM-2, has been shown to be highly active against various bacterial strains with less hemolytic activity. Here, correlations between membrane immersion depth, orientation, and salt-resistance of PEM-2 and PEM-2-W5K/A9W have been investigated via solution structure and paramagnetic resonance enhancement studies. The antimicrobial activities of PEM-2-W5K/A9W and PEM-2 against various bacterial and fungal strains including multidrug-resistant and clinical isolates under high salt conditions were tested. The activities of the salt-sensitive peptide PEM-2 were reduced and diminished at high salt concentrations, whereas the activities of PEM-2-W5K/A9W were less affected. The results indicated that the strong salt-resistance of PEM-2-W5K/A9W may arise from the peptide positioning itself deeply into microbial cell membranes and thus able to disrupt the membranes more efficiently.

Boosting salt resistance of short antimicrobial peptides.

The efficacies of many antimicrobial peptides are greatly reduced under high salt concentrations, therefore limiting their use as pharmaceutical agents. Here, we describe a strategy to boost salt resistance and serum stability of short antimicrobial peptides by adding the nonnatural bulky amino acid ß-naphthylalanine to their termini. The activities of the short salt-sensitive tryptophan-rich peptide S1 were diminished at high salt concentrations, whereas the activities of its ß-naphthylalanine end-tagged variants were less affected.