METHODS: A 56-year-old female presented with a 3-month history of blood-stained nasal discharge. She had been treated with radiotherapy for nasopharyngeal carcinoma 25 years earlier. Flexible nasal endoscopy demonstrated an exposed bone with an edematous posterior nasopharyngeal mass. Computed tomography showed a pre-vertebral mass with destruction of C1 and C2. She underwent occipito-cervical fusion followed by a combined transnasal and transoral endoscopic debridement of non-viable bone in the same perioperative setting. Healing of the raw mucosa was by secondary intention and reconstruction was not performed.
RESULTS: Histopathological examination reported ulcerated inflamed granulation tissue with no evidence of malignancy. During follow-up, she remained neurologically intact with no recurrence.
CONCLUSION: Using both nasal and oral spaces allows placement of the endoscope in the nasal cavity and surgical instruments in the oral cavity without splitting the palate. Hence, the endoscopic transnasal and transoral approach has vast potential to be effective in carefully selected cases of cervical ORN.
METHOD: The patient was started on a trial of oral cimetidine at a dose of 30 mg/kg and responded well, eventually requiring endoscopic excision only after 2 years. Subsequently, she underwent in vitro fertilisation treatment and stopped taking her cimetidine. After undergoing endoscopic clearance of her papillomata under general anaesthesia, she restarted on cimetidine during her 2nd and 3rd trimester.
RESULTS: Ensuing follow-up demonstrated stable minimal papillomata lesions on her right inferior surface of her vocal cord with no recurrence on her left vocal cord and subglottic area.
CONCLUSION: Cimetidine is generally safe and not known to be associated with any major teratogenic risks during pregnancy. RRP is postulated to worsen in pregnant women due to the increase in oestrogen levels during pregnancy. Hence, adjuvant therapy was imperative for our patient to reduce recurrent papillomata formation during her pregnancy. Larger scale studies are warranted to assess the use of long-term high-dose cimetidine in terms of efficacy and safety in pregnancy.
METHODS: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.
RESULTS: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.
CONCLUSIONS: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.