Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse.This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0–60) days and 21 (15, 29.5; range: 2–63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0–42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001].Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

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Analysis of the SARS-CoV-2 sequence revealed a multibasic furin cleavage site at the S1/S2 boundary of the spike protein distinguishing this virus from SARS-CoV. Furin, the best-characterized member of the mammalian proprotein convertases, is an ubiquitously expressed single pass type 1 transmembrane protein. Cleavage of SARS-CoV-2 spike protein by furin promotes viral entry into lung cells. While furin knockout is embryonically lethal, its knockout in differentiated somatic cells is not, thus furin provides an exciting therapeutic target for viral pathogens including SARS-CoV-2 and bacterial infections. Several peptide-based and small-molecule inhibitors of furin have been recently reported, and select cocrystal structures have been solved, paving the way for further optimization and selection of clinical candidates. This perspective highlights furin structure, substrates, recent inhibitors, and crystal structures with emphasis on furin's role in SARS-CoV-2 infection, where the current data strongly suggest its inhibition as a promising therapeutic intervention for SARS-CoV-2.

BACKGROUND: Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV.

CASE PRESENTATION: The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient's plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5' untranslated region. The patient was then subjected to direct-acting-antiviral treatment (DAA). At the end of the treatment, the patient showed a good response to the HCV treatment (i.e., no HCV-RNA was detected in the plasma), while the HPgV-RNA was still detected. Sequence alignment and phylogenetic analyses demonstrated that the detected HPgV was a novel isolate and was not previously published.

CONCLUSION: We report a new variant of HPgV in a patient suffering from hepatitis C viral infection.

BACKGROUND: Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV.

CASE PRESENTATION: The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient's plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5' untranslated region. The patient was then subjected to direct-acting-antiviral treatment (DAA). At the end of the treatment, the patient showed a good response to the HCV treatment (i.e., no HCV-RNA was detected in the plasma), while the HPgV-RNA was still detected. Sequence alignment and phylogenetic analyses demonstrated that the detected HPgV was a novel isolate and was not previously published.

CONCLUSION: We report a new variant of HPgV in a patient suffering from hepatitis C viral infection.