The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus. The corresponding gene revealed that the activity originates from PF0012, and we named this enzyme Endonuclease MS (EndoMS) as the mismatch-specific Endonuclease. The sequence similarity suggested that EndoMS is the ortholog of NucS isolated from Pyrococcus abyssi, published previously. Biochemical characterizations of the EndoMS homolog from Thermococcus kodakarensis clearly showed that EndoMS specifically cleaves both strands of double-stranded DNA into 5′-protruding forms, with the mismatched base pair in the central position. EndoMS cleaves G/T, G/G, T/T, T/C and A/G mismatches, with a more preference for G/T, G/G and T/T, but has very little or no effect on C/C, A/C and A/A mismatches. The discovery of this endonuclease suggests the existence of a novel mismatch repair process, initiated by the double-strand break generated by the EndoMS endonuclease, in Archaea and some Bacteria.

Several studies have demonstrated increased pericardial effusion during anti-PD-1 immunotherapy, and treatment in patients who have developed pericardial tamponade is controversial. In this study, we describe a 63-year-old woman with stage IVA lung adenocarcinoma given pembrolizumab as a first-line therapy. After four cycles of pembrolizumab treatment, the patient suddenly developed a pericardial tamponade. Although pericardial effusion was increased, her tumor lesions were reduced. After an emergency pericardiocentesis, she continued the pembrolizumab therapy without recurrent pericardial effusions for three months until the primary tumor and lymph node metastasis progressed. Nine months after the pericardiocentesis, the patient died of progressive lung cancer, but pericardial effusion did not recur throughout the treatment course. This case study suggests that pembrolizumab therapy can be continued with a strict follow-up in some patients with pembrolizumab-induced pericardial tamponade. Key points• Significant findings of the study Our patient developed pericardial tamponade during pembrolizumab treatment but continued pembrolizumab treatment after emergency pericardiocentesis without recurrent pericardial effusions.• What this study adds Pembrolizumab treatments may be resumed with a strict follow-up in some patients with treatment-related pericardial tamponade. Figure 1 (a) A computed tomography (CT) scan of the chest showed a mass lesion in the right upper lobe. A right supraclavicular lymph node metastasis infiltrated into the right thyroid lobe before pembrolizumab treatment. Mild pericardial effusion was observed. (b) After three cycles of pembrolizumab therapy, CT scan showed a positive response in the primary lesion and lymph node metastasis. (c) A CT revealed a sudden increase in pericardial effusion and the tumor lesions were reduced after four cycles of pembrolizumab therapy.

Background Methods have been developed for preventing delayed bleeding (DB) after gastric endoscopic submucosal dissection (GESD). However, none of the methods can completely prevent DB. We hypothesized that DB could be prevented by a modified search, coagulation, and clipping (MSCC) method for patients at low risk for DB and by combining the use of polyglycolic acid sheets and fibrin glue with the MSCC method (PMSCC method) for patients at high risk for DB (antibleeding [ABI] strategy). This study assessed the technical feasibility of this novel strategy. Method We investigated 123 lesions in 121 consecutive patients who underwent GESD in Kushiro Rosai Hospital between April 2018 and January 2020. The decision for continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment. Results Oral antithrombotic agents were administered to 28 patients (22.8%). The en bloc R0 resection rate was 98.4%. The MSCC method and the PMSCC method for preventing DB were performed in 114 and 9 lesions, respectively. The median time of the MSCC method was 16 min, and the median speed (the resection area divided by the time of method used) was 3.6 cm2/10 min. The median time of the PMSCC method was 59 min, and the median speed was 1.3 cm2/10 min. The only delayed procedural adverse event was DB in 1 (0.8%) of the 123 lesions. Conclusions The ABI strategy is feasible for preventing DB both in patients at low risk and in those at high risk for DB after GESD, whereas the PMSCC method may be necessary for reduction of time.

Background: Methods have been developed for preventing delayed bleeding (DB) after gastric endoscopic submucosal dissection (GESD). However, none of the methods can completely prevent DB. We hypothesized that DB could be prevented by a modified search, coagulation, and clipping (MSCC) method for patients at low risk for DB and by combining the use of polyglycolic acid (PGA) sheets and fibrin glue with the MSCC method (PMSCC method) for patients at high risk for DB (antibleeding [ABI] strategy). This study assessed the technical feasibility of this novel strategy.Methods: We investigated 123 lesions in 121 consecutive patients who underwent GESD in Kushiro Rosai Hospital between April 2018 and January 2020. The decision for continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment.Results: Oral antithrombotic agents were administered to 28 patients (22.8%). The en bloc R0 resection rate was 98.4%. The MSCC method and the PMSCC method for preventing DB were performed in 114 and 9 lesions, respectively. The median resection time of the MSCC method was 16 min, and the median speed (the resection area divided by the resection time) was 3.6 cm2/10 min. The median resection time of the PMSCC method was 59 min, and the median speed was 1.3 cm2/10 min. The only delayed procedural adverse event was DB in 1 (0.8%) of the 123 lesions.Conclusions: The ABI strategy is feasible for preventing DB both in patients at low risk and in those at high risk for DB after GESD, whereas the PMSCC method may be necessary for reduction of time.

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Background: Some methods have been developed for preventing delayed bleeding (DB) after gastric endoscopic submucosal dissection (GESD). However, none of the methods can completely prevent DB. We hypothesized that DB can be prevented by a modified the search, coagulation, and clipping (MSCC) method for patients at low risk of DB and by combining the use of PGA sheets and fibrin glue with the MSCC method (PMSCC method) for patients at high risk of DB (anti-bleeding [ABI] strategy). In this study, the technical feasibility of this novel strategy was assessed.Methods: We investigated 123 lesions in 121 consecutive patients who underwent GESD in Kushiro Rosai Hospital between April 2018 and January 2020. The decision for continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment.Results: Oral antithrombotic agents were administered to 28 patients (22.8%). En bloc R0 resection rate was 98.4%. The MSCC method and PMSCC method for preventing were performed in 114 and 9 lesions, respectively. The median time of the MSCC method was 16 min and the median speed was 3.6 cm2/10min. The median time of the PMSCC method was 59 min and the median speed was 1.3 cm2/10min. The only delayed procedural adverse event was DB in one (0.8%) of the 123 lesions. Conclusions: The ABI strategy is feasible for preventing DB in patients at low risk and high risk of DB after GESD, whereas the PMSCC method may be necessary for reduction of time.

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