Continuous monitoring of changes in cerebral oxygenation during hemodialysis in a patient with acute congestive heart failure.

A 71-year-old man undergoing hemodialysis (HD) was admitted to our hospital with congestive heart failure (CHF) and pneumonia. After admission, ultrafiltration with HD was urgently performed because of a lack of respiratory improvement despite the use of noninvasive positive pressure ventilation. During HD, cerebral regional saturation of oxygen (rSO2) was monitored by INVOS 5100c oxygen saturation monitor (Covidien Japan, Japan) to evaluate changes in tissue oxygenation. At HD initiation, cerebral rSO2 was very low at 34% under the fraction of inspiratory oxygen (FiO2) of 0.4. Ultrafiltration was performed at the rate of 0.5 L/h thereafter, cerebral rSO2 gradually improved even as inhaling oxygen concentration decreased. At the end of HD, cerebral rSO2 improved at 40% under a FiO2 of 0.28 as excess body fluid was removed. After pneumonia and CHF improved, he was discharged. Reports of the association between cerebral oxygenation and acute CHF status in patients undergoing HD are limited; therefore, in our experience with this case, cerebral oxygenation deteriorated with the CHF status but was improved by adequate body-fluid management during HD.

Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.