Delirium in patients with COVID-19 treated in the intensive care unit.

Coronavirus disease 2019 (COVID-19) can lead to acute organ dysfunction, and delirium is associated with long-term cognitive impairment and a prolonged hospital stay. This retrospective single-center study aimed to investigate the risk factors for delirium in patients with COVID-19 infection receiving treatment in an intensive care unit (ICU). A total of 111 patients aged >18 years with COVID-19 pneumonia who required oxygen therapy from February 2021 to April 2022 were included. Data on patient demographics, past medical history, disease severity, delirium, and treatment strategies during hospitalization were obtained from electronic health records. Patient characteristics and risk factors for delirium were analyzed. Old age (P < 0.001), hypertension (P < 0.001), disease severity (Sequential Organ Failure Assessment score) (P < 0.001), mechanical ventilator support (P < 0.001), neuromuscular blocker use (P < 0.001), and length of stay in the ICU (P < 0.001) showed statistically significant differences on the univariable analysis. Multivariable analysis with backward selection revealed that old age (odds ratio, 1.149; 95% confidence interval, 1.037-1.273; P = 0.008), hypertension (odds ratio, 8.651; 95% confidence interval, 1.322-56.163; P = 0.024), mechanical ventilator support (odds ratio, 226.215; 95% confidence interval, 15.780-3243.330; P < 0.001), and length of stay in the ICU (odds ratio, 30.295; 95% confidence interval, 2.539-361.406; P = 0.007) were significant risk factors for delirium. In conclusion, old age, ICU stay, hypertension, mechanical ventilator support, and neuromuscular blocker use were predictive factors for delirium in COVID-19 patients in the ICU. The study findings suggest the need for predicting the occurrence of delirium in advance and preventing and treating delirium.

A Modified Intraperitoneal Chemotherapy Regimen for Ovarian Cancer: Technique and Treatment Outcomes.

This study aimed to investigate treatment outcomes concerning three institutional modifications to intraperitoneal (IP) chemotherapy for patients with ovarian cancer. The medical records of 27 patients treated with IP chemotherapy were retrospectively reviewed. All patients had three IP chemotherapy institutional modifications; modified Gynecologic Oncology Group 172 regimen was used for the chemotherapy regimen. With institutional modifications, 63.0% (17/27) completed all six cycles of IP chemotherapy. Of the 17 and 10 patients with primary and recurrent ovarian cancer, respectively, 55.6% (15/27) underwent left colonic surgery, including low anterior resection. In patients with primary ovarian cancer, the IP chemotherapy completion rate was 76.5% (13/17). In patients with and without left colonic surgery, the IP chemotherapy completion rates were 53.3% (8/15) and 75.0% (9/12), respectively. No complications related to left colonic surgery during IP chemotherapy were identified. The most frequent grade 3-4 toxicities were gastrointestinal toxicities (33.3%) and neutropenia (29.6%). The median progression-free survival was 19.5 months in all patients and 25.2 months in patients with primary ovarian cancer. Three institutional modifications to IP chemotherapy increased the completion rate for planned IP chemotherapy, even after left colonic surgery. Further studies involving a larger study cohort are required to confirm survival outcomes using these modifications.

Utilization of a rapid response team and associated outcomes in patients with malignancy.

BACKGROUND: Recent advances in diagnosis and treatment have improved long-term outcomes in cancer patients. As a result, the requirement for a rapid response team (RRT) for cancer patients is also increasing. This study aimed to analyze utilization of an RRT and the associations between related factors and mortality in a population of cancer patients. METHODS: This retrospective cohort study included hospitalized patients at a single academic medical center in Seoul, Korea, who required RRT activation during a 6-year period from June 2013 to December 2018. RESULTS: Overall, 164 of the 457 patients who met the above criteria were cancer patients, and they had a significantly higher Charlson comorbidity score than the non-cancer patients (5.0 vs. 7.0, P<0.001). A significantly larger proportion of cancer patients required intensive care unit transfer (51.8% vs. 41.0%, P=0.032). Cancer patients also had significantly higher in-hospital mortality compared with other patients (39.6% vs. 10.9%, P<0.001). Furthermore, presence of cancer was independently associated with in-hospital mortality (adjusted odds ratio [OR], 2.09; 95% confidence interval [CI], 1.11 to 3.93). Among cancer patients, higher Acute Physiology and Chronic Health Evaluation (APACHE) II at the time of RRT activation was significantly associated with in-hospital mortality regardless of malignancy (adjusted OR, 1.08; 95% CI, 1.01 to 1.15). CONCLUSIONS: Cancer patients requiring RRT activation have significantly higher rates of inhospital mortality than patients not using RRT. Higher severity score at the time of RRT activation in patients with malignancy was significantly associated with in-hospital mortality.

Epidemiology and Clinical Characteristics of Rapid Response Team Activations.

BACKGROUND: To ensure patient safety and improvements in the quality of hospital care, rapid response teams (RRTs) have been implemented in many countries, including Korea. The goal of an RRT is early identification and response to clinical deterioration in patients. However, there are differences in RRT systems among hospitals and limited data are available. METHODS: In Seoul St. Mary's Hospital, the St. Mary's Advanced Life Support Team was implemented in June 2013. We retrospectively reviewed the RRT activation records of 287 cases from June 2013 to December 2016. RESULTS: The median response time and median modified early warning score were 8.6 minutes (interquartile range, 5.6 to 11.6 minutes) and 5.0 points (interquartile range, 4.0 to 7.0 points), respectively. Residents (35.8%) and nurses (59.1%) were the main activators of the RRT. Interestingly, postoperative patients account for a large percentage of the RRT activation cases (69.3%). The survival rate was 83.6% and survival was mainly associated with malignancy, Acute Physiology and Chronic Health Evaluation-II score, and the time from admission to RRT activation. RRT activation with screening showed a better outcome compared to activation via a phone call in terms of the intensive care unit admission rate and length of hospital stay after RRT activation. CONCLUSIONS: Malignancy was the most important factor related to survival. In addition, RRT activation with patient screening showed a better outcome compared to activation via a phone call. Further studies are needed to determine the effective screening criteria and improve the quality of the RRT system.

An RNA aptamer that specifically binds to the glycosylated hemagglutinin of avian influenza virus and suppresses viral infection in cells.

The influenza virus surface glycoprotein hemagglutinin (HA) is responsible for viral attachment to sialic acid-containing host cell receptors and it facilitates the initial stage of viral infection. In the present study, we isolated an RNA aptamer specific to the glycosylated receptor-binding domain of the HA protein (gHA1) after 12 cycles of the systematic evolution of ligands by exponential enrichment procedure (SELEX), and we then investigated if the selected aptamer suppresses viral infection in host cells. Nitrocellulose filter binding and enzyme-linked immunosorbent assay (ELISA) experiments revealed that 1 RNA aptamer, HA12-16, bound specifically to the gHA1 protein. Cell viability assay showed that the HA12-16 RNA aptamer suppressed viral infection in host cells by enhancing cell viability. Immunofluorescence microscopic analysis further demonstrated that the HA12-16 RNA aptamer suppresses viral attachment to host cells by neutralizing the receptor-binding site of influenza virus HA. These results indicate that the isolated RNA aptamer can be developed as an antiviral reagent against influenza through appropriate therapeutic formulation.

Crystal structure of the protein from Arabidopsis thaliana gene At5g06450, a putative DnaQ-like exonuclease domain-containing protein with homohexameric assembly.

Arabidopsis thaliana gene At5g06450 encodes a putative DnaQ-like 3'-5' exonuclease domain-containing protein (AtDECP). The DnaQ-like 3'-5' exonuclease domain is often found as a proofreading domain of DNA polymerases. The overall structure of AtDECP adopts an RNase H fold that consists of a mixed ß-sheet flanked by α-helices. Interestingly, AtDECP forms a homohexameric assembly with a central six fold symmetry, generating a central cavity. The ring-shaped structure and comparison with WRN-exo, the best structural homologue of AtDECP, suggest a possible mechanism for implementing its exonuclease activity using positively charged patch on the N-terminal side of the homohexameric assembly. The homohexameric structure of AtDECP provides unique information about the interaction between the DnaQ-like 3'-5' exonuclease and its substrate nucleic acids.

Overexpression, crystallization and preliminary X-ray crystallographic analysis of the variable lymphocyte receptor 2913 ectodomain fused with internalin B.

In jawless vertebrates, variable lymphocyte receptors (VLRs) play a crucial role in the recognition of antigens as part of the adaptive immune system. Leucine-rich repeat (LRR) modules and the highly variable insert (HVI) of VLRs contribute to the specificity and diversity of antigen recognition. VLR2913, the antigen of which is not known, contains the same HVI amino-acid sequence as that of VLR RBC36, which recognizes the H-trisaccharide from human blood type O erythrocytes. Since the HVI sequence is rarely identical among all known VLRs, identification of the antigen for VLR2913 and the main contributing factors for antigen recognition based on a comparison of VLR2913 and VLR RBC36 has been attempted. To initiate and facilitate this structural approach, the ectodomain of VLR2913 was fused with the N-terminal domain of internalin B (InlB-VLR2913-ECD). Three amino-acid residues on the concave surface of the LRR modules of InlB-VLR2913-ECD were mutated, considering important residues for hydrogen bonds in the recognition of H-trisaccharide by VLR RBC36. InlB-VLR2913-ECD was overexpressed in Escherichia coli and was crystallized at 295 K using the sitting-drop vapour-diffusion method. X-ray diffraction data were collected to 2.04 Šresolution and could be indexed in the tetragonal space group P4(1)2(1)2 (or P4(3)2(1)2), with unit-cell parameters a = 91.12, b = 91.12, c = 62.87 Å. Assuming that one monomer molecule was present in the crystallographic asymmetric unit, the calculated Matthews coefficient (V(M)) was 2.75 Å(3) Da(-1) and the solvent content was 55.2%. Structural determination of InlB-VLR2913-ECD by molecular replacement is in progress.

Overexpression, crystallization and preliminary X-ray crystallographic analysis of the C-terminal cytosolic domain of mouse anoctamin 1.

Transmembrane protein 16A (TMEM16A, also known as anoctamin 1; ANO1) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+)- and Ca(2+)-mobilizing stimuli and plays important roles in a variety of physiological functions. To elucidate the structural features of ANO1, structural analysis of the C-terminal cytosolic domain of mouse ANO1 (mANO1-CTD) was initiated. mANO1-CTD was overexpressed in Escherichia coli and was crystallized at 297 K using a reservoir solution consisting of 0.2 M sodium acetate trihydrate, 0.1 M Tris-HCl pH 8.5 and 30%(w/v) PEG 4000. X-ray diffraction data were collected to 2.3 Å resolution. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 73.96, b = 103.73, c = 114.71 Å. If it is assumed that eight copies of a monomer molecule are present in the crystallographic asymmetric unit, the crystal volume per protein mass (V(M)) is 2.38 Å(3) Da(-1) and the solvent content is 48.38%. Attempts to solve the structure of mANO1-CTD by the MAD method using selenomethionine-labelled mANO1-CTD or heavy-atom-derivatized crystals are in progress.

Preliminary X-ray crystallographic analysis of the breakage-reunion domain of the GyrA subunit of DNA gyrase from Colwellia psychrerythraea strain 34H.

DNA gyrase is a type II topoisomerase that is essential for chromosome segregation and cell division owing to its ability to modify the topological forms of bacterial DNA. In this study, the N-terminal breakage-reunion domain of the GyrA subunit of DNA gyrase from Colwellia psychrerythraea 34H was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.60 A resolution using a synchrotron-radiation source. The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 98.98, b = 101.56, c = 141.83 A. The asymmetric unit contained two molecules, with a corresponding V(M) of 3.18 A(3) Da(-1) and a solvent content of 59.9%.

Crystallization and preliminary X-ray crystallographic analysis of DNA gyrase GyrB subunit from Xanthomonas oryzae pv. oryzae.

DNA gyrase is a type II topoisomerase that is essential for chromosome segregation and cell division owing to its ability to modify the topological forms of bacterial DNA. In this study, the N-terminal fragment of the GyrB subunit of DNA gyrase from Xanthomonas oryzae pv. oryzae was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.10 A resolution using a synchrotron-radiation source. The crystal belonged to space group I4(1), with unit-cell parameters a = b = 110.27, c = 70.75 A. The asymmetric unit contained one molecule, with a V(M) of 2.57 A(3) Da(-1) and a solvent content of 50.2%.