Accuracy evaluation of mainstream and sidestream end-tidal carbon dioxide monitoring during noninvasive ventilation: a randomized crossover trial (MASCAT-NIV trial).

BACKGROUND: The end-tidal partial pressure of carbon dioxide (PETCO2) can be used to estimate the arterial partial pressure of carbon dioxide (PaCO2) in patients who undergo mechanical ventilation via endotracheal intubation. However, no reliable method for measuring PETCO2 during noninvasive ventilation (NIV) has been established. The purpose of this study was to evaluate the correlation and agreement between PaCO2 and PETCO2 measured by these two methods and to compare them in patients who underwent NIV after extubation. METHODS: This study was a randomized, open-label, crossover trial in a mixed intensive care unit. We included patients who were planned for NIV after extubation and for whom the difference between PETCO2 and PaCO2 was ≤ 5 mmHg. We compared mainstream capnography using an inner cup via face mask (the novel method) with sidestream capnography (the previous method) during NIV. The relationships between PaCO2 and PETCO2 were evaluated by computing the Pearson correlation coefficient, and the agreement between PaCO2 and PETCO2 was estimated using the Bland-Altman method. RESULTS: From April 2020 to October 2021, 60 patients were included to the study. PaCO2 and PETCO2 were well correlated in both methods (the novel methods: r = 0.92, P < 0.001; the previous method: r = 0.79, P < 0.001). Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.70 (95% confidence interval [CI], 2.15-3.26) mmHg with 95% limits of agreement (LoA) ranging from - 1.61 to 7.02 mmHg, similar to the result of measurement during SBT (mean bias, 2.51; 95% CI, 2.00-3.02; 95% LoA, - 1.45 to 6.47 mmHg). In contrast, measurement using the previous method demonstrated a larger difference (mean bias, 6.22; 95% CI, 5.22-7.23; 95% LoA, - 1.54 to 13.99 mmHg). CONCLUSION: The current study demonstrated that the novel PETCO2 measurement was superior to the previous method for PaCO2 prediction. During NIV, the novel method may collect as sufficient exhalation sample as during intubation. Continuous PETCO2 measurement combined with peripheral oxygen saturation monitoring is expected to be useful for early recognition of respiratory failure among high-risk patients after extubation. Trial registration UMIN-CTR UMIN000039459. Registered February 11, 2020.

Cloning of the SPO11 gene that complements a meiotic recombination defect in sake yeast.

Cross hybridization breeding of sake yeasts is hampered by difficulty in acquisition of haploid cells through sporulation. We previously demonstrated that typical sake yeast strains were defective in meiotic chromosome recombination, which caused poor sporulation and loss of spore viability. In this study, we screened a single copy plasmid genomic DNA library of the laboratory Saccharomyces cerevisiae GRF88 for genes that might complement the meiotic recombination defect of UTCAH-3, a strain derived from the sake yeast Kyokai no. 7 (K7). We identified the SPO11 gene of the laboratory strain (ScSPO11), encoding a meiosis-specific endonuclease that catalyzes DNA double-strand breaks required for meiotic recombination, as a gene that restored meiotic recombination and spore viability of UTCAH-3. K7SPO11 could not restore sporulation efficiency and spore viability of UTCAH-3 and a laboratory strain BY4743 spo11Δ/spo11Δ, indicating that K7SPO11 is not functional. Sequence analysis of the SPO11 genes of various Kyokai sake yeasts (K1, and K3-K10) revealed that the K7 group of sake yeasts (K6, K7, K9, and K10) had a mutual missense mutation (C73T) in addition to other three common mutations present in all Kyokai yeasts tested. ScSPO11C73T created through in vitro mutagenesis could not restore spore viability of BY4743 spo11Δ/spo11Δ. On the other hand, K8SPO11, which have the three common mutations except for C73T could restore spore viability of BY4743 spo11Δ/spo11Δ. These results suggest that C73T might be a causative mutation of recombination defect in K7SPO11. Moreover, we found that the introduction of ScRIM15 restored sporulation efficiency but not spore viability.

Recombinant Human-Soluble Thrombomodulin Contributes to Reduced Mortality in Sepsis Patients With Severe Respiratory Failure: A Retrospective Observational Study Using a Multicenter Dataset.

BACKGROUND: Recombinant human-soluble thrombomodulin (rhTM) is a novel class therapeutic agent for managing disseminated intravascular coagulation. The progression of severe respiratory failure may be related to intra-alveolar coagulation/fibrinolytic disorders. We aimed to determine the efficacy of rhTM in treating sepsis patients with severe respiratory failure. METHODS: We performed a retrospective observational study using an existing dataset collected from 42 intensive care units (ICUs) in Japan. Of 3,195 patients with severe sepsis or septic shock from the dataset, we selected sepsis patients with severe respiratory failure, and compared patient outcomes based on the administration of rhTM (rhTM group and no rhTM group). Propensity score analysis was performed between the two groups. Outcomes of interest were ICU mortality, hospital mortality, and ventilator-free days (VFDs). RESULTS: In this study, 1,180 patients (rhTM, n = 356; no rhTM, n = 824) were analyzed. After adjusting for baseline imbalances with propensity score matching, the survival-time analysis revealed a significant difference between the two groups (hazard ratio, 0.654; 95% confidence interval, 0.439-0.974, P = 0.03). ICU mortality was lower in the rhTM group (rhTM: 22.1% [33/149] vs. no rhTM: 36.2% [54/149], P = 0.01). Hospital mortality was also lower in the rhTM group (35.6% [53/149] vs. 49.7% [74/149], P = 0.02). VFDs trended to be higher in the rhTM group than the no rhTM group (12.8 ±â€Š10.1 days vs. 10.6 ±â€Š10.6 days, P = 0.09). CONCLUSIONS: Administration of rhTM was positively correlated with a reduction in mortality in sepsis patients with severe respiratory failure.

Meiotic chromosomal recombination defect in sake yeasts.

Sake yeast strains are classified into Saccharomyces cerevisiae and have a heterothallic life cycle. This feature allows cross hybridization between two haploids to breed new strains with superior characteristics. However, cross hybridization of sake yeast is very difficult because only a few spores develop in a sporulation medium, and most of these spores do not germinate. We hypothesized that these features are attributable to chromosome recombination defect in meiosis, which leads to chromosome loss. To test this hypothesis, we examined meiotic recombination of sake yeast Kyokai no. 7 (K7) using the following three methods: (i) analysis of the segregation patterns of two heterozygous sites in the same chromosome in 100 haploid K7 strains; (ii) sequencing of the whole genomes of four haploid K7 strains and comparison of the bases derived from the heterozygosities; and (iii) construction of double heterozygous disruptants of CAN1 and URA3 on the chromosome V of K7 and the examination of the genotypes of haploids after sporulation. We could not detect any recombinant segregants in any of the experiments, which indicated defect in meiotic recombination in K7. Analyses after sporulation of the same double heterozygous disruptants of K6, K9, and K10 also indicated meiotic recombination defect in these strains. Although rapamycin treatment increased the sporulation efficiency of K7, it did not increase the meiotic recombination of the double heterozygous K7. Moreover, the spo13 disruptant of the K7 derivative produced two spore asci without meiotic recombination. These results suggest that sake yeasts have defects in meiotic recombination machinery.

A retrospective study of in-hospital cardiac arrest.

Aim: In-hospital cardiac arrest is an important issue in health care today. Data regarding in-hospital cardiac arrest in Japan is limited. In Australia and the USA, the Rapid Response System has been implemented in many institutions and data regarding in-hospital cardiac arrest are collected to evaluate the efficacy of the Rapid Response System. This is a multicenter retrospective survey of in-hospital cardiac arrest, providing data before implementing a Rapid Response System. Methods: Ten institutions planning to introduce a Rapid Response System were recruited to collect in-hospital cardiac arrest data. The Institutional Review Board at each participating institution approved this study. Data for patients admitted at each institution from April 1, 2011 until March 31, 2012 were extracted using the three keywords "closed-chest compression", "epinephrine", and "defibrillation". Patients under 18 years old, or who suffered cardiac arrest in the emergency room or the intensive care unit were excluded. Results: A total of 228 patients in 10 institutions were identified. The average age was 73 ± 13 years. Males represented 64% of the patients (82/146). Overall survival after in-hospital cardiac arrest was 7% (16/228). Possibly preventable cardiac arrests represented 15% (33/228) of patients, with medical safety issues identified in 8% (19/228). Vital sign abnormalities before cardiac arrest were observed in 63% (138/216) of patients. Conclusions: Approximately 60% of patients had abnormal vital signs before cardiac arrest. These patients may have an improved clinical outcome by implementing a Rapid Response System.