Remimazolam for general anesthesia in a patient with aortic stenosis and severe obesity undergoing transcatheter aortic valve implantation.

INTRODUCTION: There is currently limited research on the clinical use of remimazolam in severely obese patients. In this report, we describe the anesthesia management of transcatheter aortic valve implantation (TAVI) in a severely obese patient using remimazolam. CASE DESCRIPTION: A 76-year-old woman (height 1.54 m; total body weight 104 kg; body mass index 43.9 kg/m2) was scheduled for TAVI via the femoral artery approach for aortic valve stenosis. Preoperative echocardiography showed an aortic valve peak flow of 4.0 m/s and an effective orifice area of 0.75 cm2. Anesthesia induction was performed with a bolus dose of 100 µg fentanyl, 15 mg remimazolam, 60 mg rocuronium, and a continuous infusion of remifentanil at 0.4 mg/h. Intraoperatively, remimazolam was administered at a rate of 35 mg/h. General anesthesia management was completed without any complications, although the patient required temporary catecholamine and inhalation anesthesia assistance due to hemodynamic changes. CONCLUSION: Owing to its pharmacological advantages, remimazolam may be an option for anesthesia induction and maintenance in severely obese patients with unstable circulation.

Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure.

BACKGROUND: In this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation. RESULTS: Compared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1ß were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1ß (202), IL-31 (169), MCP-1 (81), MIP-1ß (55), and TNF-α (47) were lower. CONCLUSIONS: The ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1ß were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Immunological Response to Subcutaneous and Intranasal Administration of SARS-CoV-2 Spike Protein in Mice.

In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not only the disease but also its infection. Currently, the SARS-CoV-2 vaccine is administered via intramuscular injection and is generally not immunogenic to the mucosa. As a result, current vaccinations fail to reduce viral shedding and transmission and ultimately do not prevent infection. We established a mouse vaccine model in which a single dose of S1 protein and aluminum oxide gel (alum) subcutaneous vaccine was followed by a booster dose of S1 protein and CpG oligodeoxynucleotide intranasal vaccine. The group that received two doses of the intranasal vaccine booster showed a significant increase in IgG and IgA antibody titers against S1 and RBD in serum and BAL, and a significant difference in neutralizing antibody titers, particularly in BAL. One intranasal vaccine booster did not induce sufficient immunity, and the vaccine strategy with two booster intranasal doses produced systemic neutralizing antibodies and mucus-neutralizing antibodies against SARS-CoV-2. It will be an important tool against the emergence of new viruses and the next pandemic.

Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.

Tracheal injury diagnosed by a sudden increase in end-tidal carbon dioxide levels during mediastinoscopic subtotal esophagectomy: a case report.

BACKGROUND: Mediastinoscopic surgery for esophageal cancer facilitates early postoperative recovery. However, it can occasionally cause serious complications. Here, we present the case of a patient with a tracheal injury diagnosed by a sudden increase in end-tidal carbon dioxide (EtCO2) during mediastinoscopic subtotal esophagectomy. CASE PRESENTATION: A 52-year-old man diagnosed with esophageal cancer was scheduled to undergo mediastinoscopic subtotal esophagectomy. During the mediastinoscopic procedure, the EtCO2 level suddenly increased above 200 mmHg, and the blood pressure dropped below 80 mmHg. We immediately asked the operator to stop insufflation and found a tracheal injury on the right side of the trachea near the carina by bronchoscopy. The endotracheal tube was replaced with a double-lumen tube, and the trachea was repaired via right thoracotomy. There were no further intraoperative complications. After surgery, the patient was extubated and admitted to the intensive care unit. CONCLUSIONS: Monitoring EtCO2 levels and close communication with the operator is important for safely managing sudden tracheal injury during mediastinoscopic esophagectomy.

Prediction of acute lung injury assessed by chest computed tomography, oxygen saturation/fraction of inspired oxygen ratio, and serum lactate dehydrogenase in patients with COVID-19.

INTRODUCTION: In treating acute hypoxemic respiratory failure (AHRF) caused by coronavirus disease 2019 (COVID-19), clinicians choose respiratory therapies such as low-flow nasal cannula oxygenation, high-flow nasal cannula oxygenation, or mechanical ventilation after assessment of the patient's condition. Chest computed tomography (CT) imaging contributes significantly to diagnosing COVID-19 pneumonia. However, the costs and potential harm to patients from radiation exposure need to be considered. This study was performed to predict the quantitative extent of COVID-19 acute lung injury using clinical indicators such as an oxygenation index and blood test results. METHODS: We analyzed data from 192 patients with COVID-19 AHRF. Multiple logistic regression was used to determine correlations between the lung infiltration volume (LIV) and other pathophysiological or biochemical laboratory parameters. RESULTS: Among 13 clinical parameters, we identified the oxygen saturation/fraction of inspired oxygen ratio (SF ratio) and serum lactate dehydrogenase (LD) concentration as factors associated with the LIV. In the binary classification of an LIV of ≥20 % or not and with the borderline LD = 2.2 × [SF ratio]-182.4, the accuracy, precision, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.828, 0.818, 23.400, and 0.870, respectively. CONCLUSIONS: These data suggest that acute lung injury due to COVID-19 pneumonia can be estimated using the SF ratio and LD concentration without a CT scan. These findings may provide significant clinical benefit by allowing clinicians to predict acute lung injury levels using simple, minimally invasive assessment of oxygenation capacity and biochemical blood tests.

Effect of acute normovolemic hemodilution in patients undergoing cardiac surgery with remimazolam anesthesia.

PURPOSE: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia. METHODS: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated. RESULTS: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01). CONCLUSION: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible.

Changes in EEG frequency characteristics during sevoflurane general anesthesia: feature extraction by variational mode decomposition.

Mode decomposition is a method for extracting the characteristic intrinsic mode function (IMF) from various multidimensional time-series signals. Variational mode decomposition (VMD) searches for IMFs by optimizing the bandwidth to a narrow band with the [Formula: see text] norm while preserving the online estimated central frequency. In this study, we applied VMD to the analysis of electroencephalogram (EEG) recorded during general anesthesia. Using a bispectral index monitor, EEGs were recorded from 10 adult surgical patients (the median age: 47.0, and the percentile range: 27.0-59.3 years) who were anesthetized with sevoflurane. We created an application named EEG Mode Decompositor, which decomposes the recorded EEG into IMFs and displays the Hilbert spectrogram. Over the 30-min recovery from general anesthesia, the median (25-75 percentile range) bispectral index increased from 47.1 (42.2-50.4) to 97.4 (96.5-97.6), and the central frequencies of IMF-1 showed a significant change from 0.4 (0.2-0.5) Hz to 0.2 (0.1-0.3) Hz. IMF-2, IMF-3, IMF-4, IMF-5, and IMF-6 increased significantly from 1.4 (1.2-1.6) Hz to 7.5 (1.5-9.3) Hz, 6.7 (4.1-7.6) Hz to 19.4 (6.9-20.0) Hz, 10.9 (8.8-11.4) Hz to 26.4 (24.2-27.2) Hz, 13.4 (11.3-16.6) Hz to 35.6 (34.9-36.1) Hz, and 12.4 (9.7-18.1) Hz to 43.2 (42.9-43.4) Hz, respectively. The characteristic frequency component changes in specific IMFs during emergence from general anesthesia were visually captured by IMFs derived using VMD. EEG analysis by VMD is useful for extracting distinct changes during general anesthesia.

Effect of a Novel Trivalent Vaccine Formulation against Acute Lung Injury Caused by Pseudomonas aeruginosa.

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294), the outer membrane domain (#190-342) of OprF (OprF#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ)). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.

Long Duration of Action of Tranexamic Acid After Cardiac Surgery in a Hemodialysis Patient: A Case Report.

A 61-year-old woman with chronic renal dysfunction was scheduled to undergo aortic valve replacement. After a bolus of 1 g tranexamic acid (TXA), the TPA (tissue-plasminogen activator)-test result with the ClotPro system demonstrated extensive inhibition of fibrinolysis. Plasma TXA level decreased from 71 to 25 µg/dL at 6 hours postoperatively; however, no further decrease was observed. Although TXA levels dropped to 6.9 µg/dL after hemodialysis on postoperative day (PoD) 1, fibrinolytic shutdown on the TPA-test remained unchanged until PoD 2. In dialysis patients, low-dose TXA <1 g may be considered for reducing seizure and thromboembolic complications after cardiac surgery.

Choice of respiratory therapy for COVID-19 patients with acute hypoxemic respiratory failure: a retrospective case series study.

Background: In the treatment of acute hypoxemic respiratory failure (AHRF) due to coronavirus 2019 (COVID-19), physicians choose respiratory management ranging from low-flow oxygen therapy to more invasive methods, depending on the severity of the patient's symptoms. Recently, the ratio of oxygen saturation (ROX) index has been proposed as a clinical indicator to support the decision for either high-flow nasal cannulation (HFNC) or mechanical ventilation (MV). However, the reported cut-off value of the ROX index ranges widely from 2.7 to 5.9. The objective of this study was to identify indices to achieve empirical physician decisions for MV initiation, providing insights to shorten the delay from HFNC to MV. We retrospectively analyzed the ROX index 6 hours after initiating HFNC and lung infiltration volume (LIV) calculated from chest computed tomography (CT) images in COVID-19 patients with AHRF. Methods: We retrospectively analyzed the data for 59 COVID-19 patients with AHRF in our facility to determine the cut-off value of the ROX index for respiratory therapeutic decisions and the significance of radiological evaluation of pneumonia severity. The physicians chose either HFNC or MV, and the outcomes were retrospectively analyzed using the ROX index for initiating HFNC. LIV was calculated using chest CT images at admission. Results: Among the 59 patients who required high-flow oxygen therapy with HFNC at admission, 24 were later transitioned to MV; the remaining 35 patients recovered. Four of the 24 patients in the MV group died, and the ROX index values of these patients were 9.8, 7.3, 5.4, and 3.0, respectively. These index values indicated that the ROX index of half of the patients who died was higher than the reported cut-off values of the ROX index, which range from 2.7-5.99. The cut-off value of the ROX index 6 hours after the start of HFNC, which was used to classify the management of HFNC or MV as a physician's clinical decision, was approximately 6.1. The LIV cut-off value on chest CT between HFNC and MV was 35.5%. Using both the ROX index and LIV, the cut-off classifying HFNC or MV was obtained using the equation, LIV = 4.26 × (ROX index) + 7.89. The area under the receiver operating characteristic curve, as an evaluation metric of the classification, improved to 0.94 with a sensitivity of 0.79 and specificity of 0.91 using both the ROX index and LIV. Conclusion: Physicians' empirical decisions associated with the choice of respiratory therapy for HFNC oxygen therapy or MV can be supported by the combination of the ROX index and the LIV index calculated from chest CT images.

Time-trend analysis of the center frequency of the intrinsic mode function from the Hilbert-Huang transform of electroencephalography during general anesthesia: a retrospective observational study.

BACKGROUND: Anesthesiologists are required to maintain an optimal depth of anesthesia during general anesthesia, and several electroencephalogram (EEG) processing methods have been developed and approved for clinical use to evaluate anesthesia depth. Recently, the Hilbert-Huang transform (HHT) was introduced to analyze nonlinear and nonstationary data. In this study, we assessed whether the changes in EEG characteristics during general anesthesia that are analyzed by the HHT are useful for monitoring the depth of anesthesia. METHODS: This retrospective observational study enrolled patients who underwent propofol anesthesia. Raw EEG signals were obtained from a monitor through a previously developed software application. We developed an HHT analyzer to decompose the EEG signal into six intrinsic mode functions (IMFs) and estimated the instantaneous frequencies (HHT_IF) for each IMF. Changes over time in the raw EEG waves and parameters such as HHT_IF, BIS, spectral edge frequency 95 (SEF95), and electromyogram parameter (EMGlow) were assessed, and a Gaussian process regression model was created to assess the association between BIS and HHT_IF. RESULTS: We analyzed EEG signals from 30 patients. The beta oscillation frequency range (13-25 Hz) was detected in IMF1 and IMF2 during the awake state, then after loss of consciousness, the frequency decreased and alpha oscillation (8-12 Hz) was detected in IMF2. At the emergence phase, the frequency increased and beta oscillations were detected in IMF1, IMF2, and IMF3. BIS and EMGlow changed significantly during the induction and emergence phases, whereas SEF95 showed a wide variability and no significant changes during the induction phase. The root mean square error between the observed BIS values and the values predicted by a Gaussian process regression model ranged from 4.69 to 9.68. CONCLUSIONS: We applied the HHT to EEG analyses during propofol anesthesia. The instantaneous frequency in IMF1 and IMF2 identified changes in EEG characteristics during induction and emergence from general anesthesia. Moreover, the HHT_IF in IMF2 showed strong associations with BIS and was suitable for depicting the alpha oscillation. Our study suggests that the HHT is useful for monitoring the depth of anesthesia.

The Perioperative Frontal Relative Ratio of the Alpha Power of Electroencephalography for Predicting Postoperative Delirium After Highly Invasive Surgery: A Prospective Observational Study.

BACKGROUND: We investigated the associations between postoperative delirium (POD) and both the relative ratio of the alpha (α)-power of electroencephalography (EEG) and inflammatory markers in a prospective, single-center observational study. METHODS: We enrolled 84 patients who underwent radical cancer surgeries with reconstruction for esophageal cancer, oral floor cancer, or pharyngeal cancer under total intravenous anesthesia. We collected the perioperative EEG data and the perioperative data of the inflammatory markers, including neutrophil gelatinase-associated lipocalin, presepsin, procalcitonin, C-reactive protein, and the neutrophil-lymphocyte ratio (NLR). The existence of POD was evaluated based on the Intensive Care Delirium Screening Checklist. We compared the time-dependent changes in the relative ratio of the EEG α-power and inflammatory markers between the patients with and without POD. RESULTS: Four of the 84 patients were excluded from the analysis. Of the remaining 80 patients, 25 developed POD and the other 55 did not. The relative ratio of the α-power at baseline was significantly lower in the POD group than the non-POD group (0.18 ± 0.08 vs 0.28 ± 0.11, P < .001). A time-dependent decline in the relative ratio of α-power in the EEG during surgery was observed in both groups. There were significant differences between the POD and non-POD groups in the baseline, 3-h, 6-h, and 9-h values of the relative ratio of α-power. The preoperative NLR of the POD group was significantly higher than that of the non-POD group (2.88 ± 1.04 vs 2.22 ± 1.00, P < .001), but other intraoperative inflammatory markers were comparable between the groups. Two multivariable logistic regression models demonstrated that the relative ratio of the α-power at baseline was significantly associated with POD. CONCLUSIONS: Intraoperative frontal relative ratios of the α-power of EEG were associated with POD in patients who underwent radical cancer surgery. Intraoperative EEG monitoring could be a simple and more useful tool for predicting the development of postoperative delirium than measuring perioperative acute inflammatory markers. A lower relative ratio of α-power might be an effective marker for vulnerability of brain and ultimately for the development of POD.

Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine.

The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.

Biological properties of Staphylococcus virus ΦSA012 for phage therapy.

Staphylococcus virus ΦSA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of ΦSA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of ΦSA012 through i.p. and i.v. injections into mice revealed that phages were reached the limit of detection in serum and accumulated notably spleens without inflammation at 48 h post-inoculation. Furthermore, inoculation of ΦSA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against ΦSA012 and other Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 or Escherichia viruses T1, T4, and T7 in vitro. Immunoelectron microscopic analysis showed that purified anti-phage IgG recognizes the long-tail fiber of staphylococcus viruses. Although S. aureus inoculation resulted in a 25% survival rate in a mouse i.p. model, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; however, the survival rate of ΦSA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that ΦSA012 possesses promise for use against staphylococcal infections but we should carefully address the appropriate dose and periods of phage administration. Our findings facilitate understandings of staphylococcus viruses for phage therapy.

A targeted educational programme improves fundamental knowledge of menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project.

RESEARCH QUESTION: Would a properly designed educational programme offered to young women improve their awareness and fundamental knowledge of menstrual pain and endometriosis? DESIGN: A multinational cross-sectional study using a pen-and-paper questionnaire among women aged 19-24 years was conducted between 2017 and 2019 to assess fundamental knowledge of menstrual pain and endometriosis. Improvement in knowledge was also analysed using a separate questionnaire completed before, and 1-3 months after, a group discussion, lecture on menstrual pain and endometriosis, or both. RESULTS: Among three groups of students (college [n = 271], medical [n = 877] and nursing [n = 763]), knowledge of menstrual pain and endometriosis was lowest among college students, modest among nursing students and fair among medical students (P < 0.001 for each). The experience of cyclical pain, even when painkillers were taken, was reported by 15.5%, 4.6% and 3.8% of students, respectively. Most students managed their cyclical pain by enduring it or by taking over-the-counter medication. An informative education programme with group discussions, lectures, or both, was successful in improving knowledge and consequences of menstrual pain and endometriosis. Proper education and dissemination of knowledge to college students failed to motivate them to visit gynaecologists; however, medical and nursing students became highly interested in visiting gynaecologists. CONCLUSIONS: An educational programme can improve awareness and knowledge of endometriosis and dysmenorrhoea among young women. The programme motivated nursing and medical students, but not college students, to seek medical attention for early detection and management of endometriosis.

A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study.

Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63-0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93-0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83-1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device.

Relationship between mortality and molecular epidemiology of methicillin-resistant Staphylococcus aureus bacteremia.

Staphylococcus aureus is the primary cause of bacteremia, and methicillin-resistant S. aureus bacteremia is associated with a high mortality rate. Methicillin-resistant S. aureus clones are widespread worldwide, and molecular epidemiological studies are important. Therefore, this study aimed to determine the characteristics of patients who died due to methicillin-resistant S. aureus bacteremia and microbiological characteristics of methicillin-resistant S. aureus strains in a tertiary teaching hospital. This single-center, retrospective study included patients with methicillin-resistant S. aureus isolated from blood bacterial culture performed at Kyoto Prefectural University of Medicine Hospital, from October 2016 to May 2019. The data analyzed included patient background, clinical strain characteristics, and molecular epidemiology. Of 41 patients with methicillin-resistant S. aureus bacteremia (median age, 60 [28-70] years; 24 (59%) were men), and 7 (17%) died due to methicillin-resistant S. aureus bacteremia. The median age of those who died in the methicillin-resistant S. aureus bacteremia group was predominantly higher than that of those in the alive group (p = 0.03). The most common cause of methicillin-resistant S. aureus bacteremia was endovascular devices, which occurred in 20 (49%), 18 (53%), and 2 (29%) patients in the total, alive, and died groups, respectively. Bacteriological characteristics showed that type IV Staphylococcal Cassette Chromosome mec genotype was most frequently detected in the total (n = 34 [83%]), alive (n = 29 [85%]), and died (n = 5 [71%]) groups. In the molecular cluster analysis, CC8, ST8, staphylococcal Cassette Chromosome mec type IV, and community-acquired-methicillin-resistant S. aureus formed the largest groups. The diversity of methicillin-resistant S. aureus clones is evident, and it is possible that clones with new virulence factors may still emerge. In the future, it will be crucial to monitor the epidemiological trends of methicillin-resistant S. aureus to respond quickly to changes in pathogenic and clonal factors, to clarify the gene expression network by identifying old and new virulence factors.

Anesthetic management of a severely obese patient (body mass index 70.1 kg/m2) undergoing giant ovarian tumor resection: a case report.

BACKGROUND: Giant ovarian tumors are rarely seen with severe obesity. There are few reports of perioperative management of giant ovarian tumors and severe obesity. Here, we report the perioperative management of physiological changes in massive intraabdominal tumors in a patient with severe obesity. CASE PRESENTATION: A 46-year-old Japanese woman (height 166 cm, weight 193.2 kg; body mass index 70.1 kg/m2) was scheduled to undergo laparotomy for a giant ovarian tumor. The patient was placed in the ramp position. Preoxygenation was performed using a high-flow nasal cannula, and awake tracheal intubation was performed using a video laryngoscope. Mechanical ventilation using a limited tidal volume with moderate positive end-expiratory pressure was applied during the surgical procedure. The aspiration speed for 15 L of tumor aspirate was set to under 1 L/minute, and the possibility of reexpansion pulmonary edema was foreseen by conventional monitoring. CONCLUSIONS: We successfully completed anesthetic management in a patient with concomitant severe obesity and giant ovarian tumors.