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OBJECTIVE: This study aimed to elucidate the association between IV contrast media CT and acute kidney injury (AKI) and in-hospital mortality among patients requiring emergency admission. DESIGN: In this retrospective observational study, we examined AKI within 48 hours after CT, renal replacement therapy (RRT) dependence at discharge, and in-hospital mortality in patients undergoing contrast-enhanced CT or nonenhanced CT. We performed 1:1 propensity score matching to adjust for confounders in the association between IV contrast media use and outcomes. Subgroup analyses were performed according to age, sex, diagnosis at admission, ICU admission, and preexisting chronic kidney disease (CKD). SETTING AND PATIENTS: This study used the Medical Data Vision database between 2008 and 2019. This database is Japan's largest commercially available hospital-based claims database, covering about 45% of acute-care hospitals in Japan, and it also records laboratory results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 144,149 patients with (49,057) and without (95,092) contrast media exposure, from which 43,367 propensity score-matched pairs were generated. Between the propensity score-matched groups of overall patients, exposure to contrast media showed no significant risk of AKI (4.6% vs. 5.1%; odds ratio [OR], 0.899; 95% CI, 0.845-0.958) or significant risk of RRT dependence (0.6% vs. 0.4%; OR, 1.297; 95% CI, 1.070-1.574) and significant benefit for in-hospital mortality (5.4% vs. 6.5%; OR, 0.821; 95% CI, 0.775-0.869). In subgroup analyses regarding preexisting CKD, exposure to contrast media was a significant risk for AKI in patients with CKD but not in those without CKD. CONCLUSIONS: In this large-scale observational study, IV contrast media was not associated with an increased risk of AKI but concurrently showed beneficial effects on in-hospital mortality among patients requiring emergency admission.

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Aims: SARS-CoV-2 causes systemic immune dysfunction, leading to severe respiratory dysfunction and multiorgan dysfunction. Granulocyte and monocyte adsorptive apheresis (GMA) therapy is designed to regulate an excessive inflammatory response and has been proposed as a potential therapeutic strategy for coronavirus disease 2019 (COVID-19). We aimed to investigate a targeted subset of granulocytes and monocytes to be removed after GMA therapy in patients with severe COVID-19 infection. Methods: We established an ex vivo experimental system to study the effects of GMA. Blood samples were collected into EDTA-treated tubes and a mixture of blood samples and cellulose acetate beads was used in GMA. After GMA, blood samples were removed, and the granulocyte and monocyte subtypes before and after GMA were determined by CyTOF mass cytometry. To analyze mass cytometry data with a self-organizing map, hierarchical clustering was used to determine the appropriate number of metaclusters from t-distributed stochastic neighbor embedding. Results: We included seven patients with severe COVID-19 and four age- and sex-matched volunteers. Granulocyte subsets removed by GMA strongly expressed CD11b, CD16, and CD66b, and weakly expressed CD11c, consistent with mature and activated neutrophils. Monocyte subsets strongly expressed CD14, weakly expressed CD33 and CD45RO, and did not express CD16. These subsets were indicated to promote the release of inflammatory cytokines and activate T cells. Conclusions: The identification of the granulocyte and monocyte subsets removed after GMA in patients with severe COVID-19 may help explain the potential mechanism underlying the effectiveness of GMA in COVID-19 and other inflammatory diseases.

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INTRODUCTION: The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin. MATERIALS AND METHODS: In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups. RESULTS: Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596-0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926-1.391, 0.853-1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265-0.751, 0.410-0.940, respectively). CONCLUSIONS: Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.

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Introduction: Vitamin B1 deficiency poses a significant risk of impaired consciousness, with manifestations ranging from anorexia and fatigue to severe neurological and cardiovascular disturbances. Wernicke's encephalopathy, a neurological disorder stemming from vitamin B1 deficiency, presents as the triad of ophthalmoplegia, altered mental state, and cerebellar ataxia. However, these symptoms are not consistently present, complicating the diagnosis. In addition, subclinical vitamin B1 deficiency can progress unnoticed until severe complications arise. Studies indicate a high rate of undiagnosed cases, emphasizing the need for early detection and intervention. Case presentation: We present the case of a 65-year-old man in whom hyperlactatemia was incidentally detected, leading to the diagnosis of vitamin B1 deficiency. The patient, presenting with vertigo and vomiting, had been eating boxed lunches bought from convenience stores following the death of his wife 3 years earlier. Vertigo gradually improved with rest, but the persistence of hyperlactatemia prompted further investigation, revealing low vitamin B1 levels and high pyruvate levels. Treatment with dietary adjustments and supplements significantly improved his symptoms. Discussion: In this case, hyperlactatemia was found in a vertigo patient, revealing asymptomatic vitamin B1 deficiency. Elevated lactate is often linked with conditions like sepsis but can also stem from overlooked factors such as low vitamin B1 levels due to poor diet habits like consuming fried foods. Conclusion: This case highlights the importance of considering vitamin B1 deficiency in patients with unexplained hyperlactatemia, even in high-income countries. Early detection can prevent progression to the severe complications associated with Wernicke's encephalopathy. Proactive measurement of lactate levels in at-risk populations may facilitate early diagnosis and intervention, ultimately improving patient outcomes.

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A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) and found for the first time in Sulawesi; it was previously reported only in the eastern Philippines and Borneo. A phytochemical study of S. oblanceolatum led to the isolation of three unprecedented meroterpenoids, syzygioblanes A-C (1-3, respectively). These compounds might be biosynthesized through [4+2] cycloaddition of various germacrane-based cyclic sesquiterpenoids with the flavone desmethoxymatteucinol to form a spiro skeleton. The unique and complex structures were elucidated by microcrystal electron diffraction analysis in addition to general analytical techniques such as high-resolution mass spectrometry, various nuclear magnetic resonance methods, and infrared spectroscopy. Synchrotron X-ray diffraction and calculations of electronic circular dichroism spectra helped to determine the absolute configurations. The newly isolated compounds exhibited collateral sensitivity to more strongly inhibit the growth of a multidrug resistant tumor cell line compared to a chemosensitive tumor cell line.

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RATIONALE: Low-velocity penetrating head injury (PHI) is rare, comprising 0.2% to 0.4% of head traumas, but can be devastating and is associated with significant morbidity and mortality. No previous case of very-low-velocity PHI due to self-inflicted stabbing with a gimlet has been reported. PATIENT CONCERNS: A 62-year-old man was admitted to the hospital with bleeding head and abdominal wounds after stabbing his abdomen with a gimlet, and then hammering the same gimlet into his forehead and removing the gimlet himself. DIAGNOSES: Upon examination at admission, stab wounds were present on the forehead and the right upper quadrant. Computed tomography (CT) of the head revealed a bone defect in the left frontal bone and showed the intracranial path of the gimlet surrounded by mild hemorrhage and pneumocephalus. Magnetic resonance imaging (MRI) confirmed a small amount of hemorrhage with pneumocephalus but no vascular injury. INTERVENTIONS: Conservative treatment without surgery. OUTCOMES: Follow-up MRI on hospital day 58 showed no abscess or traumatic intracranial aneurysm. The patient achieved full recovery of motor and mental functions with conservative treatment and was discharged on hospital day 69. LESSONS: Very-low-velocity PHI might be successfully treated with conservative treatment.

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BACKGROUND: Operative treatment of traumatic rib fractures for better outcomes remains under debate. Surgical stabilization of rib fractures has dramatically increased in the last decade. This study aimed to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) to assess the effectiveness and safety of operative treatment compared to conservative treatment in adult patients with traumatic multiple rib fractures. METHODS: A systematic literature review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines. We searched MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials and used the Cochrane Risk-of-Bias 2 tool to evaluate methodological quality. Relative risks with 95% confidence interval (CI) were calculated for outcomes: all-cause mortality, pneumonia incidence, and number of mechanical ventilation days. Overall certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with trial sequential analysis performed to establish implications for further research. RESULTS: From 719 records, we included nine RCTs, which recruited 862 patients. Patients were assigned to the operative group (received surgical stabilization of chest wall injury, n = 423) or control group (n = 439). All-cause mortality was not significantly different (RR = 0.53; 95% CI 0.21 to 1.38, P = 0.35, I2 = 11%) between the two groups. However, in the operative group, duration of mechanical ventilation (mean difference -4.62; 95% CI -7.64 to -1.60, P < 0.00001, I2 = 94%) and length of intensive care unit stay (mean difference -3.05; 95% CI -5.87 to -0.22; P < 0.00001, I2 = 96%) were significantly shorter, and pneumonia incidence (RR = 0.57; 95% CI 0.35 to 0.92; P = 0.02, I2 = 57%) was significantly lower. Trial sequential analysis for mortality indicated insufficient sample size for a definitive judgment. GRADE showed this meta-analysis to have very low to low confidence. CONCLUSION: Meta-analysis of large-scale trials showed that surgical stabilization of multiple rib fractures shortened the duration of mechanical ventilation and reduced the incidence of pneumonia but lacked clear evidence for improvement of mortality compared to conservative treatment. Trial sequential analysis suggested the need for more cases, and GRADE highlighted low certainty, emphasizing the necessity for further targeted RCTs, especially in mechanically ventilated patients. SYSTEMATIC REVIEW REGISTRATION: UMIN Clinical Trials Registry UMIN000049365.

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Background and Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world. To assess the influence of the COVID-19 pandemic on emergency medical services (EMS) for vulnerable patients transported by ambulance. Materials and Methods: This study was a retrospective, descriptive study with a study period from 1 January 2019 to 31 December 2021 using the Osaka Emergency Information Research Intelligent Operation Network (ORION) system. We included all pediatric patients, pregnant women, and elderly patients ≥ 65 years of age transported by ambulance in Osaka Prefecture. The main outcome of this study was difficult-to-transport cases. We calculated the rate of difficult-to-transport cases under several conditions. Results: For the two year-long periods of 1 January 2019 to 31 December 2019 and 1 January 2021 to 31 December 2021, a total of 887,647 patients were transported to hospital by ambulance in Osaka Prefecture. The total number of vulnerable patients was 579,815 (304,882 in 2019 and 274,933 in 2021). Multivariate logistic regression analysis showed that difficult-to-transport cases were significantly more frequent in 2021 than in 2019. Difficult-to-transport cases were significantly less frequent in the vulnerable population than in the non-vulnerable population (adjusted odds ratio 0.81, 95% confidence interval 0.80-0.83; p < 0.001). Conclusion: During the pandemic (2021), difficult-to-transport cases were more frequent compared to before the pandemic (2019); however, vulnerable patients were not the cause of difficulties in obtaining hospital acceptance for transport.

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Background: We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. Methods: This single-center, ambidirectional cohort study of 548 consecutive patients ≥20 years of age was performed in the ED of a university hospital in Japan over a 13-month period. Pairs of blood samples were collected for aerobic and anaerobic cultures from patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. Results: Potential contamination was identified in 110 of the 548 patients (20.1%). One hundred fourteen (20.8%) patients showed true-positive results for bacteremia, and 324 (59.1%) patients showed true-negative results. Multivariate analysis revealed more frequent contamination when puncture sites were disinfected with povidone-iodine (PVI) than with alcohol/chlorhexidine (ACHX) (adjusted risk difference, 19.1%; 95% confidence interval [CI]), 15.7-22.6; p < 0.001). In terms of blood collection sites, femoral and central venous (CV) catheter with PVI disinfection showed more frequent contamination than venous sites with ACHX (adjusted risk differences: 26.6%, 95% CI 21.3-31.9, p < 0.001 and 41.1%, 95% CI 22.2-59.9, p < 0.001, respectively). Conclusion: Rates of contaminated blood cultures were significantly higher when blood was collected from the CV catheter or femoral sites with PVI as the topical disinfectant.

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The models used to investigate the pathophysiological mechanisms of acute critical illness are not limited to mammalian species. The zebrafish (Danio rerio) is a popular model organism for studying diseases due to its transparency and rapid development. The genes and signaling pathways involved in acute critical illness appear highly conserved among zebrafish and humans. Forward genetics such as random mutagenesis by a chemical mutagen or reverse genetics methods represented by CRISPR/Cas9 allowed researchers to reveal multiple novel aspects of pathological processes in areas including infection, immunity, and regeneration. As a model of sepsis, transgenic zebrafish allowed the visualization of lipopolysaccharide (LPS)-induced vascular leakage in vivo and the demonstration of changes in the expression of cellular junction proteins. Other transgenic zebrafish visualizing the extravascular migration of neutrophils and macrophages have demonstrated a decrease in neutrophil numbers and an increased expression of an inflammatory gene, which replicates a phenomenon observed in humans in clinically encountered sepsis. The regenerative potential and the visibility of zebrafish organs also enabled clarification of important mechanisms in wound healing, angiogenesis, and neurogenesis. After spinal cord injury (SCI), a marker gene expressed in glial bridging was discovered. Furthermore, localized epithelial-to-mesenchymal transition (EMT) and molecular mechanisms leading to spinal cord repair were revealed. These translational studies using zebrafish show the potential of the model system for the treatment of acute critical illnesses such as sepsis, organ failure, and trauma.

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BACKGROUND: New-onset anisocoria is an important clinical clue to life-threatening intracranial injury. Anisocoria alone without impairment of extraocular muscles is a rare presentation of moderate traumatic brain injury (TBI). CASE PRESENTATION: A 79-year-old woman was transported to hospital soon after falling off a bicycle. Glasgow Coma Scale score on arrival was 11 (E3V3M5). On examination at admission, she was found to be drowsy. Bruising was seen around the right eye and pupil diameters differed (right, 4.5 mm; left, 3.0 mm; both reactive to light). Computed tomography of the head revealed hemorrhagic contusion in the left temporal lobe and left pretectal area of the midbrain, right clavicular fracture, and pulmonary contusion with fractures of the 3rd and 4th ribs. Magnetic resonance imaging confirmed hemorrhagic contusion of the midbrain. The patient achieved full recovery of motor and mental functions with conservative treatment and was discharged on hospital day 17. CONCLUSION: We encountered a case of anisocoria without major extraocular muscle impairment due to moderate TBI with midbrain contusion.

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Altered endoplasmic reticulum (ER) Ca2+ signaling has been linked with ß-cell dysfunction and diabetes development. Store-operated Ca2+ entry replenishes ER Ca2+ through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). For characterization of the in vivo impact of STIM1 loss, mice with ß-cell-specific STIM1 deletion (STIM1Δß mice) were generated and challenged with high-fat diet. Interestingly, ß-cell dysfunction was observed in female, but not male, mice. Female STIM1Δß mice displayed reductions in ß-cell mass, a concomitant increase in α-cell mass, and reduced expression of markers of ß-cell maturity, including MafA and UCN3. Consistent with these findings, STIM1 expression was inversely correlated with HbA1c levels in islets from female, but not male, human organ donors. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1Δß mice was due, in part, to loss of signaling through the noncanonical 17-ß estradiol receptor (GPER1), as GPER1 knockdown and inhibition led to a similar loss of expression of ß-cell maturity genes in INS-1 cells. Together, these data suggest that STIM1 orchestrates pancreatic ß-cell function and identity through GPER1-mediated estradiol signaling. ARTICLE HIGHLIGHTS: Store-operated Ca2+ entry replenishes endoplasmic reticulum (ER) Ca2+ through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). ß-Cell-specific deletion of STIM1 results in a sexually dimorphic phenotype, with ß-cell dysfunction and loss of identity in female but not male mice. Expression of the noncanonical 17-ß estradiol receptor (GPER1) is decreased in islets of female STIM1Δß mice, and modulation of GPER1 levels leads to alterations in expression of ß-cell maturity genes in INS-1 cells.

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The steric zipper is a common hydrophobic packing structure of peptide side chains that forms between two adjacent ß-sheet layers in amyloid and related fibrils. Although previous studies have revealed that peptide fragments derived from native protein sequences exhibit steric zipper structures, their de novo designs have rarely been studied. Herein, steric zipper structures were artificially constructed in the crystalline state by metal-induced folding and assembly of tetrapeptide fragments Boc-3pa-X1-3pa-X2-OMe (3pa: ß-(3-pyridyl)-l-alanine; X1 and X2: hydrophobic amino acids). Crystallographic studies revealed two types of packing structures, interdigitation and hydrophobic contact, that result in a class 1 steric zipper geometry when the X1 and X2 residues contain alkyl side chains. Furthermore, a class 3 steric zipper geometry was also observed for the first time among any reported steric zippers when using tetrapeptide fragments with (X1, X2) = (Thr, Thr) and (Phe, Leu). The system could also be extended to a knob-hole-type zipper using a pentapeptide sequence.

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BACKGROUND: Nutritional status of critically ill patients is an important factor affecting complications and mortality. This study aimed to investigate the impact of three nutritional indices, the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT), on mortality in patients with sepsis in Japan. METHODS: This retrospective observational study used the Medical Data Vision database containing data from 42 acute-care hospitals in Japan. We extracted data on baseline characteristics on admission. GNRI, PNI, and CONUT scores on admission were also calculated. To evaluate the significance of these three nutritional indices on mortality, we used logistic regression to fit restricted cubic spline models and constructed Kaplan-Meier survival curves. RESULTS: We identified 32,159 patients with sepsis according to the inclusion criteria. Of them, 1804 patients were treated in intensive care units, and 3461 patients were non-survivors. When the GNRI dropped below 100, the risk of mortality rose sharply, as did that when the PNI dropped below about 40. An increased CONUT score was associated with increased mortality in an apparent linear manner. CONCLUSION: In sepsis management, GNRI and PNI values may potentially be helpful in identifying patients with a high risk of death.

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Background: Bifidobacterium breve is an obligate anaerobic gram-positive bacillus mainly found in the gastrointestinal tract of human infants. Few cases of necrotizing fasciitis caused by B. breve have been reported. Case presentation: A 42-year-old Japanese man with type 2 diabetes mellitus, obesity, cellulitis of the back, and subcutaneous abscess of the right inguinal region presented with rapidly developing erythema, swelling and severe pain in the right inguinal region. Computed tomography showed widespread gas in the right leg region. Cultures of blood and a swab of the wound abscess grew gram-positive bacilli. Mass spectrography and 16 S rDNA analysis confirmed the gram-positive bacilli as B. breve. The patient recovered following extensive debridement and antibacterial therapy. Conclusion: Unidentified necrotizing fasciitis can be caused by B. breve, especially in compromised hosts.

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OBJECTIVE: We aimed to identify the proportion of each medical condition or disease contributing to dizziness and their disposition in the Emergency Department (ED). METHODS: This retrospective, descriptive study examined data from the Osaka Emergency Information Research Intelligent Operation Network system in Japan for the period from January 1, 2018 to December 31, 2020. The inclusion criteria were patients with presumptive ICD-10 codes including "dizziness" or "vertigo". Patient demographics were compared using the χ2 test and Kruskal-Wallis test. Logistic regression analysis was performed to calculate disposition from ED (emergency admission or discharge) over the 3-year study period. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate analyses. RESULTS: During the 3-year study period, a total of 1,346,457 patients (462,773 in 2018, 468,697 in 2019, and 414,987 in 2020; P < 0.001), including 53,190 patients with dizziness (18,396 in 2018, 18,649 in 2019, and 16,145 in 2020; P = 0.058), were identified as having been transported to hospitals by ambulance in Osaka Prefecture. Dizziness and giddiness (R42) was the most common form of dizziness, in 27,075 cases (9,570 in 2018, 9,613 in 2019, and 7,892 in 2020; P < 0.001; Gender composition showed 10,483 males and 16,592 females.) Vestibular Neuronitis (H81.2) showed significant increase in 2020 compared to the two preceding years (91 in 2018, 119 in 2019, and 130 in 2020, P = 0.003; including 174 males and 167 females, respectively). Of the 53,190 patients with dizziness, 11,862 (22.3%; 4,323 males, 7,539 females) were admitted to hospital. The odds ratio (OR) for emergency admission for dizziness in 2020 during the COVID-19 pandemic was 0.98 (95% confidence interval (CI), 0.93- 1.03) with reference to 2018. CONCLUSION: Patients with dizziness accounted approximately 4% of ED transportations, with about 20% requiring hospital admission, irrespective of the COVID-19 pandemic. Vestibular neuronitis was significantly increased in 2020.

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BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2, has spread rapidly around the world. OBJECTIVE: To assess the effect of the COVID-19 pandemic on the emergency medical service (EMS) and hospital admission course for children transported by ambulance. METHODS: This study was a retrospective, descriptive study with a study period from January 1, 2018 to December 31, 2020 using the Osaka Emergency Information Research Intelligent Operation Network (ORION) system. All children who were transported by ambulance in Osaka Prefecture were included. The main outcome of this study was the rate of difficult-to-transfer cases, which was calculated by univariate and multivariate Poisson regression analyses. RESULTS: Over the 3 years between January 1, 2018 and December 31 2020, 1,436,212 patients were transported to hospitals by ambulances in Osaka Prefecture, with children accounting for 102,473 (37,064, 39,590, and 25,819, in 2018, 2019, and 2020, respectively). Poisson regression analysis showed that children were negatively associated with difficult-to-transfer cases (risk ratio (RR) 0.35, 95% CI 0.33 to 0.37). With reference to 2018, 2020 was not significantly associated with difficult-to-transfer cases in children (RR 1.14, 95% CI 0.99 to 1.32, P = 0.075), but was significantly related (RR 1.24, 95% CI 1.21 to 1.27, P < 0.001) to difficult-to-transfer cases in the general population. CONCLUSION: Children were consistently associated with a reduced RR for difficult-to-transfer cases, even in the COVID-19 pandemic in 2020.

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While the Surviving Sepsis Campaign guidelines recommend an initial target value of 65 mmHg as the mean arterial pressure (MAP) in patients with septic shock, the optimal MAP target for improving outcomes remains controversial. We performed a meta-analysis to evaluate the optimal MAP for patients with vasodilatory shock, which included three randomized controlled trials that recruited 3,357 patients. Between the lower (60-70 mmHg) and higher (>70 mmHg) MAP target groups, there was no significant difference in all-cause mortality (risk ratio [RR], 1.06; 95% confidence intervals [CI], 0.98-1.16) which was similar in patients with chronic hypertension (RR, 1.10; 95% CI, 0.98-1.24) and patients aged ≥65 years (RR, 1.10; 95% CI, 0.99-1.21). No significant difference in adverse events was observed between the different MAP groups (RR, 1.04; 95% CI, 0.87-1.24); however, supraventricular arrhythmia was significantly higher in the higher MAP group (RR, 1.73; 95% CI, 1.15-2.60). Renal replacement therapy was reduced in the higher MAP group of patients with chronic hypertension (RR, 0.83; 95% CI, 0.71-0.98). Though the higher MAP control did not improve the mortality rate, it may be beneficial in reducing renal replacement therapy in patients with chronic hypertension. Systematic review registration: UMIN Clinical Trials Registry, identifier UMIN000042624.

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Aim: Prone positioning of coronavirus disease 2019 (COVID-19) patients could improve oxygenation. However, clinical data on prone positioning of intubated COVID-19 patients are limited. We investigated trends of PaO2 / FiO2 ratio values in patients during prone positioning to identify a predictive factor for early detection of patients requiring advanced therapeutic intervention such as extracorporeal membrane oxygenation (ECMO). Methods: This retrospective, observational cohort study was undertaken between April 2020 and May 2021 in a tertiary referral hospital for COVID-19 in Osaka, Japan. We included intubated adult COVID-19 patients treated with prone positioning within the first 72 h of admission to the intensive care unit and followed them until hospital discharge or death. Primary outcomes were in-hospital mortality and escalation of care to ECMO. We used unsupervised k-means clustering modeling to categorize COVID-19 patients by PaO2 / FiO2 ratio responsiveness to prone positioning. Results: The final study cohort comprised 54 of 155 consecutive severe COVID-19 patients. Three clusters were generated according to trends in PaO2 / FiO2 ratios during prone positioning (cluster A, n = 16; cluster B, n = 24; cluster C, n = 14). Baseline characteristics of all clusters were almost similar. Cluster A (no increase in PaO2 / FiO2 ratio during prone positioning) had a significantly higher proportion of patients placed on ECMO or who died (6/16, 37.5%). Numbers of patients with ECMO and with in-hospital death were significantly different between the three groups (p = 0.017). Conclusion: In Japanese patients intubated due to COVID-19, clinicians should consider earlier escalation of treatment, such as facility transfer or ECMO, if the PaO2 / FiO2 ratio does not increase during initial prone positioning.

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BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2, has spread rapidly across the world. OBJECTIVE: To assess the influence of the COVID-19 pandemic on the emergency medical service (EMS) for transportation of pregnant women by ambulance. METHODS: This study was a retrospective, descriptive study using the Osaka Emergency Information Research Intelligent Operation Network system, and included pregnant women transported by ambulance in Osaka Prefecture between January 1, 2018 and December 31, 2020. The main outcome of the study was difficulty in obtaining hospital acceptance for transfer of patients (difficult-to-transfer cases). We calculated the rates of difficult-to-transfer cases using univariate and multivariate analyses. RESULTS: Of the 1 346 457 total patients transported to hospitals by ambulance in Osaka Prefecture during the study period, pregnant women accounted for 2586 (909, 943, and 734, in 2018, 2019, and 2020, respectively). Logistic regression analysis revealed that pregnant women were negatively associated with difficult-to-transfer cases (adjusted OR 0.36, 95% CI 0.26-0.50). Compared with 2018, 2020 was significantly associated with difficult-to-transfer cases (adjusted OR 1.27, 95% CI 1.24-1.30). CONCLUSION: Pregnant women were consistently associated with reduced odds for being difficult-to-transfer cases. The COVID-19 pandemic might have influenced difficult-to-transfer cases in 2020.

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