Association of Relative Dysglycemia With Hospital Mortality in Critically Ill Patients: A Retrospective Study.

OBJECTIVES: Relative dysglycemia has been proposed as a clinical entity among critically ill patients in the ICU, but is not well studied. This study aimed to clarify associations of relative hyperglycemia and hypoglycemia during the first 24 hours after ICU admission with in-hospital mortality and the respective thresholds. DESIGN: A single-center retrospective study. SETTING: An urban tertiary hospital ICU. PATIENTS: Adult critically ill patients admitted urgently between January 2016 and March 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximum and minimum glycemic ratio (GR) was defined as maximum and minimum blood glucose values during the first 24 hours after ICU admission divided by hemoglobin A1c-derived average glucose, respectively. Of 1700 patients included, in-hospital mortality was 16.9%. Nonsurvivors had a higher maximum GR, with no significant difference in minimum GR. Maximum GR during the first 24 hours after ICU admission showed a J-shaped association with in-hospital mortality, and a mortality trough at a maximum GR of approximately 1.12; threshold for increased adjusted odds ratio for mortality was 1.25. Minimum GR during the first 24 hours after ICU admission showed a U-shaped relationship with in-hospital mortality and a mortality trough at a minimum GR of approximately 0.81 with a lower threshold for increased adjusted odds ratio for mortality at 0.69. CONCLUSIONS: Mortality significantly increased when GR during the first 24 hours after ICU admission deviated from between 0.69 and 1.25. Further evaluation will necessarily validate the superiority of personalized glycemic management over conventional management.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Wet Beriberi Associated with Hikikomori Syndrome.

Wet beriberi, characterized by high cardiac output with predominantly right-sided heart failure and lactic acidosis, is a disease caused by thiamine deficiency, and is rarely seen in modern society. However, patients with social withdrawal syndrome, also known as hikikomori syndrome, may be a new population at risk of thiamine deficiency. Hikikomori syndrome, first recognized in Japan, is becoming a worldwide issue. A 39-year-old Japanese patient was brought to our hospital, with a 3-week history of progressive shortness of breath and generalized edema. The patient had right-sided high-output heart failure, lactic acidosis, and Wernicke-Korsakoff syndrome. Because of his history of social isolation, we diagnosed hikikomori syndrome according to the Japanese government's definition, which is as follows: lifestyle centered at home; no interest or willingness to attend school or work; persistence of symptoms beyond 6 months; and exclusion of other psychiatric and developmental disorders. Considering his diagnosis of hikikomori syndrome and social isolation, we suspected malnutrition, particularly thiamine deficiency, and successfully treated him. Clinicians should be aware of the potential risk of thiamine deficiency associated with hikikomori syndrome and initiate thiamine replacement in cases of high-output heart failure associated with lactic acidosis.

Combined cumulative sum (CUSUM) and chronological environmental analysis as a tool to improve the learning environment for linear-probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) trainees: a pilot study.

BACKGROUND: Cumulative sum (CUSUM) analysis can be used to continuously monitor the performance of an individual or process and detect deviations from a preset or standard level of achievement. However, no previous study has evaluated the utility of CUSUM analysis in facilitating timely environmental assessment and interventions to improve performance of linear-probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The aim of this study was to evaluate the usefulness of combined CUSUM and chronological environmental analysis as a tool to improve the learning environment for EBUS-TBNA trainees. METHODS: This study was an observational chart review. To determine if performance was acceptable, CUSUM analysis was used to track procedural outcomes of trainees in EBUS-TBNA. To investigate chronological changes in the learning environment, multivariate logistic regression analysis was used to compare several indices before and after time points when significant changes occurred in proficiency. RESULTS: Presence of an additional attending bronchoscopist was inversely associated with nonproficiency (odds ratio, 0.117; 95% confidence interval, 0-0.749; P = 0.019). Other factors, including presence of an on-site cytopathologist and dose of sedatives used, were not significantly associated with duration of nonproficiency. CONCLUSIONS: Combined CUSUM and chronological environmental analysis may be useful in hastening interventions that improve performance of EBUS-TBNA.

A Case of Scurvy Associated With Intracerebral Hemorrhage in a Patient With Alcohol Use Disorder.

Vitamin C deficiency, also known as scurvy, causes abnormalities in connective tissues and varied symptoms. We describe a patient with putaminal hemorrhage, a very rare presentation of scurvy. A 39-year-old man presented with weakness in the left arm and left leg. Right putaminal hemorrhage was initially diagnosed, and he underwent evacuation of the intracerebral hemorrhage. Scurvy was suspected when repeated physical examinations revealed a bleeding tendency and multiple untreated dental caries, missing teeth, and gingivitis. A diagnosis of scurvy was further supported by the patient's history of smoking, alcohol use disorder, poor diet, and low plasma vitamin C concentration. After receiving oral nutritional supplementation including vitamin C, the bleeding tendency quickly improved. This case highlights the importance of including scurvy in a differential diagnosis for patients with bleeding tendencies, especially those with a poor diet or unknown dietary history. Empirical administration of vitamin C is a reasonable treatment.

Proposed Clinical Algorithm for Pleuroparenchymal Fibroelastosis (PPFE).

Pleuroparenchymal fibroelastosis (PPFE) is characterized by fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes. As PPFE appears to occur in patients with heterogeneous etiologies, the disease course is thus also heterogenous, with some patients showing rapid progression while others have slow progression. Therefore, it is very difficult to predict prognosis with PPFE. Needless to say, this problematic matter has influenced the treatment strategy of PPFE patients. In fact, until now no evidence has been shown for use in creating an appropriate management algorithm for PPFE. We speculate that "uncoordinated breathing" is the most important reason for dyspnea in PPFE patients. Because monitoring of physique and not just pulmonary function and radiological evaluation is also very important, particularly in PPFE patients, this review focused on the characteristics of PPFE through an overview of previous studies in this field, and we proposed an algorithm as precision medicine based on the current evidence. Multiple views by the pulmonologist are needed to standardize a clinical algorithm that is necessary to correctly assess PPFE patients under the premise of maintenance of physique by providing appropriate nutritional care and pulmonary rehabilitation.

Case Report: An Imported Case of Severe Leptospirosis with Septic Cardiomyopathy Requiring Venoarterial Extracorporeal Membrane Oxygenation in Japan.

A 29-year-old Japanese man presenting with fever, joint pain, and diarrhea was admitted to the intensive care unit for cardiogenic and distributive shock. We suspected leptospirosis based on conjunctival hyperemia, skin rash, elevated bilirubin, and renal involvement; a travel history to Laos was also suggestive. We confirmed the diagnosis with blood and urine polymerase chain reaction and microscopic agglutination tests using paired serum samples. His hemodynamics were unstable, and his echocardiogram showed diffuse and severe left ventricular systolic dysfunction on day 2. He initially required venoarterial extracorporeal membrane oxygenation (V-A ECMO) support but responded and recovered on antimicrobial therapy. His cardiac function and hemodynamics improved on day 5. Severe leptospirosis may cause jaundice, renal failure, pulmonary hemorrhage, acute respiratory distress syndrome, and central nervous system involvement; however, few studies have reported severe cardiac manifestations. Herein, we report the first case of septic cardiomyopathy secondary to leptospirosis that was successfully managed with V-A ECMO. Leptospirosis should be included in the differential diagnosis when a patient returning from an endemic area presents with cardiogenic shock. Furthermore, intensive care management with prompt initiation of V-A ECMO should be considered to reverse septic cardiomyopathy.

Efficacy of tyrosine kinase inhibitors in patients with non-small-cell lung cancer with performance status 4: a case series and review of the literature.

BACKGROUND: Current guidelines for non-small-cell lung cancer (NSCLC) recommend that each tyrosine kinase inhibitor (TKI) is indicated even for driver mutation-positive patients with a poor performance status (PS). In previous studies, most patients had a PS of 2-3, but those with a PS of 4 were very few. Therefore, the efficacy of TKIs in patients with NSCLC with a PS of 4 remains unclear. CASE PRESENTATION: We retrospectively reviewed the clinical records of four patients with NSCLC with PS 4 treated with TKIs: an 89-year-old Japanese woman (Case 1), a 80-year-old Japanese woman (Case 2), an 50-year-old Japanese man (Case 3), and a 81-year-old Japanese woman (Case 4). Genetic alterations were epidermal growth factor receptor (EGFR), MET exon 14 skipping, BRAFV600E, and ROS1 proto-oncogene receptor tyrosine kinase (ROS1). One case with ROS1 fusion showed a significant response with the recovery of PS. However, in the remaining three cases (i.e., EGFR, MET exon 14 skipping, and BRAFV600E mutations), patients died despite the administration of TKIs. These three patients had to be hospitalized at the end of their life to receive treatment. CONCLUSIONS: This is the first case series to summarize the efficacy of TKIs in patients with NSCLC with a PS of 4. Additionally, this case series poses a question concerning the indication of TKIs for older patients with a PS of 4.

Validation study of EuroSCORE II for dialysis patients: A single-center study in Japan.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II is a predictive model for in-hospital mortality after cardiac surgery. Although it has good performance among the general population undergoing cardiac surgery, it has not been validated among dialysis patients, who have a higher rate of mortality after cardiac surgery. This study aimed to evaluate the performance of the model in predicting in-hospital mortality in maintenance dialysis patients undergoing cardiac surgery. METHODS: This retrospective, single-center study included adult patients on maintenance dialysis who underwent open cardiac surgery at our institution. Calibration performance of EuroSCORE II for in-hospital death was determined based on the comparison between expected and observed mortalities for low- (EuroSCORE II <4 %), intermediate- (4-8 %), and high-risk (>8 %) groups. The area under receiver operating characteristic curve (AUROC) was investigated to determine the model's discrimination performance. RESULTS: A total of 163 patients (male, 73.6 %; median age, 70 years; median dialysis vintage, 9 years; median EuroSCORE II, 3.3 %) were included. The mortality rate was 9.2 %. The observed mortality rates (vs. mean expected mortality) rates were 2.1 % (vs. 2.4 %), 7.5 % (vs. 5.5 %), and 34.5 % (vs. 21.1 %) in the low-, intermediate-, and high-risk groups, respectively. Its AUROC was 0.825 (95 % confidence interval, 0.711-0.940). CONCLUSIONS: Although EuroSCORE II model adequately estimated in-hospital mortality in the low-and intermediate-risk groups (EuroSCORE II <8 %), it underestimated in-hospital mortality in the high-risk group (EuroSCORE II >8 %) among maintenance dialysis patients. The discrimination performance of the model for in-hospital death was good among maintenance dialysis patients.

Feasibility of Nurse-Led Advance Care Planning Before Pre-cardiac Procedures: A Descriptive Study.

Background Shared decision-making is important for deciding whether to perform surgery, especially high-risk surgery, or end-of-life care in cases of serious complications after the surgery. In shared decision-making, surgeons should be aware of patients' values. Therefore, advance care planning (ACP) before the surgery is important. In Japan, the feasibility of ACP, particularly preoperative nurse-led ACP, is yet to be evaluated. Methodology This retrospective, single-center, descriptive study included all adult candidates for open-heart or thoracic aortic surgery and transcutaneous aortic valve implantation (TAVI) referred by their surgeon for a nurse-led preoperative ACP between April 1, 2020 and December 31, 2021. The nurse conducted semi-structured interviews with patients regarding goals of care, unacceptable conditions, undesired procedures, advance directives, and their surrogates and documented them. The content of these interviews and their influence on decision-making were retrospectively investigated. Results Sixty-four patients (median age, 82 years; Society of Thoracic Surgeons (STS) score, 7.9; EuroSCORE II, 4.2; JapanSCORE, 7.0) were included (open-heart or thoracic aortic surgery 24, TAVI 40). Among them, 63 (98.4%), 56 (87.5%), and 13 (20.3%) patients articulated their goals of care, unacceptable conditions, and undesired procedures. Only one (1.6%) had a written advance directive. Although all of the patients could designated their surrogate, only 11 (17.2%) had shared their values disclosed in the pre-procedure ACP communication with their surrogates. Two patients who planned to undergo open-heart surgery disclosed their wish not to undergo the surgery only to the nurses but could not tell their surgeon; thereafter, the surgery was canceled. Three patients died after the procedure; however, the patients' value disclosed in ACP was not used for the end-of-life decision. Conclusion Nurse-led ACP can be implemented before high-risk cardiac procedures. It may have an impact on the decision-making of surgery although the ACP content may not be utilized for the end-of-life discussion after the procedures between surgeons and the family member.

Correction: Comparison of professionalism between emergency medicine resident physicians and faculty physicians: A multicenter cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0230186.].

Efficacy of Higher Positive End-Expiratory Pressure Ventilation Strategy in Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Previous systematic reviews and meta-analyses assessing the pooled effects of higher positive end-expiratory pressure (PEEP) failed to show significantly reduced mortality in patients with acute respiratory distress syndrome (ARDS). Some new randomized controlled trials (RCTs) have been reported and an updated systematic review is needed to evaluate the use of higher PEEP in patients with ARDS. We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Igaku-Chuo-Zasshi, ICTRP, the National Institute of Health Clinical Trials Register, and the reference list of recent guidelines. We included RCTs to compare the higher PEEP ventilation strategy with the lower strategy in patients with ARDS. Two authors independently assessed the eligibility of the studies and extracted the data. The primary outcomes were 28-day mortality. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology was used to evaluate the certainty of the evidence. Among the 6530 screened records, 16 randomized trials involving 4150 patients were included in our meta-analysis. When comparing higher PEEP versus lower PEEP, the pooled risk ratio (RR) for 28-day mortality was 0.85 (15 studies, n=4108, 95% CI 0.72 to 1.00, I2=58%, low certainty of evidence). Subgroup analysis by study participants with a low tidal volume (LTV) strategy showed an interaction (P for interaction, 0.001). Our study showed that in patients with ARDS, the use of higher PEEP did not significantly reduce 28-day mortality compared to the use of lower PEEP.

Dabrafenib plus trametinib treatment for a patient with BRAF V600E-mutated large-cell lung carcinoma and a poor performance status.

Dabrafenib plus trametinib is active against metastatic lung cancer with the BRAF V600E mutation. However, the feasibility of dabrafenib plus trametinib for patients with a poor performance status (PS) has not been reported. We report the case of an 80-year-old woman was diagnosed with metastatic large-cell lung carcinoma. Her general statuses worsened due to cancer, resulting in a PS of 4. Genotype testing revealed a BRAF V600E mutation. The patient received dabrafenib plus trametinib without significant adverse effects. This report is the first to describe dabrafenib plus trametinib administration for large-cell lung carcinoma in a patient with a poor PS.

Usefulness of low tidal volume ventilation strategy for patients with acute respiratory distress syndrome: a systematic review and meta-analysis.

The effects of lower tidal volume ventilation (LTV) were controversial for patients with acute respiratory distress syndrome (ARDS). This systematic review and meta-analysis aimed to evaluate the use of LTV strategy in patients with ARDS. We performed a literature search on MEDLINE, CENTRAL, EMBASE, CINAHL, "Igaku-Chuo-Zasshi", clinical trial registration sites, and the reference of recent guidelines. We included randomized controlled trials (RCTs) to compare the LTV strategy with the higher tidal volume ventilation (HTV) strategy in patients with ARDS. Two authors independently evaluated the eligibility of studies and extracted the data. The primary outcomes were 28-day mortality. We used the GRADE methodology to assess the certainty of evidence. Among the 19,864 records screened, 13 RCTs that recruited 1874 patients were included in our meta-analysis. When comparing LTV (4-8 ml/kg) versus HTV (> 8 ml/kg), the pooled risk ratio for 28-day mortality was 0.79 (11 studies, 95% confidence interval [CI] 0.66-0.94, I2 = 43%, n = 1795, moderate certainty of evidence). Subgroup-analysis by combined high positive end-expiratory pressure with LTV showed interaction (P = 0.01). Our study indicated that ventilation with LTV was associated with reduced risk of mortality in patients with ARDS when compared with HTV. Trial registration: UMIN-CTR (UMIN000041071).

Culturally Adapted Consensus Definition and Action Guideline: Japan's Advance Care Planning.

CONTEXT: A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making. OBJECTIVES: A consensus definition of advance care planning with action guideline adapted to Japanese society. METHODS: We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan. RESULTS: The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future. CONCLUSION: Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Diagnostic delay of acute mitral regurgitation during the coronavirus disease 2019 pandemic: a case report.

BACKGROUND: Diagnostic errors or delays can cause serious consequences for patient safety, especially in the emergency department. Anchoring bias is one of the major factors leading to diagnostic error. During the coronavirus disease 2019 (COVID-19) pandemic, the high probability of COVID-19 in febrile patients could be a major cause of anchoring bias leading to diagnostic error. In addition, certain evaluations such as auscultation are difficult to perform on a casual basis due to the increased risk of contact infection, which lead to inadequate assessment of the patients with valvular disease. Acute mitral regurgitation (MR) could be a fatal disease in the emergency department, especially if there is a diagnostic error or delay in diagnosis. It is often reported that diagnosis can be difficult even though there is no treatment other than emergent surgery. The diagnosis of acute MR has become more difficult because coronavirus disease 2019 (COVID-19) pandemic could affect our daily practice especially in febrile patients. We report a case of a diagnostic delay of a febrile patient because of anchoring bias during the COVID-19 pandemic. CASE PRESENTATION: A 45-year-old man presented to the emergency department complaining of acute dyspnea and fever. Based on vital signs and computed tomography of the chest, acute pneumonia due to COVID-19 was suspected. Auscultation was avoided because of facility rule based on concern of contact infection. After admission to the intensive care unit, Doppler echocardiography revealed acute mitral regurgitation, and transesophageal echocardiography revealed mitral valve tendon rupture. After confirming the negative result for the polymerase chain reaction of severe acute respiratory syndrome coronavirus 2, mitral valvuloplasty was performed on the third day after admission. The patient was discharged 14 days after admission without complications. CONCLUSIONS: In COVID-19 pandemic, anchoring bias suspecting COVID-19 among febrile patients becomes a strong heuristic factor. A thorough history and physical examination is still important in febrile patients presenting with dyspnea to ensure the correct diagnosis of acute mitral regurgitation.

Acute Lower Extremity Arterial Thrombosis Associated with Osimertinib-Induced Erythrocytosis.

BACKGROUND Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. CASE REPORT A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient's left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. CONCLUSIONS This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.