Multifunctional Cell Regulation Activities of the Mussel Lectin SeviL: Induction of Macrophage Polarization toward the M1 Functional Phenotype.

SeviL, a galactoside-binding lectin previously isolated from the mussel Mytilisepta virgata, was demonstrated to trigger apoptosis in HeLa ovarian cancer cells. Here, we show that this lectin can promote the polarization of macrophage cell lines toward an M1 functional phenotype at low concentrations. The administration of SeviL to monocyte and basophil cell lines reduced their growth in a dose-dependent manner. However, low lectin concentrations induced proliferation in the RAW264.7 macrophage cell line, which was supported by the significant up-regulation of TOM22, a component of the mitochondrial outer membrane. Furthermore, the morphology of lectin-treated macrophage cells markedly changed, shifting from a spherical to an elongated shape. The ability of SeviL to induce the polarization of RAW264.7 cells to M1 macrophages at low concentrations is supported by the secretion of proinflammatory cytokines and chemokines, as well as by the enhancement in the expression of IL-6- and TNF-α-encoding mRNAs, both of which encode inflammatory molecular markers. Moreover, we also observed a number of accessory molecular alterations, such as the activation of MAP kinases and the JAK/STAT pathway and the phosphorylation of platelet-derived growth factor receptor-α, which altogether support the functional reprogramming of RAW264.7 following SeviL treatment. These results indicate that this mussel ß-trefoil lectin has a concentration-dependent multifunctional role in regulating cell proliferation, phenotype, and death in macrophages, suggesting its possible involvement in regulating hemocyte activity in vivo.

Jugular Venous Response for Risk Stratification in Heart Failure.

BACKGROUND:  The response of jugular venous pressure (JVP) to increased preload with inspiration has been recognized as a method of stratifying risk in the management of heart failure (HF). Whether the JVP response to inspiration may be more effective than other simple approaches in this setting remains unclear. METHODS:  This study enrolled 79 patients with stable HF. JVP was assessed from the right internal jugular vein in the sitting position and was considered high if visible above the right clavicle at rest. JVP responses to inspiration, the five-repetition sit-to-stand test (5-STS), and squatting were also evaluated. The primary outcome was a composite of all-cause death and hospitalization for worsening HF. RESULTS:  JVP assessment after 5-STS and during squatting was not conducted in two and 14 HF patients, respectively, due to physical limitations. During a mean follow-up of 837 days, the primary outcome was associated with a high JVP at rest (hazard ratio, 2.47; 95% confidence interval [CI], 1.09 to 5.60; P <0.05), with inspiration (hazard ratio, 2.53; 95% CI, 1.17 to 5.46; P <0.05), after 5-STS (hazard ratio, 2.61; 95% CI, 1.23 to 5.97; P <0.05), and during squatting (hazard ratio, 2.40; 95% CI, 1.03 to 6.06; P <0.05). Among patients without a high JVP at rest, the specificity of the primary outcome at one year was greater for the JVP response to inspiration (89%) and squatting (92%) than for the response to 5-STS (80%). CONCLUSIONS:  JVP response to increased preload with inspiration may be a simple and practical method for risk assessment in patients with stable HF.

A Case of Sinus Venosus Atrial Septal Defect: Physical Examination as a Diagnostic Clue.

An atrial septal defect (ASD) may be detected later in life due to its asymptomatic status. We report a case of superior sinus venosus ASD, a rare type of ASD, in which bedside physical examination was useful for the diagnosis. A 72-year-old male was referred to cardiology during the treatment of a cerebral infarction. On examination, a right ventricular heave, a split-second heart sound with an increased pulmonary component, and a systolic ejection murmur in the pulmonary region were noted. Transthoracic echocardiography showed a systolic pulmonary artery pressure of 50 mmHg with right heart enlargement, but there was no shunt flow. Because an agitated saline contrast study was positive, transesophageal echocardiography was performed and demonstrated direct flow between the left atrium and superior vena cava. Our report highlights the importance of considering ASD, such as sinus venosus type, even in the absence of transthoracic echocardiographic findings suggestive of this condition, when patients present with a bedside physical examination consistent with ASD.

Rapid Response System and Limitations of Medical Treatment Among Children With Clinical Deterioration in Japan: A Multicenter Retrospective Cohort Study.

Objective: We investigated the role of rapid response systems (RRSs) in limitations of medical treatment (LOMT) planning among children, their families, and health care providers. Methods: This multicenter retrospective cohort study examined children with clinical deterioration using the Japanese RRS registry between 2012 and 2021. Results: Children (n = 348) at 28 hospitals in Japan who required RRS calls were analyzed. Eleven (3%) of the 348 patients had LOMT before RRS calls and 11 (3%) had newly implemented LOMT after RRS calls. Patients with LOMT were significantly less likely to be admitted to an intensive care unit compared with those without (36% vs. 61%, p < 0.001) and were more likely to die within 30 days (45% vs. 11%, p < 0.001). Conclusions: LOMT issues existed in 6% of children who received RRS calls. RRS calls for clinically deteriorating children with LOMT were associated with less intensive care and higher mortality.

Infective Endocarditis Caused by Staphylococcus lugdunensis.

Staphylococcus lugdunensis, a minor species of coagulase-negative staphylococci, has attracted attention because of its formidable pathogenicity. We present a case of infective endocarditis (IE) caused by S. lugdunensis in a 72-year-old woman with a history of breast cancer and metastases who presented with fever. Two of two blood culture bottles were positive for gram-positive cocci. Transesophageal echocardiography revealed vegetation attached to the right cusp of the aortic valve and an abscess in the annulus, which was less evident on transthoracic echocardiography. This case underscores the importance of considering S. lugdunensis as a potential cause of IE.

Jugular Venous Pressure and Kussmaul's Sign as Predictors of Outcome in Heart Failure.

Simplifying the estimation of internal jugular venous pressure (JVP) as visible or not visible above the right clavicle in the sitting position has attracted attention for risk assessment in patients with heart failure (HF). It remains unclear whether this simple assessment, combined with its inspiration response known as Kussmaul's sign, is useful in patients with HF who vary in features such as HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).This study consisted of 246 patients who were admitted for the management of HF. JVP was assessed before discharge and considered high if visible at rest. The inspiration response was also examined. The primary outcome was a composite of all-cause death and hospitalization for worsening HF.One year after discharge, primary outcome events occurred in 91 patients (37%). The incidence of primary outcome was higher in patients with a high JVP at rest (odds ratio, 5.06; 95% confidence interval, 2.31-11.1; P = 0.0001) or with inspiration (odds ratio, 5.93; 95% confidence interval, 2.14-16.4; P < 0.01) than in patients without high JVP conditions. These findings were similarly observed among patients with HFrEF and HFpEF (odds ratios, 3.53 and 6.76; 95% confidence intervals, 1.68-8.68 and 2.19-15.5; P = 0.01 and < 0.01, respectively) and in subgroup analysis stratified by baseline characteristics of the patients.A high JVP at rest and with inspiration as assessed by this simple, practical method may be useful for risk assessment in patients with HF, independent of baseline characteristics.

Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023).

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.

Takotsubo cardiomyopathy induced by acute coronary syndrome: A case report.

Takotsubo cardiomyopathy (TC) can be provoked by various triggers. It should be differentiated from acute coronary syndrome (ACS). Herein, we report a case of TC triggered by ACS. An 80-year-old woman was referred to the emergency room because of prolonged chest pain and ST-segment elevations. Echocardiography demonstrated left ventricular apical ballooning, findings suggestive of TC rather than ACS. Emergency coronary angiography revealed severe stenosis of the first diagonal branch of the left anterior descending coronary artery with distal flow delay. Recanalization of the diagonal branch was achieved by stent implantation and her chest pain was resolved. Cardiac magnetic resonance imaging showed increased signal intensities in the apex and the inner layer of the anterior wall on fat-suppressed, T2-weighted imaging. The present case highlights the importance of recognizing TC in relation to ACS not only as a differential diagnosis but also as a possibly concomitant condition unless clinical features fit one diagnosis. Learning objective: Takotsubo cardiomyopathy can be provoked by various conditions and differentiated from acute coronary syndrome based on the presence or absence of coronary artery stenosis. Our case highlights the importance of acknowledging that takotsubo cardiomyopathy may be induced by acute coronary syndrome.

Physical Examination as a Clue to Transthyretin Cardiac Amyloidosis: A Case Report.

Transthyretin (ATTR) cardiac amyloidosis has recently received increased attention; however, the diagnosis is often delayed. We present a case of ATTR cardiac amyloidosis in which a comprehensive history-taking and focused physical examination played an important role in establishing the diagnosis. A 75-year-old man was referred to the cardiology department for left ventricular hypertrophy on electrocardiography. No fourth sound was audible despite concentric biventricular hypertrophy and diastolic dysfunction on echocardiography. Additional history-taking revealed that he had undergone bilateral carpal tunnel syndrome surgery almost 35 years earlier and had a biceps tendon rupture about 15 years earlier; bunching of the arm on flexion, or Popeye's sign, was noted. Technetium-99m-pyrophosphate showed diffuse uptake not only in both ventricles but also in both atria. The findings were consistent with the absence of the fourth sound. The present case highlights the importance of a focused physical examination as well as history-taking as a clue to ATTR cardiac amyloidosis in patients with unexplained left ventricular hypertrophy.

A Case of Docetaxel-Induced Left Ventricular Outflow Tract Obstruction.

Docetaxel, a taxoid chemotherapy agent, may induce fluid retention. We present a case of metastatic breast cancer in which high output caused by docetaxel-induced fluid retention resulted in heart failure due to left ventricular outflow tract (LVOT) obstruction. A 58-year-old woman presented with exertional dyspnea and anasarca. The jugular venous pressure was elevated, and the carotid pulse was pulsus bisferiens with a spike-and-dome configuration. On auscultation, a mid-late systolic murmur that did not radiate to the neck but increased with the Valsalva maneuver was noted. Echocardiography revealed a left ventricular ejection fraction of 63% with systolic anterior motion (SAM) of the mitral valve, resulting in LVOT obstruction with a resting pressure gradient of 64 mmHg and moderate to severe mitral regurgitation. Treatment with carvedilol, trichlormethiazide, and an increased dose of furosemide gradually improved her symptoms, physical findings, and echocardiographic abnormalities. This case highlights the importance of recognizing high-output heart failure along with LVOT obstruction in patients scheduled to receive docetaxel.

Incidence and factors associated with newly implemented do-not-attempt-resuscitation orders among deteriorating patients after rapid response system activation: A retrospective observational study using a Japanese multicenter database.

Aim: The rapid response system (RRS) was initially aimed to improve patient outcomes. Recently, some studies have implicated that RRS might facilitate do-not-attempt-resuscitation (DNAR) orders among patients, their families, and healthcare providers. This study aimed to examine the incidence and factors independently associated with DNAR orders newly implemented after RRS activation among deteriorating patients. Methods: This observational study assessed patients who required RRS activation between 2012 and 2021 in Japan. We investigated patients' characteristics and the incidence of new DNAR orders after RRS activation. Furthermore, we used multivariable hierarchical logistic regression models to explore independent predictors of new DNAR orders. Results: We identified 7904 patients (median age, 72 years; 59% male) who required RRS activation at 29 facilities. Of the 7066 patients without pre-existing DNAR orders before RRS activation, 394 (5.6%) had new DNAR orders. Multivariable hierarchical logistic regression analyses revealed that new DNAR orders were associated with age category (adjusted odds ratio [aOR], 1.56; 95% confidence interval, 1.12-2.17 [65-74 years old reference to 20-64 years old], aOR, 2.56; 1.92-3.42 [75-89 years old], and aOR, 6.58; 4.17-10.4 [90 years old]), malignancy (aOR, 1.82; 1.42-2.32), postoperative status (aOR, 0.45; 0.30-0.71), and National Early Warning Score 2 (aOR, 1.07; 1.02-1.12 [per 1 score]). Conclusion: The incidence of new DNAR orders was one in 18 patients after RRS activation. The factors associated with new DNAR orders were age, malignancy, postoperative status, and National Early Warning Score 2.

Clinical Significance of Physical Examination for Hypertrophic Cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) show various physical findings, but their clinical significance has not been systematically evaluated.Methods and Results: This study evaluated 105 consecutive patients with HCM who had undergone phonocardiography and external pulse recording. Physical examinations included a visible jugular a-wave (Jug-a), audible 4th sound (S4), and double or sustained apex beat. The primary outcome was a composite of all-cause death and hospitalization for cardiovascular disease. A total of 104 non-HCM subjects served as controls. The prevalence of visible Jug-a in the seated or supine position, audible S4, and a sustained or double apex beat in patients with HCM were 10%, 71%, 70%, 42%, and 27%, respectively, all of which were significantly higher than in the controls (0%, 20%, 11%, 17%, and 2%; P<0.001 for all comparisons). The combination of visible Jug-a in the supine position and audible S4 yielded a specificity of 94% and sensitivity of 57%. During a follow-up period of 6.6 years, 6 patients died and 10 were hospitalized. The absence of audible S4 was a predictor of cardiovascular events (hazard ratio, 3.91; 95% confidence interval, 1.41 to 10.8; P=0.005). CONCLUSIONS: Detection of these findings has clinical importance in the diagnosis and risk stratification of HCM prior to the use of advanced imaging techniques.

Systolic Ejection Murmurs Due to Unruptured Aneurysm of the Sinus of Valsalva.

Aneurysm of the sinus of Valsalva is a rare condition with variable clinical presentation. We present a case of an unruptured aneurysm of the right sinus of Valsalva, in which a systolic ejection murmur was instrumental in the diagnosis. An asymptomatic 72-year-old man was referred to the cardiology department because of a heart murmur. Physical examination was unremarkable except for a grade 3 systolic murmur, loudest at the third left sternal border. Echocardiography revealed a sac-like structure protruding into the right ventricle and attached to the right sinus of Valsalva with a right ventricular outflow tract obstruction during end-systole. Multidetector computed tomography showed an aneurysm of the right sinus of Valsalva with a diameter of 28 × 19 mm; no contrast leakage from the aneurysm was detected. A diagnosis of an unruptured aneurysm of the right sinus of Valsalva was made. Surgical repair was successfully performed, and the murmur disappeared postoperatively. This case underscores the importance of physical examination even in the era of advanced imaging techniques and the need to recognize the wide range of causes of heart murmurs.

Pulmonary Hypertension Associated With Hyperthyroidism: A Case Report.

Pulmonary hypertension (PH) has various etiologies and its prognosis is unfavorable without appropriate treatment. We report a case in whom hyperthyroidism was considered as a cause of PH. A 32-year-old woman presented with exertional palpitation and dyspnea. Echocardiography showed an estimated systolic pressure in the pulmonary artery of 50 mmHg (reference value, 15 to 30) with no evidence suggestive of congenital heart disease or acquired heart disease. The level of D-dimer was normal and pulmonary perfusion scintigraphy was unremarkable. Thyroid function tests revealed a biochemically hyperthyroid state with elevated anti-thyroid peroxidase antibodies and thyroid stimulating hormone receptor antibodies, findings consistent with Graves' disease. After the administration of treatment with potassium iodide and thiamazole, her symptoms and PH gradually abated and finally disappeared without any specific treatment for PH.

The research environment of critical care in three Asian countries: A cross-sectional questionnaire survey.

Although inadequate research support for intensivists can be one major reason of the poor research productivity, no study has investigated the current research environment in critical care medicine in Asia. The objective of this study was to describe Asian academia in critical care from the research environment perspective. We conducted a cross-sectional questionnaire survey targeting all physician members of the Societies of Intensive/Critical Care Medicine in Japan, South Korea, and Singapore. We collected the characteristics of the participants and their affiliated institutions and the research environment. The outcome was the number of peer-reviewed publications. Multivariable logistic regression analyses examined the association between the outcome and the following five research environmental factors (i.e., country of the respondents, availability of secured time for research activities or research supporting staff for the hospital, practice at a university-affiliated hospital, and years of clinical practice of 10 years or longer). Four hundred ninety responded (overall response rate: 5.6%) to the survey between June 2019 and January 2020. Fifty-five percent worked for a university-affiliated hospital, while 35% worked for a community hospital. Twenty-four percent had secured time for research within their full-time work hours. The multivariable logistic model found that a secured time for the research activities [odds ratio (OR): 2.77; 95% confidence interval (CI), 1.46-5.24], practicing at a university-affiliated hospital (OR: 2.61; 95% CI, 1.19-5.74), having clinical experience of 10 years or longer (OR:11.2; 95%CI, 1.41-88.5), and working in South Korea (OR: 2.18; 95% CI, 1.09-4.34, Reference: Japan) were significantly associated with higher research productivity. Intensivists in the three countries had limited support for their research work. Dedicated time for research was positively associated with the number of research publications.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (July 2022).

Background: Coronavirus disease (COVID-19), an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. Methods: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of recommendations. The first edition of this guideline was released on September 9, 2020, and this is the revised edition (version 5.0; released on July 15, 2022). Clinical questions (CQs) were set for the following 10 drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), casirivimab/imdevimab (CQ9-1), sotrovimab (CQ9-2), molnupiravir (CQ10), and nirmatrelvir/ritonavir (CQ11). Recommendations: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with mild COVID-19 who do not require oxygen, and patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (both GRADE 2B). Corticosteroids are recommended for moderate and severe COVID-19 (GRADE 1B, 1A). However, their administration is not recommended for mild COVID-19 (GRADE 1B). Tocilizumab is suggested for moderate and severe COVID-19 (GRADE 2B, 2C). Anticoagulant administration is recommended for moderate and severe COVID-19 (Good Practice Statement). Baricitinib is suggested for moderate and severe COVID-19 (both GRADE 2C). Casirivimab/imdevimab and sotrovimab are recommended for mild COVID-19 (both GRADE 2C). Molnupiravir and nirmatrelvir/ritonavir are recommended for mild COVID-19 (both GRADE 2C). SARS-CoV-2 mutant strains emerge occasionally, and each time, the treatment policy at clinics is forced to change drastically. We ask health-care professionals in the field to refer to the recommendations in these guidelines and use these to keep up to date with COVID-19 epidemiological information.

[Measurement of Absorbed Dose in the Air in X-ray CT Examination Rooms Using a Special Protective Shield for CT].

PURPOSE: X-ray CT examinations are required not only in routine medical examinations but also in various situations such as emergency medical care. Although medical staff may be exposed to radiation when assisting patients, the distribution of air-absorbed doses in the CT examination room when using a special protective shield for CT has not been clarified. Here, we measured air-absorbed doses at several points simultaneously to clarify the distribution of these doses and the effect of a special protective shield for CT in reducing them. METHOD: A human phantom was imaged with an X-ray CT system. The absorbed dose in the air dose profile distribution was measured with an OSL dosimeter in the presence and absence of a special protective shield for CT. RESULTS: The highest air absorbed doses of 4.27 mGy were at 0 cm in the horizontal direction, 120 cm in the vertical direction, and 50 cm in the body axis direction. The largest reduction in air absorbed dose following installation of the special protective shield for CT was 91.7%, obtained at 0 cm in the horizontal direction, 150 cm in the vertical direction, and 50 cm in the body axis direction. CONCLUSION: A 91.7% reduction in air-absorbed dose was o directly behind the special protective shield for CT. The reduction in air-absorbed dose was 65.8% at the location of a gap between the special protective shield for CT and gantry.