Height status matters for risk of mortality in critically ill children.

BACKGROUND: Anthropometric measurements are crucial in pediatric critical care, but the impact of height on ICU outcomes is underexplored despite a substantial number of short-for-age children in ICUs. Previous studies suggest that short stature increases the risk of poor clinical outcomes. This study examines the relationship between short stature and ICU outcomes. METHODS: We conducted a retrospective cohort study using a Japanese nationwide database (the Japanese Intensive Care Patient Database; JIPAD), which included pediatric patients under 16 years admitted to ICUs from April 2015 to March 2020. Height standard deviation scores (SD scores) were calculated based on age and sex. Short-stature patients were defined as height SD score < - 2. The primary outcome was all-cause ICU mortality, and the secondary outcome was the length of stay in ICU. RESULTS: Out of 6,377 pediatric patients, 27.2% were classified as having short stature. The ICU mortality rate was significantly higher in the short-stature group compared to the normal-height group (3.6% vs. 1.4%, p < 0.01). Multivariable logistic regression showed that short stature was independently associated with increased ICU mortality (OR = 2.73, 95% CI 1.81-4.11). Additionally, the Fine-Gray subdistribution hazards model indicated that short stature was associated with a lower chance of ICU discharge for each additional day (HR 0.85, 95% CI 0.81-0.90, p < 0.01). CONCLUSIONS: Short stature is a significant risk factor for increased ICU mortality and prolonged ICU stay in critically ill children. Height should be considered in risk assessments and management strategies in pediatric intensive care to improve outcomes.

Action protocol of medical staff for airway obstruction after anterior cervical spine surgery: A systematic review of case reports.

BACKGROUND: Postoperative airway obstruction after anterior cervical spine surgery (ACSS) can be a fatal complication. Occasionally, it rapidly progresses to complete obstruction. There are no established standardized protocols on how medical staff should assess for signs and symptoms, seek help, or facilitate airway management after ACSS to prevent unfavorable events. This study aimed to primarily describe a systematic approach by assessing the signs and treatment outcomes of airway compromise in patients who underwent ACSS. Further, it recommended an action protocol after extubation for medical staff according to patients' symptoms to prevent unfavorable outcomes. METHODS: An extensive literature search was performed on PubMed, Web of Science, and the Cochrane Library to identify case reports, case series, and cohort studies restricted to English and published between January 1990 and March 2023. We included cases that described the signs, symptoms, and treatment of airway obstruction after ACSS. Meanwhile, cases involving complications of other known causes, cases of trauma or occipital-cervical fixation, or those using bone morphogenetic protein were excluded. RESULTS: Twenty cases from 17 studies were obtained, and their study quality was acceptable. Four patients died, and two presented with hypoxic ischemic encephalopathy. Further, five of six patients had fatal complications that initially developed within 7 h after surgery. Then, 9 (69%) of 13 patients with evidence of hematoma (69%) showed initial symptoms within 12 h after surgery. Finally, 9 of 11 patients with early-stage symptoms had favorable outcomes, and patients who developed late-stage symptoms commonly had unfavorable outcomes. CONCLUSION: The early identification of signs and symptoms and immediate treatment are important, particularly within 12 h postoperatively. We suggest a novel action protocol for medical staff according to symptom urgency, which includes the measurement of neck circumference using a string for evaluating neck swelling.

Postintensive care syndrome family: A comprehensive review.

Families of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS-F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS-F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post-traumatic syndrome is 20-40%, and that of non-physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS-F was frequently conducted at 3- or 6-month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS-F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow-up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS-F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS-F to facilitate acute care physicians' understanding of PICS-F.

Association of excess visceral fat and severe illness in hospitalized COVID-19 patients in Japan: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Obesity, defined by body mass index (BMI), is a well-known risk factor for the severity of coronavirus disease 2019 (COVID-19). Adipose tissue distribution has also been implicated as an important factor in the body's response to infection, and excess visceral fat (VF), which is prevalent in Japanese, may contribute significantly to the severity. Therefore, this study aimed to evaluate the association of obesity and VF with COVID-19 severe illness in Japan. SUBJECTS/METHODS: This retrospective cohort study involved 550 COVID-19 patients admitted to a tertiary care hospital with BMI and body composition data, including VF. The primary endpoint was severe illness, including death, due to COVID-19 during hospitalization. Logistic regression analysis was applied to examine the quartiles of BMI and VF on severe illness after adjusting for covariates such as age, sex, subcutaneous fat, paraspinal muscle radiodensity, and comorbidities affecting VF (COPD, cancer within 5 years, immunosuppressive agent use). RESULTS: The median age was 56.0 years; 71.8% were males. During hospitalization, 82 (14.9%) experienced COVID-19 severe illness. In the multivariate logistic regression analysis, Q4 of BMI was not significantly associated with severe illness compared to Q1 of BMI (OR 1.03; 95% CI 0.37-2.86; p = 0.95). Conversely, Q3 and Q4 of VF showed a higher risk for severe illness compared to Q1 of VF (OR 2.68; 95% CI 1.01-7.11; p = 0.04, OR 3.66; 95% CI 1.30-10.26; p = 0.01, respectively). Stratified analysis by BMI and adjusted for covariates showed the positive association of VF with severe illness only in the BMI < 25 kg/m2 group. CONCLUSIONS: High BMI was not an independent risk factor for COVID-19 severe illness in hospitalized patients in Japan, whereas excess VF significantly influenced severe illness, especially in patients with a BMI < 25 kg/m2.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Increased platelet counts and activation are observed during the course of KD, and elevated platelet counts are associated with higher risks of developing intravenous immunoglobulin resistance and coronary artery aneurysms. However, the role of platelets in KD pathogenesis remains unclear. Here, we analyzed transcriptomics data generated from the whole blood of patients with KD and discovered changes in the expression of platelet-related genes during acute KD. In the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, LCWE injection increased platelet counts and the formation of monocyte-platelet aggregates (MPAs), upregulated the concentration of soluble P-selectin, and increased circulating thrombopoietin and interleukin 6 (IL-6). Furthermore, platelet counts correlated with the severity of cardiovascular inflammation. Genetic depletion of platelets (Mpl-/- mice) or treatment with an anti-CD42b antibody significantly reduced LCWE-induced cardiovascular lesions. Furthermore, in the mouse model, platelets promoted vascular inflammation via the formation of MPAs, which likely amplified IL-1B production. Altogether, our results indicate that platelet activation exacerbates the development of cardiovascular lesions in a murine model of KD vasculitis. These findings enhance our understanding of KD vasculitis pathogenesis and highlight MPAs, which are known to enhance IL-1B production, as a potential therapeutic target for this disorder.

An anthropometric evidence against the use of age-based estimation of bodyweight in pediatric patients admitted to intensive care units.

Age-based bodyweight estimation is commonly used in pediatric settings, but pediatric ICU patients often have preexisting comorbidity and resulting failure to thrive, hence their anthropometric measures may be small-for-age. Accordingly, age-based methods could overestimate bodyweight in such settings, resulting in iatrogenic complications. We performed a retrospective cohort study using pediatric data (aged < 16 years) registered in the Japanese Intensive Care Patient Database from April 2015 to March 2020. All the anthropometric data were overlaid on the growth charts. The estimation accuracy of 4 age-based and 2 height-based bodyweight estimations was evaluated by the Bland-Altman plot analysis and the proportion of estimates within 10% of the measured weight (ρ10%). We analyzed 6616 records. The distributions of both bodyweight and height were drifted to the lower values throughout the childhood while the distribution of BMI was similar to the general healthy children. The accuracy in bodyweight estimation with age-based formulae was inferior to that with height-based methods. These data demonstrated that the pediatric patients in the Japanese ICU were proportionally small-for-age, suggesting a special risk of using the conventional age-based estimation but supporting the use of height-based estimation of the bodyweight in the pediatric ICU.

Effectiveness of remdesivir with corticosteroids for COVID-19 patients in intensive care unit: A hospital-based observational study.

The effectiveness of remdesivir on survival in coronavirus disease 2019 (COVID-19), especially in cases treated in the intensive care unit (ICU), is controversial. We investigated the effectiveness of remdesivir with corticosteroids on the survival of COVID-19 patients in a real ICU clinical practice. For laboratory-confirmed COVID-19 patients admitted to the ICU of a tertiary hospital in Tokyo (April 2020-November 2021) and who received corticosteroids, the effectiveness of remdesivir for survival, stratified by interval length (within 9 or 10+ days), was retrospectively analyzed using Cox regression model. A total of 168 patients were included: 35 with no remdesivir use (control), 96 with remdesivir use within 9 days, and 37 with remdesivir use with an interval of 10+ days. In-hospital mortality was 45.7%, 10.4%, and 16.2%, respectively. After adjusting for possible covariates including comorbidities, laboratory data, oxygen demand, or level of pneumonia, remdesivir use within 9 days from symptom onset reduced mortality risk (hazard ratio [HR]: 0.10; 95% confidence interval (CI): 0.025-0.428) compared to the control group. However, remdesivir use with an interval of 10+ days showed no significant association with mortality (HR: 0.42; 95% CI: 0.117-1.524). Among COVID-19 patients who received corticosteroids in ICU, remdesivir use within 9 days from symptom onset was associated with reduced in-hospital mortality risk.

Case of laryngeal venous malformations requiring repeated advanced airway management in the perioperative course.

Laryngeal venous malformations rarely but do cause airway obstruction resulting in life-threatening events. The perioperative airway management for the patients with them has not been well established. We suggest a strategy for laryngeal venous malformations management in the patients who undergo surgery in addition to planning for airway management.

Rapid and sensitive SARS-CoV-2 detection using a homogeneous fluorescent immunosensor Quenchbody with crowding agents.

Antigen tests for SARS-CoV-2 are widely used by the public during the ongoing COVID-19 pandemic, which demonstrates the societal impact of homogeneous immunosensor-related technologies. In this study, we used the PM Q-probe and Quenchbody technologies to develop a SARS-CoV-2 nucleocapsid protein (N protein) homogeneous immunosensor based on a human anti-N protein antibody. For the first time, we uncovered the crowding agent's role in improving the performance of the double-labeled Quenchbody, and the possible mechanisms behind this improvement are discussed. The 5% polyethylene glycol 6000 significantly improved both the response speed and sensitivity of SARS-CoV-2 Quenchbodies. The calculated limit of detection for recombinant N protein was 191 pM (9 ng mL-1) within 15 min of incubation, which was 9- to 10-fold lower than the assay without adding crowding agent. We also validated the developed immunosensor in a point-of-care test by measuring specimens from COVID-19-positive patients using a compact tube fluorometer. In brief, this work shows the feasibility of Quenchbody homogeneous immunosensors as rapid and cost-efficient tools for the diagnosis and high-throughput analysis of swab samples in large-scale monitoring and epidemiological studies of COVID-19 or other emerging infectious diseases.

Overexpressed angiotensin-converting enzyme in neutrophils suppresses glomerular damage in crescentic glomerulonephritis.

While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FcγRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FcγRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FcγRII/III, ameliorating glomerular injury.NEW & NOTEWORTHY We studied immune complex (IC)-mediated crescentic glomerulonephritis in NeuACE mice that overexpress ACE only in neutrophils. Such mice show no significant defects in humoral immunity but strongly resist nephrotoxic serum nephritis (less proteinuria, milder histological damage, reduced IC deposits, and more glomerular neutrophils). NeuACE neutrophils enhanced IC uptake via increased surface expression of CR1/2 and FcgRII/III, as well as elevated serum complement C3b. These results suggest neutrophil ACE as a novel approach to reducing glomerulonephritis.

Tracheobronchial aspergillosis presenting with black mucus plugs and tracheal ulcers.

Tracheobronchial aspergillosis is a rare but lethal disease with characteristic findings of tracheal plaques and ulcers. It requires appropriate airway management for possible tracheal obstruction with the black mucus plug.

We Should Pay Attention to "Referred Pain" - A Case of Acute Myocardial Infarction That Masked and Delayed the Diagnosis of Esophageal Perforation.

We herein report a 93-year-old woman diagnosed with acute myocardial infarction (AMI) based on typical laboratory findings of severe chest pain accompanied by throat pain. This condition was initially interpreted as referred pain of cardiac origin. However, the patient had persistent throat pain after successful percutaneous coronary intervention. Upper esophageal perforation with life-threatening acute mediastinitis was unexpectedly identified by a further examination. Clinicians should have a high index of suspicion in cases with persistent symptoms thought to be referred pain among AMI patients, as these symptoms may not be of cardiac origin but rather a sign of another concomitant critical disease.

COVID-19 case of ventilator-induced lung injury on extracorporeal membrane oxygenation: Physicians' clinical struggle and ethical conflict in a novel pandemic.

Resource scarcity was concerned in the initial surge of the COVID-19 pandemic. To open slots for Extracorporeal Membrane Oxygenation (ECMO), we tried ECMO weaning allowing invasive ventilation in a 66-year-old male with severe COVID-19, backfiring as ventilator-induced lung injury. We will discuss ethical conflict in pandemics in this report.

Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

Impact of extensive negative pressure wound therapy on neonatal respiration: A case report.

An extensive topical negative pressure wound therapy (NPWT) from the abdominal to chest walls in neonates may decrease the compliance of the chest wall. Therefore, it is important to monitor respiratory function carefully during the procedure.