Early Sepsis-Associated Acute Kidney Injury and Obesity.

Importance: The prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation. Objective: To explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis. Design, Setting, and Participants: This nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded. Exposures: Sepsis and hospitalization in the ICU. Main Outcomes and Measures: The primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable. Results: Of the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI. Conclusions and Relevance: In this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.

Factors influencing sleep quality in the intensive care unit: a descriptive pilot study in Korea.

BACKGROUND: As sleep disturbances are common in the intensive care unit (ICU), this study assessed the sleep quality in the ICU and identified barriers to sleep. METHODS: Patients admitted to the ICUs of a tertiary hospital between June 2022 and December 2022 who were not mechanically ventilated at enrollment were included. The quality of sleep (QoS) at home was assessed on a visual analog scale as part of an eight-item survey, while the QoS in the ICU was evaluated using the Korean version of the Richards-Campbell Sleep Questionnaire (K-RCSQ). Good QoS was defined by a score of ≥50. RESULTS: Of the 30 patients in the study, 19 reported a QoS score <50. The Spearman correlation coefficient showed no meaningful relationship between the QoS at home and the overall K-RCSQ QoS score in the ICU (r=0.16, P=0.40). The most common barriers to sleep were physical discomfort (43%), being awoken for procedures (43%), and feeling unwell (37%); environmental factors including noise (30%) and light (13%) were also identified sources of sleep disruption. Physical discomfort (median [interquartile range]: 32 [28.0-38.0] vs. 69 [42.0-80.0], P=0.004), being awoken for procedures (36 [20.0-48.0] vs. 54 [36.0-80.0], P=0.04), and feeling unwell (31 [18.0-42.0] vs. 54 [40.0-76.0], P=0.01) were associated with lower K-RCSQ scores. CONCLUSIONS: In the ICU, physical discomfort, patient care interactions, and feeling unwell were identified as barriers to sleep.

Association between the timing of ICU admission and mortality in patients with hospital-onset sepsis: a nationwide prospective cohort study.

BACKGROUND: Based on sparse evidence, the current Surviving Sepsis Campaign guideline suggests that critically ill patients with sepsis be admitted to the intensive care unit (ICU) within 6 h. However, limited ICU bed availability often makes immediate transfer difficult, and it is unclear whether all patients will benefit from early admission to the ICU. Therefore, the purpose of this study was to determine the association between the timing of ICU admission and mortality in patients with hospital-onset sepsis. METHODS: This nationwide prospective cohort study analyzed patients with hospital-onset sepsis admitted to the ICUs of 19 tertiary hospitals between September 2019 and December 2020. ICU admission was classified as either early (within 6 h) or delayed (beyond 6 h). The primary outcome of in-hospital mortality was compared using logistic regression adjusted for key prognostic factors in the unmatched and 1:1 propensity-score-matched cohorts. Subgroup and interaction analyses assessed whether in-hospital mortality varied according to baseline characteristics. RESULTS: A total of 470 and 286 patients were included in the early and delayed admission groups, respectively. Early admission to the ICU did not significantly result in lower in-hospital mortality in both the unmatched (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 0.99-1.85) and matched cohorts (aOR, 1.38; 95% CI, 0.94-2.02). Subgroup analyses showed that patients with increasing lactate levels (aOR, 2.10; 95% CI, 1.37-3.23; P for interaction = 0.003), septic shock (aOR, 2.06; 95% CI, 1.31-3.22; P for interaction = 0.019), and those who needed mechanical ventilation (aOR, 1.92; 95% CI, 1.24-2.96; P for interaction = 0.027) or vasopressor support (aOR, 1.69; 95% CI, 1.17-2.44; P for interaction = 0.042) on the day of ICU admission had a higher risk of mortality with delayed admission. CONCLUSIONS: Among patients with hospital-onset sepsis, in-hospital mortality did not differ significantly between those with early and delayed ICU admission. However, as early intensive care may benefit those with increasing lactate levels, septic shock, and those who require vasopressors or ventilatory support, admission to the ICU within 6 h should be considered for these subsets of patients.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

Analysis of Breakthrough Reactions in 1,143 Desensitization Procedures in a Single Tertiary Hospital Using a One-Bag Desensitization Protocol.

Background: Drug desensitization is helpful for patients who have experienced significant hypersensitivity reactions (HSRs) to antineoplastic agents. One-bag desensitization protocols, attracting attention in recent years, need to be validated on their safety and efficacy in a large number. Methods: One-bag desensitization procedures conducted from 2018 to 2020 were analyzed; their outcomes and the risk factors for breakthrough reactions (BTRs) were assessed in desensitization procedures to major drug types (platins, taxanes, and monoclonal antibodies). Results: A total of 1,143 procedures of one-bag desensitization were performed in 228 patients with 99% completion rate. BTRs occurred in 26% of the total desensitization procedures-34% in platins, 12% in taxanes, and 18% in mAbs. BTR occurrence rate decreased along the desensitization process with 80% of BTRs occurring within the 6th desensitization attempts. Severe BTR occurred more frequently with severe initial HSRs (1% in mild to moderate initial HSRs vs. 16% in severe). Severe initial HSR was also a significant risk factor for moderate to severe BTR in platins (odds ratio 1.56, 95% confidence interval [CI] 1.06-2.29, p = 0.025). The use of steroid was also associated with lower occurrence of moderate to severe BTR (odds ratio 0.50, 95% CI 0.35-0.72, p < 0.001). Conclusion: Most patients with HSRs to antineoplastic agents can safely receive chemotherapy through a one-bag desensitization protocol. Further studies on each drug with larger sample size can help verify the risk factors of BTRs and evaluate the efficacy of steroid premedication in improving the safety of desensitization in high-risk patients.

Validation of Practical Pathway in Patients With Anaphylaxis to Low Osmolar Contrast Media: A Retrospective Cohort Study.

BACKGROUND: An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis. OBJECTIVES: To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM. METHODS: A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone. RESULTS: Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group. CONCLUSIONS: We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.

Allergic-like Hypersensitivity Reactions to Gadolinium-based Contrast Agents: An 8-year Cohort Study of 154 539 Patients.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7, P = .041) and changing the type of GBCA (OR = 0.2, P < .001) showed preventative effects in patients with a history of acute HSRs, only premedication (OR = 0.2, P = .016) significantly reduced the incidence of HSRs in patients with a history of delayed reactions. The risk of an HSR to GBCA was higher in those with a history of an HSR to iodinated contrast media (OR = 4.6, P < .001). Conclusion The rate of hypersensitivity reactions (HSRs) to gadolinium-based contrast agents (GBCAs) was 0.4%. The absence of premedication, repeated exposures to the culprit GBCA, and a history of HSRs to iodinated contrast media and GBCAs were risk factors for HSRs to GBCAs. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kallmes and McDonald in this issue.

Incidence and risk factors of late adverse reactions to low-osmolar contrast media: A prospective observational study of 10,540 exposures.

PURPOSE: To evaluate the incidence and risk factors of late adverse reactions (ARs) to non-ionic low-osmolar contrast media (LOCM). METHODS: The occurrence of late AR was monitored on day 1 and from day 7 to day 28 in all patients who received enhanced computed tomography using LOCM during a 5-week study period in a single tertiary hospital. Patients who experienced late AR were followed up for three years. RESULTS: Among the total 10,540 LOCM exposures, 315 ARs (3.0%) were reported; acute ARs occurred in 108 LOCM exposures (1.0%) and late ARs occurred in 207 LOCM exposures (2.0%) (90.9% within one week, 9.1% developed afterwards by day 20). Previous history of drug allergy (odds ratio [OR] = 4.59; 95% confidence interval [CI] 2.17-9.71) and allergic diseases (OR = 2.54; 95% CI 1.32-4.91) were risk factors of late ARs to LOCM. Although the recurrence rate was lowered with premedication from 8.5% to 1.7% (8/94 vs. 3/178; p = 0.016), LOCM change did not make difference compared to reuse of the culprit LOCM (2/38 vs. 9/234; p = 0.655). In patients with a history of late AR to LOCM, the risk of recurrent reactions decreased with longer time intervals between exposures (OR = 0.86; 95% CI: 0.77-0.97; p = 0.025) and with the use of antihistamine premedication (OR = 0.27; 95% CI: 0.06-0.99; p = 0.049). CONCLUSIONS: Late ARs to LOCM occurred mostly within one week. The use of premedication may be helpful in reducing the recurrence of late ARs.

Ultra-high-resolution computed tomography shows changes in the lungs related with airway hyperresponsiveness in a murine asthma model.

In vivo presentation of airway hyper-responsiveness (AHR) at the different time points of the allergic reaction is not clearly understood. The purpose of this study was to investigate how AHR manifests in the airway and the lung parenchyma in vivo following exposure to different stimuli and in the early and late phases of asthma after allergen exposure. Ovalbumin (OVA)-induced allergic asthma model was established using 6-week female BALB/c mice. Enhanced pause was measured with a non-invasive method to assess AHR. The dynamic changes of the airway and lung parenchyma were evaluated with ultra-high-resolution computed tomography (128 multi-detector, 1024 × 1024 matrix) for 10 h. While the methacholine challenge showed no grossly visible changes in the proximal airway and lung parenchyma despite provoking AHR, the OVA challenge induced significant immediate changes manifesting as peribronchial ground glass opacities, consolidations, air-trapping, and paradoxical proximal airway dilatations. After resolution of immediate response, multiple episodes of AHRs occurred with paradoxical proximal airway dilatation and peripheral air-trapping in late phase over a prolonged time period in vivo. Understanding of airflow limitation based on the structural changes of asthmatic airway would be helpful to make an appropriate drug delivery strategy for the treatment of asthma.