Two-photon intravital imaging is a powerful method by which researchers are able to directly observe biological phenomena in live organisms. Researchers in various biomedical research fields have applied two-photon imaging to a variety of target organs by utilizing this technology’s ability to penetrate to significant depths with minimal phototoxicity. The mouse respiratory system in inflammation models is a good example, as two-photon intravital imaging can provide insights as to how the immune system is activated in response to inflammation within the respiratory system. Inflammation models can be generated via influenza viral, bacterial, or lipopolysaccharide injection. To exteriorize the lungs or trachea, thoracotomy or tracheotomy is performed, respectively; the appropriate combination of inflammation induction and organ exposure is selected depending on the study purpose. On the other hand, visualizing the movement of leukocytes is also an important component; to this end, immune cell populations of interest are either labeled via the genetic attachment of fluorescent proteins or stained with antibodies or dyes. With the proper selection of methods at each step, twophoton intravital imaging can yield visual evidence regarding immune responses to inflammation.
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The inpatient treatment process is becoming more and more complicated with advanced treatments, aging of the patient population, and multiple comorbidities. During the process, patients often experience unexpected deterioration, about half of which might be preventable. Early identification of patient deterioration and the proper response are priorities in most healthcare facilities. A rapid response system (RRS) is a safety net to identify antecedents of these adverse events and to respond in a timely manner. The RRS has become an essential part of the medical system worldwide, supported by all major quality improvement organizations. An RRS consists of a trigger system and response team and needs constant assessment and process improvement. Although the effectiveness and cost-benefit of RRS remain controversial, according to previous studies, it may be beneficial by decreasing in-hospital cardiac arrest and mortality. Since the first implementation of RRS in Korea in 2008, it has been developed in over 15 medical centers and continues to expand. Recent accreditation standards and an RRS pilot program by the Korean government will promote the proliferation of RRSs in Korea.
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Background The current Surviving Sepsis Campaign guidelines recommend the remeasurement of lactate levels if the initial lactate level is elevated; however, the prognostic value of lactate kinetics is limited and inconsistent. We attempted to determine the efficacy of the lactate area score (calculated from repeated lactate measurements during initial resuscitation) as a prognostic marker of septic shock in the emergency department (ED).
Methods We performed a retrospective study of adult patients with septic shock in the ED of a single tertiary medical center. Serial lactate levels were measured five times within 12 hours. We also compared the initial lactate level, maximum lactate level, and lactate area score. The lactate area score was defined as the sum of the area under the curve measured at 2, 4, 6, and 12 hours following the initial measurement.
Results A total of 362 patients were enrolled in this study, and the overall 28-day mortality was 31.8%. The lactate area score of serial lactate levels as well as the initial (median [interquartile range], 4.9 [3.4 to 10.5]; P=0.003) and maximum (7.3 [4.2 to 13.2]; P<0.001) lactate levels were significantly higher in the non-survivor group. However, in multivariate analysis, only the lactate area score (odds ratio, 1.013; 95% confidence interval, 1.007 to 1.019) was significantly associated with 28-day mortality.
Conclusions The early lactate area score may be a possible prognostic marker for predicting the 28-day mortality of adult septic shock patients. Further prospective interventional studies should be conducted to validate our results.
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Background Overactivation of inflammatory cells, including macrophages and neutrophils, is associated with acute lung injury. BMS-470539 is a selective agonist of melanocortin 1 receptor, which triggers the inhibition of proinflammatory responses, suppressing neutrophil infiltration and protecting tissue. This study evaluated the effects of BMS-470539 on lipopolysaccharide-induced acute lung injury in a mouse model.
Methods Mice received a subcutaneous injection of saline or BMS-470539 (18.47 mg/kg) 1 hour before an intratracheal injection of saline or lipopolysaccharide (20 μg). Mice were sacrificed to analyze the severity of pulmonary edema (lung wet-to-dry weight [W/D] ratio) and inflammatory responses (level of leukocytes, polymorphonuclear neutrophils [PMNs] and tumor necrosis factor alpha [TNF-α] in bronchoalveolar lavage fluid [BALF]), and neutrophil infiltration (myeloperoxidase activity). TNF-α activation was also measured in neutrophils from bone marrow. Survival was investigated in a second-hit sepsis mouse model.
Results BMS-470539 improved sepsis-induced pulmonary edema, as demonstrated by a decreased W/D ratio (5.76%±0.83% to 3.81%±0.86%, P<0.05). The inflammatory response also improved, as shown by decreased levels of leukocytes (551±116 to 357±86×10²/mm³, P<0.05), PMNs (51.52%±16.23% to 18.41%±7.25%, P<0.01), and TNF-α (550±338 to 128±52 pg/ml, P<0.01) in the BALF. BMS-470539 also improved the inflammatory response, as shown by TNF-α levels (850±158 to 423±59 pg/ml, P<0.01) in neutrophils. BMS-470539 downregulated neutrophil infiltration in the lung (myeloperoxidase: 654±98 to 218±89 U/g, P<0.001). Lastly, BMS improved the survival rate (0% to 70%, P<0.01) in a mice multiple organ failure model.
Conclusions BMS-470539 improved lipopolysaccharide-induced acute lung injury and mortality in mice by affecting the inflammatory response.
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Background Hemoglobin levels are a critical parameter for oxygen delivery in patients with shock. On comparing target hemoglobin levels upon transfusion initiation, the correlation between the severity of decrease in hemoglobin levels and patient outcomes remains unclear. We evaluated the association between initial hemoglobin levels and mortality in patients with septic shock treated with protocol-driven resuscitation bundle therapy at an emergency department.
Methods Data of adult patients diagnosed with septic shock between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Patients were classified into four groups according to initial hemoglobin levels: ≥9.0 g/dl, 8.0−8.9 g/dl, 7.0−7.9 g/dl, and <7.0 g/dl. The primary endpoint was 90-day mortality.
Results In total, 2,265 patients (male, 58.3%; median age, 70.0 years [interquartile range, 60 to 78 years]) with septic shock were included. For the four groups, 90-day mortality rates were as follows: 29.1%, 43.0%, 46.5%, and 46.9% for ≥9.0 g/dl (n=1,808), 8.0−8.9 g/dl (n=217), 7.0−7.9 g/dl (n=135), and <7.0 g/dl (n=105), respectively (P<0.001). Multivariate logistic regression showed that initial hemoglobin levels were an independent factor associated with 90-day mortality and mortality proportionally increased with decreasing hemoglobin levels (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.36 to 2.61 for 8.0−8.9 g/dl; OR, 1.97; 95% CI, 1.31 to 2.95 for 7.0–7.9 g/dl; and OR, 2.35; 95% CI, 1.52 to 3.63 for <7.0 g/dl).
Conclusions Low hemoglobin levels (<9.0 g/dl) were observed in approximately 20% of patients with septic shock, and the severity of decrease in these levels correlated with mortality.
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Background Although extracorporeal membrane oxygenation (ECMO) has been used for the treatment of acute high-risk pulmonary embolism (PE), there are limited reports which focus on this approach. Herein, we described our experience with ECMO in patients with acute high-risk PE.
Methods We retrospectively reviewed medical records of patients diagnosed with acute highrisk PE and treated with ECMO between January 2014 and December 2018.
Results Among 16 patients included, median age was 51 years (interquartile range [IQR], 38 to 71 years) and six (37.5%) were male. Cardiac arrest was occurred in 12 (75.0%) including two cases of out-of-hospital arrest. All patients underwent veno-arterial ECMO and median ECMO duration was 1.5 days (IQR, 0.0 to 4.5 days). Systemic thrombolysis and surgical embolectomy were performed in seven (43.8%) and nine (56.3%) patients, respectively including three patients (18.8%) received both treatments. Overall 30-day mortality rate was 43.8% (95% confidence interval, 23.1% to 66.8%) and 30-day mortality rates according to the treatment groups were ECMO alone (33.3%, n=3), ECMO with thrombolysis (50.0%, n=4) and ECMO with embolectomy (44.4%, n=9).
Conclusions Despite the vigorous treatment efforts, patients with acute high-risk PE were related to substantial morbidity and mortality. We report our experience of ECMO as rescue therapy for refractory shock or cardiac arrest in patients with PE.
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