Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

How to determine the focus of emergent medical care in healthcare policy: Proposal of treatable death.

INTRODUCTION: The global provision of essential healthcare stands as a critical concern. Consequently, healthcare policies play a pivotal role in determining the allocation of resources. However, the optimal indicators for prioritizing such policies remain uncertain. This study proposes that employing the concept of treatable mortality in a stepwise manner could serve as a viable approach to setting healthcare policy priorities. Furthermore, it aims to demonstrate this concept through the application of real-world data. METHODS: A model was developed to assess treatable mortality at a national level focusing on severe emergency conditions. We established stepwise targets, encompassing short-term, mid-term, and long-term goals to reduce mortality rates and enhance healthcare efficiency. The short-term target consists of directing attention to regions exhibiting in-hospital mortality rates surpassing the national average within a specific disease category and reducing them to the national average. The mid-term objective entails decreasing the in-hospital mortality rate of the specific disease group to match that of the region with the lowest rate nationwide. As for long-term target, it aligns the in-hospital mortality rate with that of OECD countries possessing average or lowest rates. The model was applied using data from South Korea's National Emergency Department Information System, specifically analyzing acute myocardial infarction (AMI), stroke, and sepsis. RESULTS: Reaching the short-term target resulted in the treatable deaths for AMI numbered 191, for stroke 249, and for sepsis 546. Meeting the mid-term target led to treatable deaths for AMI at 749, for stroke at 958, and for sepsis at 1552. Finally, achieving the long-term target yielded the treatable deaths for AMI at 2606, for stroke at 1642, and for sepsis at 2619. Consequently, a reallocation of more healthcare resources to sepsis over AMI or stroke is recommended. CONCLUSIONS: This study proposes the utilization of treatable mortality as a metric for establishing healthcare policies. The stepwise approach provides valuable insights for policymaking at various levels. Despite limitations, the model offers a foundation for resource allocation and international mortality rate comparisons, aiming for achievable rates worldwide.

Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Development and derivation of bacteremia prediction model in patients with hepatobiliary infection.

INTRODUCTION: Hepatobiliary infections are common in the emergency department (ED), and the mortality rate for this condition is high. A suitable bacteremia prediction model would support prompt identification of bacteremia and appropriate management of hepatobiliary infections in the ED. Therefore, we attempted to produce a bacteremia prediction model with both internal and external validation for hepatobiliary infections in the ED. METHODS: Patients with hepatobiliary infection were extracted from retrospective cohort databases of two tertiary hospitals from January 2018 to December 2019 and from January 2016 to December 2019, respectively. Independent risk factors were determined using multivariable logistic regression in a developmental cohort. We assigned a weighted value to predictive factors and developed a prediction model, which was validated both internally and externally. We assessed discrimination using the area under the receiver operating characteristics curve (AUC). RESULTS: One hospital cohort of 1568 patients was randomly divided into a developmental group of 927 patients (60%) and an internal validation group of 641 patients (40%), and 736 people from the other hospital cohort were used for external validation. Bacteremia rates were 20.5%, 18.1%, and 23.1% in the developmental, internal, and external validation cohorts, respectively. Nine significant factors were used for predicting bacteremia, including age, three vital signs, and five laboratory tests. After applying our bacteremia prediction rule to the validation cohort, 56.5% and 53.8% of the internal and external validation groups were classified as low-risk bacteremia groups (bacteremia rates: 8.6% and 13.9%, respectively). The AUCs were 0.727 (95% confidence interval [CI]: 0.686-0.767), 0.730 (95% CI: 0.679-0.781), and 0.715 (95% CI: 0.672-0.758) for the developmental, internal, and external validation cohorts, respectively. The sensitivity and specificity for internal validation/external validation was 73.2%/67.6% and 63.0%/60.2%, respectively. CONCLUSION: A bacteremia prediction model for hepatobiliary infection might be useful to predict the risk of bacteremia. It might also reduce the need for blood culture in low-risk patients.

Modified Cardiovascular Sequential Organ Failure Assessment Score in Sepsis: External Validation in Intensive Care Unit Patients.

BACKGROUND: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients. METHODS: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively. RESULTS: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677-0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611-0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715-0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration. CONCLUSION: In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality.

Development of Adaptive Point-Spread Function Estimation Method in Various Scintillation Detector Thickness for X-ray Imaging.

An indirect conversion X-ray detector uses a scintillator that utilizes the proportionality of the intensity of incident radiation to the amount of visible light emitted. A thicker scintillator reduces the patient's dose while decreasing the sharpness. A thin scintillator has an advantage in terms of sharpness; however, its noise component increases. Thus, the proposed method converts the spatial resolution of radiographic images acquired from a normal-thickness scintillation detector into a thin-thickness scintillation detector. Note that noise amplification and artifacts were minimized as much as possible after non-blind deconvolution. To accomplish this, the proposed algorithm estimates the optimal point-spread function (PSF) when the structural similarity index (SSIM) and feature similarity index (FSIM) are the most similar between thick and thin scintillator images. Simulation and experimental results demonstrate the viability of the proposed method. Moreover, the deconvolution images obtained using the proposed scheme show an effective image restoration method in terms of the human visible system compared to that of the traditional PSF measurement technique. Consequently, the proposed method is useful for restoring degraded images using the adaptive PSF while preventing noise amplification and artifacts and is effective in improving the image quality in the present X-ray imaging system.

Optimization Method to Predict Optimal Noise Reduction Parameters for the Non-Local Means Algorithm Based on the Scintillator Thickness in Radiography.

The resulting image obtained from an X-ray imaging system depends significantly on the characteristics of the detector. In particular, when an X-ray image is acquired by thinning the detector, a relatively large amount of noise inevitably occurs. In addition, when a thick detector is used to reduce noise in X-ray images, blurring increases and the ability to distinguish target areas deteriorates. In this study, we aimed to derive the optimal X-ray image quality by deriving the optimal noise reduction parameters based on the non-local means (NLM) algorithm. The detectors used were of two thicknesses (96 and 140 µm), and images were acquired based on the IEC 62220-1-1:2015 RQA-5 protocol. The optimal parameters were derived by calculating the edge preservation index and signal-to-noise ratio according to the sigma value of the NLM algorithm. As a result, a sigma value of the optimized NLM algorithm (0.01) was derived, and this algorithm was applied to a relatively thin X-ray detector system to obtain appropriate noise level and spatial resolution data. The no-reference-based blind/referenceless image spatial quality evaluator value, which analyzes the overall image quality, was best when using the proposed method. In conclusion, we propose an optimized NLM algorithm based on a new method that can overcome the noise amplification problem in thin X-ray detector systems and is expected to be applied in various photon imaging fields in the future.

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

The Effects of Mitochondrial Transplantation on Sepsis Depend on the Type of Cell from Which They Are Isolated.

Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.

Modified cardiovascular SOFA score in sepsis: development and internal and external validation.

BACKGROUND: The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. METHODS: We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock. RESULTS: We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%). CONCLUSIONS: Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model.

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.

A simple and novel equation to estimate the degree of bleeding in haemorrhagic shock: mathematical derivation and preliminary in vivo validation.

Determining blood loss [100% - RBV (%)] is challenging in the management of haemorrhagic shock. We derived an equation estimating RBV (%) via serial haematocrits (Hct1, Hct2) by fixing infused crystalloid fluid volume (N) as [0.015 × body weight (g)]. Then, we validated it in vivo. Mathematically, the following estimation equation was derived: RBV (%) = 24k / [(Hct1 / Hct2) - 1]. For validation, nonongoing haemorrhagic shock was induced in Sprague-Dawley rats by withdrawing 20.0%-60.0% of their total blood volume (TBV) in 5.0% intervals (n = 9). Hct1 was checked after 10 min and normal saline N cc was infused over 10 min. Hct2 was checked five minutes later. We applied a linear equation to explain RBV (%) with 1 / [(Hct1 / Hct2) - 1]. Seven rats losing 30.0%-60.0% of their TBV suffered shock persistently. For them, RBV (%) was updated as 5.67 / [(Hct1 / Hct2) - 1] + 32.8 (95% confidence interval [CI] of the slope: 3.14-8.21, p = 0.002, R2 = 0.87). On a Bland-Altman plot, the difference between the estimated and actual RBV was 0.00 ± 4.03%; the 95% CIs of the limits of agreements were included within the pre-determined criterion of validation (< 20%). For rats suffering from persistent, non-ongoing haemorrhagic shock, we derived and validated a simple equation estimating RBV (%). This enables the calculation of blood loss via information on serial haematocrits under a fixed N. Clinical validation is required before utilisation for emergency care of haemorrhagic shock.

Acupuncture ameliorates not only atopic dermatitis-like skin inflammation but also acute and chronic serotonergic itch possibly through blockade of 5-HT2 and 5-HT7 receptors in mice.

Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT2 receptor agonist α-methylserotonin and selective 5-HT7 receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT2A, 5-HT2B and 5-HT7 receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT2 and 5-HT7 receptors.

The immune modulatory effects of mitochondrial transplantation on cecal slurry model in rat.

BACKGROUND: Sepsis has a high mortality rate, but no specific drug has been proven effective, prompting the development of new drugs. Immunologically, sepsis can involve hyperinflammation, immune paralysis, or both, which might pose challenges during drug development. Recently, mitochondrial transplantation has emerged as a treatment modality for various diseases involving mitochondrial dysfunction, but it has never been tested for sepsis. METHODS: We isolated mitochondria from L6 muscle cells and umbilical cord mesenchymal stem cells and tested the quality of the isolated mitochondria. We conducted both in vivo and in vitro sepsis studies. We investigated the effects of intravenous mitochondrial transplantation on cecal slurry model in rats in terms of survival rate, bacterial clearance rate, and the immune response. Furthermore, we observed the effects of mitochondrial transplantation on the immune reaction regarding both hyperinflammation and immune paralysis. To do this, we studied early- and late-phase cytokine production in spleens from cecal slurry model in rats. We also used a lipopolysaccharide (LPS)-stimulated human PBMC monocyte model to confirm the immunological effects of mitochondrial transplantation. Apoptosis and the intrinsic apoptotic pathway were investigated in septic spleens. RESULTS: Mitochondrial transplantation improved survival and bacterial clearance. It also mitigated mitochondrial dysfunction and apoptosis in septic spleens and attenuated both hyperinflammation and immune paralysis in the spleens of cecal slurry model in rats. This effect was confirmed with an LPS-stimulated human PBMC study. CONCLUSIONS: In rat polymicrobial cecal slurry model, the outcome is improved by mitochondrial transplantation, which might have an immunomodulatory effect.

Application of Blind Deconvolution Based on the New Weighted L1-norm Regularization with Alternating Direction Method of Multipliers in Light Microscopy Images.

This study aimed to develop and evaluate a blind-deconvolution framework using the alternating direction method of multipliers (ADMMs) incorporated with weighted L1-norm regularization for light microscopy (LM) images. A presimulation study was performed using the Siemens star phantom prior to conducting the actual experiments. Subsequently, the proposed algorithm and a total generalized variation-based (TGV-based) method were applied to cross-sectional images of a mouse molar captured at 40× and 400× on-microscope magnifications and the results compared, and the resulting images were compared. Both simulation and experimental results confirmed that the proposed deblurring algorithm effectively restored the LM images, as evidenced by the quantitative evaluation metrics. In conclusion, this study demonstrated that the proposed deblurring algorithm can efficiently improve the quality of LM images.

Effectiveness of Non-Local Means Algorithm with an Industrial 3 MeV LINAC High-Energy X-Ray System for Non-Destructive Testing.

Industrial high-energy X-ray imaging systems are widely used for non-destructive testing (NDT) to detect defects in the internal structure of objects. Research on X-ray image noise reduction techniques using image processing has been widely conducted with the aim of improving the detection of defects in objects. In this paper, we propose a non-local means (NLM) denoising algorithm to improve the quality of images obtained using an industrial 3 MeV high-energy X-ray imaging system. We acquired X-ray images using various castings and assessed the performance visually and by obtaining the intensity profile, contrast-to-noise ratio, coefficient of variation, and normalized noise power spectrum. Overall, the quality of images processed by the proposed NLM algorithm is superior to those processed by existing algorithms for the acquired casting images. In conclusion, the NLM denoising algorithm offers an efficient and competitive approach to overcome the noise problem in high-energy X-ray imaging systems, and we expect the accompanying image processing software to facilitate and improve image restoration.

Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury.

The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation is poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.Using a custom-made intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualisation of the pulmonary microcirculation and circulating cells in vivo We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that this decrease resulted from the generation of dead space, which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behaviour, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved hypoxaemia.Using the intravital lung imaging system, we observed that Mac-1-upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation that was recovered by a Mac-1 inhibitor in sepsis-induced ALI.

Relative tachycardia is associated with poor outcomes in post-cardiac arrest patients regardless of therapeutic hypothermia.

BACKGROUND: To investigate whether the relationship between heart rate and neurological outcome is independent of therapeutic hypothermia (TH) and whether heart rate is related to hemodynamic instability post-cardiac arrest. METHODS: Retrospective review of an out-of-hospital cardiac arrest registry was performed. The primary exposure was heart rate quartiles at 24 h post-cardiac arrest. The primary outcome was a poor neurological outcome, which was defined as having a cerebral performance category (CPC) of 3-5 at 28 days. Secondary outcomes were mean blood pressure and serum lactate at 24 h and Sequential Organ Failure Assessment (SOFA) scores at admission. RESULTS: In total, 155 patients were enrolled. The proportion of patients with a poor CPC was significantly greater in higher heart rate quartiles; similar results were observed in patients who did and did not undergo TH. Serum lactate levels at 24 h were significantly higher in the 3rd and 4th quartile groups than in the 1st quartile group. Additionally, SOFA scores were significantly higher in the 4th quartile group than in the 1st and 3rd quartile groups. CONCLUSIONS: Relative tachycardia is associated with poor neurological outcomes in post-cardiac arrest patients, independent of TH, and with higher serum lactate levels and admission SOFA scores.

Prognostic performance of disease severity scores in patients with septic shock presenting to the emergency department.

BACKGROUND: An accurate disease severity score that can quickly predict the prognosis of patients with sepsis in the emergency department (ED) can aid clinicians in distributing resources appropriately or making decisions for active resuscitation measures. This study aimed to compare the prognostic performance of quick sequential organ failure assessment (qSOFA) with that of other disease severity scores in patients with septic shock presenting to an ED. METHODS: We performed a prospective, observational, registry-based study. The discriminative ability of each disease severity score to predict 28-day mortality was evaluated in the overall cohort (which included patients who fulfilled previously defined criteria for septic shock), the newly defined sepsis subgroup, and the newly defined septic shock subgroup. RESULTS: A total of 991 patients were included. All disease severity scores had poor discriminative ability for 28-day mortality. The sequential organ failure assessment and acute physiology and chronic health evaluation II scores had the highest area under the receiver-operating characteristic curve (AUC) values, which were significantly higher than the AUC values of other disease severity scores in the overall cohort and the sepsis and septic shock subgroups. The discriminative ability of each disease severity score decreased as the mortality rate of each subgroup increased. CONCLUSIONS: All disease severity scores, including qSOFA, did not display good discrimination for 28-day mortality in patients with serious infection and refractory hypotension or hypoperfusion; additionally, none of the included scoring tools in this study could consistently predict 28-day mortality in the newly defined sepsis and septic shock subgroups.

A Practice Guideline for Postreduction Management of Intussusception of Children in the Emergency Department.

OBJECTIVES: The aim of this study was to evaluate the effects of a practice guideline of postreduction management of intussusception in children on the length of stay (LOS) from reduction in the pediatric emergency department (PED) and on the incidence of recurrence. METHODS: We developed a practice guideline of postreduction management of intussusception in the PED. The practice guideline involved feeding 2 hours after reduction and discharge 2 hours after successful feeding. The guideline was implemented on October 1, 2012. Retrospective quasi-experimental study was conducted for evaluation of the difference in LOS in the PED after reduction of intussusceptions, and the recurrence rate of intussusceptions between the preimplementation and postimplementation periods. Piecewise regression was performed to determine the differences between groups. RESULTS: In total, 45 and 52 patients were included in the preimplementation and postimplementation periods, respectively. The median LOS in the postimplementation period was significantly shorter than that in the preimplementation period (289 vs 532 minutes, respectively; P = 0.001). The slope of the LOS changed from 0.68 to -0.29. The slope decreased by 0.97 after practice guideline implementation. This difference was not statistically significant (P = 0.123), but it changed from a positive to negative gradient. The recurrence rate was not significantly different between the 2 periods (P = 0.605). CONCLUSIONS: Implementation of a practice guideline involving early feeding and discharge after reduction of intussusception resulted in a reduced LOS from reduction of intussusception in the PED and was not associated with recurrence of intussusception.