Mortality at 180-days is affected by serum haptoglobin levels in septic patients with high magnitude serum high mobility group box-1 levels.

AIM: High mobility group box-1 (HMGB1) is a lethal mediator of sepsis that binds to haptoglobin (Hp) and is associated with its prognosis. We investigated the effect of the combination of HMGB1 and Hp on sepsis prognosis. METHODS: This single-center, retrospective study registered 78 patients with sepsis according to Sepsis-3 criteria on day 1 of diagnosis from July 2016 to November 2018. We divided the patients into four groups according to the serum concentration of 6.2 ng/mL HMGB1 and the median value of Hp. The 180-day mortality rates and cytokine concentrations of the low and high HMGB1 groups were compared. RESULTS: There was no difference in the 180-day mortality rate between the low Hp group and the high Hp group in the low HMGB1 group (P = 0.691). In the high HMGB1 group, a statistically significant difference was found between the low Hp group and the high Hp group (P = 0.002). In the high HMGB1 group, high Hp was associated with a better prognosis in univariate analysis (odds ratio, 0.131; 95% confidence interval [CI], 0.027-0.629; P = 0.011), and multivariate analysis (adjusted odds ratio, 0.086; 95% CI, 0.013-0.582; P = 0.009). In addition, in the high HMGB1 group, interleukin-8 levels were significantly higher in the low Hp group than in the high Hp group (P = 0.004). CONCLUSION: Patients with sepsis-induced high serum HMGB1 levels and low serum Hp levels could have a poor long-term prognosis.

Correlations between cardiovascular parameters and image parameters on dynamic chest radiographs in a porcine model under fluid loading.

Latest digital radiographic technology permits dynamic chest radiography during the cardiac beating and/or respiration, which allows for real-time observation of the lungs. This study aimed to assess the capacity of dynamic flat-panel detector (FPD) imaging without the use of contrast media to estimate cardiovascular parameters based on image parameters of a porcine model under fluid loading. Three domestic pigs were intubated, and mechanical ventilation was provided using a ventilator under anesthesia. A porcine model involving circulatory changes induced by fluid loading (fluid infusion/blood removal) was developed. Sequential chest radiographs of the pigs were obtained using a dynamic FPD system within the first 5 min after fluid loading. Image parameters such as the size of the heart shadow and mean pixel values in the lungs were measured, and correlations between fluid loading and cardiovascular parameters (blood pressure [BP], cardiac output [CO], central venous pressure [CVP], and pulmonary arterial pressure [PAP]) were analyzed based on freedom-adjusted coefficients of determination (Rf2). Fluid loading was correlated with radiographic lung density and the size of the heart shadow. Radiographic lung density was correlated with the left and right heart system-related parameters BP, CO, CVP, and PAP. The size of the heart shadow correlated with the left heart system-related parameters CO and BP. Dynamic FPD imaging allows for the relative evaluation of cardiovascular parameters based on image parameters. This diagnostic method provides radiographic image information and estimates relative circulatory parameters.

Impact of abdominal aortic calcification on 90-day mortality in sepsis patients: a pilot retrospective cohort study.

AIM: We aimed to investigate the association between aortic calcification and 90-day mortality in sepsis patients admitted to the intensive care unit. METHODS: We evaluated adult patients (≥18 years) diagnosed with sepsis based on the Sepsis-3 criteria and admitted to our intensive care unit between April 2011 and March 2015. They were classified according to the degree of abdominal aortic calcification (severe and non-severe), grouped per age (<65, 65-75, and >75 years), and matched. Survival curves were generated, and between-group differences were evaluated. RESULTS: Overall, 164 patients were included. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were not significantly different between the severity groups, whereas there were significant differences in age (P < 0.001), sex (P = 0.017), and presence of diabetes mellitus (P < 0.001), hypertension (P < 0.001), dyslipidemia (P = 0.048), and maintenance dialysis (P = 0.001). The severe abdominal aortic calcification group showed significantly poorer prognosis than the non-severe group (log-rank P = 0.009). The adjusted odds ratio of severe calcification was the highest in patients aged <65 years (7.167; 95% confidence interval, 1.042-49.28, P = 0.045). Twenty-eight patients from each group were matched. The 90-day survival rate of the severe calcification group remained significantly lower than that of the non-severe calcification group (53.6% [15/28] versus 82.1% [23/28], P = 0.022). CONCLUSIONS: Severe abdominal aortic calcification is associated with the 90-day mortality of sepsis patients, particularly among those aged <65 years. Thus, caution is necessary in patients younger than 65 years; they may need to be treated with as much care as the elderly.

Detection of Pulmonary Embolism Using a Novel Dynamic Flat-Panel Detector System in Monkeys.

BACKGROUND: Recently, dynamic chest radiography (DCR) was developed to evaluate pulmonary function using a flat-panel detector (FPD), which can evaluate blood flow in the pulmonary artery without injection of contrast agents. This study investigated the ability of a FPD to measure physiological changes in blood flow and to detect pulmonary embolism (PE) in monkeys.Methods and Results:DCR was performed in 5 monkeys using a FPD. Regions of interest (ROI) were placed in both lung fields of the image, and maximum changes in pixel value (∆pixel value) in the ROI were measured during 1 electrocardiogram cardiac cycle. Next, a PE model was induced using a Swan-Ganz catheter and additional images were taken. The ∆pixel value of the lungs in normal and PE models were compared in both supine and standing positions. The lung ∆pixel value followed the same cycle as the monkey electrocardiogram. ∆pixel values in the upper lung field decreased in the standing as compared to the supine position. In the PE model, the ∆pixel value decreased in the area of pulmonary blood flow occlusion and increased in the contralateral lung as compared to the normal model (normal model 1.287±0.385, PE model occluded side 0.428±0.128, PE model non-occluded side 1.900±0.431). CONCLUSIONS: A FPD could detect postural changes in pulmonary blood flow and its reduction caused by pulmonary artery occlusion in a monkey model.

Association between plasma complement factor H concentration and clinical outcomes in patients with sepsis.

AIM: The complement system is important for defending against pathogens, however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway. We investigated the association between plasma CFH levels on admission to the intensive care unit (ICU) and 90-day mortality, severity scores, and organ dysfunction in patients with sepsis. METHODS: We assessed the relationship between the plasma CFH on admission to the ICU and 90-day mortality, severity scores such as the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score 2, and organ dysfunction. RESULTS: This analysis included 62 patients. The plasma CFH levels were significantly lower in 90-day non-survivors than in survivors (70.0 µg/mL [interquartile range, 51.2-97.6] versus 104.8 µg/mL [interquartile range, 66.8-124.2]; P = 0.006) . The plasma CFH levels were associated with 90-day mortality (odds ratio 0.977; 95% confidence interval, 0.957-0.994; P = 0.01). The plasma CFH levels were negatively correlated with severity scores. The Sequential Organ Failure Assessment scores for the coagulation and neurological components were negatively correlated with the CFH concentration. CONCLUSION: Lower plasma levels of CFH were associated with increased severity and mortality in patients with sepsis on admission to the ICU and were correlated with central nervous system dysfunction and coagulopathy.

Vasovagal Reaction and Ischemic Colitis Following Blood Donation.

Vasovagal reactions are the most common type of adverse reaction after blood donation; however, there are no reports of ischemic colitis as an adverse reaction after blood donation. A previously healthy 55-year-old woman suffered loss of consciousness at the end of her first plasma donation. She was diagnosed with a vasovagal reaction and received hydration. However, she developed persistent left flank pain and watery diarrhea, followed by bloody diarrhea. Abdominal computed tomography confirmed ischemic colitis. She was asked to fast and was eventually discharged 7 days later. We should consider the possibility of ischemic colitis if patients develop persistent abdominal pain after transient hypotension, such as that observed during a vasovagal reaction.

"Impact of timing of polymyxin B-immobilized fiber column direct hemoperfusion on outcome in patients with septic shock: a single-center observational study".

AIM: The effect of polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is controversial. The present study investigates whether outcome in septic shock patients is affected by the time until PMX-DHP initiation and the location of the infection site (intra- or extra-abdominal infection (IAI/EAI)]. METHODS: This retrospective observational study included patients receiving PMX-DHP for septic shock but excluded those treated after cardiac surgery or cardiac arrest. Based on the median and/or quartile time from catecholamine treatment to PMX-DHP initiation, the patient cohort was divided into four groups and the IAI and EAI groups into two subgroups. RESULTS: Among the 49 eligible patients, overall 90-day mortality in group 1 (PMX-DHP within 6 h) at 8.3% was significantly lower than in groups 2 (6-9 h; 46.1%), 3 (9-29 h; 58.3%) and 4 (>29 h; 75.0%) (P = 0.021). Multivariate logistic regression analysis showed that the duration from catecholamine treatment to PMX-DHP initiation correlated with 90-day mortality (odds ratio 1.060; 95% confidence interval, 1.004-1.117; P = 0.028). Among the 29 IAI patients, 90-day mortality was significantly lower in the early (within 9 h) than the late group (>9 h) (13.3% versus 64.2%; P = 0.003), but no significant intergroup difference was noted among the 20 EAI patients. CONCLUSION: Our results suggest that early PMX-DHP initiation (within 9 h after catecholamine treatment) reduces mortality from septic shock, especially in IAI patients.

Propofol infusion syndrome complicated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a case report.

BACKGROUND: Propofol infusion syndrome (PRIS) is a rare but lethal complication of propofol use. It has been suggested that the pathological mechanism of PRIS involves mitochondrial disorder caused by propofol. CASE PRESENTATION: A 24-year-old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes was admitted to our hospital with impaired consciousness and myoclonus. To control the non-convulsive status epilepticus, propofol was administered. Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated. The patient was diagnosed with PRIS. We treated her with interruption of propofol. She required mechanical ventilation for 25 days. After rehabilitation, she recovered and was discharged. CONCLUSION: Mitochondrial disorder is a risk factor for PRIS. It is important for clinicians to be aware that mitochondrial disorder is a risk factor for PRIS, especially under conditions of critical illness and status epilepticus.

Detection of Pulmonary Embolism Based on Reduced Changes in Radiographic Lung Density During Cardiac Beating Using Dynamic Flat-panel Detector: An Animal-based Study.

RATIONALE AND OBJECTIVES: To assess the capacity of dynamic flat-panel detector imaging without the use of contrast media to detect pulmonary embolism (PE) based on temporal changes in radiographic lung density during cardiac beating. MATERIALS AND METHODS: Sequential chest radiographs of six pigs were acquired using a dynamic flat-panel detector system. A porcine model of PE was developed, and temporal changes in pixel values in the imaged lungs were analyzed during a whole cardiac cycle. Mean differences in temporal changes in pixel values between affected and unaffected lobes were assessed using the paired t test. To facilitate visual evaluation, temporal changes in pixel values were depicted using a colorimetric scale and were compared to the findings of contrast-enhanced images. RESULTS: Affected lobes exhibited a mean reduction of 49.6% in temporal changes in pixel values compared to unaffected lobes within the same animals, and a mean reduction of 41.3% compared to that before vessel blockage in the same lobe. All unaffected lobes exhibited significantly-increased changes in pixel values after vessel blockage (p < 0.01). In all PE models, there were color-deficient areas with shapes and locations that matched well with the perfusion defects confirmed in the corresponding contrast-enhanced images. CONCLUSION: Dynamic chest radiography enables the detection of perfusion defects in the lobe unit based on temporal changes in image density, even without the use of contrast media. Quantification and visualization techniques provide a better understanding of the circulation-induced changes depicted in dynamic chest radiographs.

Pulmonary Function Diagnosis Based on Respiratory Changes in Lung Density With Dynamic Flat-Panel Detector Imaging: An Animal-Based Study.

OBJECTIVES: The aims of this study were to address the relationship between respiratory changes in image density of the lungs and tidal volume, to compare the changes between affected and unaffected lobes, and to apply this new technique to the diagnosis of atelectasis. MATERIALS AND METHODS: Our animal care committee approved this prospective animal study. Sequential chest radiographs of 4 pigs were obtained under respiratory control with a ventilator using a dynamic flat-panel detector system. Porcine models of atelectasis were developed, and the correlation between the tidal volume and changes in pixel values measured in the lungs were analyzed. The mean difference in respiratory changes in pixel values between both lungs was tested using paired t tests. To facilitate visual evaluation, respiratory changes in pixel values were visualized in the form of a color display, that is, as changes in color scale. RESULTS: Average pixel values in the lung regions changed according to forced respiration. High linearity was observed between changes in pixel values and tidal volume in the normal models (r = 0.99). Areas of atelectasis displayed significantly reduced changes in pixel values (P < 0.05). Of all atelectasis models with air trapping and air inflow restriction, 92.7% (19/20) were visualized as color-defective or color-marked areas on functional images, respectively. CONCLUSION: Dynamic chest radiography allows for the relative evaluation of tidal volume, the detection of ventilation defects in the lobe unit, and a differential diagnosis between air trapping and air inflow restriction, based on respiratory changes in image density of the lungs, even without the use of contrast media.

Non-REM sleep-disordered breathing affects performance on the psychomotor vigilance task.

PURPOSE: Although many studies have investigated the clinical importance of sleep apnea on rapid eye movement (REM) and non-REM (NREM) sleep, the relationship between behavioral performance and apneic events during different sleep phases remains unclear. In the present study, we sought to investigate the effect of sleep phase fragmentation due to sleep-disordered breathing (SDB) during REM and NREM on the vigilance and sustainability of attention based on psychomotor vigilance task (PVT) performance. METHODS: From a pool of subjects who underwent consecutive diagnostic polysomnography (PSG) for obstructive sleep apnea, 163 adult subjects with both REM and NREM sleep ≥ 30 min were enrolled for our study and performed a standardized 10-min PVT. The main outcome variables of the PVT were mean reaction time (RT), PVT Lapse count, and the slope of the reciprocal RT. Subjective sleepiness was measured using the Epworth Sleepiness Scale (ESS). RESULTS: After multivariate linear regression analysis with adjustment for age, sex, body mass index, and the apnea-hypopnea index (AHI) of the counterpart sleep phase, we found that AHI during NREM (AHINREM) compared to AHI during REM (AHIREM) was significantly associated with PVT lapses. CONCLUSIONS: Our results suggest that SDB during NREM has a significant impact on vigilance lapses compared to that of REM.

Presence of osteoclasts in middle ear cholesteatoma: a study of undecalcified bone sections.

CONCLUSIONS: Osteoclasts are unlikely to be involved in bone resorption in middle ear cholesteatoma. OBJECTIVE: The authors searched for osteoclasts in undecalcified bone sections in patients with middle ear cholesteatoma to determine whether and to what extent these cells are involved in this disease. METHODS: Twelve patients, eight men and four women, aged 30-87 years, who underwent tympanomastoidectomy were enrolled. Six patients had primary acquired middle ear cholesteatoma (cholesteatoma group) and the other six patients had other otologic diseases including otosclerosis, non-cholesteatomatous chronic otitis media, adhesive otitis media, perilymphatic fistula and ossicular malformation (control group). The scutum bone was collected during surgery, fixed with ethanol, stained with Villanueva bone stain, and embedded in methyl methacrylate. Five-micrometer-thick sections were prepared and examined under a polarizing microscope. Images were analyzed using a semiautomatic graphics system. RESULTS: No osteoclasts were seen in any of the samples in either group. To avoid the risk of under-estimating the presence of osteoclasts, the number of osteoclasts was considered to be <1 in each sample, and the osteoclast density was calculated. The osteoclast densities in both the cholesteatoma and control groups were significantly lower than the sex- and age-matched standard value of the normal iliac cortical bone (p = .028).

Revision Myringoplasty Using Thin-Sliced Cartilage for Postoperative Reperforation in Patients with Chronic Otitis Media.

Myringoplasty is one of the basic procedures in otologic surgery, and is important to achieve good hearing outcome. The temporal fascia is most widely used and considered to be a stable graft in this procedure, although 10-20% of patients develop reperforation after surgery, which is often hard to repair, even by revision surgery. We herein conducted revision myringoplasty using a cartilage graft to repair postoperative reperforation in 7 patients (8 ears) with chronic otitis media. The patients were 3 males and 4 females, aged 13-80 years with an average of 53.9 years. A cartilage graft was harvested from the tragus, sliced in 0.3 mm thickness with perichondrium attached on one side, and trimmed into an appropriate shape and size. The graft was then underlaid beneath the perforation and fixed with fibrin glue. The operation was Wullstein type I tympanoplasty in 5 ears and myringoplasty in 3 ears, using the temporal fascia in 7 ears and subcutaneous tissue in 1 ear. The postoperative follow-up period ranged from 16 to 44 months with an average of 30.0 months. Perforation of the tympanic membrane was successfully closed in 7 ears (87.5%). Hearing outcome was judged successful in 5 ears (62.5%) according to the criteria of the Otological Society of Japan (postoperative hearing level < 30 dB, hearing gain > 15 dB, or postoperative air-bone gap < 15 dB). These results indicate that cartilage is a stable and reliable graft material for revision myringoplasty to repair postoperative reperforation in patients with chronic otitis media.

Electrical Impedance and Expression of Tight Junction Components of the Nasal Turbinate and Polyp.

PURPOSE: We investigated the electrical impedance and expression of tight junction components of the turbinate mucosa, nasal polyp, and normal skin. PROCEDURES: The inferior turbinate and nasal polyp of patients with chronic rhinosinusitis and the postauricular skin of patients with otitis media were examined. Electrical impedance was measured in vivo using a tissue conductance meter. Expressions of claudin-1 and tricellulin were examined by fluorescence immunohistochemistry and quantitative RT-PCR. RESULTS: Electrical impedance was higher in the skin than in the turbinate and polyp, but did not differ between the turbinate and polyp. Immunoreactivities for claudin-1 and tricellulin were seen in the epithelial/epidermal layer. Expression of claudin-1 was higher in the skin than in the turbinate and polyp. The polyp tended to show higher expression of claudin-1 but showed lower expression of tricellulin than the turbinate. The ratio of claudin-1 to tricellulin was highest in the skin and lowest in the turbinate. The correlation between expressions of the two tight junction components was strongly positive in the skin (r = 0.964) and negative (r = -0.527) in the turbinate and polyp. CONCLUSIONS: These results suggest that the roles of claudin-1 and tricellulin in barrier function may be complementary, and may thereby maintain a constant level of permeability of the mucosal tissues.

Association of the Plasma Platelet-Derived Microparticles to Platelet Count Ratio with Hospital Mortality and Disseminated Intravascular Coagulopathy in Critically Ill Patients.

AIM: The role of platelet-derived microparticles (PDMPs) in the crosstalk between coagulopathy and inflammation in critically ill patients remains unclear. The aim of this cohort observational study was to investigate the associations between the PDMP levels and hospital mortality or disseminated intravascular coagulopathy (DIC). METHODS: This study included 119 patients who were admitted to the ICU. The PDMP levels were measured using an enzyme-linked immunosorbent assay three times a week, for a total of 372 samples. We calculated the maximum (max) PDMP value, max PDMP/platelet (PDMP/Plts) ratio (converted to the PDMP levels per 10(4) platelets) and nadir platelet count during the ICU stay. Baseline patient data and scores, including the Japanese Association for Acute Medicine (JAAM) DIC score, were collected, and potential predictors were analyzed for possible associations with hospital mortality. RESULTS: The max PDMP/Plts ratio was significantly different comparing the survivors (n=98: median, 2.54) and non-survivors (n=21: median 17.59; p＜0.001). There was a weak but statistically significant negative correlation between the max PDMP level and nadir platelet count (r=-0.332, p＜0.001). The max PDMP level and max PDMP/Plts ratio were higher in the DIC group (81.48 and 9.27, respectively) than in the non-DIC group (34.88 and 2.35, p=0.001 and p＜0.001, respectively). The max PDMP/Plts ratio was the only variable found to be independently associated with hospital mortality according to a multivariate logistic regression analysis. CONCLUSIONS: PDMPs are involved in the development of DIC but are not related to hospital mortality. There is a good association between the PDMP/Plts ratio and hospital mortality and/or DIC in critically ill patients.

Prediction of hearing outcomes by multiple regression analysis in patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: This study aimed to create a multiple regression model for predicting hearing outcomes of idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: The participants were 205 consecutive patients (205 ears) with ISSNHL (hearing level ≥ 40 dB, interval between onset and treatment ≤ 30 days). They received systemic steroid administration combined with intratympanic steroid injection. Data were examined by simple and multiple regression analyses. Three hearing indices (percentage hearing improvement, hearing gain, and posttreatment hearing level [HLpost]) and 7 prognostic factors (age, days from onset to treatment, initial hearing level, initial hearing level at low frequencies, initial hearing level at high frequencies, presence of vertigo, and contralateral hearing level) were included in the multiple regression analysis as dependent and explanatory variables, respectively. RESULTS: In the simple regression analysis, the percentage hearing improvement, hearing gain, and HLpost showed significant correlation with 2, 5, and 6 of the 7 prognostic factors, respectively. The multiple correlation coefficients were 0.396, 0.503, and 0.714 for the percentage hearing improvement, hearing gain, and HLpost, respectively. Predicted values of HLpost calculated by the multiple regression equation were reliable with 70% probability with a 40-dB-width prediction interval. CONCLUSION: Prediction of HLpost by the multiple regression model may be useful to estimate the hearing prognosis of ISSNHL.

Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.

Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

The ability of endotoxin adsorption during a longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column in patients with septic shock.

The patients' hemodynamic conditions of septic shock due to intra-abdominal infection were improved by the longer duration of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX), reducing plasma endotoxins measured by the novel endotoxin detection method, named endotoxin scattering photometry (ESP) method; however, turbidimetric method could not detect endotoxins. We also observed the reduction in the endotoxin after passing through column by ESP method even after the longer duration of PMX. ESP method may more sensitively detect endotoxins than the ordinary turbidimetric method. Moreover, we demonstrated the ability of endotoxin adsorption in spite of the longer duration of PMX.