Imaging mass spectrometry to visualise increased acetylcholine in lungs of asthma model mice.

Acetylcholine (ACh) is a crucial neurotransmitter that is involved in airway constriction. In fact, excessive ACh binding to M3 muscarinic receptor leads to airflow obstruction via smooth muscle contraction. Previous studies have suggested cholinergic malfunction in the pathogenesis of asthma; however, the distribution and abundance of ACh in asthmatic lungs remain unclear because of the challenges of imaging ACh in lung tissue. In this study, we successfully detected and visualised ACh in mouse lung tissue by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Here, we applied the ACh imaging method to the two groups of house dust mite-sensitised asthma model mice harbouring different inflammatory levels. The imaging results showed that the lungs of mice had a relatively uniform ACh distribution with some areas of heterogeneity. The lungs of asthma model mice had significantly more ACh than control mice, and the ACh increase was potentiated with intense eosinophil infiltration without acetylcholinesterase deficits. These results indicate that ACh hypersecretion is mediated by an increased infiltration of eosinophils in asthma aggravation. This study provides the first evidence that secreted ACh is elevated with asthma severity in the lungs of asthma model animals by a direct ACh imaging technique with FT-ICR-MS.

Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study.

BACKGROUND: To compare the efficacy of three antiseptic solutions [0.5%, and 1.0% alcohol/chlorhexidine gluconate (CHG), and 10% aqueous povidone-iodine (PVI)] for the prevention of intravascular catheter colonization, we conducted a randomized controlled trial in patients from 16 intensive care units in Japan. METHODS: Adult patients undergoing central venous or arterial catheter insertions were randomized to have one of three antiseptic solutions applied during catheter insertion and dressing changes. The primary endpoint was the incidence of catheter colonization, and the secondary endpoint was the incidence of catheter-related bloodstream infections (CRBSI). RESULTS: Of 1132 catheters randomized, 796 (70%) were included in the full analysis set. Catheter-tip colonization incidence was 3.7, 3.9, and 10.5 events per 1000 catheter-days in 0.5% CHG, 1% CHG, and PVI groups, respectively (p = 0.03). Pairwise comparisons of catheter colonization between groups showed a significantly higher catheter colonization risk in the PVI group (0.5% CHG vs. PVI: hazard ratio, HR 0.33 [95% confidence interval, CI 0.12-0.95], p = 0.04; 1.0% CHG vs. PVI: HR 0.35 [95% CI 0.13-0.93], p = 0.04). Sensitivity analyses including all patients by multiple imputations showed consistent quantitative conclusions (0.5% CHG vs. PVI: HR 0.34, p = 0.03; 1.0% CHG vs. PVI: HR 0.35, p = 0.04). No significant differences were observed in the incidence of CRBSI between groups. CONCLUSIONS: Both 0.5% and 1.0% alcohol CHG are superior to 10% aqueous PVI for the prevention of intravascular catheter colonization. TRIAL REGISTRATION: Japanese Primary Registries Network; No.: UMIN000008725 Registered on 1 September 2012.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Impact of urgent resuscitative surgery for life-threatening torso trauma.

PURPOSE: This study investigated the advantages of performing urgent resuscitative surgery (URS) in the emergency department (ED); namely, our URS policy, to avoid a delay in hemorrhage control for patients with severe torso trauma and unstable vital signs. METHODS: We divided 264 eligible cases into a URS group (n = 97) and a non-URS group (n = 167) to compare, retrospectively, the observed survival rate with the predicted survival using the Trauma and Injury Severity Score (TRISS). RESULTS: While the revised trauma score and the injury severity score were significantly lower in the URS group than in the non-URS group, the observed survival rate was significantly higher than the predicted rate in the URS (48.5 vs. 40.2%; p = 0.038). URS group patients with a systolic blood pressure (SBP) <90 mmHg and a Glasgow coma scale (GCS) score of ≥9 had significantly higher observed survival rates than predicted survival rates (0.433 vs. 0.309, p = 0.008), (0.795 vs. 0.681, p = 0.004). The implementation of damage control surgery (DCS) was found to be a significant predictor of survival (OR 5.23, 95% CI 0.113-0.526, p < 0.010). CONCLUSION: The best indications for the URS policy are an SBP <90 mmHg, a GCS ≥9 on ED arrival, and/or the need for DCS. By implementing our URS policy, satisfactory survival of patients requiring immediate hemostatic surgery was achieved.

Dispatch of Helicopter Emergency Medical Services Via Advanced Automatic Collision Notification.

BACKGROUND: Advanced automatic collision notification (AACN) is a system for predicting occupant injury from collision information. If the helicopter emergency medical services (HEMS) physician can be alerted by AACN, it may be possible to reduce the time to patient contact. OBJECTIVE: The purpose of this study was to validate the feasibility of early HEMS dispatch via AACN. METHODS: A full-scale validation study was conducted. A car equipped with AACN was made to collide with a wall. Immediately after the collision, the HEMS was alerted directly by the operation center, which received the information from AACN. Elapsed times were recorded and compared with those inferred from the normal, real-world HEMS emergency request process. RESULTS: AACN information was sent to the operation center only 7 s after the collision; the HEMS was dispatched after 3 min. The helicopter landed at the temporary helipad 18 min later. Finally, medical intervention was started 21 min after the collision. Without AACN, it was estimated that the HEMS would be requested 14 min after the collision by fire department personnel. The start of treatment was estimated to be at 32 min, which was 11 min later than that associated with the use of AACN. CONCLUSIONS: The dispatch of the HEMS using the AACN can shorten the start time of treatment for patients in motor vehicle collisions. This study demonstrated that it is feasible to automatically alert and activate the HEMS via AACN.

Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition.

INTRODUCTION: The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity. METHODS: The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe. RESULTS: Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO2/FIO2 ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO2/FIO2 ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO2/FIO2 ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001). CONCLUSIONS: Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability. TRIAL REGISTRATION: UMIN-CTR ID UMIN000003627.

Development of an educational program for the helicopter emergency medical services in Japan.

INTRODUCTION: The Japanese helicopter emergency medical service (HEMS) system provides advanced prehospital treatment at the scene. The education of the dispatched HEMS physicians is important for guaranteeing the quality of medical and safety management, but there is no nationally established training program. This study aimed to determine the validity of the HEMS educational program developed by our team. METHODS: A 3-step educational program was designed for HEMS trainees: step 1, 20 HEMS missions as an observer; step 2, 80 missions of on-the-job training; and step 3, certifying examination conducted by a supervisor. As an evaluation standard, scene time, defined as time from landing at the scene to taking off for a hospital, was determined retrospectively. RESULTS: For trainees, scene time was significantly longer (16.3 ± 5.4 min, 95% CI 15.5-17.1) than for experts (doctors who completed >200 HEMS missions; 15.2 ± 6.7 min, 95% CI 14.7-15.8; P = 0.040) but was significantly shorter than for doctors trained before establishment of the HEMS program (17.5 ± 7.0 min, 95% CI 16.9-18.2; P = 0.030). In cases of trauma or intrinsic disease, there was no significant difference in scene time between trainees (17.4 ± 5.6 min and 14.9 ± 4.8 min, respectively) and experts (16.4 ± 7.8 min and 14.2 ± 5.5 min, respectively). CONCLUSION: The finding that scene time was shortened for program trainees demonstrates the validity of our HEMS educational program. The quality of HEMS missions will be better ensured through this educational system.

The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome.

INTRODUCTION: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. METHODS: The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. RESULTS: Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). CONCLUSION: PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. TRIAL REGISTRATION: UMIN-CTR ID UMIN000003627.

Clinical Feasibility of a Saliva-Based Antigen Qualitative Test for Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Nasopharyngeal swabs (NPS) are generally used as specimen samples for antigen qualitative tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The principle of the reaction to the antigen protein is the same when saliva is used, and saliva samples were reported to be as accurate as NPS for real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) testing to identify SARS-CoV-2. Unlike NPS collection, self-collected saliva does not expose healthcare workers to the risk of infection. In this study, we evaluated the feasibility of using saliva samples for a SARS-CoV-2 antigen qualitative test (TA2107SA) under development. METHODS: Saliva samples were collected from patients with confirmed or suspected COVID-19 infection and analyzed. The sensitivity, specificity, and concordance index of the antigen qualitative test were calculated using an RT-qPCR test as reference. RESULTS: Saliva samples were collected from 105 patients. The mean interval from onset to specimen collection was 5.7 days. The mean cycle threshold (Ct) value of RT-qPCR was 31.3. The sensitivity, specificity, and concordance index were 70.7%, 100%, and 0.85, respectively. In 33 patients with Ct values <30, the results of both the RT-qPCR and antigen tests were positive. The sensitivity of the saliva-based TA2107SA SARS-CoV-2 antigen qualitative test was slightly lower than that of the conventional antigen qualitative test using NPS samples from the same patient. CONCLUSION: Saliva-based antigen qualitative tests for SARS-CoV-2 are an alternative option during a pandemic.

Serum Glucose-To-Potassium Ratio as a Prognostic Predictor for Severe Traumatic Brain Injury.

BACKGROUND: Initial management of severe traumatic brain injury is important and includes treatment decision-making and prediction of prognosis. We examined whether biomarkers at admission could be useful prognostic predictors. We focused on electrolytes and blood glucose, which can be measured easily at any facility and for which results can be obtained promptly, before those of other biomarkers, such as D-dimer. METHODS: All trauma patients with head injuries treated at Chiba Hokusoh Hospital between 2014 and 2017 were investigated. Cases of multiple trauma accompanied by fatal trauma, hemorrhagic shock, or cardiopulmonary arrest, and pediatric cases, were excluded from this study. Blood gas data at the initial hospital visit were reviewed retrospectively. A poor outcome was defined as death during hospitalization or a vegetative state due to head injury. Factors related to poor outcomes were analyzed. RESULTS: Of the 185 male and 79 female patients studied, 34 had poor outcomes. Poor outcome was significantly correlated with potassium (P = 0.003), glucose (P < 0.001), and glucose-to-potassium ratio (P < 0.001) at arrival. The odds ratio was 4.079 for a glucose-to-potassium ratio of ≥50. CONCLUSIONS: We evaluated blood gas data at the initial hospital visit, as these results can be obtained more quickly than those of other biomarkers assessed previously. Serum glucose-to-potassium ratio at admission may be a potential predictor of prognosis for severe traumatic brain injury.

Revision of 'golden hour' for hemodynamically unstable trauma patients: an analysis of nationwide hospital-based registry in Japan.

BACKGROUND: The 'golden hour' is a well-known concept, suggesting that shortening time from injury to definitive care is critically important for better outcome of trauma patients. However, there was no established evidence to support it. We aimed to validate the association between time to definitive care and mortality in hemodynamically unstable patients for the current trauma care settings. METHODS: The data were collected from the Japan Trauma Data Bank between 2006 and 2015. The inclusion criteria were patients with systolic blood pressure (SBP) <90 mm Hg and heart rate (HR) >110 beats/min or SBP <70 mm Hg who underwent definitive care within 4 hours from the onset of injury and survived for more than 4 hours. The outcome measure was in-hospital mortality. We evaluated the relationship between time to definitive care and mortality using the generalized additive model (GAM). Subgroup analysis was also conducted using GAM after dividing the patients into the severe (SBP <70 mm Hg) and moderate (SBP ≥70 mm Hg and <90 mm Hg, and HR >110 beats/min) shock group. RESULTS: 1169 patients were enrolled in this study. Of these, 386 (33.0%) died. Median time from injury to definitive care was 137 min. Only 61 patients (5.2%) received definitive care within 60 min. The GAM models demonstrated that mortality remained stable for the early phase, followed by a decrease over time. The severe shock group presented with a paradoxical decline of mortality with time, whereas the moderate shock group had a time-dependent increase in mortality. DISCUSSION: We did not observe the association of shorter time to definitive care with a decrease in mortality. However, this was likely an offset result of severe and moderate shock groups. The result indicated that early definitive care could have a positive impact on survival outcome of patients with moderate shock. LEVEL OF EVIDENCE: Level Ⅳ, prognostic study.

Can the global end-diastolic volume index guide fluid management in septic patients? A multicenter randomized controlled trial.

AIM: An index that accurately measures intravascular volume is paramount for the optimal resuscitation of sepsis. Selecting an adequate indicator to substitute for central venous pressure (CVP) has remained an issue. The objective of our study was to compare the usefulness of standard early goal-directed therapy (EGDT) with CVP (EGDT-CVP) and modified EGDT with global end-diastolic volume index (GEDI; EGDT-GEDI) for sepsis. METHODS: This was a multicenter prospective randomized controlled study. All patients with sepsis who were expected to require mechanical ventilator support for a minimum of 48 h were included. The patients were classified into an EGDT-CVP group and an EGDT-GEDI group. All participants underwent the extubation protocol. The primary outcome was the ventilator-free days over a 28-day period. RESULTS: The ventilator-free days was not significantly different between the two groups (P = 0.59). However, the EGDT-GEDI group showed a trend of shorter ventilator support duration (5.1 days [2.0-8.7 days] versus 3.9 days [2.4-5.7 days], P = 0.27) and length of stay in the intensive care unit (7.2 days [3.8-10.7 days] versus 5.1 days [3.7-8.8 days], P = 0.05) and a smaller 3-day infusion balance than the EGDT-CVP group (4,405 mL [1,092-8,163 mL] versus 3,046 mL [830-6,806 mL], P = 0.34), but the differences were not statistically significant. CONCLUSION: Although there was no significant efficacy, EGDT guided by GEDI showed a trend of shorter length of stay in the intensive care unit and lower 3-day infusion balance than the EGDT-CVP group in sepsis. The GEDI monitoring did not appear to improve the ventilator-free days over a 28-day period.

The effect of comorbidities for the prognosis of community-acquired pneumonia: an epidemiologic study using a hospital surveillance in Japan.

OBJECTIVE: Pneumonia is a common but serious illness that continues to present significant morbidity and mortality. Although the effect of severity at admission on outcome has been well reported, the role of comorbidity is still not widely understood. The Charlson Comorbidity Index measures comorbidity with a well-established history of predicting long-term outcome but its utility in pneumonia prognosis is still limited. Here, we use the Charlson Comorbidity Index and hospital surveillance data to investigate associations between comorbidities and in-hospital mortality due to community-acquired pneumonia. RESULTS: Among the 535 eligible adult patients (69.0% male, median [IQR] age, 79 [70-84] years), 100 (18.7%) acquired severe to extremely severe pneumonia. The median [IQR] CCI was 1 [1-3]. Malignancy (129 of 535, 24.1%), chronic pulmonary diseases (113 of 535, 21.1%) and congestive heart failure (103 of 535, 19.3%) were frequent. Higher Charlson Comorbidity Index scores were associated with higher risk of in-hospital mortality (OR 1.28; 95% CI 1.07-1.53). These results support the inclusion of comorbid burden in predicting community-acquired pneumonia outcome.

Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study.

OBJECTIVE: Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. METHODS: This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. RESULTS: Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). CONCLUSIONS: The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

A case of abdominal aortic injury caused by a traffic accident.

A 30-year-old man was injured when the large motorcycle he was riding crashed into a power pole. Upon arrival at our institution, the patient complained of abdominal pain; blood pressure at admission was 160/70 mmHg, and the heart rate was 112 bpm. Abdominal ultrasonography showed a small collection of fluid in Morrison's pouch. A chest X-ray film showed a right rib fracture. Multidetector computed tomography (MD-CT) revealed pleural effusion, a hepatic lesion, and a dissection of the abdominal aorta distal to the renal artery. Because of the complicated intraluminal injuries, the insertion of a stent graft was difficult. On the 34th day after injury, elective surgery was performed. Because dissection of the lumen was observed, the vessel was replaced with an artificial graft. Medial degeneration of the aorta wall was not observed upon pathological examination, and no degenerative disorders have occurred. The postoperative progress was favorable, and the patient was discharged from hospital.

[De novo aneurysm after ten days from the onset of SAH].

A 56-year-old man presented with severe headache. Neurological examinations found no abnormalities and no disturbance of consciousness. CT revealed a subarachnoid hemorrhage. DSA showed an aneurysm located at the junction of the right internal carotid artery and the anterior choroidal artery. Next day, neck clipping was performed. The aneurysm adhered to the temporal lobe, and it seemed without doubt that it was a ruptured aneurysm. On day 10, we performed a carotid angiography on schedule. DSA revealed a newly arisen aneurysm originating from the middle cerebral artery close to the origin of the lenticulostriate artery and a vasospasm in the internal carotid artery and the middle cerebral artery. On day 14, we again performed surgery. The aneurysm was embedded in the insular cortex, but it seemed to be a non-ruptured aneurysm. After surgery, the patient had no apparent neurological deficits, and he returned to normal daily life. De novo aneurysms have been discovered after at least a few years. This case is very rare because the aneurysmal formation is of much a short interval.

Clinical outcomes after initial treatment of methicillin-resistant Staphylococcus aureus infections.

OBJECTIVE: To evaluate the clinical outcomes associated with anti-methicillin-resistant Staphylococcus aureus (MRSA) antimicrobials. METHODS: We reviewed a prospective database of 247 consecutive patients with clinically and microbiologically confirmed MRSA infections, hospitalized in 7 Japanese hospitals between April 2014 and March 2015, and treated with anti-MRSA pharmaceuticals. Survival was measured at 30 days. We examined the relationships between initial antimicrobial administered and survival and organ toxicity. HR and 95% CIs were calculated. RESULTS: Overall 30-day mortality was 12%. The lungs were infected in 105 (41%), skin and soft tissue in 73 (30%), and bones and joints in 21 (9%) patients. Bacteremia complicated the illness in 69 patients (28%). Among 5 pharmaceuticals, vancomycin was prescribed to 174 (71%), linezolid to 38 (16%), teicoplanin to 22 (9%), and daptomycin to 11 (5%) patients. Vancomycin tended to be associated with the lowest survival (HR=2.47; 95% CI=0.93-6.51; P=0.067), particularly in the lung-infected subgroup (HR=4.85; 95% CI=1.12-20.94; P=0.034) after adjustments for baseline illness severity. The incidence of renal dysfunction tended to be higher in patients with trough serum concentrations of vancomycin >15 mg/dL. CONCLUSION: In this observational study reflecting real-world conditions, vancomycin was associated with higher 30-day mortality and incidence of kidney dysfunction than other anti-MRSA agents. The significance of the differences observed among antimicrobials other than vancomycin is uncertain.

Delayed Expression of Circulating TGF-ß1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

BACKGROUND: The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-ß1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. MATERIALS AND METHODS: We performed a comprehensive analysis of plasma TGF-ß1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-ß1 and BMP-2 were measured at each time point using a solid-phase ELISA. RESULTS: TGF-ß1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-ß1 was found at 3-week. In normal union group, TGF-ß1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-ß1 or BMP-2 level was not significantly different between normal union and nonunion groups. CONCLUSION: The expression levels of TGF-ß1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study.

OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute pancreatitis (SAP) according to the segment presenting with low enhanced pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography. METHODS: This was a post hoc analysis of a multicenter, retrospective study conducted at 44 institutions in Japan. Patients diagnosed as having SAP according to the Japanese Severity Score between January 2009 and December 2013 were included. We compared the effect of LEPP in each segment on mortality. RESULTS: A total of 1097 patients were assessed. The numbers of patients with LEPP in the pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was significantly related to mortality (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67 [P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70; 95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early contrast-enhanced computed tomography was independently associated with increased mortality in SAP. These patients require close observation to ensure timely and adequate intervention.