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Study objective We sought to examine how physicians understand the role of law enforcement in the emergency department (ED) and to identify how the presence of law enforcement officers may impact the delivery of emergency medical care. Methods In this qualitative study, we conducted semistructured interviews with 20 emergency physicians practicing in county EDs across 3 health care systems in Northern California between November 2017 and September 2018. Participants were recruited using snowball sampling and included 10 board-certified physicians and 10 resident physicians. We analyzed the interview content using grounded theory, where concepts from interview data were coded, grouped by theme, and compared over consecutive interviews to identify recurrent themes. Results Participants reported interacting frequently with law enforcement officers while treating patients. Most participants characterized their experiences with law enforcement as “mixed” or “variable.” Positive interactions with officers, who were described as helpful and collegial, contrasted with instances in which respondents felt police presence led to interruptions in treatment, breaches in health privacy, and potentially diminished patient trust. Participants reported that, at times, the authority of officers in the ED felt unclear and ill-defined, leading to contentious interactions between officers and health care personnel. Conclusion Lack of clear definition of the role of law enforcement officers in the ED may lead to contentious interactions with emergency physicians. Further research on the medical impacts of police presence in health care settings and on best practices for mitigating negative impacts is needed.

The purpose was to examine the incidence of positive cultures in a highly susceptible subset of trauma patients admitted to the surgical intensive care unit (SICU) for mechanical ventilation and to examine the impact of their timing on outcomes.A retrospective review was conducted of blunt trauma patients admitted to the SICU for mechanical ventilation at a level I trauma center over a five-year period. All urine, blood, and sputum cultures were abstracted. Patients with at least one positive culture were compared with those with negative or no cultures. The primary outcome was mortality. A Cox regression model with a time-dependent variable was utilized to calculate the adjusted hazard ratio (AHR).The median age of 635 patients meeting inclusion criteria was 46 and 74.2% were male. A total of 298 patients (46.9%) had at least one positive culture, with 28.9% occurring within two days of admission. Patients with positive cultures were more likely to be severely injured with an injury severity score (ISS) ≥16 (68.5% vs. 45.1%, p 0.001). Overall mortality was 22%. Patients who had their first positive culture within two and three days from admission had a significantly higher AHR for mortality (AHR: 14.46, p 0.001 and AHR: 10.59, p = 0.028, respectively) compared to patients with a positive culture at day six or later.Early positive cultures are common among trauma patients requiring mechanical ventilation and are associated with higher mortality. Early identification with "damage control cultures" obtained on admission to aid with early targeted treatment might be justified.

Background Massive transfusion protocols (MTPs) are necessary for hemodynamically unstable trauma patients with active bleeding. Thrombotic events have been associated with blood transfusion; however, the risk factors for the development of venous thromboembolism (VTE) in trauma patients receiving MTP are unknown. Methods A retrospective review was conducted by reviewing the electronic medical records of all trauma patients admitted to a Level I trauma center who received MTP from 2011 to 2016. Data were collected on patient demographics, mechanism of injury, injury severity scores, quantity of blood products transfused during MTP activation, incidence of VTE, intensive care unit length of stay (LOS), hospital LOS, and ventilator days. The primary outcome was VTE. Results Of the 59 patients who had MTP activated, 15 (25.4%) developed a VTE during their hospital admission. Patients who developed VTE were compared with those who did not. Age (40 y versus 35 y, P = 0.59), sex (60% versus 73% male, P = 0.52), and mechanism of injury (47% versus 59% blunt, P = 0.40) were similar. Intensive care unit LOS, hospital LOS, and ventilator days were longer in the patients who were diagnosed with a VTE. Multivariable analysis revealed an increase in the odds for developing a VTE with increasing packed red blood cell transfusion (adjusted odds ratio = 2.61, P = 0.03). Conclusions The risk for VTE in trauma patients requiring massive transfusion is proportional to the number of packed red blood cells transfused. Liberal screening protocols and maintenance of a high index of suspicion for VTE in these high-risk patients is justified.

Introduction Extended stay in the emergency department (ED) is associated with worse outcomes in critically ill trauma patients. We conducted a human factors analysis to better understand impediments for patient flow when a surgical ICU (SICU bed is available in order to reduce ED LOS. Methods This is a retrospective review of all trauma patients admitted to a protected SICU through the ED during 2011 and 2014. In 2010, a 24-hour protected SICU bed protocol was implemented to make a bed readily available. During 2013 human factors analysis helped to describe flow disruptions; related interventions were introduced to facilitate rapid transport from the ED to SICU. The interventions required the following prior to CT scanning: immediate ICU bed orders placed by the ED physician and ED to ICU personnel communication. Direct transport from the CT scanner to the ICU was mandated. Data including patient demographics, injury severity, ED LOS, ICU LOS, and hospital LOS was collected and compared between 2011 (PRE) and 2014 (POST). Results A total of 305 trauma patients admitted from the ED to the SICU were analyzed; 174 patients in 2011 (PRE) and 131 in 2014 (POST). Average age was 46 years and patients had a mean admission GCS and injury severity score (ISS) of 12.3 and 15.9, respectively. The cohorts were similar in age, mechanism of injury, initial vital signs, and injury severity. After implementing the human factors interventions, decreases were noted in the mean ED LOS (2.4 v. 3.0 hours, p=0.005) and ICU LOS (4.0 v. 4.8 days, p=0.023). No differences in hospital LOS or mortality were observed. Conclusions While an open SICU bed protocol may facilitate rapid transport of trauma patients from the ED to the ICU, additional human factors interventions emphasizing improved communication and coordination can further reduce time spent in the ED. Level of Evidence Level IV, Economic/Decision.

Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated.In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores. Heparin-induced thrombocytopenia-positive patients were defined as those with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay (optical density, ≥ 0.40) and positive serotonin release assay results.Urban tertiary medical center.Patients admitted to the surgical and cardiac ICU who were presumed to have heparin-induced thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked immunosorbent assay and serotonin release assay testing between January 1, 2011, and August 1, 2014.None.A total of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, and serotonin release assay scores. A total of 11 patients (8.1%) had positive serotonin release assay and 80 patients had positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were identified as heparin-induced thrombocytopenia positive. Positive serotonin release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density greater than or equal to 2.0, compared with one of 22 patients (4.5%) with optical density values of 0.85-1.99, and one of 102 patients (1.0%) with optical density values of 0-0.84. Out of 135 patients, 29 patients (21.5%) received treatment with argatroban, lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative patients (15%).Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold.

Background The optimal heart rate (HR) for children after trauma is based on values derived at rest for a given age. As the stages of shock are based in part on HR, a better understanding of how HR varies after trauma is necessary. Admission HRs of pediatric trauma patients were analyzed to determine which ranges were associated with lowest mortality. Materials and methods The National Trauma Data Bank was used to evaluate all injured patients ages 1–14 years admitted between 2007 and 2011. Patients were stratified into eight groups based on age. Clinical characteristics and outcomes were recorded, and regression analysis was used to determine mortality odds ratios (ORs) for HR ranges within each age group. Results A total of 214,254 pediatric trauma patients met inclusion criteria. The average admission HR and systolic blood pressure were 104.7 and 120.4, respectively. Overall mortality was 0.8%. The HR range associated with lowest mortality varied across age groups and, in children ages 7–14, was narrower than accepted resting HR ranges. The lowest risk of mortality for patients ages 5–14 was captured at HR 80–99. Conclusions The HR associated with lowest mortality after pediatric trauma frequently differs from resting HR. Our data suggest that a 7y old with an HR of 115 bpm may be in stage III shock, whereas traditional HR ranges suggest that this is a normal rate for this child. Knowing when HR is critically high or low in the pediatric trauma population will better guide treatment.

β-Adrenergic receptor blockers (BBs) administered after trauma blunt the cascade of immune and inflammatory changes associated with injury. BBs are associated with improved outcomes after traumatic brain injury (TBI). Propranolol may be an ideal BB because of its nonselective inhibition and ability to cross the blood-brain barrier. We determined if early administration of propranolol after TBI is associated with lower mortality.All adults (age ≥ 18 years) with moderate-to-severe TBI (head Abbreviated Injury Scale [AIS] score, 3-5) requiring intensive care unit (ICU) admission at a Level I trauma center from January 1, 2013, to May 31, 2015, were prospectively entered into a database. Administration of early propranolol was dosed within 24 hours of admission at 1 mg intravenous every 6 hours. Patients who received early propranolol after TBI (EPAT) were compared with those who did not (non-EPAT). Data including demographics, hospital length of stay (LOS), ICU LOS, and mortality were collected.Over 29 months, 440 patients with moderate-to-severe TBI met inclusion criteria. Early propranolol was administered to 25% (109 of 440) of the patients. The EPAT cohort was younger (49.6 years vs. 60.4 years, p0.001), had lower Glasgow Coma Scale (GCS) score (11.7 vs. 12.4, p = 0.003), had lower head AIS score (3.6 vs. 3.9, p = 0.001), had higher admission heart rate (95.8 beats/min vs. 88.4 beats/min, p = 0.002), and required more days on the ventilator (5.9 days vs. 2.6 days, p0.001). Similarities were noted in sex, Injury Severity Score (ISS), admission systolic blood pressure, hospital LOS, ICU LOS, and mortality rate. Multivariate regression showed that EPAT was independently associated with lower mortality (adjusted odds ratio, 0.25; p = 0.012).After adjusting for predictors of mortality, early administration of propranolol after TBI was associated with improved survival. Future studies are needed to identify additional benefits and optimal dosing regimens.Therapeutic study, level IV.

Purpose The purpose of the study is to determine if excessive fluid administration is associated with a prolonged hospital course and worse outcomes. Materials and methods In July 2013, all normotensive trauma patients admitted to the surgical intensive care unit (ICU) were administered crystalloids at 30 mL/h (“to keep open [TKO]”) and were compared to patients admitted during the preceding 6 months who were placed on a rate between 125 mL/h to 150 mL/h (non-TKO). The primary outcomes were ICU, hospital, and ventilator days. Results A total of 101 trauma patients met inclusion criteria: 56 (55.4%) in the TKO and 45 (44.6%) in the non-TKO group. Overall, the 2 groups were similar in regard to age, Injury Severity Score, Acute Physiology and Chronic Health Evaluation IV scores, and the need for mechanical ventilation. TKO had no effect on renal function compared to non-TKO with similarities in maximum hospital creatinine. TKO patients had lower ICU stay (2.7 ± 1.5 vs 4.1 ± 4.6 days; P = .03) and ventilator days (1.4 ± 0.5 vs 5.5 ± 4.8 days; P Conclusions A protocol that encourages admission basal fluid rate of TKO or 30 mL/h in normotensive trauma patients is safe, reduces fluid intake, and may be associated with a shorter intensive care unit course and fewer ventilator days.

The source of coagulopathy in traumatic brain injury (TBI) is multifactorial and may include adrenergic stimulation. The aim of this study was to assess coagulopathy after TBI using thromboelastography (TEG), and to investigate the implications of β-adrenergic receptor knockout. Adult male wild type c57/bl6 (WT) and β1/β2-adrenergic receptor knockout (BKO) mice were assigned to either TBI (WT-TBI, BKO-TBI) or sham injury (WT-sham, BKO-sham). Mice assigned to TBI were subject to controlled cortical impact (CCI). At 24 h post-injury, whole blood samples were obtained and taken immediately for TEG. At 24 h after injury, a trend toward increased fibrinolysis was seen in WT-TBI compared to WT-sham although this did not reach significance (EPL 8.1 vs. 0 %, p = 0.18). No differences were noted in fibrinolysis in BKO-TBI compared to BKO-sham (LY30 2.6 vs. 2.5 %, p = 0.61; EPL 3.4 vs. 2.9 %, p = 0.61). In addition BKO-TBI demonstrated increased clot strength compared to BKO-sham (MA 76.6 vs. 68.6, p = 0.03; G 18.2 vs. 11.3, p = 0.03). In a mouse TBI model, WT mice sustaining TBI demonstrated a trend toward increased fibrinolysis at 24 h after injury while BKO mice did not. These findings suggest β-blockade may attenuate the coagulopathy of TBI and minimize progression of intracranial hemorrhage by reducing fibrinolysis and increasing clot strength.

Objectives To examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism. Methods The association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the “NinJa” Registry, one of the largest cohorts of Japanese RA patients. In vitro enhancement of TNFα-induced NF-κB activation and subsequent proinflammatory cytokine production by cigarette chemical components was examined by RT-PCR, qPCR, ELISA, and western blotting using an immortalized rheumatoid synovial cell line, MH7A. Results The rate of drug-discontinuation due to poor therapeutic response was higher in the current smoking group than in the never- or ever-smoking groups (the odds ratio of current/never smoking: 2.189, 95%CI; 1.305–3.672,P = 0.003; current/ever: 1.580, 95%CI; 0.879–2.839,P = 0.126) in the TNF inhibitor (TNFi) treatment group. However, this tendency was not observed in either the IL-6 or T cell inhibitor treatment groups. Cigarette smoke chemical components, such as benzo[α]pyrene, known as aryl hydrocarbon receptor (AhR) ligands, themselves activated NF-κB and induced proinflammatory cytokines, IL-1β and IL-6. Furthermore, they also significantly enhanced TNFα-induced NF-κB activation and proinflammatory cytokine production. This enhancement was dominantly inhibited by Bay 11-7082, an NF-κB inhibitor. Conclusions These results suggest a crosstalk between TNFα signaling and AhR signaling in NF-κB activation which may constitute one of the molecular mechanisms underlying the higher incidence of drug-discontinuation in RA patients undergoing TNFi treatment with smoking habits.

Severe traumatic brain injury (TBI) is associated with increased risk for early clinical and subclinical seizures. The use of continuous electroencephalography (cEEG) monitoring after TBI allows for identification and treatment of seizures that may otherwise occur undetected. Benefits of "routine" cEEG after TBI remain controversial. We examined the rate of subclinical seizures identified by cEEG in TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma patients with moderate to severe TBI (head Abbreviated Injury Score ≥3) who received cEEG within seven days of admission between October 2011 and May 2015. Demographics, clinical data, injury severity, and costs were recorded. Clinical characteristics were compared between those with and without seizures as identified by cEEG. A total of 106 TBI patients with moderate to severe TBI received a cEEG during the study period. Most were male (74%) with a mean age of 55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of patients. Ninety-three per cent were on antiseizure prophylaxis at the time of cEEG. Patients who had subclinical seizures were significantly older than their counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were similar in both groups. Of all TBI patients who were monitored with cEEG, seizures were identified in only 3.8 per cent. Seizures were more likely to occur in older patients with severe head injury. Given the high cost of routine cEEG and the low incidence of subclinical seizures, we recommend cEEG monitoring only when clinically indicated.

Patients with traumatic brain injury (TBI) are often resuscitated with crystalloids in the emergency department (ED) to maintain cerebral perfusion. The purpose of this study was to evaluate whether crystalloid resuscitation volume impacts mortality in TBI patients. This was a retrospective study of trauma patients with head abbreviated injury scale score ≥2, who received crystalloids during ED resuscitation between 2004 and 2013. Clinical characteristics and volume of crystalloids received in the ED were collected. Patients who received2 L of crystalloids were categorized as low volume (LOW), whereas those who received ≥2 L were considered high volume (HIGH). Mortality and outcomes were compared. Multivariable regression analysis was used to determine the odds of mortality while controlling for confounders. Over 10 years, 875 patients met inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty-two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age were similar between the groups. The HIGH cohort had lower admission systolic blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10 vs 12, P0.001), higher head abbreviated injury scale (3.8 vs 3.3, P0.001), and higher injury severity score (25 vs 18, P0.001). The LOW group had a lower unadjusted mortality (10 vs 26%, P0.001). Multivariable analysis adjusting for confounders demonstrated that those resuscitated with ≥2 L of crystalloids had increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume crystalloid resuscitation after TBI is associated with increased mortality, thus limited resuscitation for TBI patients may be indicated.

To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers.The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year.The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P0.001). The safety issues were comparable between the two groups.This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology.Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed.All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum.Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

A 72-year-old man presented with persistent oligoarthritis and positive results for rheumatoid factor and was suspected of having rheumatoid arthritis (RA). However, the musculoskeletal ultrasonography (MSUS) findings were not consistent with those of typical RA. He had undergone surgery for carpal tunnel syndrome, which allowed both histopathological and microbiological examinations to be performed. A synovial tissue culture was positive for Sporothrix schenckii, and he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal therapy, and the sporotrichal tenosynovitis resolved. This case suggests that MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be considered in the differential diagnosis of RA.

BACKGROUND Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the United States, especially in the elderly, who have the highest rates of TBI-related hospitalizations and deaths among all age groups. Sepsis is one of many risk factors that is associated with higher mortality and longer length of hospital stay in this population partially due to the immunosuppressive effects of TBI. The significance of early indicators of infection, such as a positive blood, sputum, or urine culture, is not well described. The purpose of this study was to determine if early positive cultures predict higher mortality in elderly patients with TBI. METHODS All trauma patients aged ≥65 years with TBI, admitted between January 1, 2009 and December 31, 2013 to the surgical intensive care unit, were retrospectively reviewed. Clinical data including results from sputum, blood, and urine cultures were reviewed. RESULTS Overall, 288 elderly patients with TBI were identified, and 92 (32%) had a positive culture. Patients with positive cultures had longer intensive care unit (median 6.0 versus 2.0 days, P

Cross-sectional study.To identify the physical impairments and walking function required for community ambulation in patients with cervical incomplete spinal cord injury (ISCI).Chubu Rosai Hospital, Nagoya, Japan.Forty patients with cervical ISCI (mean age: 49.9 years, American Spinal Injury Association Impairment Scale D) were included. The primary outcome measure was community ambulation based on Spinal Cord Independence Measure outdoor scores for a distance of480 m. We measured the upper- and lower-extremity motor scores (UEMS and LEMS), sensory and spasticity. The walking tests included 10 m of walking at a comfortable- and maximum-walking speed (CWS and MWS; m s(-1)), 6 min walking test (6 MWT; m) and the walking index for spinal cord injury II (WISCI II). Multivariate logistic regression models were used to assess the physical impairments associated with community ambulation. Receiver operating characteristic curves were analyzed to determine the cutoff points for physical impairment and walking function.The LEMS (beta coefficient (β)=0.71) and UEMS (β=0.41) were independently associated with community ambulation in patients with cervical ISCI. The cutoff points of the LEMS, UEMS, CWS, MWS, 6MWT and WISCI II were 41.5, 36.5, 1.00 m s(-1), 1.32 m s(-1), 472.5 m and 17.5, respectively, which suggests moderate to high accuracy.The LEMS and UEMS were the most important factors affecting community ambulation in patients with cervical ISCI. The cutoff points of the walking function tests were highly accurate; therefore, these points can serve as targets for walking training in the future.

Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD.A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD.Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups.Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

Elderly trauma patients may be at increased risk for underassessment and inadequate pain control in the emergency department (ED). We sought to characterize risk factors for oligoanalgesia in the ED in elderly trauma patients and determine whether it impacts outcomes in elderly trauma patients. We included elderly patients (age ≥55 years) with Glasgow Coma Scale scores 13 to 15 and Injury Severity Score (ISS) ≥9 admitted through the ED at a Level I trauma center. Patient characteristics and outcomes were compared between those who reported pain and received analgesics medication in the ED (MED) and those who did not (NO MED). A total of 183 elderly trauma patients were identified over a three-year study period, of whom 63 per cent had pain assessed via verbal pain score; of those who reported pain, 73 per cent received analgesics in the ED. The MED and NO MED groups were similar in gender, race, ED vitals, ISS, and hospital length of stay. However, NO MED was older, with higher head Abbreviated Injury Scale score and longer intensive care unit length of stay. Importantly, as patients aged they reported lower pain and were less likely to receive analgesics at similar ISS. Risk factors for oligoanalgesia may include advanced age and head injury.

Liberal emergency department (ED) resuscitation after trauma may lead to uncontrolled hemorrhage, reduced organ perfusion, and compartment syndrome. Recent guidelines reduced the standard starting point for crystalloid resuscitation from 2 L to 1 L and emphasized "balanced" resuscitation. The purpose of this study was to characterize how an urban, Level 1 trauma center has responded to changes in crystalloid resuscitation practices over time and to describe associated patient outcomes.This is a retrospective review of trauma patients who sustained moderate to severe injury (ISS 9) and received crystalloid resuscitation in the ED during 1/2004-12/2013 at an urban, Level 1 trauma center. Patient data collected included age, gender, Glasgow Coma Scale (GCS) score, initial systolic blood pressure (SBP), mechanism of injury, regional Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), volume of blood products and crystalloids administered in the ED. Patients who received2 L of crystalloid were considered low-volume while those who received ≥2 L were high-volume patients. Clinical characteristics and outcomes were compared between high- and low-volume cohorts, and multivariate regression was used to adjust for confounders. Trend analysis examined changes in variables over time.1571 moderate to severely injured patients received crystalloid resuscitation; 1282 (82%) were low-volume and 289 (18%) were high-volume. Compared to high-volume patients, low-volume patients presented with a higher median SBP (134 vs. 122 mmHg, p 0.001) and GCS (15 vs. 14, p 0.001). Low-volume patients also had lower median ISS (15 vs. 19, p 0.001). Unadjusted mortality was lower in the low-volume cohort (7% vs. 19%, p 0.001). Multivariate analysis demonstrated that high-volume patients had increased odds of mortality compared to low-volume patients (AOR 1.88, p = 0.008). Decreased rates of high-volume resuscitation and overall mortality were demonstrated over the 10-year study period.The observed decrease in high-volume crystalloid resuscitations in the ED paralleled a reduction in mortality over the ten-year period. In addition, adjusted mortality was higher in those receiving high-volume resuscitation.

BackgroundCritically ill cirrhotics require liver transplantation urgently, but are at high risk for perioperative mortality. The Model for End-stage Liver Disease (MELD) score, recently updated to incorporate serum sodium, estimates survival probability in patients with cirrhosis, but needs additional evaluation in the critically ill. The purpose of this study was to evaluate the predictive power of ICU admission MELD scores and identify clinical risk factors associated with increased mortality.Study designThis was a retrospective review of cirrhotic patients admitted to the ICU between January 2011 and December 2014. Patients who were discharged or underwent transplantation (survivors) were compared with those who died (nonsurvivors). Demographic characteristics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression was used to identify independent predictors of mortality, and measures of model performance were assessed to determine predictive accuracy.ResultsOf 276 patients who met inclusion criteria, 153 were considered survivors and 123 were nonsurvivors. Survivor and nonsurvivor cohorts had similar demographic characteristics. Nonsurvivors had increased MELD, gastrointestinal bleeding, infection, mechanical ventilation, encephalopathy, vasopressors, dialysis, renal replacement therapy, requirement of blood products, and ICU length of stay. The MELD demonstrated low predictive power (c-statistic 0.73). Multivariate analysis identified MELD score (adjusted odds ratio [AOR]= 1.05), mechanical ventilation (AOR= 4.55), vasopressors (AOR= 3.87), and continuous renal replacement therapy (AOR= 2.43) as independent predictors of mortality, with stronger predictive accuracy (c-statistic 0.87).ConclusionsThe MELD demonstrated relatively poor predictive accuracy in critically ill patients with cirrhosis and might not be the best indicator for prognosis in the ICU population. Prognostic accuracy is significantly improved when variables indicating organ support (mechanical ventilation, vasopressors, and continuous renal replacement therapy) are included in the model.

Importance Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti–factor Xa (anti-Xa) trough level is not well described. Objective To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients. Design, Setting, and Participants Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti-Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels. Exposures Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments. Main Outcomes and Measures Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk. Results A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19). Conclusions and Relevance In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding.

Supratherapeutic vancomycin trough levels are common after trauma and associated with both increased acute kidney injury (AKI) and mortality. We sought to limit the adverse effects of vancomycin in trauma patients through more frequent trough monitoring.Beginning in January 2011, trauma patients treated with vancomycin had trough levels (VT) monitored daily until steady state was reached. Trauma patients admitted from January 2011 to May 2015 (POST) were compared with those admitted from January 2006 to December 2010 (PRE). Inclusion criteria required administration of intravenous vancomycin, admission serum creatinine (SCr), and SCr within 72 hours of highest VT. Acute kidney injury was defined as an increase in SCr of at least 0.3 mg/dL or 50% from admission to post-vancomycin administration. Those in the POST group were prospectively followed up until discharge or death.Two hundred sixty-three patients met inclusion criteria in the PRE-phase and 115 in the POST-phase. The two groups were similar in age, gender, race, body mass index, pre-existing comorbidities, admission systolic blood pressure, Glasgow Coma Scale, and head Abbreviated Injury Scale. Injury Severity Score was higher in the POST cohort (18 PRE vs. 25 POST, p0.001). Compared with PRE, the POST cohort had lower rates of supratherapeutic VT (20 mg/L) (34.6% PRE vs. 22.6% POST, p = 0.02) and AKI (30.4% PRE vs. 19.1% POST, p = 0.026). After adjusting for confounders, the POST group had a significantly lower risk of AKI with an adjusted odds ratio of 0.457 (p = 0.027). There was a trend toward decreased mortality in the POST cohort, but this did not reach significance (10% PRE vs. 5.2% POST, p = 0.162).A reduction in AKI was observed in trauma patients with daily vancomycin trough levels monitored until steady state. Increased awareness regarding closer surveillance of VT in trauma patients may limit the incidence of vancomycin-related nephrotoxicity.Therapeutic study, level IV.

Trauma centers require reliable metrics to better compare the quality of care delivered. We compared mortality after a reported complication, termed failure to rescue (FTR), and FTR in the elderly (age >65 years) (FTRE) to determine which is a superior metric to assess quality of care delivered by trauma centers. This was a retrospective review of the National Trauma Databank (NTDB) research data sets 2010 and 2011. Patients ≥16 years admitted to centers reporting ≥80% of AIS and/or ≥ 20% of comorbidities with > 200 subjects in the NTDB were selected. Centers were classified based on the rate of FTR and FTRE (

The purpose of this study was to compare the proton-density (PD)-weighted fast spin-echo (FSE) and fast-recovery FSE (FRFSE) sequences for the evaluation of the anatomical structures of the knee.24 healthy volunteers who underwent MRI by both sagittal PD-weighted FSE and FRFSE sequences were evaluated. The signal-to-noise ratio, contrast-to-noise ratio (CNR) and anatomical detail visualisation were compared for the two techniques.The mean CNRs and reader ratings for both readers were significantly higher for the PD-weighted FRFSE images than for the PD-weighted FSE images in the cartilages/the femorotibial joint effusion and the cruciate ligaments/the effusion around the cruciate ligaments; however, the mean CNRs and reader ratings for both readers were significantly higher for the PD-weighted FSE sequences than for the PD-weighted FRFSE sequences in the cartilages/the menisci and the cruciate ligaments.The main advantages of the PD-weighted FRFSE sequence are the increase in contrast between fluid and non-fluid tissues and the time saved by using the procedure. However, in the absence of joint effusion, the PD-weighted FRFSE sequence generates a poorer contrast between the cartilage and meniscus, the cruciate ligaments and fat of the intercondylar fossa.

A prospective study was made to seek for a convenient biomarker to predict progression of bone destruction (PBD) in early stages of rheumatoid arthritis (ERA). All participated patients had definite RA and their radiographic stages were mild less than stage II of the Steinbrocker classification, naïve for treatment of any DMARDs or corticosteroids. After the entry, they were treated according to the 2002 ACR management guideline for RA. The candidate biomarkers (RF-IgM, RF-IgG, CARF, ACPA, CRP, ESR, NTx, MMP-3, IL-6 and osteopontin) were measured at the entry. PBD was assessed radiographically by interval changes in the modified Sharp scores (ΔSHS) for 24 months. The associations between ΔSHS and baseline biomarkers were assessed statistically by multivariate regression analyses. Both the baseline ACPA and IL-6 levels correlated with PBD, suggesting that they could predict PBD in ERA.

We evaluated the diagnostic value of anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies and other potential diagnostic biomarkers (IgM rheumatoid factor, anti-agalactosyl IgG antibodies, matrix metalloproteinase 3, C-reactive protein) for predicting early development of rheumatoid arthritis (RA). Patients were defined as having recent-onset undifferentiated arthritis (UA) if they had developed arthritis in two or more joints within the previous 2 years and could not be classified with a well-defined arthropathy. Baseline levels of biomarkers were measured in blood samples collected at the entry of the study and the patients were followed for 1 year to monitor development of RA. Diagnoses of RA and non-RA arthropathies were made according to individual standard diagnostic criteria. A total of 146 patients were enrolled in the study. In the follow-up year, 18 patients developed RA, 54 developed non-RA arthropathies, and 60 remained in the UA category. The sensitivity and specificity of the presence of anti-CCP2 antibodies for the diagnosis of RA were 83.3 and 93.0%, respectively. The positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of anti-CCP2 antibodies for RA (65.2, 97.2, and 91.7%, respectively) were higher than for any other biomarker. Combination of anti-CCP2 with any other biomarker only slightly improved each diagnostic value compared to the presence of anti-CCP2 alone. Among the anti-CCP2-positive patients, the average titer was significantly higher in those with RA than in non-RA or UA patients (163.7 +/- 138.4 vs 55.2 +/- 72.0 U/ml, p = 0.017). Anti-CCP2 antibodies are superior to any other single biomarker for predicting early development of RA in patients with recent-onset UA and the diagnostic value of anti-CCP2 alone is similar to that for biomarker combinations. Moreover, the anti-CCP2 antibody titer is useful to discriminate between patients at high risk for early developing RA from those at risk of developing non-RA arthropathies.

Background Hemophagocytic lymphohistiocytosis associated with autoimmune diseases is seen in patients with systemic juvenile idiopathic arthritis, adult-onset Still’s disease, and systemic lupus erythematosus, whereas it is rarely seen in patients with dermatomyositis. In addition, central nervous system involvement with dermatomyositis is rare. To the best of our knowledge, this is the first case of hemophagocytic lymphohistiocytosis complicated by leukoencephalopathy in a patient with dermatomyositis accompanied with peripheral T-cell lymphoma. Case presentation A 17-year-old Asian male adolescent with dermatomyositis and hemophagocytic lymphohistiocytosis that were controlled with corticosteroid therapy presented to our hospital with high fever and altered consciousness. Brain magnetic resonance imaging revealed multiple cerebral lesions. We diagnosed the central nervous system lesions as leukoencephalopathy secondary to dermatomyositis and hemophagocytic lymphohistiocytosis. Because corticosteroid and cyclophosphamide pulse therapy was ineffective, he was treated with a modified hemophagocytic lymphohistiocytosis-2004 protocol, which resulted in the disappearance of the lesions of his central nervous system. Conclusions Our findings suggest that the hemophagocytic lymphohistiocytosis-2004 protocol including etoposide should be initiated immediately in patients with hemophagocytic lymphohistiocytosis who respond poorly to treatment for the underlying disease. Moreover, irrespective of the underlying disease, patients with hemophagocytic lymphohistiocytosis with central nervous system lesions might require bone marrow transplantation.

The objectives of this study were to establish a magnetic resonance imaging-based classification system for canine hyperadrenocorticism according to pituitary gland extension, determine indications for trans-sphenoidal hypophysectomy, and clarify the prognosis for each disease grade.A 5-point classification system (Grades 1 to 5) was developed based on tumour extension in dorsal and cranio-caudal directions. Cases were then classified as Type A: no arterial circle of Willis or cavernous sinus involvement and Type B: cases in which these blood vessels were involved.Medical records and magnetic resonance imaging data of 37 cases with hyperadrenocorticism were reviewed. Thirty-three cases underwent surgery; 4 Grade 5 cases did not have appropriate indications for surgery, and other therapies were used. Complete resection was achieved for 3, 3, 22 and 1 Grade 1A, 2A, 3A and 3B cases, respectively. Resection was incomplete in 1, 1 and 2 Grade 3A, 3B and 4B cases, respectively. Remission was achieved in 29 cases. Recurrence occurred in 4 cases, all of which were classified as Grade 3.Dogs with Type A, Grade 1 to 3 hyperadrenocorticism had a good prognosis following trans-sphenoidal hypophysectomy. Grade 3B, 4 and 5 cases may not be suitable for this surgery.

As bicycling has become more popular, admissions after bicycle trauma are on the rise. The impact of alcohol use on bicycle trauma has not been well studied. The aim of this study was to examine the effect of alcohol intoxication on injury burden following bicycle-related crashes.A retrospective review of trauma patients presenting to a Level I trauma center after bicycle-related crashes from January 2002 to December 2011 was conducted. Demographics, injury data, alcohol intoxication, helmet use, and clinical outcomes were reviewed. Blood alcohol level (BAL) was considered positive if0.01 g/dL. Variables were compared between patients based on BAL: negative, 0.01-0.16 g/dL, and0.16 g/dL.During the 10 year study period, 563 patients met study criteria; mean age was 33.5 ± 16.5 years, 87% were male, and mortality was 1%. On average, bicycle crashes increased over the study period by 4.4 collisions per year. BAL was tested in 211 (38%) patients. Mean BAL was 0.24 g/dL, with 37% of these patients being intoxicated (BAL ≥ 0.010 g/dL). Intoxicated patients were significantly less likely to wear a helmet (4.7% vs. 22.2%, p = 0.002) and to be involved in motor vehicle crash (59.0% vs. 81.2%, p0.001). There was no difference noted in the injury burden including ISS ≥ 16 (14.3% vs. 19.5%, p = 0.335) and AIS Head ≥ 3 (17.9% vs. 21.8%, p = 0.502). When comparing patients according to their BAL, there was a decreasing risk of motor vehicle collision with increasing BAL (81.2% for undetected, 76.5% for BAL ≤ 0.16 g/dL and 54.1% for BAL0.16 g/dL, p0.001). The risk for a severe head injury (AIS Head ≥ 3) was significantly lower in helmeted patients (8.4% vs. 15.8%, p = 0.035).The incidence of bicycle-related crashes is increasing and more than a third of patients tested for alcohol after bicycle-related crashes are found to be intoxicated. The injury burden in intoxicated patients, including head trauma, was not different compared to non-intoxicated patients. In addition, the risk for a collision with a motor vehicle was significantly lower. Nonetheless, these patients rarely utilize a helmet. The findings from this study can be used for the development and implementation of preventive strategies to minimize the injury burden associated with bicycle crashes and intoxicated cyclists.

Trauma patients with diabetes mellitus (DM) represent a unique population as the acute injury and the underlying disease may both cause hyperglycemia that leads to poor outcomes. We investigated how insulin-dependent DM (IDDM) and noninsulin-dependent DM (NIDDM) impact mortality after serious trauma without brain injury.The National Trauma Data Bank (NTDB) version 7.0 was queried for all patients with moderate to severe traumatic injury [injury severity score (ISS) 9]. Patients were excluded if missing data, age 10 years, severe brain injury [head abbreviated injury scale (AIS) 3], dead on arrival or any AIS = 6. Logistic regression modeled the association between DM and mortality as well as IDDM, NIDDM and mortality.Overall 166,103 trauma patients without brain injury were analyzed. Mortality was 7.6 and 4.4 % in patients with and without DM, respectively (p 0.01). Mortality was 9.9 % for patients with IDDM and 6.7 % for NIDDM (p 0.01). The increased mortality associated with DM was only significantly higher for DM patients in their forties (5.6 vs. 3.3 %, p 0.01). Regression analyses demonstrated that DM (AOR 1.14, p = 0.04) and IDDM (AOR 1.46, p 0.01) were predictors of mortality compared to no DM, but NIDDM was not (AOR 1.02, p = 0.83).While DM was a predictor for higher mortality after serious trauma, this increase was only observed in IDDM and not NIDDM. Our findings suggest IDDM patients who present after serious trauma are unique and attention to their hyperglycemia and related insulin therapy may play a critical role in recovery.

Although beta-adrenergic receptor blockade may improve outcomes after traumatic brain injury (TBI), its early use is not routine. We hypothesize that judicious early low-dose propranolol after TBI (EPAT) will improve outcomes without altering bradycardia or hypotensive events.We conducted a prospective, observational study on all patients who presented with moderate-to-severe TBI from March 2010-August 2013. Ten initial patients did not receive propranolol (control). Subsequent patients received propranolol at 1-mg intravenous every 6 h starting within 12 h of intensive care unit (ICU) admission (EPAT) for a minimum of 48 h. Heart rate and blood pressure were recorded hourly for the first 72 h. Bradycardia and hypotensive events, mortality, and length of stay (LOS) were compared between cohorts to determine significant differences.Thirty-eight patients were enrolled; 10 control and 28 EPAT. The two cohorts were similar when compared by gender, emergency department (ED) systolic blood pressure, ED heart rate, and mortality. ED Glasgow coma scale was lower (4.2 versus 10.7, P 0.01) and injury severity score higher in control. EPAT patients received a mean of 10 ± 14 doses of propranolol. Hypotensive events were similar between cohorts, whereas bradycardia events were higher in control (5.8 versus 1.6, P = 0.05). ICU LOS (15.4 versus 30.4 d, P = 0.02) and hospital LOS (10 versus 19.1 d, P = 0.05) were lower in EPAT. Mortality rates were similar between groups (10% versus 10.7%, P = 0.9). The administration of propranolol led to no recorded complications.Although bradycardia and hypotensive events occur early after TBI, low-dose intravenous propranolol does not increase their number or severity. Early use of propranolol after TBI appears to be safe and may be associated with decreased ICU and hospital LOS.

Background Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal-enhancing action for FD treatment. Methods Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) -induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2-adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free-moving condition. Key Results Exogenous acylated ghrelin supplementation restored UCN1-induced delayed GE. Alpha2-AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co-administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito. Conclusions & Inferences The UCN1-induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders.

Objective Interferon alpha (IFN-α) is a key cytokine associated with systemic lupus erythematosus (SLE). IFN-α induces the expression of CD64 on monocytes (mCD64). Although enhanced mCD64 expression has been reported in patients with SLE, it has never been assessed quantitatively. The aim of this study was to investigate whether or not mCD64 expression correlates with SLE disease activity. Methods The mCD64 expression levels were assessed quantitatively in 40 patients with active or inactive SLE by using flow cytometry. The mCD64 expression levels were subsequently compared with the SLE disease activity index (SLEDAI) and levels of existing SLE activity biomarkers, such as anti-DNA antibody, complements, and so on. Results The mCD64 expression was significantly higher in active disease than in inactive disease SLE (median molecules/cell, interquartile range: 34,648, 8174–24,932 and 20,865, 6357–21,503, respectively; p Conclusion The mCD64 expression is a simple and useful biomarker for evaluating disease activity in patients with SLE.

Gamma/delta T-cell lymphoma (GDTL) is an uncommon lymphoma that was initially reported to involve only the liver and spleen. GDTL other than the hepatosplenic type is extremely rare. Frequent primary sites include skin and subcutaneous tissue, intestine, or nasal region. We report a case of GDTL of the omentum in a 54 year-old-man. The tumor cells are CD2-, CD3+, CD4-, CD5-, CD8+, CD56+, TIA-1+, granzyme B+/-. They expressed the identical phenotype of intestinal GDTL. The patient was treated with 2 courses of CHOP which comprised cyclophosphamide, doxorubicin, vincristine and prednisolone, and 3 courses of EPOCH which comprised etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin. However, he failed to obtain remission. During the fourth course of EPOCH, muscle weakness of the lower extremities developed and intracranial masses were observed by computed tomographic scan of the brain. Dissemination of lymphoma to the central nervous system was considered and it may be attributable to the expression of CD56 in this case. High dose methotrexate (HD-MTX) chemotherapy successfully eliminated the omental tumor and reduced the size of the intracranial masses, thus HD-MTX appears to be an effective treatment against GDTL.

We studied total nitric oxide (nitrite + nitrate) (NO) levels in cerebrospinal fluid (CSF) of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years) by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group), ossification of yellow ligament (thoracic disease group), and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group). NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD) were significantly higher than that in the control group (2.53+/-0.94 micromol/l). An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

Conservative treatment is ineffective for ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine, and surgical treatment is indicated for most cases, while such cases are not often experienced. In the present study, the results of surgical management involving mainly posterior decompression for this disease were evaluated clinically. The study included 9 patients (1 man and 8 women) who underwent surgical treatment for OPLL of the thoracic spine between 1984 and 1993. Laminectomy was performed in 5 patients, and laminectomy plus anterior decompression of the OPLL via the posterior approach based on Otsuka's method was performed in 2 patients. In 1 patient, laminoplasty for OPLL of the cervical spine was combined with laminectomy of the symptomatic lesion in the thoracic spine. One patient underwent anterior decompression and fusion. The results were evaluated using the Japanese Orthopaedic Association score (JOA score) and recovery rate. The postoperative follow-up period ranged from 1 year to 10 years and 3 months (mean, 4 years and 6 months). The mean JOA score was 4.8 before surgery and improved to 7.6 at the final examination. This was a mean recovery rate of 50.1%. Symptoms caused by OPLL in the thoracic spine can be alleviated by posterior decompression where OPLL extends from the upper to the middle thoracic spine or extends from the middle to the lower thoracic spine. It seems, however, that OPLL localized to the middle thoracic spine requires anterior decompression.

Angiogenesis in rat sponge implants, as determined from the concentration of hemoglobin in the sponge granuloma tissues, was gradually increased over a 14-day experimental period. The inducible cyclooxygenase COX-2 was detected in the sponge granuloma tissues at day 4 by Western blot analysis using specific mouse COX-2 antibody. Angiogenesis in the sponge implants was enhanced by daily topical injections of human recombinant basic fibroblast growth factor (bFGF) or human recombinant epidermal growth factor (EGF) (100 or 1000 ng/sponge/day) for 4 days. These treatments clearly enhanced the expression of COX-2 in the sponge granuloma tissues. In immunohistochemical studies, COX-2-positive staining was mainly observed in the endothelial cells of the neovasculature and in the fibroblasts of the granuloma capsule. Administration of the selective COX-2 inhibitor NS-398 (p.o., 3 mg/kg, 3 times a day) for 14 days significantly inhibited the angiogenesis. The angiogenesis enhanced with bFGF or EGF (day 4) was inhibited by administration of indomethacin or NS-398, both in the above regimen, and fell to the level obtained without growth factor treatment. These results suggest that COX-2 induced in the sponge granuloma tissues may participate in neovascularization through prostaglandin formation.

Metabolites of cytochrome P-450 are produced in cells when arachidonic acid cascade is activated. Fever genesis depends largely on the cyclooxygenase branch of arachidonic acid cascade, which is caused by many stimuli, such as interleukin (IL)-1, IL-6, and interferon-alpha. To assess the significance of cytochrome P-450 branch in fever, murine recombinant IL-1 beta was bilaterally microinjected (1 ng/microliter) into the medial preoptic area and anterior hypothalamus in conscious rats treated 60 min previously with or without the cytochrome P-450 inhibitor econazole (15 mg/kg im). The IL-1 beta-induced rise in colonic temperature was enhanced after the plateau phase of fever (from 240 min after IL-1 beta) in econazole-pretreated rats (P < 0.001). Another cytochrome P-450 inhibitor, clotrimazole (15 mg/kg im), also enhanced IL-1 beta-induced fever from 160 min after IL-1 beta injection (P < 0.001). Econazole also enhanced the fever when it was given 120 min before injection of IL-1 beta (P < 0.001). The cytochrome P-450 inhibitor, however, did not affect the fever when given 10 min after IL-1 beta (P = 0.95). Econazole and clotrimazole did not alter normal body temperature (P = 0.65 and 0.73, respectively). The results suggest that the metabolite(s) of cytochrome P-450 affect the falling phase after the plateau phase of fever and act as putative endogenous antipyretic(s).

Background: Gallbladder perforation often occurs during laporoscopic cholecystectomy. Methods: The frequency and causes of gallbladder perforation as well as the relevant clinical background factors were investigated in 110 patients undergoing laparoscopic cholecystectomy. We also evaluated intraperitoneal contamination by bacteria and gallstones at the time of gallbladder perforation and investigated whether perforation caused early or late postoperative complications. Results: Intraoperative gallbladder perforation occurred in 29 of the 110 patients (26.3%). It was caused by injury with an electric knife during dissection of the gallbladder bed, injury during gallbladder retraction with grasping forceps, injury during gallbladder extraction from the abdomen, and slippage of cystic duct clips (potentially causing bile and stone spillage). Perforation was more frequent in patients with positive bile cultures and in those with pigment stones (p

Neuropathy is one of the typical features of chronic complications of diabetes mellitus. Recent analyses indicate that subjects with impaired glucose tolerance (IGT) already have disturbance of peripheral nerve function. To test the role of adipocytokines, that tend to be abnormal in IGT subjects, on diabetic neuropathy, we analyzed the relationship between plasma adipocytokine levels (TNFalpha, adiponectin, and leptin) and nerve conduction velocity in 105 type 2 diabetic subjects (M/F = 66/39, age = 60.8 +/- 11.8 years, BMI = 24.7 +/- 5.0kg/m2). Adipocytokines were measured by ELISA, and motor conduction velocity (MCV) and sensory conduction velocity (SCV) in median, ulnar, and tibial nerve were measured by electrical stimulation. Motor conduction velocity and SCV were corrected by age to be 1.0 as the normal value, and the average of three nerves were used to be the representative value. Relationship between corrected MCV or corrected SCV as a dependent variable and the duration of diabetes, HbA1C, BMI, TNFalpha, adiponectin, and leptin concentrations as independent variables were analyzed by multiple regression. Duration of diabetes and HbA1C were highly related with both corrected MCV (P < 0.02 and P < 0.001) and SCV (P < 0.02 and P < 0.05) by this analysis. Only corrected SCV was related significantly with TNFalpha (P < 0.05), and close to significantly with leptin (P = 0.059) concentrations. These results indicate that increased plasma glucose levels and duration of diabetes are the major factors that modulate diabetic neuropathy. However, nerve function may be affected by plasma cytokine levels like TNFalpha, and this effect was more significant on sensory nerves than motor nerves. The present results suggest that adipocytokines may play a role not only on angiopathy but also on neuropathy in diabetics.

Background Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model. Methods The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously. Results Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. Conclusions The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.

Background Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H). Methods Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. Results Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. Conclusions Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.

A recently identified gene encoding a metalloprotease-like, disintegrin-like, cysteine-rich protein (MDC) represents a candidate tumor suppressor gene for human breast cancer based on its location within a minimal region of chromosome 17q21 previously defined by tumor deletion mapping. The work reported here has shown that the MDC gene consists of 28 exons interrupted by relatively short introns, most of them 67 bp to 5 kb in length. We have identified two forms of transcripts generated by alternative splicing. The more abundant form encodes a protein of 769 amino acids; the other, a previously described cDNA, encodes 524 amino acids. Exons 1a, 1b, 1c, 1d, and 2–7 encode a proprotein domain; exons 7–13, a metalloprotease-like domain; exons 14–17, a disintegrin domain; exons 18–22, a cysteine-rich domain, including an epidermal growth factor (EGF)-like repeat domain within exons 21 and 22; exon 23, a transmembrane domain; and exons 24 and 25, a short cytoplasmic domain. These results show that human MDC contains a mosaic of exons capable of encoding several functional domains.

Background and aims : Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO 2 ) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO 2 insufflation vs. standard air insufflation during esophageal ESD. Patients and methods : A total of 27 patients who had undergone esophageal ESD with insufflation of CO 2 between July 2009 and March 2010 were enrolled in this study (CO 2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. Results : Mediastinal emphysema detected by chest radiography was 0 % in the CO 2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO 2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO 2 group. Conclusions : Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO 2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO 2 can be considered as insufflating gas for esophageal ESD.

We have previously described a T helper cell 2-type clone, A3, of rat T cells that provides help for antibody production to Actinobacillus actinomycetemcomitans in vitro and in vivo in normal (euthymic) isogeneic Rowett strain recipient rats. Adoptive transfer of this T helper cell clone to euthymic rats also protects them from periodontal bone loss induced by oral infection with A. actinomycetemcomitans. In the present study, to assess the cell requirement for protection, A3 clone T lymphocytes (10(6)) or naive lymph node (6 x 10(4)) T cells, or A3 plus naive lymph node T cells (6 x 10(4)) were adoptively transferred to groups (n = 7-9) of 30-day-old Rowett athymic nude (rnu/rnu) rats. All recipients were also immunized (intraperitoneally) with 10(7) killed A. actinomycetemcomitans on the day of T cell transfer and orally infected with these bacteria on each of the next 5 days. Recipients of the combined A3+lymph node T cell transfer showed significantly increased serum immunoglobulin G (IgG) and IgM antibody to A. actinomycetemcomitans and in vitro proliferation of spleen lymphocytes to A. actinomycetemcomitans as antigen compared with nude animals receiving lymph node T cells only. Although other possibilities are discussed, we inferred that these differences might be due to successful population of the congenitally athymic rats by A3 clone cells given with a small number of normal autologous naive lymph node T cells. The result of this co-transfer of naive T cells with the A3 clone cells seemed to be greatly increased antibody production and protection from periodontal bone loss.

In a pediatric setting, the need for lifetime oral anticoagulation is increasing because of currency of extracardiac total cavo-pulmonary connection (TCPC) and pediatric valve surgery. We evaluated a new compact device "CoaguChek XS" for measuring prothrombin time-internatinal normalized ratio (PT-INR).The international normalized ratio (INR) values obtained from 71 patients (223 samples) by a CoaguChek XS were compared with those obtained by a laboratory-based coagulation analyzer.The values from the CoaguChek XS had a significant correlation with the laboratory based results. (r2 = 0.92, p0.01, regression line y = 1.05 x -0.02).The CoaguChek XS will be useful in pediatric management.

Growth hormone deficiency associated with hypogammaglobulinemia has been reported only in a few publications. Our patient was a male with recurrent episodes of infections. Serum immunoglobulin (Ig) G was extremely low although IgM concentration was much greater than the normal limit. Growth hormone responses to insulin, 1-Dopa and growth hormone-releasing hormone were low. The mean growth hormone concentration during sleep was less than the normal limit. These results are consistent with hyper-IgM immunodeficiency associated with growth hormone deficiency. The mode of transmission appears to be autosomal dominant. This combination has not been reported previously.