Citations

Background and Purpose— The prognostic significance of subarachnoid extension of intracerebral hemorrhage was determined in the INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2) study. Methods— INTERACT2 was an open randomized controlled trial of early intensive compared with guideline-recommended blood pressure lowering in patients with elevated systolic blood pressure within 6 hours of intracerebral hemorrhage. Independent predictors of death or major disability (scores 3–6 on the modified Rankin Scale) at 90 days were analyzed in logistic regression models. Results— Of 2582 participants, 192 (7%) had subarachnoid extension, which was associated with larger hematoma volumes ( P <0.0001) and higher National Institute of Health Stroke Scale score ( P <0.0001). Subarachnoid extension predicted death or major disability at 90 days (71% versus 53%; unadjusted odds ratio, 2.25; 95% confidence interval, 1.63–3.10; P <0.0001). The association remained significant after adjusting for age, region, lipid-lowering therapy, systolic blood pressure, glucose, location of hematoma, intraventricular extension, and randomized treatment (odds ratio, 2.17; 95% confidence interval, 1.50–3.14; P <0.0001), but not after further adjustment for baseline hematoma volume ( P =0.62). Conclusions— Subarachnoid extension of intracerebral hemorrhage is associated with poor prognosis, which is determined by a larger volume of the underlying intraparenchymal hematoma. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Objectives Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI. Design The study was designed as a population-based retrospective case–control study. Setting This population-based study was conducted in Olmsted County, Minnesota. Participants The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls. Primary and secondary outcome measures Only community-acquired E coli BSI cases as the primary outcome was included. Asthma status as an exposure was ascertained by predetermined criteria. An adjusted OR and 95% CI for the association between asthma and risk of community-acquired E coli BSI was calculated using conditional logistic regression. Results Of 259 eligible cases, 179 (69%) were women and mean age was 61±22 years. Of the 259 cases 37 (14%) and 16 (6%) of 259 controls had a prior history of asthma (adjusted OR 2.74; 95% CI 1.11 to 6.76; p=0.029). The population attributable risk of asthma for community-acquired E coli BSI was 9%. Although not statistically significant, there was a borderline association between having a history of food allergy and increased risk of community-acquired E coli BSI (6% vs 2%; adjusted OR 3.51; 95% CI 0.94 to 13.11; p=0.062). Conclusions Based on the findings of the current population-based, case–control investigation, a history of asthma may be associated with risk of community-acquired E coli BSI. The impact of asthma on risk of microbial infections may go beyond airways.

Hepatic stellate cells (HSC) and liver endothelial cells (LEC) migrate to sites of injury and perpetuate alcohol-induced liver injury. High-mobility group box 1 (HMGB1) is a protein released from the nucleus of injured cells that has been implicated as a proinflammatory mediator. We hypothesized that HMGB1 may be released from ethanol-stimulated liver parenchymal cells and contribute to HSC and LEC recruitment. Ethanol stimulation of rat hepatocytes and HepG2 cells resulted in translocation of HMGB1 from the nucleus as assessed by Western blot. HMGB1 protein levels were increased in the supernatant of ethanol-treated hepatocytes compared with vehicle-treated cells. Migration of both HSC and LEC was increased in response to conditioned medium for ethanol-stimulated hepatocytes (CMEtOH) compared with vehicle-stimulated hepatocytes (CMVEH) ( P < 0.05). However, the effect of CMEtOHon migration was almost entirely reversed by treatment with HMGB1-neutralizing antibody or when HepG2 cells were pretransfected with HMGB1-siRNA compared with control siRNA-transfected HepG2 cells ( P < 0.05). Recombinant HMGB1 (100 ng/ml) also stimulated migration of HSC and LEC compared with vehicle stimulation ( P < 0.05 for both HSC and LEC). HMGB1 stimulation of HSC increased the phosphorylation of Src and Erk and HMGB1-induced HSC migration was blocked by the Src inhibitor PP2 and the Erk inhibitor U0126. Hepatocytes release HMGB1 in response to ethanol with subsequent recruitment of HSC and LEC. This pathway has implications for HSC and LEC recruitment to sites of ethanol-induced liver injury.

A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.

Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphorylation. To search for novel protein-protein interactions mediated by the Pyk2 FERM domain, we utilized a yeast two-hybrid genetic selection to identify the mammalian Ste20 homolog MAP4K4 as a binding partner for the Pyk2 FERM domain. MAP4K4 coimmunoprecipitated with Pyk2 and was a substrate for Pyk2 but did not coimmunoprecipitate with the closely related focal adhesion kinase FAK. Knockdown of MAP4K4 expression inhibited glioma cell migration and effectively blocked Pyk2 stimulation of glioma cell. Increased expression of MAP4K4 stimulated glioma cell migration; however, this stimulation was blocked by knockdown of Pyk2 expression. These data support that the interaction of MAP4K4 and Pyk2 is integrated with glioma cell migration and suggest that inhibition of this interaction may represent a potential therapeutic strategy to limit glioblastoma tumor dispersion.

SUMMARYFibrosis of the subsynovial connective tissue (SSCT) in the carpal tunnel is the most common histological finding in carpal tunnel syndrome (CTS). Fibrosis may result from damaged SSCT. Previous studies found that with low‐velocity (2 mm/s), tendon excursions can irreversibly damage the SSCT. We investigated the effect of tendon excursion velocity in the generation of SSCT damage. Nine human cadaver wrists were used. Three repeated cycles of ramp‐stretch testing were performed simulating 40%, 60%, 90%, and 120% of the middle finger flexor tendon superficialis physiological excursion with an excursion velocity of 60 mm/s. Energy and force were calculated and normalized by values obtained in the first cycle for each excursion level. Data were compared with low‐velocity excursion data. For high‐velocity excursions, a significant drop in the excursion energy ratio was first observed at an excursion level of 60% physiological excursion (p < 0.024) and that for low‐velocity excursions was first observed at 90% physiological excursion (p < 0.038). Furthermore, the energy ratio was lower at 60% for high velocities (p ≤ 0.039). Increasing velocity lowers the SSCT damage threshold. This finding may be relevant for understanding the pathogenesis of SSCT fibrosis, such as that accompanying CTS, and a relationship with occupational factors. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:123–128, 2014.

Introduction Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF). While it is known the severity of left atrial (LA) enlargement affect the success of AF ablation, little is known the impact of intracardiac pressure on the ablation outcome. Methods This prospective study consisted of 63 patients (mean age 57±9 years, 73% male) who underwent catheter-based pulmonary vein isolation for drug refractor symptomatic AF (48% paroxysmal, 52% persistent). All patients underwent simultaneous echocardiography and haemodynamic measurements including left ventricular end systolic pressure (LVEDP), mean left atrial pressure (LAP) and dP/dtmax using Millar catheter at the time of procedure during AF. Left atrial volume (LAV) was measure by biplane area length method. Recurrence of AF was defined as episodes of AF more than 5 min documented in 24h ambulatory ECG or event monitor. Results After a mean follow-up duration of 16±7 months, AF elimination off anti-arrhythmic drugs was achieved in 70 % (44/63) of patients. Among the echographic and haemodynamic measurements, the baseline LAV and mean LAP were 57.62±25.39 ml and 12.19±4.57 mm Hg in AF free patients compared to 81.20±40.88 ml (p=0.02) and 16.46±4.14 mm Hg (p=0.01) in AF recurrence groups. Univariate and multivariate analysis showed LAP was the only independent predictor of the recurrence with an adjusted odd ratio of 1.27 (95% CI 1.04 to 1.54, p=0.03, table). Conclusion LAP is a determinant of AF recurrence after AF ablation. Therapies towards reduction of LA filling pressure, especially in patients with elevated LAP, may improve the outcome of ablation. Table Baseline clinical characters in the recurrence group and non-recurrence group Non-recurrence (N=44) recurrence (N=19) Univariate Multivariate P 95% CI P 95% CI Age (ys) 57.39±9.92 59.26±10.47 0.49 0.97, 1.08 – – AF type, persistent AF no. (%) 23 (53%) 10 (50%) 0.97 0.34, 2.98 – – AF duration (ys) 5.84±5.43 8.08±7.66 0.20 0.99, 1.05 – – LA volume (mL) 57.62±25.39 81.20±40.88 0.02 1.01, 1.05 0.30 0.99, 1.05 LVEDP (mm Hg) 10.25±14.54 11.25±5.75 0.81 0.96, 1.06 – – dP/dt max (mm Hg/s) 1294.02±337.13 1211.77±225.36 0.47 0.99, 1.02 – – Mean LAPmean (mm Hg) 12.19±4.57 16.46±4.14 0.01 1.06, 1.50 0.02 1.04, 1.54 Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF) but the success rate ranged wide. This study aimed to investigate the effect of LAP on AF recurrence.

Introduction Lateral or posteriolateral coronary vein has been considered the optimal location of left ventricular (LV) lead placement for cardiac resynchronisation therapy (CRT). However, the long-term clinical outcomes of CRT based on LV lead location have not been sufficiently addressed. Methods Seven hundred and eighteen CRT-P/CRT-D recipients from Jan 2002 to Dec 2008 were studied. At the CRT implant, the LV lead placement was prioritised as posterolateral/lateral (PL, 50%), anterior lateral (AL, 31%), anterior interventricular (AI, 12%) or middle cardiac veins (MC, 7%). NYHA class and echocardiography were assessed before and after CRT. Clinical outcomes of CRT were compared among 4 LV lead locations. Results Patient baseline demographics, except the gender (P=0.03), were similar among four groups. After CRT, the improvement in NYHA class, LV ejection fraction (EF), and LV diastolic diameter were significantly improved comparably across four LV lead locations (table). The increase in LVEF by >5% were 46%, 47%, 41% and 42% in PL, AL, AI and MC groups (p=0.87). Conclusion The present study suggests that LV lead positioned in the alternative coronary veins, other than posteriolateral or lateral location, achieve comparable benefit in improvement of HF symptoms, and LV function after CRT. Table Comparison of clinic outcomes before and after CRT in different LV lead locations Lateral vein (N=359) Anterolateral vein (N=226) middle cardiac vein (N=49) anterior interventricular vein (N=84) Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT NYHA 3.02±0.46 2.34±0.81* 2.92±0.53 2.34±0.89* 3.10±0.45 2.70±0.85* 2.98±0.52 2.43±0.86* LVEF (%) 23.57±7.28 30.82±11.67* 24.19±7.96 30.44±12.06* 24.97±7.62 30.72±11.43* 22.45±7.25 28.40±11.73* LVEDD (mm) 65.71±9.12 63.00±9.73* 65.79±8.87 63.88±9.88* 65.39±9.32 62.61±10.25* 68.48±8.92 64.86±9.67* LVESD (mm) 57.91±9.89 52.83±11.68* 56.69±10.23 53.03±12.01* 56.18±11.56 52.24±13.11* 59.09±10.04 55.32±13.30 RVD (mm) 0.90±0.86 0.82±0.85 0.85±0.92 0.82±0.85 0.86±0.83 1.01±0.84 0.56±0.77 0.78±0.91 RV dysfunction 1.05±0.92 0.88±0.92* 1.03±0.93 0.93±0.91 1.06±0.97 1.06±0.90 0.74±0.86 0.79±0.96 MR (m/s) 1.54±0.78 1.30±0.75* 1.57±0.83 1.35±0.75* 1.53±0.71 1.15±0.70* 1.36±0.69 1.19±0.68 * P<0.05 compared to pre-CRT.