Long-Term Mortality After Charcot Reconstruction.

Charcot neuroarthropathy is a complicated phenomenon with the potential to cause significant deformity, morbidity, and mortality. Costs associated with Charcot-related complications are substantial, with thousands of amputations occurring annually. The purpose of this study was to retrospectively review a single surgeon's experience and record the 10-year mortality rate among patients after Charcot reconstruction at a single institution between 2007 and 2013. Lower-extremity limb salvage is crucial to reduce the burden of Charcot neuroarthropathy. This article provides an example of the potential long-term success of reconstruction surgery for this condition.

Prevalence of Ankle Charcot Neuroarthropathy Presenting in a Tertiary Care Center.

Charcot neuroarthropathy's (CN) anatomic classification was originally formulated by the Brodsky article and the Trepman et al modification, including midfoot (type 1), rearfoot (type 2), ankle (type 3a), calcaneus (type 3b), multiarticular (type 4), and forefoot (type 5). In these classic studies, ankle joint and multijoint CN are reported as 9% and 6% to 9%, respectively, but we believe ankle CN to be more common than that in a tertiary setting. We retrospectively reviewed patients presenting initially or as referral between 2004 and 2020. Initial presentation radiographs were reviewed and classified by 3 authors based on Brodsky's model with Trepman and colleagues' modification, and any discrepancies were reviewed by the fourth author. A total of 175 patients (205 feet) were assessed. This revealed 80 cases classified as type 1 (39.0%), 23 cases type 2 (11.2%), 17 cases type 3a (8.3%), 2 cases type 3b (1.0%), and 83 cases type 4 (40.5%). After subdividing type 4, total prevalence included 150 with type 1 anatomic location (73.2%), 103 type 2 (50.2%), 44 type 3a (21.5%), and still 2 type 3b (1.0%). This study revealed a similar prevalence of isolated ankle CN (8.5%) compared to the Trepman et al article (9%), however, in total, ankle CN (21.5%) occurred 2.4-times more than the original 9%. Our study also found there to be a higher prevalence of ankle CN in the setting of multiarticular CN, which has not been evaluated in past studies. The prevalence of multiarticular CN was found to be 4.5-fold greater than the Trepman article (6%-9%).

Impact of Phlebotomy Volume Knowledge on Provider Laboratory Ordering and Transfusion Practices in the Pediatric Cardiac ICU.

OBJECTIVES: Phlebotomy can account for significant blood loss in post-surgical pediatric cardiac patients. We investigated the effectiveness of a phlebotomy volume display in the electronic medical record (EMR) to decrease laboratory sampling and blood transfusions. Cost analysis was performed. DESIGN: This is a prospective interrupted time series quality improvement study. Cross-sectional surveys were administered to medical personnel pre- and post-intervention. SETTING: The study was conducted in a 19-bed cardiac ICU (CICU) at a Children's hospital. PATIENTS: One hundred nine post-surgical pediatric cardiac patients weighing 10 kg or less with an ICU stay of 30 days or less were included. INTERVENTIONS: We implemented a phlebotomy volume display in the intake and output section of the EMR along with a calculated maximal phlebotomy volume display based on 3% of patient total blood volume as a reference. MEASUREMENTS AND MAIN RESULTS: Providers poorly estimated phlebotomy volume regardless of role, practice setting, or years in practice. Only 12% of providers reported the availability of laboratory sampling volume. After implementation of the phlebotomy display, there was a reduction in mean laboratories drawn per patient per day from 9.5 to 2.5 ( p = 0.005) and single electrolytes draw per patient over the CICU stay from 6.1 to 1.6 ( p = 0.016). After implementation of the reference display, mean phlebotomy volume per patient over the CICU stay decreased from 30.9 to 14.4 mL ( p = 0.038). Blood transfusion volume did not decrease. CICU length of stay, intubation time, number of reintubations, and infections rates did not increase. Nearly all CICU personnel supported the use of the display. The financial cost of laboratory studies per patient has a downward trend and decreased for hemoglobin studies and electrolytes per patient after the intervention. CONCLUSIONS: Providers may not readily have access to phlebotomy volume requirements for laboratories, and most estimate phlebotomy volumes inaccurately. A well-designed phlebotomy display in the EMR can reduce laboratory sampling and associated costs in the pediatric CICU without an increase in adverse patient outcomes.

From the inside out: Interoceptive feedback facilitates the integration of visceral signals for efficient sensory processing.

Neuroscientific studies have mainly focused on the way humans perceive and interact with the external world. Recent work in the interoceptive domain indicates that the brain predictively models information from inside the body such as the heartbeat and that the efficiency with which this is executed can have implications for exteroceptive processing. However, to date direct evidence underpinning these hypotheses is lacking. Here, we show how the brain predictively refines neural resources to process afferent cardiac feedback and uses these interoceptive cues to enable more efficient processing of external sensory information. Participants completed a repetition-suppression paradigm consisting of a neutral repeating face. During the first face presentation, they heard auditory feedback of their heartbeat which either coincided with the systole of the cardiac cycle, the time at which cardiac events are registered by the brain or the diastole during which the brain receives no internal cardiac feedback. We used electroencephalography to measure the heartbeat evoked potential (HEP) as well as auditory (AEP) and visual evoked potentials (VEP). Exteroceptive cardiac feedback which coincided with the systole produced significantly higher HEP amplitudes relative to feedback timed to the diastole. Elevation of the HEP in this condition was followed by significant suppression of the VEP in response to the repeated neutral face and a stepwise decrease of AEP amplitude to repeated heartbeat feedback. Our results hereby show that exteroceptive heartbeat feedback coinciding with interoceptive signals at systole enhanced interoceptive cardiac processing. Furthermore, the same cue facilitating interoceptive integration enabled efficient suppression of a visual stimulus, as well as repetition suppression of the AEP across successive auditory heartbeat feedback. Our findings provide evidence that the alignment of external to internal signals can enhance the efficiency of interoceptive processing and that cues facilitating this process in either domain have beneficial effects for internal as well as external sensory processing.

Multisensory integration of anticipated cardiac signals with visual targets affects their detection among multiple visual stimuli.

Many studies have elucidated the multisensory processing of different exteroceptive signals (e.g., auditory-visual stimuli), but less is known about the multisensory integration of interoceptive signals with exteroceptive information. Here, we investigated the perceptual outcomes and electrophysiological brain mechanisms of cardio-visual integration by using participants' electrocardiogram signals to control the color change of a visual target in dynamically changing displays. Reaction times increased when the target change coincided with strong cardiac signals concerning the state of cardiovascular arousal (i.e., presented at the end of ventricular systole), compared to when the target change occurred at a time when cardiac arousal was relatively low (i.e., presented at the end of ventricular diastole). Moreover, the concurrence of the target change and cardiac arousal signals modulated the event-related potentials and the beta power in an early period (~100 ms after stimulus onset), and decreased the N2pc and the beta lateralization in a later period (~200 ms after stimulus onset). Our results suggest that the multisensory integration of anticipated cardiac signals with a visual target negatively affects its detection among multiple visual stimuli, potentially by suppressing sensory processing and reducing attention toward the visual target. This finding highlights the role of cardiac information in visual processing and furthers our understanding of the brain dynamics underlying multisensory perception involving both interoception and exteroception.

Machine Learning-Enabled Fully Automated Assessment of Left Ventricular Volume, Ejection Fraction and Strain: Experience in Pediatric and Young Adult Echocardiography.

BACKGROUND: Left ventricular (LV) volumes, ejection fraction (EF), and myocardial strain have been shown to be predictive of clinical and subclinical heart disease. Automation of LV functional assessment overcomes difficult technical challenges and complexities. We sought to assess whether a fully automated assessment of LV function could be reliably used in children and young adults. METHODS: Fifty normal volunteers (22/28, female/male) were prospectively recruited for research echocardiography. LV volumes, EF, and strain were measured both manually and automatically. An experienced sonographer performed all the manual analysis and recorded the analysis timing. The fully automated analyses were accomplished by 5 groups of observers with different knowledge and medical background. AutoLV and AutoSTRAIN (TomTec) were employed for the fully automated LV analysis. The LV volumes, EF, strain, and analysis time were compared between manual and automated methods, and among the 5 groups of observers. RESULTS: Software-determined endocardial border detection was achievable in all subjects. The analysis times of the experienced sonographer were significantly shorter for AutoLV and AutoSTRAIN than manual analyses (both p < 0.001). Strong correlations were seen between conventional EF and AutoLV (r = 0.8373), and between conventional three view global longitudinal strain (GLS) and AutoSTRAIN (r = 0.9766). The volumes from AutoLV and three view GLS from AutoSTRAIN had strong correlations among different observers regardless of level of expertise. EF from AutoLV analysis had moderately strong correlations among different observers. CONCLUSION: Automated pediatric LV analysis is feasible in normal hearts. Machine learning-enabled image analysis saves time and produces results that are comparable to traditional methods.

Role of health plan administrative claims data in participant recruitment for pragmatic clinical trials: An Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) example.

AIM: The purpose of this study is to evaluate HealthCore/Anthem Research Network recruitment strategies, compare response and enrollment rates for different recruitment strategies, and describe demographic and clinical characteristics of responders and enrollees. METHODS: HealthCore/Anthem Research Network, a part of the Health Plan Research Network of the Patient-Centered Clinical Data Research Network, used administrative claims data to identify eligible health plan members for potential participation in the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness study. We approached health plan members, identified with a validated Patient-Centered Clinical Data Research Network common data model computable phenotype, and their clinical providers during November 2017 to August 2018. Providers were offered the option to exclude their patients' participation in Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness prior to our direct patient (member) outreach. Member identification was in two phases: Phase 1: 1 January 2006 to 1 April 2017, and Phase 2: 1 January 2006 to 2 February 2018. Phase 1 consisted of two batches of mail and one phone call per patient. In Phase 2, which included two similar batches of patients, outreach was via either mail or brochure and one phone call. RESULTS: Phase 1 and Phase 2 included 133,373 and 51,777 members, respectively. We engaged 28,593 providers in Phase 1, and 5077 in Phase 2. In Phase 1, 264,158 mixed email/mail messages were delivered to 133,373 members, followed by 90,481 phone calls from November 2017 to February 2018. In Phase 2, after simple randomization to letter or brochure, 51,777 members were sent email/mail or mailed brochure in three waves from May 2018 to July 2018. In this 9-week period, 51,623 communications were sent to 25,914 members in the email/mail group, and 50,160 brochures to 25,863 in the brochure group. Following email/mail or mailed brochure outreach, 16,624 and 16,580 calls were made to the groups, respectively. Overall, 1549 health plan members visited the study portal by 1 September 2018; 355 electronically signed the Informed Consent Form and enrolled. Mailed brochures drove more portal visits in Phase 2, but a lower percentage of responders enrolled. Recruitment was better in Phase 2-2.3 enrollees per 1000 outreach members versus 1.8 in Phase 1. CONCLUSION: This study showed the ability of a health plan within Patient-Centered Clinical Data Research Network to identify potential study participants with administrative claims, and use different outreach methods to facilitate recruitment and enrollment for pragmatic clinical trials.

I feel what I do: Relating interoceptive processes and reward-related behavior.

Interoceptive signalling has been shown to contribute to action regulation and action experience. Here, we assess whether motor behaviour can be influenced by anticipated homeostatic feeling states induced through different predictable contexts. Participants performed a reward incentive paradigm in which accurate responses increased (gain) or avoided the depletion (averted loss) of a credit score. Across two types of blocks, we varied the predictability of the outcome state. In predictable blocks, a cue signaled a gain, loss or control trial (motor response did not affect the credit score). This allowed participants to anticipate the interoceptive feeling state associated with the outcome. In unpredictable blocks, the cue had no relation to the type of outcome. Thus, participants were unable to anticipate the feeling state it produced. Via EEG, we measured the Heartbeat Evoked Potential (HEP) and the Contingent Negative Variation (CNV) as indices of interoceptive and motor processing respectively. In addition, we measured feedback P3 amplitude following outcome presentation and accuracy and reaction times of the required motor response. We observed higher HEP and CNV amplitudes as well as faster and more accurate motor responses in predictable compared to unpredictable outcome blocks. Similarly, feedback-related P3 amplitudes were significantly lower for predictable relative to unpredictable outcomes. Crucially, HEP amplitudes measured prior to feedback predicted feedback-related P3 amplitudes for anticipated outcome events. Results suggest that accurate anticipation of homeostatic feeling states associated with gain, loss or control outcomes facilitates motor execution and outcome evaluation. Findings are hereby the first to empirically assess the link between interoceptive and motor domains and provide primary evidence for a joint processing structure.

Affective interoceptive inference: Evidence from heart-beat evoked brain potentials.

The perception of internal bodily signals (interoception) is central to many theories of emotion and embodied cognition. According to recent theoretical views, the sensory processing of visceral signals such as one's own heartbeat is determined by top-down predictions about the expected interoceptive state of the body (interoceptive inference). In this EEG study we examined neural responses to heartbeats following expected and unexpected emotional stimuli. We used a modified stimulus repetition task in which pairs of facial expressions were presented with repeating or alternating emotional content, and we manipulated the emotional valence and the likelihood of stimulus repetition. We found that affective predictions of external socially relevant information modulated the heartbeat-evoked potential, a marker of cardiac interoception. Crucially, the HEP changes highly relied on the expected emotional content of the facial expression. Thus, expected negative faces led to a decreased HEP amplitude, whereas such an effect was not observed after an expected neutral face. These results suggest that valence-specific affective predictions, and their uniquely associated predicted bodily sensory state, can reduce or amplify cardiac interoceptive responses. In addition, the affective repetition effects were dependent on repetition probability, highlighting the influence of top-down exteroceptive predictions on interoception. Our results are in line with recent models of interoception supporting the idea that predicted bodily states influence sensory processing of salient external information.

The Role of the Basement Plate in Physeal Bar Formation.

BACKGROUND: Physeal fractures and resultant physeal bars can pose significant problems in skeletal development for the injured growing child. Although now well-recognized, only a small body of experimental literature covering this problem is available. The goal of this study was to help further develop an understanding of the different regions of the physis and the way in which each region responds to injury/fracture. METHODS: This Institutional Animal Care and Use Committee (IACUC)-approved study assessed bar formation using radiologic and histologic methods and measured leg lengths of skeletally immature rats. The right tibia was used as the control to measure leg length discrepancy (LLD), and the left tibia received either a fracture only (F), an epiphyseal scrape (ES), an epiphyseal drilling procedure (ED), or metaphyseal drilling (MD). Radiographs and LLD measurements were obtained at postoperative days 0, 21, and 56. RESULTS: A significant LLD was present at day 56 in the ED group (P=0.01). Radiographic identification of bars showed significant evidence of bar formation for the ES and ED groups at 21 days and the ED group at 56 days (P<0.05). Histologic examination showed a high incidence of histologic physeal bar formation in the ES, ED, and MD groups at 21 and 56 days. CONCLUSIONS: Findings showed that the physis was able to continue to grow following an injury to the physis' hypertrophic region. MD produced little effects with few physeal bars and little LLD. By postoperative day 56, ED animals showed greater LLD than ES animals. Penetration of the basement plate was more likely to lead to bar formation/growth retardation than was ablation of the epiphyseal region of the physis (including resting cells). CLINICAL RELEVANCE: Data presented here provides insight into the importance of different regions of the physis and its repair/continued growth after physeal fracture. We suggest that a better understanding of the physiological cause of physeal arrest after physeal fracture will be important for the development of treatments to prevent physeal arrest or to treat physeal arrest after it occurs.

Traditional Long-Term Central Venous Catheters Versus Transhepatic Venous Catheters in Infants and Young Children.

OBJECTIVES: Children with congenital heart disease may require long-term central venous access for intensive care management; however, central venous access must also be preserved for future surgical and catheterization procedures. Transhepatic venous catheters may be an useful alternative. The objective of this study was to compare transhepatic venous catheters with traditional central venous catheters regarding complication rate and duration of catheter service. DESIGN: Retrospective review of 12 congenital heart disease patients from September 2013 to July 2015 who underwent placement of one or more transhepatic venous catheters. SETTING: Single freestanding pediatric hospital located in the central United States. PATIENTS: Pediatric patients with congenital heart disease who underwent placement of transhepatic venous catheter. INTERVENTIONS: Cohort's central venous catheter complication rates and duration of catheter service were compared with transhepatic venous catheter data. MEASUREMENTS AND MAIN RESULTS: Twelve patients had a total of 19 transhepatic venous lines. Transhepatic venous lines had a significantly longer duration of service than central venous lines (p = 0.001). No difference between the two groups was found in the number of documented thrombi, thrombolytic burden, or catheter sites requiring wound care consultation. A higher frequency of infection in transhepatic venous lines versus central venous lines was found, isolated to four transhepatic venous lines that had a total of nine infections. All but one was successfully managed without catheter removal. The difference in the proportion of infections to catheters in transhepatic venous lines versus central venous lines was significant (p = 0.0001), but no difference in the rate of infection-related catheter removal was found. CONCLUSIONS: Without compromising future central venous access sites, transhepatic venous lines had superior duration of service without increased thrombosis, thrombolytic use, or insertion site complications relative to central venous lines. Transhepatic venous catheters had a higher infection rate, and further investigation into the etiology is warranted.

The impact of experienced stress on aged spatial discrimination: Cortical overreliance as a result of hippocampal impairment.

A large body of neuroscientific work indicates that exposure to experienced stress causes damage to both cortical and hippocampal cells and results in impairments to cognitive abilities associated with these structures. Similarly, work within the domain of cognitive aging demonstrates that elderly participants who report experiencing greater amounts of stress show reduced levels of cognitive functioning. The present article attempted to combine both findings by collecting data from elderly and young participants who completed a spatial discrimination paradigm developed by Reagh and colleagues [Reagh et al. (2013) Hippocampus 24:303-314] to measure hippocampal-mediated cognitive processes. In order to investigate the effect of stress on the cortex and, indirectly, the hippocampus, it paired the paradigm with electroencephalographic recordings of the theta frequency band, which is thought to reflect cortical/hippocampal interactions. Findings revealed that elderly participants with high levels of experienced stress performed significantly worse on target recognition and lure discrimination and demonstrated heightened levels of cortical theta synchronization compared with young and elderly low stress counterparts. Results therefore provided further evidence for the adverse effect of stress on cognitive aging and indicate that impaired behavioral performance among high stress elderly may coincide with an overreliance on cortical cognitive processing strategies as a result of early damage to the hippocampus.

Clinical Implications of a Multivariate Stratification Model for the Estimation of Prognosis in Ventricular Septal Defect.

OBJECTIVES: To derive and validate a multivariate stratification model for prediction of survival free from intervention (SFFI) in ventricular septal defect (VSD). A secondary aim is for this model to serve as proof of concept for derivation of a more general congenital heart disease prognostic model, of which the VSD model will be the first component. STUDY DESIGN: For 12 years, 2334 subjects with congenital heart disease were prospectively and consecutively enrolled. Of these, 675 had VSD and form the derivation cohort. One hundred seven other subjects with VSD followed in another practice formed the validation cohort. The derivation cohort was serially stratified based on clinical and demographic features correlating with SFFI. RESULTS: Six strata were defined, the most favorable predicting nearly 100% SFFI at 10 years, and the least favorable, a high likelihood of event within weeks. Strata with best SFFI had many subjects with nearly normal physiology, muscular VSD location, or prior intervention. In the validation cohort, the relation between predicted and actual SFFI at 6 months, 1 year, 2 years, and 5 years follow-up had areas under the receiver operating characteristic curves 0.800 or greater. CONCLUSIONS: A prediction model for SFFI in VSD has been derived and validated. It has potential for clinical application to the benefit of patients and families, medical trainees, and practicing physicians.

Epidemiology of falls in older adults in Texas.

OBJECTIVES: The expected increase in the US older adult population implies an increased risk of fall-related injury among these individuals. We describe the epidemiology of fall morbidity among older adults in Texas, a large US state with a diverse population base. METHODS: Texas Behavioral Risk Factor Surveillance System 2010 data were analyzed. The falls outcome was defined as falling: any fall in the past 3 months and a serious fall: a fall resulting in limited activities for at least 1 day or requiring medical attention. RESULTS: A total of 5996 subjects were included in this analysis; 17.6% (n = 1055) reported falling 1 to 5 times in the previous 3 months, and 361 (6%) experienced serious falls. Risk of falling had a significant positive association among respondents who rated their general health as fair to poor (relative risk [RR] 2.39, 95% confidence interval [CI] 1.55-3.68) and a negative association for those who reported regular physical activity (RR 0.59, 95% CI 0.42-0.82). A similar model examined the risk of serious falls and found statistically positive associations in respondents who reported fair or poor general health (RR 3.29, 95% CI 2.00-5.43). Negative associations were found for those who reported regular physical activity (RR 0.56, 95% CI 0.38-0.83) and for men (RR 0.62, 95% CI 0.39-0.98). No statistically significant correlations for either of the fall outcomes were found with residence, obesity, education, income, age, ethnicity, employment, marital status, diabetes mellitus, or cardiovascular disease. CONCLUSIONS: Interventions aimed at the prevention of falls should focus on maintaining and improving general health and promoting physical activity among older adults.

Bundled payments for care improvement initiative: the next evolution of payment formulations: AAHKS Bundled Payment Task Force.

The Patient Protection and Affordable Care Act contains a number of provision for improving the delivery of healthcare in the United States, among the most impactful of which may be the call for modifications in the packaging of and payment for care that is bundled into episodes. The move away from fee for service payment models to payment for coordinated care delivered as comprehensive episodes is heralded as having great potential to enhance quality and reduce cost, thereby increasing the value of the care delivered. This effort builds on the prior experience around delivering care for arthroplasty under the Acute Care Episode Project and offers extensions and opportunities to modify the experience moving forward. Total hip and knee arthroplasties are viewed as ideal treatments to test the effectiveness of this payment model. Providers must learn the nuances of these modified care delivery concepts and evaluate whether their environment is conducive to success in this arena. This fundamental shift in payment for care offers both considerable risk and tremendous opportunity for physicians. Acquiring an understanding of the recent experience and the determinants of future success will best position orthopaedic surgeons to thrive in this new environment. Although this will remain a dynamic exercise for some time, early experience may enhance the chances for long term success, and physicians can rightfully lead the care delivery redesign process.

Response inhibition is disrupted by interoceptive processing at cardiac systole.

The present study investigated how cardiac signals influence response inhibition at both behavioral and electrophysiological levels by using participants' electrocardiogram signals to control the occurrence of events in a stop-signal task, in which the go cue was unpredictably followed by a stop signal requiring the cancellation of the prepotent response. We observed prolonged stop-signal reaction times, reduced stop-signal P3 amplitudes, and higher heartbeat evoked potential amplitudes when the stop signal was presented at cardiac systole, compared to presentation randomly within the cardiac cycle. These effects were independent of the emotional attribute of the stop signal (i.e., emotional facial expression change or non-emotional color change). Our results suggest that coupling stop signals to peripheral autonomic cardiac signals has an impeding effect on response inhibition, probably via shifting attention from exteroception to interoception. Our findings help clarify the precise impact of interoceptive signals on inhibitory control.

Nicotinic acetylcholine receptor α1 promotes calpain-1 activation and macrophage inflammation in hypercholesterolemic nephropathy.

The nicotinic acetylcholine receptor α1 (nAChRα1) was investigated as a potential proinflammatory molecule in the kidney, given a recent report that it is an alternative urokinase plasminogen activator (uPA) receptor, in addition to the classical receptor uPAR. Two animal models and in vitro monocyte studies were involved: (1) In an ApoE(-/-) mouse model of chronic kidney disease, glomerular-resident cells and monocytes/macrophages were identified as the primary cell types that express nAChRα1 during hypercholesterolemia/uninephrectomy-induced nephropathy. Silencing of the nAChRα1 gene for 4 months (6 months on Western diet) prevented the increases in renal monocyte chemoattractant protein-1 and osteopontin expression levels and F4/80+ macrophage infiltration compared with the nonsilenced mice. These changes were associated with significantly reduced transforming growth factor-ß1 mRNA (50% decrease) and α smooth muscle actin-positive (αSMA+) myofibroblasts (90% decrease), better glomerular and tubular basement membranes (GBM/TBM) preservation (threefold less disintegration), and better renal function preservation (serum creatinine 40% lower) in the nAChRα1-silenced mice. The nAChRα1 silencing was also associated with significantly reduced renal tissue calcium deposition (78% decrease) and calpain-1 (but not calpain-2) activation (70% decrease). (2) The nAChRα1 was expressed in vitro by mouse monocyte cell line WEHI-274.1. The silencing of nAChRα1 significantly reduced both calpain-1 and -2 activities, and reduced the degradation of the calpain substrate talin. (3) To further explore the role of calpain-1 activity in hypercholesterolemic nephropathy, disease severities were compared in CAST(-/-)ApoE(-/-) (calpain overactive) mice and ApoE(-/-) mice fed with Western diet for 10 months (n=12). Macrophages were the main cell type of renal calpain-1 production in the model. The number of renal F4/80+ macrophages was 10-fold higher in the CAST(-/-)ApoE(-/-) mice (P<0.05), and was associated with a significantly higher level of αSMA+ cells, increased GBM/TBM destruction, and higher serum creatinine levels. Our studies suggest that the receptor nAChRα1 is an important regulator of calpain-1 activation and inflammation in the chronic hypercholesterolemic nephropathy. This new proinflammatory pathway may also be relevant to other disorders beyond hyperlipidemic nephropathy.

Anti-Xa levels in critically ill children receiving enoxaparin for venothromboembolism prophylaxis.

Venothrombolism (VTE) prophylaxis is increasingly utilized in pediatric intensive care units (PICUs). Enoxaparin, a low-molecular weight heparin, is frequently used for this purpose. Enoxaparin can also be used for therapeutic anticoagulation in cases of known thrombus. In such cases, monitoring involves obtaining serum anti- Xa levels with a target value of 0.5-1 units/mL. No monitoring recommendations currently exist for enoxaparin when intended for pediatric VTE prophylaxis. We hypothesize that a clinically important number of patients on VTE prophylaxis with enoxaparin have serum anti-Xa levels consistent with values targeted for therapeutic anticoagulation. We found that over 20% of patients on VTE prophylaxis with enoxaparin had serum anti-Xa levels consistent with true therapeutic anticoagulation (anti-Xa level 0.5-1 units/mL) during their enoxaparin course and 5% achieved values of supratherapeutic anticoagulation (anti-Xa level >1 units/mL). Serum anti-Xa level did not correlate with once versus twice daily dosing, body mass index (BMI), or creatinine level. Blood urea nitrogen (BUN) was found to have a positive odds ratio for an anti-Xa level ≥ 0.5 units/mL. We believe that this incidence of unintended therapeutic anticoagulation indicates a clinically significant number and therefore routine anti-Xa evaluation while on VTE prophylaxis is warranted within our population.

Useful products from complex starting materials: common chemicals from biomass feedstocks.

A rapidly expanding area of inquiry is the use of plant biomass for the industrial production of organic compounds for which there is high demand. This interest is fuelled largely by the anticipated decline in the supply of petroleum, and the inevitable concomitant rise in cost. Over the past 30 years, significant progress has been made toward the large-scale conversion of plant biomass to common chemicals such as methanol, ethanol, glycerol, substituted furans, and carboxylic acids. However, examination of the list of top production organic chemicals reveals numerous opportunities for future development, including simple halocarbons, alkenes and arenes. Progress toward efficient and economical production of these challenging targets from biomass has recently been reported, and future success is likely to continue through academic and industrial collaboration.

Interprosthetic fractures of the femur: treatment with a single-locked plate.

Interprosthetic fractures of the femur, those between an ipsilateral hip and knee arthroplasty, are challenging to treat secondary to limited bone available for fixation, osteopenic bone, a compromised intramedullary blood supply, and an often elderly patient population. From 2002 to 2006, 22 consecutive patients with an interprosthetic femur fracture were treated with a single-locking plate. Follow-up averaged 17.7 months, with fracture union achieved an average of 13.8 weeks postoperatively. All patients regained their preoperative ambulatory status and subjectively reported unchanged function of their hip and knee arthroplasties. Single-locked plating is an effective method of treatment of interprosthetic fractures of the femur. Emphasis on preservation of the soft tissue envelope and sufficient cortical purchase both above and below the fracture is of paramount importance.