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Objectives The aim of this study was to evaluate clinical characteristics, mechanisms of failure, and outcomes of transcatheter aortic valve replacement (TAVR) explantation. Background Surgical explantation following TAVR may be required for structural valve degeneration, paravalvular leak, infection, or other reasons. However, in-depth data on indications and outcomes are lacking. Methods Data from a multicenter, international registry (EXPLANT-TAVR) of patients who underwent TAVR explantation were reviewed retrospectively. Explantations performed during the same admission as initial TAVR were excluded. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 6.7 months (interquartile range [IQR]: 1.0-18.8 months) after TAVR explantation and was 97.7% complete at 30 days and 86.1% complete at 1 year. Results From November 2009 to September 2020, 269 patients across 42 centers with a mean age of 72.7 ± 10.4 years underwent TAVR explantation. About one quarter (25.9%) were deemed low surgical risk at index TAVR, and median Society of Thoracic Surgeons risk at TAVR explantation was 5.6% (IQR: 3.2%-9.6%). The median time to explantation was 11.5 months (IQR: 4.0-32.4 months). Balloon-expandable and self-expanding or mechanically expandable valves accounted for 50.9% and 49.1%, respectively. Indications for explantation included endocarditis (43.1%), structural valve degeneration (20.1%), paravalvular leak (18.2%), and prosthesis-patient mismatch (10.8%). Redo TAVR was not feasible because of unfavorable anatomy in 26.8% of patients. Urgent or emergency cases were performed in 53.1% of patients, aortic root replacement in 13.4%, and 54.6% had concomitant cardiac procedures. Overall survival at last follow-up was 76.1%. In-hospital, 30-day, and 1-year mortality rates were 11.9%, 13.1%, and 28.5%, respectively, and stroke rates were 5.9%, 8.6%, and 18.7%, respectively. Conclusions The EXPLANT-TAVR registry reveals that surgical risks associated with TAVR explantation are not negligible and should be taken into consideration in the lifetime management of aortic stenosis.

Objectives The aim of this study was to determine clinical and echocardiographic characteristics, mechanisms of failure, and outcomes of mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). Background Although >100,000 mitral TEER procedures have been performed worldwide, longitudinal data on MV surgery after TEER are lacking. Methods Data from the multicenter, international CUTTING-EDGE registry were retrospectively analyzed. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 9.0 months (interquartile range [IQR]: 1.2-25.7 months) after MV surgery, and follow-up was 96.1% complete at 30 days and 81.1% complete at 1 year. Results From July 2009 to July 2020, 332 patients across 34 centers underwent MV surgery after TEER. The mean age was 73.8 ± 10.1 years, median Society of Thoracic Surgeons risk for MV repair at initial TEER was 4.0 (IQR: 2.3-7.3), and primary/mixed and secondary mitral regurgitation were present in 59.0% and 38.5%, respectively. The median interval from TEER to surgery was 3.5 months (IQR: 0.5-11.9 months), with overall median Society of Thoracic Surgeons risk of 4.8% for MV replacement (IQR: 2.8%-8.4%). The primary indication for surgery was recurrent mitral regurgitation (33.5%), and MV replacement and concomitant tricuspid surgery were performed in 92.5% and 42.2% of patients, respectively. The 30-day and 1-year mortality rates were 16.6% and 31.3%, respectively. On Kaplan-Meier analysis, the actuarial estimates of mortality were 24.1% at 1 year and 31.7% at 3 years after MV surgery. Conclusions In this first report of the CUTTING-EDGE registry, the mortality and morbidity risks of MV surgery after TEER were not negligible, and only

INTRODUCTION: Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. AREAS COVERED: This review covers the history of antiobesity drugs, efficacy and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization. EXPERT OPINION: In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.

Background Around 40% of school leavers in the UK attend university and individual universities generally host thousands of students each academic year. Bringing together these student communities during the COVID-19 pandemic may require strong interventions to control transmission. Prior modelling analysis of SARS-CoV-2 transmission within universities that use compartmental modelling approaches suggest that outbreaks are almost inevitable. Methods We constructed a network-based model to capture the interactions of a student population in different settings (housing, social and study). For a single academic term of a representative campus-based university, we ran a susceptible-latent-infectious-recovered type epidemic process, parameterised according to available estimates for SARS-CoV-2. We investigated the impact of: adherence to (or effectiveness of) isolation and test and trace measures; single-room isolation of cases; supplementary mass testing. Results Incorporating uncertainty in the asymptomatic fraction of cases and their associated infectivity, in the absence of interventions our model estimated that 69% (55% - 75%) of the student population could be infected during the autumn term. With full adherence to test, trace and isolate measures, we found lower cumulative infection estimates of 19% (5% - 39%). Irrespective of the adherence to isolation measures, on average a higher proportion of students resident on-campus became infected than off-campus. Room isolation generated minimal benefits. A one-off instance of mass testing would not drastically reduce the term-long case load, though if performed a couple of weeks before the end-of-term it could reduce the expected end-of-term prevalence. Regular testing, together with high adherence to isolation, test and trace measures, could reduce the proportion infected during the term by more than 50% compared to having no mass testing. Conclusions Our findings suggest SARS-CoV-2 may readily transmit in a university setting if there is limited adherence to nonpharmaceutical interventions and/or there are delays in receiving test results. Following isolation guidance and effective contact tracing curbed transmission and reduced the expected time an adhering student would spend in isolation. Additionally, widespread adherence throughout the term suppresses the amount of unwitting asymptomatic transmission to family and community members in the students’ domicile regions after term ends.

Spinal cord injury is a devastating condition interrupting voluntary movement and motor control. In response to unloading, skeletal muscle undergoes numerous adaptations, including rapid and profound atrophy, intramuscular fat accumulation, impaired muscular glucose metabolism and decreased force generation and muscle performance. Functional electrical stimulation (FES) involves electrically stimulating affected muscles to contract in a coordinated manner to create a functional movement or task. Effects of FES-cycling, rowing and resistance training on muscle health are described here. Briefly, FES-cycling and resistance training may slow muscle atrophy or facilitate muscle hypertrophy, and all modalities benefit muscle composition and performance to some extent. These interventions show promise as future rehabilitative tools after spinal cord injury.

Background In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multiphase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children’s role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children.

Background The introduction of SARS-CoV-2, the virus that causes COVID-19 infection, in the UK in early 2020, resulted in the introduction of several control policies to reduce disease spread. As part of these restrictions, schools were closed to all pupils in March (except for vulnerable and key worker children), before re-opening to certain year groups in June. Finally, all school children returned to the classroom in September. Methods Here, we analyse data on school absences in late 2020 as a result of COVID-19 infection and how that varied through time as other measures in the community were introduced. We utilise data from the Department for Education Educational Settings database and examine how pupil and teacher absences change in both primary and secondary schools. Results Our results show that absences as a result of COVID-19 infection rose steadily following the re-opening of schools in September. Cases in teachers declined during the November lockdown, particularly in regions previously in tier 3, the highest level of control at the time. Cases in secondary school pupils increased for the first 2 weeks of the November lockdown, before decreasing. Since the introduction of the tier system, the number of absences with confirmed infection in primary schools was observed to be (markedly) lower than that in secondary schools. In December, we observed a large rise in the number of absences per school in secondary school settings in the South East and London, but such rises were not observed in other regions or in primary school settings. We conjecture that the increased transmissibility of the new variant in these regions may have contributed to this rise in secondary school cases. Finally, we observe a positive correlation between cases in the community and cases in schools in most regions, with weak evidence suggesting that cases in schools lag behind cases in the surrounding community. Conclusions We conclude that there is no significant evidence to suggest that schools are playing a substantial role in driving spread in the community and that careful monitoring may be required as schools re-open to determine the effect associated with open schools upon community incidence.

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create ‘COVID-secure’ workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread., Author summary As part of a collective effort to protect public health by disrupting viral transmission of SARS-CoV-2, businesses have implemented measures to minimise exposure to coronavirus in workplaces and premises open to the public. Adjustments in working practices can result in changes to patterns of interaction, altering the dynamics of viral spread. To assess the impact of workplace targeted non-pharmaceutical disease controls against epidemic spread of SARS-CoV-2 amongst a population of workers, we present a network-based model with layered contacts capturing multiple encounter settings (workplaces, households, social and other). Informed by UK data, the model accounts for work sector, workplace size and the division of time between work and home. We study three workplace focused interventions: (i) a specified fraction of each work sector working from home; (ii) temporally asynchronous work patterns; (iii) introduction of COVID-secure workplaces. We also examine the role of adherence to isolation and test and trace measures. Following isolation guidance and engaging with contact tracing alone is an effective tool to curb transmission, but is highly sensitive to adherence levels. Given the heterogeneity of demographic attributes across worker roles, we demonstrate the utility of a network model approach to investigate workplace-targeted control measures against infectious disease spread.

This study examined the relationship between having training in key disaster behavioral health (DBH) interventions and trauma health (compassion fatigue, burnout and compassion satisfaction), resilience, the number of crisis responses participated in within the last year, and the frequency of assembling to practice crisis interventions skills. Data was collected from a convenience sample of disaster behavioral health responders (N = 139) attending a training conference in Michigan. Measures included the Professional Quality of Life Scale, the 14-item Resilience Scale, and a demographic questionnaire. Point biserial correlations revealed that having training in large and small group crisis interventions and individual and peer crisis interventions was significantly correlated with higher resilience and lower levels of burnout. Psychological First Aid was not significantly associated with any of the trauma health variables or with resilience. Compassion fatigue and compassion satisfaction were not significantly associated with DBH training. Chi-square tests for independence found no significant association between key DBH training strategies and the number of crisis responses participated in within the past year and the frequency of assembling to practice crisis interventions skills. These findings suggest that completing training in both, large and small group and individual and peer crisis intervention techniques may help to increase resiliency and reduce burnout among disaster behavioral health providers.

School nurses address mental health issues of youth on a daily basis. These mental health issues include substance abuse, anxiety, depression, and even suicidal ideation. Mental health first aid is a process that seeks to help medical professionals and laypeople recognize and address someone that is having a mental health or substance abuse crisis. This article will describe an experience with a student having suicidal ideations and how the mental health action plan was used.

School health is a specialty practice of nursing positioned at the intersection of public health and population health. This article discusses the redesign of a program’s curriculum with the hope of advancing and elevating the practice of school nursing. The redesign is based on NASN’s Framework for 21st Century School Nursing Practice and is the result of a New Jersey Nursing Initiative grant awarded to a trio of adjunct faculty from Rutgers University Camden in July 2016.

Because heart rate affects ventricular filling, the aim of the present study was to assess the effects of increasing heart rate and tidal volume on stroke volume variability to determine whether this dynamic index is heart-rate dependent.Prospective, randomized study.Single university hospital.Eighteen vascular surgery patients having general anesthesia and endotracheal intubation with an arterial catheter connected to the Vigileo FloTrac system (Edwards Lifesciences, Irvine, CA) and a transesophageal atrial pacemaker (CardioComman Inc, Tampa, FL).A 2 × 2 factorial study of changes in heart rate (80 bpm and 110 bpm) and tidal volume (6 mL/kg and 10 mL/kg).With tidal volume at 6 mL/kg, increasing heart rate from 80 mL/kg to 110 bpm caused stroke volume variability to increase from 12.2% ± 5.7% to 13.2% ± 5.3% (p0.05), and with tidal volume at 10 mL/kg, increasing heart rate from 80 mL/kg to 110 bpm caused stroke volume variability to increase from 19.7% ± 7.9% to 22.0% ± 8.6% (p0.05). In comparison, increasing tidal volume from 6 mL/kg to 10 mL/kg produced a significantly greater effect on stroke volume variability than increasing heart rate.Stroke volume variability is sensitive to increases in heart rate in addition to tidal volume. Increasing heart rate caused stroke volume variability to increase significantly, although not to the same magnitude as increasing tidal volume. When using dynamic volume indices, clinicians should be aware of increases in heart rate, although its clinical impact may be relatively minor compared with changes in tidal volume.

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of patients with symptomatic severe aortic stenosis considered to have prohibitive surgical risk. However, there is significant variability in methods used to size the aortic valve annulus for TAVI device selection.

Background The purpose of this study was to analyze the long-term outcomes associated with interruption of incompetent perforator veins (IPV) using minimally invasive techniques as adjunctive therapies in the management of patients with chronic venous insufficiency (CVI). Methods This is a retrospective review of a prospectively maintained venous database collected over 6 years (2005–2011). The study cohort included 64 patients with CVI stage C5 or C6 who underwent minimally invasive perforator interruption with subfascial endoscopic perforator surgery (SEPS) or radiofrequency ablation of IPV (RFA-IPV) as part of the management of their CVI. All patients were referred for evaluation after having failed conservative treatment with compression dressings. Relevant patient characteristics and comorbidities were recorded along with symptom resolution, venous ulcer healing, recurrence, and surgical complications. In addition to clinic follow-up examination by a surgical provider, chart notes from other subspecialties were also reviewed. We also conducted telephone assessments in patients who had been lost to clinic follow-up in order to provide complete outcome data. Results In this subset ( n = 64) of patients with CVI who had adjunctive IPV treatment, 41 (64%) underwent SEPS and 23 (36%) patients underwent RFA-IPV along with ablation of the greater saphenous vein for C5 or C6 disease. The mean patient follow-up was 37 months. There were no differences in patient demographics or risk factors. Twenty-three (88%) SEPS and 12 (100%) RFA-IPV patients ( P = NS) with C6 disease went on to completely heal their venous ulcers after the procedure with an average healing time of 5.2 (SEPS) and 4.4 (RFA-IPV) months ( P = NS). Overall, 7 (17%) SEPS and 6 (23%) RFA-IPV patients ( P = NS) developed a recurrent ulcer after surgical treatment. Procedural complications were seen in 14 (34%) SEPS and 2 (9%) RFA-IPV patients ( P = NS), mostly minor. Major complications only occurred in the SEPS group consisting of 2 major amputations caused by pain from nonhealing ulcers and 1 deep venous thrombosis. Conclusions This study supports the premise that in patients with advanced venous disease, there may be a demonstrable benefit directly attributable to perforator interruption. Our recurrent ulceration rates are acceptable, with low complication rates in patients undergoing RFA-IPV, thereby making this procedure more attractive in patients with multiple comorbidities. We support an aggressive approach to patients with C5/C6 disease that includes perforator elimination when appropriate.

Difficult iliac artery access remains one of the limiting factors in the successful application of endovascular management of abdominal and thoracic aortic pathologies. An understanding of the scope of the problem, as well as the recognition of patient characteristics that increase the likelihood of difficult access are paramount in preoperative planning. Herein we discuss the specific challenges of aorto-iliac access as well as provide a treatment algorithm for avoiding aorto-iliac complications. Alternative access strategies and emergency bail-out procedures are discussed. A thorough understanding of the preoperative anatomy and imaging is key to successful endovascular aortic surgery.

Acute ischemic stroke triggers complex neurovascular, neuroinflammatory and synaptic alterations. Aspirin and docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, have beneficial effects on cerebrovascular diseases. DHA is the precursor of neuroprotectin D1 (NPD1), which downregulates apoptosis and, in turn, promotes cell survival. Here we have tested the effect of aspirin plus DHA administration and discovered the synthesis of aspirin-triggered NPD1 (AT-NPD1) in the brain. Then we performed the total chemical synthesis of this molecule and tested in the setting of 2h middle cerebral artery occlusion (MCAo) in Sprague-Dawley rats. Neurological status was evaluated at 24h, 48 h, 72 h, and 7 days. At 3h post-stroke onset, an intravenous administration of 333 μg/kg of AT-NPD1 sodium salt (AT-NPD1-SS) or methyl-ester (AT-NPD1-ME) or vehicle (saline) as treatment was given. On day 7, ex vivo magnetic resonance imaging (MRI) of the brains was conducted on 11.7 T MRI. T2WI, 3D volumes, and apparent diffusion coefficient (ADC) maps were generated. In addition, infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/macrophages) and SMI-71-positive vessels were counted in the cortex and striatum at the level of the central lesion. All animals showed similar values for rectal and cranial temperatures, arterial blood gases, and plasma glucose during and after MCAo. Treatment with both AT-NPD1-SS and AT-NPD1-ME significantly improved neurological scores compared to saline treatment at 24h, 48 h, 72 h and 7 days. Total lesion volumes computed from T2WI images were significantly reduced by both AT-NPD1-SS and AT-NPD1-ME treatment in the cortex (by 44% and 81%), striatum (by 61% and 77%) and total infarct (by 48% and 78%, respectively). Brain edema, computed from T2WI in the cortex (penumbra) and striatum (core), was elevated in the saline group. In contrast, both AT-NPD1 decreased water content in the striatum on day 7. 3D volumes, computed from T2WI, were dramatically reduced with both AT-NPD1 and the lesion was mostly localized in the subcortical areas. Treatment with both AT-NPD1-SS and AT-NPD1-ME significantly reduced cortical (by 76% and 96%), subcortical (by 61% and 70%) and total (69% and 84%, respectively) infarct volumes as defined by histopathology. In conclusion, a novel biosynthetic pathway that leads to the formation of AT-NPD1 mediator in the brain was discovered. In addition, administration of synthetic AT-NPD1, in either its sodium salt or as the methyl ester, was able to attenuate cerebral ischemic injury which leads to a novel approach for pharmaceutical intervention and clinical translation.

Portal vein aneurysms (PVA) are a rare vascular anomaly of the portal system, representing fewer than 3% of all venous aneurysms, with only 150 known cases since first reported in l956 by Barzilai and Kleckner. PVA can be divided into 2 categories: extrahepatic and intrahepatic with acquired and congenital etiologies. Bimodal treatment includes medical and surgical approaches. With increased use of noninvasive radiological imaging, PVA will be increasingly recognized in the practice of vascular surgery.

Endoluminal treatment of symptomatic varicose veins (VV) reduces or eliminates inpatient hospital stays, lowers complication rates, and increases revenue for vein care centers adopting the technique. This study compares the outcomes and economics of two treatments for VV.Since May 2007, endovenous radiofrequency ablation (RFA) of symptomatic VV has been performed at our institution. For outcome measurements, a cohort of 100 RFA procedures (26% CEAP class C5 and C6) was compared with 100 open greater or lesser saphenous stripping and ligation procedures (SL, 18% C5 and C6). Procedures were performed between August 2002 and October 2007. The time frame was chosen to allow for a 6-mo follow-up. Patients who had adjunctive removal of secondary varicosities were included in both cohorts. Cost estimates are based on the actual total direct costs derived from the hospital's charge sheets for 20 of the 100 patients in each of the cohorts (n = 40). The actual direct costs are based on 2009-dollar values and do not include the surgeons' professional fees.Seventy-nine percent of the RFA therapies were performed in an outpatient clinic treatment room with the remaining 21% performed in an operating room (OR). For the SL group, all procedures were performed in the OR with 68% of patients requiring at least one night of hospital stay (average length of stay 1.2 d). The estimated direct cost of performing RFA in the treatment room was $906. This was considerably less than the estimated $4241 total direct cost for open SL followed by in-hospital observation. Outpatient open SL cost $2622, which is only slightly more than the $2533 cost for outpatient RFA performed in the OR. The use of RFA was associated with an earlier return to normal leisure activities (3.3 d versus 26 d, P0.05), fewer total hospital nights (3 d versus 82 d, P0.05), and less use of general anesthesia (16% versus 95%, P0.05). There were no major complications in the RFA group compared with three major complications in the SL group.With the introduction of endovenous techniques at our institution, there has been a significant increase in the volume of patients seeking this less invasive treatment modality. This is due largely to the ease and comfort with which patients can now be treated as well as the reduced length of stay, reduction of general anesthetic use, and the speed at which they can return to normal activities. We recommend endovenous ablation techniques as both cost-saving and patient-preferred.

Background and Purpose— Docosahexaenoic acid (DHA; 22:6n-3), an ω-3 essential fatty acid family member, is the precursor of neuroprotectin D1, which downregulates apoptosis and, in turn, promotes cell survival. This study was conducted to assess whether DHA would show neuroprotective efficacy when systemically administered in different doses after middle cerebral artery occlusion (MCAo) in rats. Methods— Sprague-Dawley rats were anesthetized with isoflurane and subjected to 2 hour of MCAo. Animals were treated with either DHA (low doses=3.5 or 7 mg/kg; medium doses=16 or 35 mg/kg; and high dose=70 mg/kg) or an equivalent volume of saline intravenously 3 hours after MCAo onset. Neurologic status was evaluated during occlusion (60 minutes) and on days 1, 2, 3, and 7 after MCAo. Seven days after MCAo, brains were perfusion-fixed, and infarct areas and volumes were determined. Results— Only the low and medium doses of DHA significantly improved the neurologic score compared with vehicle-treated rats at 24 hours, 48 hours, 72 hours, and 7 days. DHA markedly reduced total corrected infarct volume in all treated groups compared with vehicle-treated rats (3.5 mg/kg, 26±9 mm 3 ; 7 mg/kg, 46±12 mm 3 ; 16 mg/kg, 37±5 mm 3 ; and 35 mg/kg, 34±15 mm 3 vs vehicle, 94±12 mm 3 ). Cortical and striatal infarct volumes were also significantly reduced by treatment with DHA. No neuroprotective effects were observed with 70 mg/kg DHA. Conclusions— We conclude that DHA experimental therapy at low and medium doses improves neurologic and histologic outcomes after focal cerebral ischemia and might provide benefits in patients after ischemic stroke.

Platelet-activating factor (PAF) is a bioactive phospholipid that accumulates during ischemia-reperfusion and is involved in the activation of platelets, neutrophils, and pro-inflammatory signaling. PAF has been suggested to enhance brain ischemia-reperfusion damage. LAU-0901, a novel PAF receptor antagonist, was examined in models of focal cerebral ischemia in rats and mice. Sprague–Dawley rats were anesthetized and received 2-hour middle cerebral artery occlusion (MCAo) by intraluminal suture. LAU-0901 (30, 60, 90 mg/kg; n = 9–11) or vehicle (n = 11) was administered i.p. at 2 h after onset of MCAo. The neurological status was evaluated at 60 min, and on days 1, 2, 3 and 7 after MCAo. In the dose–response study in mice, C57BL/6 mice were anesthetized and received 1 h MCAo by intraluminal suture. LAU-0901 (15, 30, 60 mg/kg; n = 7–9) or vehicle (n = 8) was given i.p. at 1 h after onset of MCAo. Local cerebral blood flow (LCBF) was measured at 1, 2, 4, and 6 h after MCAo in mice. LAU-0901 treated rats showed improved neurological score throughout the 7-day survival period. LAU-0901 treatment (30, 60 and 90 mg/kg) reduced total corrected infarct volume compared to vehicle rats by 76, 88 and 90%, respectively. Mice treated with LAU-0901 (30 and 60 mg/kg) reduced total infarction by 29% and 66%, respectively. LCBF was improved by treatment with LAU-0901 (30 mg/kg) by 77% of baseline at 6 h. In conclusion, we demonstrate for the first time that LAU-0901 improves behavioral scores, LCBF and reduces infarct volume after focal cerebral ischemia in rats and mice. Thus, this PAF receptor antagonist exhibits potent and sustained neuroprotection that may be of value for the design of stroke therapies., NIH Grant NS23002 (NGB)

Carotid angioplasty and stenting (CAS) is a valid alternative to conventional carotid endarterectomy for treatment of carotid artery stenosis in a select group of patients. Distal embolization of atherosclerotic debris and air causing neurologic deficits during CAS has been one of the most significant concerns limiting widespread application of CAS technology. A variety of distal embolic protection devices have been designed to minimize the risk of major embolization causing stroke. This review will examine the types of available devices, including strengths and weaknesses of each, and present the available evidence and rationale for their routine use during CAS.

ObjectiveType 2 endoleak occurs in up to 20% of patients after endovascular aneurysm repair (EVAR), but its long-term significance is debated. We reviewed our experience to evaluate late outcomes associated with type 2 endoleak.MethodsDuring the interval January 1994 to December 2005, 873 patients underwent EVAR. Computed tomography (CT) scan assessment was performed ≤1 month of the operation and at least annually thereafter. Sequential 6-month CT scan follow-up was adopted for those patients with persistent type 2 endoleaks, and reintervention was limited to those with sac enlargement >5 mm. Study end points included overall survival, aneurysm sac growth, reintervention rate, conversion to open repair, and abdominal aortic aneurysm (AAA) rupture. Preoperative variables and anatomic factors potentially associated with these endpoints were assessed using multivariate analysis.ResultsWe identified 164 (18.9%) patients with early (at the first follow-up CT scan) type 2 endoleaks. Mean follow-up was 32.6 months. In 131 (79.9%) early type 2 endoleaks, complete and permanent leak resolution occurred ≤6 months. Endoleaks persisted in 33 patients (3.8% of total patients; 20.1% of early type 2 endoleaks) for >6 months. Transient type 2 endoleak (those that resolved ≤6 months of EVAR) was not associated with adverse late outcomes. In contrast, persistent endoleak was associated with several adverse outcomes. AAA-related death was not significantly different between patients with and without a type 2 endoleak (P = .78). When evaluating patients with no early endoleak vs persistent endoleak, freedom from sac expansion at 1, 3, and 5 years was 99.2%, 97.6%, and 94.9% (no leak) vs 88.1%, 48.0%, and 28.0% (persistent) (P < .001). Patients with persistent endoleak were at increased risk for aneurysm sac growth vs patients without endoleak (odds ratio [OR], 25.9; 95% confidence interval [CI] 11.8 to 57.4; P < .001). Patients with a persistent endoleak also had a significantly increased rate of reintervention (OR, 19.0; 95% CI, 8.0 to 44.7); P < .001). Finally, aneurysm rupture occurred in 4 patients with type 2 endoleaks. Freedom from rupture at 1, 3, and 5 years for patients with a persistent type 2 endoleak was 96.8%, 96.8%, and 91.1% vs 99.8%, 98.5%, and 97.4% for patients without a type 2 endoleak. Multivariate analysis demonstrated persistent type 2 endoleak to be a significant predictor of aneurysm rupture (P = .03).ConclusionsPersistent type 2 endoleak is associated with an increased incidence of adverse outcomes, including aneurysm sac growth, the need for conversion to open repair, reintervention rate, and rupture. These data suggest that patients with persistent type 2 endoleak (>6 months) should be considered for more frequent follow-up or a more aggressive approach to reintervention.

The McGivney hemorrhoidal ligator (MHL), a band designed to cause tissue necrosis, is the preferred experimental tool to create hindlimb ischemia-reperfusion (I/R) injury in rodents. This report defines and compares the ex vivo band tension exerted by MHL and orthodontic rubber bands (ORBs) along with select in vivo characteristics of I/R. As to method, ex vivo band tension was measured over relevant diameters using a tensiometer. In vivo assessment of murine limb perfusion during ischemia with ORB and MHL was compared using laser Doppler imaging and measurement of wet weight-to-dry weight ratio. Neuromuscular scoring and histological extent of muscle fiber injury after I/R with MHL and ORB were also compared. A dose-response curve, between the duration of ORB-induced I/R with both mitochondrial activity (methyl-thiazol-tetrazolium) or tail perfusion [laser Doppler imaging (LDI)], was generated. As a results, ex vivo measurements showed that ORB exerted significantly less force than the MHL. Despite less tension in ORB, in vivo testing of the ORB confirmed complete ischemia by both LDI and wet weight-to-dry weight ratio. After I/R, caused by ORB, there was significantly less neuromuscular dysfunction. Histological assessment confirmed similar degrees of muscle fiber injury after I/R with either the MHL or ORB. Increasing durations of ischemia created by the ORB followed by reperfusion significantly decreased mitochondrial activity and tail perfusion after 24 h of ischemia. In conclusions, ORB produced similar levels of tissue ischemia in murine models of limb I/R with fewer levels of nonspecific injury. ORB may be the preferred model for selected studies of limb I/R.

Open vascular repair of ischemic myocardium and aortic aneurysms results in a systemic inflammatory response that influences the mortality and morbidity of these procedures. Recent studies in animal models of complex vascular reconstruction indicate that the activity of poly(ADP-ribose) polymerase (PARP) may influence the mortality and morbidity of these kinds of reconstructions. PARP's activity, localized to nuclei and mitochondria, is stimulated by deoxyribonucleic acid (DNA) strand breaks. Activation of PARP results in synthesis of poly(ADP-ribose) sugar moieties, whose primary role is to protect DNA from degradation during cytotoxic stress. Paradoxically, when stressful conditions similar to those experienced during vascular reconstructions result in overactivation of PARP, depletion of cellular levels of adenosine triphosphate and nicotinamide adenine dinucleotide can result in exacerbation of tissue injury. Herein we review the role of PARP in inflammation and its relevance to cardiovascular reconstructions.

Purpose To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management. Design Retrospective and descriptive case series. Participants Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003. Methods Review of patient case notes. Main Outcome Measures Age, laterality, clinical features, and anti-streptococcal lysin O titers. Results Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis. Conclusions Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

A model of flavor release from encapsulated flavor particles immersed in water has been developed that correlates well with experimental data. Flavor release from particles was determined by measuring both the quantities released from the particle to water and from water to air in the headspace. The model presented here predicts a very different release with time from the encapsulated flavor if the particle develops a hydrogel at the surface (swelling) compared to gradual erosion. Controlled heating showed more retention of flavor when the particle swells compared to a more rapid flavor release under conditions of particle erosion. © 2004 American Institute of Chemical Engineers AIChE J, 50: 3257–3270, 2004

In brachial plexus lesions and their revision, evaluation of nerve stumps is very important for the reconstructive strategy. We intraoperatively perform cryostat sections, Haematoxilin-Eosin (HE) stained, and compare the clinical appearance of the nerves to the microscopic results. Toluidine blue staining is later used to validate the structural details. Intraneural fibrosis can be traced safely with both staining methods, in root avulsions a histology is helpful, too. For more proximal, intraforaminal lesions semithin section stained with toluidine-blue are less informative than are HE-stained cryostat sections. In these lesions the clinical control by electrical stimulation and evoked potentials is superior.

Purpose: Underdeployment of an intravascular stent has been identified as a cause of restenosis or occlusion of a treated arterial lesion. Intravascular ultrasound (IVUS) has been shown to initially improve the anatomic and clinical stenting. The purpose of this study was to determine whether the use of IVUS increased long-term patency of this intervention. Methods: Between March 1992 and October 1995, 71 limbs (52 patients) with symptomatic aortoiliac occlusive disease underwent balloon angioplasty with primary stenting. IVUS and arteriography were used in 49 limbs (36 patients) to evaluate stent deployment. Arteriography alone was used in 22 limbs (16 patients) to evaluate stent deployment. Patients were captured prospectively in a vascular registry and retrospectively reviewed. Results: Mean age of patients treated with IVUS was 61.1 ± 9.0 years (range, 38-85) versus 70.0 ± 10.1 years (range, 57-87) in patients treated without IVUS (P

Endovenous thermal ablation has emerged as an alternative therapy for the treatment of chronic superficial venous insufficiency (CVI) of the lower extremities. Recanalization, or anatomic failure, of a vein after endovenous radiofrequency ablation (RFA) has been described, albeit an infrequent occurrence. This study was performed to demonstrate risk factors associated with the efficacy of RFA and recanalization in the treatment of CVI.Data were collected in an ongoing multicenter registry, which was retrospectively reviewed. This study reviewed 249 limbs that underwent RFA of either the great saphenous vein (GSV) or the small saphenous vein (SSV) over a three-year period, including only patients for whom an intermediate (6 month) follow-up venous duplex ultrasound was available. Patients in whom recanalization was demonstrated via duplex (n = 17, 6.8%) were analyzed for patient-level characteristics. Logistic regression analysis was performed to determine the existence of any significant clinical risk factors associated with anatomic failure. The need for secondary interventions because of clinical symptoms associated with recanalization was analyzed as well.In this cohort, the initial vein occlusion rate was 93.1%. Segmental (n = 9, 53%) or complete (n = 8, 47%) recanalization was seen in 17 limbs (6.8%) after initial successful GSV ablation. All SSV remained persistently ablated. Anatomic failure was associated with higher rate of clinical symptom recurrence (41% vs. 21%; relative risk (RR), 2.75; 95% confidence interval [CI], 0.99-7.6; P0.05) and an increased need for secondary vein procedures in the affected limbs (35% vs. 12%; RR, 3.96; 95% CI, 1.3-11.7; P0.05). Two recanalized GSVs required repeated endothermal ablation, in efforts to aid in the healing of ulcerations. Patient factors including diabetes, hypertension, hyperlipidemia, anticoagulation or antiplatelet agent usage, presence of deep venous reflux, or tobacco use did not increase the risk of RFA failure. Comparatively, patients with GSV recanalization had a longer mean follow-up time (63.3 vs. 41.6 weeks) but no difference in disease severity (C4, 35% vs. 17%; C5, 18% vs. 15%; C6, 6% vs. 8%; not significant).Endothermal ablation is an efficacious treatment for CVI with most patients remaining reflux free. Recanalization of an isolated vein segment after RFA, although shown in recent literature to be effected by anatomic risk factors, appears to be a sporadic phenomenon with respect to clinical risk factors. Nevertheless, in our cohort, anatomic failure was associated with a 2-fold increase in symptom recurrence and the need for interval secondary vein procedures. Ultrasound interrogation is recommended especially in patients with persistent or recurrent symptoms or nonhealing ulcerations.

Background: Ten percent of people may experience pain under the heel (plantar heel pain) at some time. Injections, insoles, heel pads, strapping and surgery have been common forms of treatment offered. The absolute and relative effectiveness of these interventions are poorly understood. Objectives: The objective of this review was to identify and evaluate the evidence for effectiveness of treatment in treating plantar heel pain. Search strategy: MEDLINE (from 1966 to December 1997), EMBASE and the Cochrane Library were searched. Three podiatry journals (The Foot, The Chiropodist (later The Journal of British Podiatric Medicine), and The British Journal of Podiatric Medicine) were handsearched. We contacted known investigators in the field to identify unpublished data or research in progress. Non-English language reports were excluded from the review. Selection criteria: Randomized and quasi-randomized trials of interventions for plantar heel pain in adults. Data collection and analysis: Two reviewers independently evaluated studies for inclusion, extracted data and assessed study quality. Additional information was obtained by direct contact with investigators. No poolable data were identified. Where measures of variance were available we have calculated the weighted mean differences based on visual analogue scale (VAS) scores. Main results: Eleven randomized trials involving 465 participants were included. Study quality was generally poor, and pooling of data was not possible. All studies measured a reduction in heel pain as the primary outcome. Seven trials evaluated interventions against placebo/dummy or no treatment. There was limited evidence for the effectiveness of topical corticosteroid, administered by iontophoresis in reducing pain. There was no evidence for the effectiveness of injected corticosteroid. There was limited evidence for the effectiveness of low energy extracorporeal shock wave therapy in reducing night pain, resting pain and pressure pain in the short term (12 weeks). In individuals with chronic pain (longer than six months), there was limited evidence for the effectiveness of dorsiflexion night splints in reducing pain. There was no evidence to support the effectiveness of therapeutic ultrasound, low-intensity laser therapy, exposure to an electron generating device or insoles with magnetic foil. No randomized trials evaluating orthotic devices, surgery, or radiotherapy against a control population were identified. There was limited evidence for the superiority of corticosteroid injections over orthotic devices. Conclusions: Although there is limited evidence for the effectiveness of local corticosteroid therapy, the effectiveness of other frequently employed treatments in altering the clinical course of plantar heel pain has not been established in comparative studies. Well designed and conducted randomized studies are required.

Objective. To establish the eYcacy for treatments of pain on the plantar aspect of the heel. Methods. Systematic review of the published and unpublished literature. Electronic search of Medline, BIDS and the Cochrane database of clinical trials. An assessment of the quality of the reporting was made of studies included in the review. Main outcome measure: patients’ pain scores. Study selection: randomized controlled trials, published or unpublished, that evaluated treatments used for plantar heel pain. Foreign language papers were excluded. Results. Eleven randomized controlled trials were included in the review. These evaluated some of the most frequently described treatments (steroid injections and orthoses) and some experimental therapies (extracorporeal shock wave therapy and directed electrons). The methodological assessment scores of the published trials were low; small sample sizes and failure to conceal the treatment allocation from study participants prevents more definitive statements about the eYcacy of treatments. In 10 of the included trials, patients in both the intervention and control arms reported improved pain scores at the final outcome measure. Conclusions. Although much has been written about the treatment of plantar heel pain, the few randomized controlled trials involve small populations of patients and do not provide robust scientific evidence of treatment eYcacy.

As an inflammatory airway disease, asthma is expected to be associated with an increase in airway blood flow. We therefore compared airway mucosal blood flow (Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n = 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS) therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/- 7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p0.01), and 55.4 +/- 5.3 microl . min-1 . ml-1 in GS-treated asthmatics (p0.05). Ten minutes after administration of 180 microg albuterol by metered dose inhaler, mean Qaw increased by 83 +/- 26% in normal subjects (p0.01), but did not change significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics. These results demonstrate that Qaw is increased in stable asthmatics and resistant to further increase by a standard inhaled dose of a beta-adrenergic agonist.

BACKGROUND Chronic suppurative otitis media (CSOM) is common among children in southern Africa. Managing associated co-morbidities may result in earlier disease resolution. METHODS Children 4 weeks were recruited to the study. Each child underwent a full clinical examination, a blood count, an HIV test and CD4 cell count, if found to be infected. RESULTS The study included 86 children, and the median age was 4.6 years. HIV infection was present in 45 of 83 children (54.2%), of which 23 (51.1%) were receiving antiretroviral treatment at the time of presentation. Underweight was present in 22 of 85 (25.9%) children and in 17 of the 45 (37.8%) HIV-infected children. One or more clinical signs (not aural-related) were found in 46 of 86 (53.4%) children. Cholesteatoma was found in 23 of 113 (20.4%) ears, and 9 of 86 (10.5%) children had serious associated aural or intracranial complications. CONCLUSIONS A high percentage of children with CSOM have associated pathology that needs to be diagnosed to optimally manage CSOM.

Ein 59 jahriger Mann wurde wegen eines zu einer Hypophyseninsuffizienz fuhrenden Hypophysenadenoms transnasal operiert, ein halbes Jahr spater wegen residualen Adenomgewebes nachoperiert und anschliesend einer Strahlentherapie unterzogen. Der Tumor wurde als gering granuliertes Hypophysenadenom vom Prolaktinzelltyp mit Prolaktin- und FSH-Bildung klassifiziert. Zwei Jahre spater wurde bei einer extrem hohen Hyperprolaktinamie ein Lebertumor festgestellt, der sich im Biopsat als solider endokriner Tumor mit immunhistochemisch nachgewiesener Prolaktinbildung herausstellte. Wegen der strukturellen Ahnlichkeit und des weitgehend identischen Markerverhaltens muste er als Metastase des Hypophysentumors angesehen werden. Nach funfmonatiger Therapiedauer verstarb der Patient an den Folgen von thrombembolischen Komplikationen. Die Sektion konnte die Diagnose eines metastasierenden prolaktinbildenden Karzinoms bestatigen, da weitere extrahepatische Tumormanifestationen und somit mogliche alternative Primartumoren nicht darstellbar waren. Der Fall ist mit nur 6 anderen bisher beschriebenen Kasuistiken weitgehend vergleichbar und bestatigt die Erfahrung aus 35 in der moderneren Literatur gesicherten Hypophysenkarzinomen, das maligne Hypophysentumoren erst nach Hypophysenoperationen manifest werden und nicht am Primartumor, sondern nur an den Metastasen diagnostiziert werden konnen.

Background Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats. Methods and Results Rats underwent 2 h of middle cerebral artery occlusion (MCAo). DHA, neuroprotectin D1 (NPD1) or vehicle (saline) was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle. Conclusions We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.