ValTer2 and ForesTer : From a relational term bank to hypertext on the Web

Abstract

Long-term data from the swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

The second law of thermodynamics and the global climate system : A review of the maximum entropy production principle

The long-term mean properties of the global climate system and those of turbulent fluid systems are reviewed from a thermodynamic viewpoint. Two general expressions are derived for a rate of entropy production due to thermal and viscous dissipation (turbulent dissipation) in a fluid system. It is shown with these expressions that maximum entropy production in the Earth s climate system suggested by Paltridge, as well as maximum transport properties of heat or momentum in a turbulent system suggested by Malkus and Busse, correspond to a state in which the rate of entropy production due to the turbulent dissipation is at a maximum. Entropy production due to absorption of solar radiation in the climate system is found to be irrelevant to the maximized properties associated with turbulence. The hypothesis of maximum entropy production also seems to be applicable to the planetary atmospheres of Mars and Titan and perhaps to mantle convection. Lorenz s conjecture on maximum generation of available potential energy is shown to be akin to this hypothesis with a few minor approximations. A possible mechanism by which turbulent fluid systems adjust themselves to the states of maximum entropy production is presented as a selffeedback mechanism for the generation of available potential energy. These results tend to support the hypothesis of maximum entropy production that underlies a wide variety of nonlinear fluid systems, including our planet as well as other planets and stars

Endovascular abdominal aneurysm repair and impact of systematic preoperative embolization of collateral arteries: endoleak analysis and long-term follow-up.

PURPOSE: To report our results of endovascular aneurysm repair (EVAR) over a 10-year period using systematic preoperative collateral artery embolization. METHODS: From 1999 until 2009, 124 patients (117 men; mean age 70.8 years) with abdominal aortic aneurysm (AAA) underwent embolization of patent lumbar and/or inferior mesenteric arteries prior to elective EVAR procedures. Embolization was systematically attempted and, whenever possible, performed using microcoils and a coaxial technique. Follow-up included computed tomography and/or magnetic resonance imaging and abdominal radiography. RESULTS: The technical success for EVAR was 96% (119/124), with 4 patients dying within 30 days (3.2% perioperative mortality) and 1 type III endoleak accounting for the failures. Collateral arteries were occluded spontaneously or by embolization in 60 (48%) of 124 patients. The endoleak rate was 50.9% (74 in 61 patients), most of which were type II (19%). Over a mean clinical follow-up of 60.5±34.1 months (range 1-144), aneurysm sac dimensions decreased in 66 patients, increased in 19 patients, and were stable in 35. The endoleak rate was significantly higher in the patients with increasing sac diameter (p<0.001). Among the patients with patent collateral arteries, 38/64 (59.3%) developed 46 leaks, while 28 leaks appeared in 23 (41%) of 56 patients with collateral artery occlusion (p=0.069). The type II endoleak rate significantly differed between these two groups (47.8% vs. 3.6%, p<0.001). CONCLUSION: Preoperative collateral embolization seems to be a valid method of reducing the incidence of type II endoleak, improving the long-term outcome.

Short-term moderate hypocapnia augments detection of optimal cerebral perfusion pressure.

An autoregulation-oriented strategy has been proposed to guide neurocritical therapy toward the optimal cerebral perfusion pressure (CPPOPT). The influence of ventilation changes is, however, unclear. We sought to find out whether short-term moderate hypocapnia (HC) shifts the CPPOPT or affects its detection. Thirty patients with traumatic brain injury (TBI), who required sedation and mechanical ventilation, were studied during 20 min of normocapnia (5.1±0.4 kPa) and 30 min of moderate HC (4.4±3.0 kPa). Monitoring included bilateral transcranial Doppler of the middle cerebral arteries (MCA), invasive arterial blood pressure (ABP), and intracranial pressure (ICP). Mx -autoregulatory index provided a measure for the CPP responsiveness of MCA flow velocity. CPPOPT was assessed as the CPP at which autoregulation (Mx) was working with the maximal efficiency. During normocapnia, CPPOPT (left: 80.65±6.18; right: 79.11±5.84 mm Hg) was detectable in 12 of 30 patients. Moderate HC did not shift this CPPOPT but enabled its detection in another 17 patients (CPPOPT left: 83.94±14.82; right: 85.28±14.73 mm Hg). The detection of CPPOPT was achieved via significantly improved Mx-autoregulatory index and an increase of CPP mean. It appeared that short-term moderate HC augmented the detection of an optimum CPP, and may therefore usefully support CPP-guided therapy in patients with TBI.

Anemia on admission predicts short- and long-term outcomes in patients with acute ischemic stroke.

BACKGROUND: It is still debatable whether anemia predicts stroke outcome. AIM: To describe the characteristics of patients with acute ischemic stroke (AIS) and anemia and identify whether hemoglobin status on admission is a prognostic factor of AIS outcome. METHODS: All 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) between January 2003 and June 2011 were selected. Demographics, risk factors, prestroke treatment, clinical, radiological and metabolic variables in patients with and without anemia according to the definition of the World Health Organization were compared. Functional disability and mortality were recorded up to 12 months from admission. RESULTS: Anemic patients (17.5%) were older, had lower body mass index, higher rates of coronary artery disease (CAD), atrial fibrillation, diabetes mellitus and peripheral artery disease. Anemia was associated with more severe stroke manifestations, lower systolic and diastolic blood pressure measurements, worse estimated glomerular filtration rate and elevated C-reactive protein concentrations upon admission and with increased modified Rankin scores during the follow-up. Anemic patients had higher 7-day, 3-month and 12-month mortality, which was associated with hemoglobin status and other factors, including age, CAD, stroke severity, and baseline C-reactive levels. Hemoglobin levels were inversely associated with recurrent stroke and mortality throughout the 12-month follow-up. CONCLUSION: Anemia is common among AIS patients and is associated with cardiovascular comorbidities. Low hemoglobin status independently predicts short and long-term mortality.

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P&lt;0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P&lt;0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P &lt; 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Use of long-term suppressive acyclovir after hematopoietic stem-cell transplantation: impact on herpes simplex virus (HSV) disease and drug-resistant HSV disease.

The effect that long-term use of suppressive acyclovir (ACV) has on both overall herpes simplex virus (HSV) disease and ACV-resistant HSV disease was examined in 3 consecutive cohorts of hematopoietic stem-cell transplant (HCT) recipients (n=2049); cohort 1 received ACV for 30 days after HCT, cohort 2 received it for 1 year after HCT, and cohort 3 received it for an extended period (i.e., >1 year) if the patient's immunosuppression continued after 1 year. The 2-year probability of HSV disease was 31.6% (95% confidence interval [CI], 28.0%-35%) in cohort 1, 3.9% (95% CI, 2.7%-5.2%) in cohort 2, and 0% in cohort 3 (P<.001). ACV-resistant HSV disease developed in 10 patients in cohort 1 (2-year probability, 1.3% [95% CI, 0.8%-2.7%]), in 2 patients in cohort 2 (2-year probability, 0.2% [95% CI, 0%-0.8%]; P=.006), and in 0 patients in cohort 3 (cohort 2 vs. cohort 3, P=.3). Long-term use of suppressive prophylactic ACV appears to prevent the emergence of drug-resistant HSV disease in HCT.

Comparative short-term response and remission rates for tacrolimus, cyclosporine, and infliximab for steroid-refractory ulcerative colitis

BACKGROUND: Calcineurin inhibitors (cyclosporine (CsA) and tacrolimus (Tcl)) and the anti-TNF-antibody infliximab (IFX) are established therapeutic options in steroid-refractory ulcerative colitis (UC). In acute severe UC failing steroids, a randomized trial showed an 85% short term response to CsA or IFX, with avoidance of colectomy. Comparative responses to the three drugs in outpatients with steroid-refractory UC are unknown. METHOD: Response to treatment in patients with steroid-refractory moderate to severe UC was retrospectively studied in three cohorts of patients: Cohort A (n=24) treated with oral Tcl (initially 0.05mg/kg twice daily, aiming for serum trough levels of 5-10 ng/mL); Cohort B (n=19) treated with intravenous CsA 2mg/kg/daily and then oral CsA 5mg/kg/daily; Cohort C. (n= 41) treated with IFX (5mg/kg intravenously at week 0, 2, 6 and then every 8 weeks). After successful rescue therapy with Tcl or CsA, thiopurine maintenance therapy was introduced. The endpoint was evaluation of clinical remission or response at week 6, on the basis of modified Truelove-Witts severity index (MTWSI). RESULTS: After 6 weeks, 42% (10/24) of patients treated with Tcl achieved remission (MTWSI score ≤4) compared to 47% (9/ 19) on CsA and 66% (27/41) of patients treated with IFX (Tcl & CsA vs IFX p=0.127). Clinical response (decrease of MTWSI score of more than 4 points) at week 6 was reached in 25% (6/24) patients on Tcl, compared to 11% (2/19) on CsA and 20% (8/41) given IFX (p=0.484). Subgroup analysis showed the highest rates of remission in those with moderate steroid-refractory UC treated with IFX: 29% (2/7) in Tcl group compared to 50% (2/4) in CsA group and 76 % (19/25) in IFX group (Tcl &CsA vs IFX p= 0.058) Patients with severe colitis showed similar rates of remission in all three groups: 47% (8/17) on Tcl, 47% (7/ 15) on CsA and 50% (8/16) on IFX (p= 0.700). Colectomy within 6 weeks occurred in 4% (1/24) after Tcl, 5% (1/19) after CsA and 0% (0/41) after IFX. Adverse effects in the first 6 weeks were observed in 13% (3/24) on Tcl, 26% (5/19) on CsA, and 10% (4/41) on IFX (p=0.224) CONCLUSION: No significant differences in response, remission, colectomy rate or adverse events between the three agents were found, although the study is too small for definitive conclusions. There are intriguing differences, with potentially greater response to IFX in moderate, steroid-refractory UC.

The Relevance of Long-Term Adherence to Non Pharmacological and Pharmacological Treatment of Hypertension

Current hypertension guidelines point to the necessity of achieving sustained and strict blood pressure control in every hypertensive patient. To reach this goal the patient should comply both with hygienic measures and pharmacologic treatment. This remains a difficult task, particularly since hypertension is generally asymptomatic and since any therapeutic intervention might adversely alter the patient's quality of life. Long-term persistence with antihypertensive therapy is facilated when the treatment is initiated with well tolerated antihypertensive agents, especially blockers of the renin-angiotensin system. Having a normal blood pressure during treatment is also an important determinant of persistence. This explains the growing interest for fixed-dose combinations, which have the main advantage to be at the same time efficient and well tolerated. These simple to use preparations have even gained acceptance as first-line drug regimen.

Long-term voice outcome following partial cricotracheal resection in children for severe subglottic stenosis.

OBJECTIVE: To correlate the postoperative voice outcome to preoperative glottic involvement, following partial cricotracheal resection (PCTR) in children. The glottic involvement was analysed based on the extent of subglottic stenosis (SGS) in the endoscopic image and functional dynamic assessment using flexible endoscopy. METHODS: We conducted an interobserver study in which two ENT surgeons, blinded to one another's interpretation, independently rated the extent of SGS based on the endoscopic image along with the dynamic functional airway assessment, of 108 children who underwent PCTR for grade III or IV stenosis. Based on the observation, the glottic involvement was rated into 4 categories: Evaluation of the voice was based on a parent/patient proxy questionnaire sent in 2008 to assess the current functional status of the patient's voice. RESULTS: Among the 77 patients available for long-term outcome with a minimum 1-year follow-up, 31 patients had isolated SGS free from vocal cords (group A) and 30 had SGS reaching the under surface of vocal cords with partial or no impairment of abduction of vocal cords (group B). Twelve patients belonged to group C with posterior glottic stenosis and/or vocal cord fusion (without cricoarytenoid ankylosis) and 4 patients had transglottic stenosis and or/bilateral cricoarytenoid ankylosis (group D). The long-term voice outcome following PCTR as perceived by the parent or patient was normal in 18% (14 of 77 patients) and the remaining 63 patients demonstrated mild to severe dysphonia. Patients belonging to group A and B exhibited either normal voice or mild dysphonia. Patients in group C demonstrated dysphonia, which was moderate in severity in the majority (83%). All patients in group D with transglottic stenosis and/or CAA showed severe dysphonia. CONCLUSION: Children with associated glottic involvement are at high risk for poor voice outcome following PCTR. The severity of dysphonia was found to be proportional to the preoperative glottic involvement. Preoperative rating of the extent of glottic involvement based on endoscopic image and dynamic assessment was found to be useful in prognosticating the voice outcome.

Animal Tissue Response To Mid-Term Electronic Modular Artificial Sphincter Implantation

Introduction and objectives: The AMS 800TM is considered the gold standard for sphincter replacement. However, the one-ring design can erode the urethra and lead to severe complications. A mechanism that could alternatively compress successive segments of the urethra would limit such deleterious outcome. We report 12 weeks animal urethral tissue analysis following implantation of a new modular artificial sphincter. METHODS: The device is composed by three parts: the contractile unit, two rings and an integrated microprocessor. The contractile unit is made of Nitinol fibers. The rings are placed around the urethra to control the flow of urine by squeezing the urethra. They work in a sequential alternative mode and are controlled by a microprocessor connected to an external computer. The computer can reveal specific failure of device components. The device was impkanted in eight male sheep. The rings were positioned around the urethra and the control unit was placed 5cm away. The device was working twenty hours per day; it was open 10min. per hour to allow urination. The animals were sacrificed after 12 weeks. The urethra and the tissues surrounding the control unit were macroscopically and microscopically examined. Two transversal sections crossing the sphincter and two transversal sections crossing the urethra alone were obtained and stained with modified Paragon after resin embedding. Urethra was also embedded in paraffin. The first section was stained with safranin-hematoxylin-eosin, the second section was stained with Masson's Trichrome and the remaining eight sections were available for immunolabelling of the macrophages.Results: The chronic study went uneventful. No clinical infection or pain was observed. The computer registered no specific failure in ring function, Nitinol wires and tube connectors. At explantation, except for a slight grade of lymphocytes in two out of eight specimens, no urethral stricture or atrophy could be observed. Immunohistochemistry confirmed the absence of macrophages. Tissue structure and organization of the urethra with and without artificial sphincter were similar. No migration of the device was observed.Conclusions: The study clearly showed no tissue damage or inflammation of the urethra. Electronic design, preservation of urethral vascularisation and adjustability after implantation are the key ideas to improve the actual AUS. Further studies will be carried out to evaluate this potential.

Iowa Department on Aging Office of the State Long-Term Care Ombudsman Annual Report 2009, (Federal Fiscal Year October 1, 2008 through September 30, 2009), January 2010.

The State Long-Term Care Ombudsman program operates as a unit within the Iowa Department on Aging. Duties of all long-term care ombudsmen are mandated by the Older Americans Act. This office serves people living in nursing facilities, skilled nursing facilities, residential care facilities, nursing facilities in hospitals, elder group homes and assisted living programs. In order to carry out all of the mandates of the Older Americans Act this office recommends to increase the number of staff and create a volunteer ombudsman program. NOTE: The second file includes a correction to the report on page 8.

Generation of short-term murine natural killer cell clones to analyze Ly49 gene expression.

Natural killer (NK) cellsexpress receptors specific for class I major histocompatibility complex (MHC) molecules. In the mouse, the class I specific receptors identified to date belong to the polymorphic Ly49 receptor family. Engagement of Ly49 receptors with their respective MHC ligands results in negative regulation of NK cell effector functions, consistent with a critical role of these receptors in "missing self" recognition. The Ly49 receptors analyzed so far are clonally distributed such that multiple distinct Ly49 receptors can be expressed by individual NK cells (for review see refs. 1-3). The finding that most NK cells that express the Ly49A receptor do so from a single Ly49A allele (whereby expression can occur from the maternal or the paternal chromosome) may thus reflect a putative receptor distribution process that restricts the number of Ly49 receptors expressed in a single NK cell (3-5).

Multi-modal assessment of long-term erythropoietin treatment after neonatal hypoxic-ischemic injury in rat brain.

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.