The impact of flow PRA on outcome in pediatric heart recipients in modern era: An analysis of the Pediatric Heart Transplant Study database.

Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA > 20%. Patients with a PRA > 20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%. Patients with higher PRA% determined by SPA were predictive of a positive retrospective cross-match determined by flow cytometric method (P < .001). A PRA > 50% determined by SPA was independently associated with worse overall graft survival after first month of transplant in both unadjusted and adjusted for all other risk factors. In this large multicenter series of pediatric heart transplant recipients, an elevated PRA determined by SPA remains a significant risk factor in the modern era.

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Evidence for the improvement of fatigue in fibromyalgia: A 4-week left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation randomized-controlled trial.

BACKGROUND: Fibromyalgia is a complex chronic disorder with few effective treatments currently available. One promising treatment option is repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique that has shown promise in disorders effecting the central nervous system. METHODS: We assessed the efficacy of a course of high-frequency (10 Hz) left-hemisphere dorsolateral prefrontal cortex (DLPFC) rTMS in 26 patients (14 active; 12 sham) with a diagnosis of fibromyalgia. Participants underwent a double-blind stimulation protocol of daily (Monday-Friday) rTMS sessions over four consecutive weeks (total of 20 sessions; 75 × 4-s 10 Hz trains at 120% resting motor threshold). Assessments were conducted at baseline, 4 weeks and at 1-month follow-up. RESULTS: Using mixed-model analysis we did not identify a group difference for our primary outcome measures. However, we found that patients in the active group compared to sham treatment group had significantly greater improvement in the Physical Fatigue (p = 0.045) and General Fatigue (p = 0.023) scales of the Multidimensional Fatigue Inventory-20 at the 1 month follow-up. In a responder analysis, we also found the active group was significantly more likely (2.84 times) to achieve a minimum 30% improvement in pain intensity ratings. (p = 0.024). CONCLUSIONS: High-frequency rTMS applied daily for 4 weeks to the left DLPFC induces significant relief from fatigue and a greater chance of clinically meaningful improvement in pain intensity in patients with fibromyalgia. These results suggest DLPFC rTMS may be a relevant therapy for fibromyalgia. SIGNIFICANCE: This study provides evidence that 4-weeks of daily rTMS to the left DLPFC is able to improve fatigue in fibromyalgia. This novel finding provides impetus for the further investigation of the utility of TMS approaches for the relief of fatigue, an otherwise difficult-to-treat symptom, in fibromyalgia and related disorders.

Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma.

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients.

CSP #221 is a randomized multiinstitutional clinical trial to assess the efficacy of 10 d of perioperative total parenteral nutrition (TPN) in reducing morbidity and mortality in malnourished patients undergoing intraperitoneal and/or intrathoracic operations. In this paper a detailed protocol for the clinical efficacy trial is presented primarily as a reference document for use in interpretation of the results of the clinical trial. It is also anticipated, however, that review of this protocol may be useful to other investigators planning future clinical nutrition intervention trials.

Are activated clotting times helpful in the management of anticoagulation with subcutaneous low-molecular-weight heparin?

BACKGROUND: Enoxaparin has recently been shown to be superior to unfractionated heparin in patients with unstable angina/non-ST-elevation myocardial infarction. Theoretical advantages of low-molecular-weight heparin versus unfractionated heparin include a higher ratio of anti-Xa to anti-IIa activity (3:1 for enoxaparin), a more predictable dose response that precludes the need for frequent monitoring, and the convenience of subcutaneous administration. Both activated partial thromboplastin time and activated clotting time (ACT) are used to monitor anticoagulation with heparin, and ACTs are now standard during percutaneous coronary intervention (PCI) with heparin. At doses of up to 90 mg, subcutaneous enoxaparin leads to a modest dose-related increase in activated partial thromboplastin time, but the effect on ACT is unknown. METHODS: Thrombolysis In Myocardial Infarction (TIMI) 11A was a multicenter, dose-ranging trial to evaluate the safety and tolerability of subcutaneous enoxaparin in patients with unstable angina/non-ST-elevation myocardial infarction. We obtained peak (mean 4.3 hours after enoxaparin) and trough (mean 11.5 hours after enoxaparin) anti-Xa levels and ACTs for 26 patients in the TIMI 11A trial. RESULTS: Despite doses of enoxaparin in the range of 89 +/- 19 mg every 12 hours and significant increases in anti-Xa levels even at trough, there was no change in the ACT measured by HemoTec and only a small increase with Hemachron. The correlation of peak Hemachron ACT with peak anti-Xa levels was poor (R = 0.5, P =.08). CONCLUSIONS: In contrast to heparin, ACTs are not useful for assessment of anticoagulation with subcutaneous enoxaparin and should not be relied on in patients receiving enoxaparin who require acute PCI. Studies to determine the optimal dose, safety, and efficacy of enoxaparin in patients undergoing PCI are underway.

Characterizing the peak in the cosmic microwave background angular power spectrum

A peak has been unambiguously detected in the cosmic microwave background angular spectrum. Here we characterize its properties with fits to phenomenological models. We find that the TOCO and BOOM/NA data determine the peak location to be in the range 175-243 and 151-259, respectively (at 95% confidence) and determine the peak amplitude to be between approximately 70 and 90 &mgr;K. The peak shape is consistent with inflation-inspired flat, cold dark matter plus cosmological constant models of structure formation with adiabatic, nearly scale invariant initial conditions. It is inconsistent with open models and presents a great challenge to defect models.

Annihilating cold dark matter

Structure formation with cold dark matter (CDM) predicts halos with a central density cusp, which are observationally disfavored. If CDM particles have an annihilation cross section sigmav approximately 10(-29)(m/GeV) cm(2), then annihilations will soften the cusps. We discuss plausible scenarios for avoiding the early Universe annihilation catastrophe that could result from such a large cross section. The predicted scaling of core density with halo mass depends upon the velocity dependence of sigmav, and s-wave annihilation leads to a core density nearly independent of halo mass, which seems consistent with observations.

Energy expenditure in malnourished patients with colorectal cancer.

To evaluate energy expenditure in patients who have colorectal cancer with varying stages of disease and to examine the possible determinants of energy expenditure in a group of patients with cancer who have the same type of tumor, we studied 73 patients with biopsy proven and pathologically staged adenocarcinomas of the colon and rectum. Resting energy expenditure (REE) was measured by indirect calorimetry and compared with predicted energy expenditure (PEE), which was calculated from the Harris-Benedict formulas. Nutritional and tumor characteristics were examined. Forty-nine percent of patients had abnormal REE (normal = PEE +/- 10%). One quarter of the patients were hypometabolic (REE less than 90% PEE). The abnormalities persisted despite normalization of REE to metabolic body size (kg0.75) or predicted values based on weight, height, age, and sex. There were no differences in nutritional status, as judged by the percent of weight loss and visceral protein levels, between those patients in the hypometabolic, normometabolic, or hypermetabolic categories, and there were no significant relationships between energy expenditure and the tumor burden. The mean duration of disease in the normometabolic group was 4.5 months, while the hypometabolic and hypermetabolic groups had mean durations of 9.5 and 14.2 months, respectively. The tumor site and duration of the disease are important variables in studies of energy expenditure in patients with cancer.

Treatment effects of parenteral vitamins in total parenteral nutrition patients.

To determine the prevalence of abnormal vitamin levels in an adult hospitalized population requiring total parenteral nutrition (TPN) and to assess the effect of routine parenteral vitamin therapy on vitamin levels, we studied 35 general surgical patients. Assays for 12 vitamins were performed both before and after a standard 10-day course of TPN. Patients were given nothing by mouth. The first 25 patients received a daily parenteral vitamin mixture tailored to the recommendations of the Nutrition Advisory Group of The American Medical Association (maintenance dose). The final 10 patients were given a parenteral multivitamin dose providing substantially greater amounts of most vitamins (repletion dose). Only 58% (190/324) of pre-TPN vitamin levels were normal, 25% were low, and 17% were high. No patient had fewer than two abnormal baseline levels. Vitamin levels did not correlate with serum albumin, body weight, or nitrogen balance. After 10 days of treatment, only 39% of low pre-TPN vitamin levels improved; most (45/62) of the low posttreatment levels were low at baseline. The higher repletion dose resulted in a significantly (p less than 0.01) greater percent increase in vitamin A, C, and pyridoxine levels. The prevalence of abnormal vitamin levels in this population is high (42%). Standard parenteral vitamin therapy leads to marginal improvement in abnormally low pre-TPN vitamin levels.

Repair of congenital sternal clefts in adolescence and infancy.

Two cases of sternal cleft not associated with ectopia cordis are presented. An 11-year-old girl with a superior incomplete sternal cleft underwent reconstruction of the sternum with autologous rib, cartilage, and sternal periosteum. At the 1-year follow-up her sternal appearance was normal. The second patient, a full-term baby girl, had complete sternal cleft diagnosed by ultrasonography at 21 weeks' gestation. She underwent primary repair in the neonatal period and currently is asymptomatic with a normal-appearing sternum (10 months postoperatively). Primary repair in the neonatal period is the best type of management for this rare condition. For older patients, autologous repair is appropriate and avoids problems associated with the use of prosthetic materials.

Effect of route of administration and age on the pharmacokinetics of amikacin administered by the intravenous and intraosseous routes to 3 and 5-day-old foals.

The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly different from the mean +/- sd peak concentration (32.92 +/- 2.63 micrograms/ml) achieved after i.v. administration. The plasma amikacin concentration-time profiles for the i.o. and i.v. routes were not different and both were appropriately described by a 2-compartment open pharmacokinetic model. No significant differences attributable to route of administration were found in values for the major pharmacokinetic variables. The degree of inter-individual variation in values for indices of clearance was considerably greater than the degree of variation attributable to age. Despite this, values for body clearance (ClB) were significantly higher (P < 0.05) and values for area under the plasma amikacin concentration-time curve (AUC) and concentration of amikacin in plasma at 8 h [Cp(8h)] were significantly lower in 5- than in 3-day-old foals, indicating that amikacin was more rapidly cleared by the older foals. Technical difficulties were not encountered during i.o. needle placement in the medial aspect of the proximal tibia. Mild diffuse soft tissue swelling which developed at the i.o. site resolved completely within 1-2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative swab culture versus tissue biopsy: a comparison in chronic wounds.

Soft tissue infection present a significant obstacle to the healing of chronic wounds. Historically, the gold standard for determining wound bacterial bioburden has been the quantitative tissue biopsy. Nevertheless, tissue biopsies are not universally used in today's healthcare setting. Likely reasons include damage to healing tissue, the lack of facilities to process tissue biopsies, significant pain in sensate soft tissue, and increased expense with this modality. More recently, quantitative tissue swab culture has been suggested as a means to determine the wound bioburden. The authors prospectively studied 38 patients with chronic wounds of various etiologies to evaluate the correlation between quantitative wound biopsy and swab culture. Of the 38 biopsies performed, 74% indicated infection. Simultaneous swab culture of these 28 biopsies indicated infection in 22 of the 28 cases for a correlation of 79%. The authors concluded that quantitative swab culture provides a valuable adjunct in the management of chronic wounds.

Ethics and nutritional support in the intensive care unit.

Provision of nutrition and hydration through artificial means is an invasive medical intervention. As such, procedures for supplying nutrition and hydration impose burdens as well as provide benefits and may, under certain circumstances, be foregone. However, in the intensive care unit, the needs of most patients are best served by providing nutritional support. For many critically ill patients, the long-term prognosis and potential for response to treatment are uncertain. For these reasons, the presumption should be in favor of providing nutrition and hydration.

Ethical issues in nutritional support nursing. Withholding and withdrawing nutritional support.

A new and controversial debate in bioethics concerns the question, "Is it ever acceptable to withhold or withdraw specialized nutritional support from the dying adult patient?" In the opinion of many, the answer to this question is yes, but for only a very small number of patients. Provision of nutrition through artificial means is an invasive medical intervention. As such, procedures for supplying nutritional support impose burdens as well as provide benefits and may, under certain circumstances, be foregone. However, the needs of the vast majority of dying patients will best be served by providing specialized nutritional support.