Systematic review and meta-analysis of enhanced recovery programmes in surgical patients.

BACKGROUND: Enhanced recovery programmes (ERPs) have been developed over the past 10 years to improve patient outcomes and to accelerate recovery after surgery. The existing literature focuses on specific specialties, mainly colorectal surgery. The aim of this review was to investigate whether the effect of ERPs on patient outcomes varies across surgical specialties or with the design of individual programmes. METHODS: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to January 2013 for randomized or quasi-randomized trials comparing ERPs with standard care in adult elective surgical patients. RESULTS: Thirty-eight trials were included in the review, with a total of 5099 participants. Study design and quality was poor. Meta-analyses showed that ERPs reduced the primary length of stay (standardized mean difference -1·14 (95 per cent confidence interval -1·45 to -0·85)) and reduced the risk of all complications within 30 days (risk ratio (RR) 0·71, 95 per cent c.i. 0·60 to 0·86). There was no evidence of a reduction in mortality (RR 0·69, 95 per cent c.i. 0·34 to 1·39), major complications (RR 0·95, 0·69 to 1·31) or readmission rates (RR 0·96, 0·59 to 1·58). The impact of ERPs was similar across specialties and there was no consistent evidence that elements included within ERPs affected patient outcomes. CONCLUSION: ERPs are effective in reducing length of hospital stay and overall complication rates across surgical specialties. It was not possible to identify individual components that improved outcome. Qualitative synthesis may be more appropriate to investigate the determinants of success.

The Metabolic Matrix: Re-engineering ultraprocessed foods to feed the gut, protect the liver, and support the brain.

Ultraprocessed food is established as a metabolic disruptor acting to increase adiposity, reduce mitochondrial efficiency, drive insulin resistance, alter growth, and contribute to human morbidity and mortality. Consumer packaged goods (CPG) companies are beginning to understand the detrimental impact of the food they market, and have employed substitution strategies to reduce salt, sugar, and fat. However, the harms of ultraprocessed foods are far more complex than any single component, and are not ameliorated by such simple substitutions. Over the past 2 years, the authors have worked with the Kuwaiti Danish Dairy Company (KDD) to conduct a comprehensive scientific evaluation of their entire commercial food and beverage portfolio. Assay of the macronutrients, micronutrients, additives, and toxins contained in each of their products was undertaken to determine the precise nature of each product's ingredients as well as the health impacts of processing. The authors formed a Scientific Advisory Team (SAT) and developed a tiered "Metabolic Matrix" founded in three science-based principles: (1) protect the liver, (2) feed the gut, and (3) support the brain. The Metabolic Matrix categorizes each product and provides the criteria, metrics, and recommendations for improvement or reformulation. Real-time consultation with the KDD Executive and Operations teams was vital to see these procedures through to fruition. This scientific exercise has enabled KDD to lay the groundwork for improving the health, well-being, and sustainability of their entire product line, while maintaining flavor, economic, and fiscal viability. This process is easily transferrable, and we are sharing this effort and its approaches as a proof-of-concept. The key aim of our work is to not only make ultraprocessed food healthier but to urge other food companies to implement similar analysis and reformulation of their product lines to improve the metabolic health and well-being of consumers worldwide.

The potential for underutilized crops to improve security of food production.

Staple crops face major challenges in the near future and a diversification away from over-reliance on staples will be important as part of the progress towards the goal of achieving security of food production. Underutilized or neglected crops species are often indigenous ancient crop species which are still used at some level within the local, national or even international communities, but have the potential to contribute further to the mix of food sources than they currently do. The most cost-effective and easily disseminated changes that can be made to a crop are changes to the genetics, as these are contained within the seed itself and, for many species, the seed is a pure breeding, self-replicating, resource. This article focuses on the potential of underutilized crops to contribute to food security and, in particular, whether genetics and breeding can overcome some of the constraints to the enhanced uptake of these species in the future. The focus here is on overview rather than detail and subsequent articles will examine the current evidence base.

Intraguild interactions between the entomopathogenic fungus Pandora neoaphidis and an aphid predator and parasitoid at the population scale.

The interactions that occur between the entomopathogenic fungus Pandora neoaphidis and a predator (Coccinella septempunctata) and a parasitoid (Aphidius ervi) were assessed in microcosm and polytunnel experiments. Transmission of P. neoaphidis to the pea aphid, Acyrthosiphon pisum, was enhanced in the presence of both C. septempunctata and A. ervi in microcosm experiments done under fixed abiotic conditions. In contrast, the reproductive success of A. ervi was reduced in the presence of P. neoaphidis. Despite the increased fungal transmission in the presence of C. septempunctata, there was no additional decrease in the aphid population indicating that P. neoaphidis is functionally redundant in the presence of the coccinellid. In polytunnel experiments the reproductive success of A. ervi was not affected by P. neoaphidis. These results do not support those of the microcosm and may be due to the more natural abiotic conditions in the polytunnel reducing the competitive advantage of the fungus. Microcosms therefore provide an arena in which the interactions between fungal pathogens and other aphid-natural enemies can be assessed however, further assessments at increased spatial scales under more natural abiotic conditions are also required to accurately determine the outcome of these interactions.

Phenolic content and antioxidant capacity of hybrid variety cocoa beans.

Cocoa (Theobroma cacao L.) is a major, economically important, international crop and has been associated with several nutritional benefits including high antioxidant capacity. New cocoa hybrids have been developed in Ghana that exhibit resistance to pest damage during storage. The aim of this work was to assess the phenolic content and antioxidant capacity of these new hybrids in comparison to more traditional cocoa varieties. Total extractable phenolics were similar in all the four hybrids tested ranging from 69.9 to 81.6FAEg(-1). These levels were very similar to that extracted from traditional beans (73.8±2.5FAEg(-1)). The "phenolic profile" was determined by HPLC. A total of 25 peaks was observed but there were only minor differences in this profile between traditional and hybrid bean extracts. Antioxidant capacity was determined using the FRAP assay and traditional beans were found to possess 12.4µmolTEg(-1). In comparison the hybrid beans had antioxidant capacities ranging from 21.6 to 45.5µmolTEg(-1), and these were significantly higher than in the traditional beans for three out of the four hybrids. Since the phenolic and antioxidant levels and in these hybrid varieties were either similar to, or higher than, that obtained from traditional beans, the introduction of these new varieties would be unlikely to impact detrimentally on these nutritional components of the beans.

A novel stacked generalization of models for improved TB detection in chest radiographs.

Chest x-ray (CXR) analysis is a common part of the protocol for confirming active pulmonary Tuberculosis (TB). However, many TB endemic regions are severely resource constrained in radiological services impairing timely detection and treatment. Computer-aided diagnosis (CADx) tools can supplement decision-making while simultaneously addressing the gap in expert radiological interpretation during mobile field screening. These tools use hand-engineered and/or convolutional neural networks (CNN) computed image features. CNN, a class of deep learning (DL) models, has gained research prominence in visual recognition. It has been shown that Ensemble learning has an inherent advantage of constructing non-linear decision making functions and improve visual recognition. We create a stacking of classifiers with hand-engineered and CNN features toward improving TB detection in CXRs. The results obtained are highly promising and superior to the state-of-the-art.

Use of isotopic immunoglobulin in therapy.

Antibodies raised in heterologous species against tumor-associated antigens such as ferritin and carcinoembryonic antigen may be utilized in diagnostic scanning and in cancer therapy. The radiolabeled (131I) antibodies have a mean effective half-life of 3 days. The tumor-bearing regions retain activity which was associated with objective evidence of remission in primary hepatic cancers. Major organ toxicity was not apparent in eight of nine patients treated with radioactive antibody. Objective evidence of clinical remission was documented by computer-assisted axial tomography scan remission in sequential studies that determine residual tumor in the same planar cuts. Future possible improvements in radioimmunoglobulin are discussed in light of the clinical findings.

Peak regional acceleration: a method to identify subtle regional ventricular dysfunction from gated blood pool scans at rest in patients with coronary artery disease.

Peak regional acceleration images were obtained from gated blood pool scans at rest in 10 normal subjects, 16 patients who underwent cardiac catheterization for unstable angina or nontransmural infarction and were found to have normal ejection fraction and wall motion and 10 patients with prior infarction and regional dyssynergy. The second derivative of the time-activity curve of each pixel was generated and the maximal systolic value of the derivative for each pixel was displayed as a functional image (peak regional acceleration). Anterior and left anterior oblique views were evaluated for abnormalities and the presence and location of defects were correlated with the coronary anatomy. The scans from the 10 normal subjects were used to establish the normal range for regional second derivative values. Both gated blood pool scans and second derivative images showed regional abnormalities in all 10 patients with prior transmural infarction. Regional abnormalities were present in the second derivative images in the distribution of 17 of the 20 coronary arteries with greater than 50% stenosis; there were no regional abnormalities in the distribution of 7 of the 8 arteries with less than 50% stenosis. In addition, regional second derivative image abnormalities were present in 15 of the 16 patients with unstable angina and normal wall motion and global ejection fraction. These 16 patients showed regional abnormalities on second derivative images in the distribution of 19 of the 23 coronary arteries with significant stenosis and no regional abnormalities in the distribution of 21 of the 23 coronary arteries without significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Rapid in vivo monitoring of chemotherapeutic response using weighted sodium magnetic resonance imaging.

A novel pulse sequence strategy uses sodium magnetic resonance imaging to monitor the response to chemotherapy of mouse xenograft tumors propagated from human prostate cancer cell lines. An inversion pulse suppresses sodium with long longitudinal relaxation times, weighting the image toward intracellular sodium nuclei. Comparing these weighted sodium images before and 24 h after administration of antineoplastics, we measured a 36 +/- 4% (P < 0.001; n = 16) increase in signal intensity. Experiments with these same drugs and cells, treated in culture, detected a significant intracellular sodium elevation (10-20 mM) using a ratiometric fluorescent dye. Flow cytometry studies showed that this elevation preceded cell death by apoptosis, as determined by fluorescent end-labeling of apoptotic nuclei or Annexin V binding. Histopathology on formalin-fixed sections of explanted tumors confirmed that drug administration reduces proliferation (2.2 versus 8.6 mitotic figures per high power field; P < 0.0001), an effect that inversely correlates with the sodium magnetic resonance image response on a tumor-to-tumor basis (P < 0.02; n = 10). Morphological features, such as central zones of nonviable cells, rims of active apoptosis, and areas of viable tumor, could be distinguished by comparing weighted and unweighted images. Advantages of this sodium imaging technique include rapid determination of drug efficacy, improved diagnosis of lesions, ease of coregistration with high resolution proton magnetic resonance imaging, and absence of costly or toxic reagents.

Corticosteroids for acute traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability. Corticosteroids have been widely used in treating people with traumatic brain injury. OBJECTIVES: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. SEARCH STRATEGY: Electronic sources: MEDLINE, EMBASE, Cochrane Library and specialised database searches. Additional hand searching and contact with trialists. Date of the most recent search October 2004. SELECTION CRITERIA: All randomised controlled trials of corticosteroid use in acute traumatic brain injury with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Quality of allocation concealment was scored. Data on numbers of participants randomised, numbers lost to follow up, length of follow up, case fatality rates, disablement, infections and gastrointestinal bleeds were extracted independently and checked. MAIN RESULTS: We identified 20 trials with 12303 randomised participants. The effect of corticosteroids on the risk of death was reported in 17 included trials. Due to significant heterogeneity we did not calculate a pooled estimate of the risk of death. The largest trial, with about 80% of all randomised participants, found a significant increase in the risk ratio of death with steroids 1.18 (1.09 to 1.27). For the nine trials that reported death or severe disability, the pooled relative risk was 1.01 (0.91 to 1.11), although this does not yet contain data from the largest trial. For infections the pooled risk ratio from five trials was 1.03 (0.99 to 1.07) and for the ten trials reporting gastrointestinal bleeding 1.23 (0.91 to 1.67). AUTHORS' CONCLUSIONS: In the absence of a meta-analysis, we feel most weight should be placed on the result of the largest trial. The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury.

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia.

BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy. OBJECTIVES: To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia. SEARCH STRATEGY: We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004. SELECTION CRITERIA: Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators. MAIN RESULTS: Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials. AUTHORS' CONCLUSIONS: We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.

Rapid monitoring of intraoperative cerebral blood flow using 133Xe.

This study examined the feasibility of rapid rCBF monitoring using 133Xe as a tracer during operative procedures. We compared the initial slope index derived from two bicompartmental and one monocompartmental physiological models. The single-compartment model requires only 3 min of monitoring, whereas the bicompartmental models, thought to be more reliable, require 11 min of clearance. Data were collected from 26 patients undergoing carotid endarterectomy. Approximately 20 mCi of 133Xe in saline was injected i.v. for up to five measurements per patient, for a total of 117 measurements. The robustness of the regression for the three parameters (r = 0.781-0.99, p less than 0.0001) suggests that the three parameters are closely related. This is supported by similarity of the slopes of the regression lines (between 0.944 and 1.25) and the mean +/- SD of the three rCBF models (24.9-27.5 +/- 12.0-14.3 ml 100 g-1 min-1). Similar results were obtained for individual detectors, despite the expected higher variability. For intraoperative use in surgical procedures in which physiological conditions may change rapidly and i.v. injections of tracer must be used, a rCBF index that quickly and accurately reflects flow conditions is useful. Our data suggest that the single-compartmental Wyper index may be used to provide information about cerebral perfusion that is as accurate and robust as bicompartmental models, but requires only one-quarter of the data collection time.

Optimal utilization of computerized cranial tomography and radionuclide brain imaging.

The results of computerized cranial tomography and radionuclide brain imaging in 490 patients were compared in relationship to the patients' clinical presentation. In 195 patients with focal neurologic abnormalities, both tests detected most lesions, but computerized cranial tomography was slightly more accurate overall. Results of both studies were normal in 69 percent of 295 patients with nonfocal neurologic presentations, and radionuclide imaging failed to detect lesions in only five patients with nonfocal presentations. These results suggest that radionuclide imaging can be used to accurately screen most patients with nonfocal neurologic presentations. An exception is the patient presenting with dementia, in whom computerized cranial tomography provides details of the anatomy of the ventricular cavities and cerebral cortex. This study demonstrates a continuing role of importance for radionuclide imaging in the evaluation of patients with neurologic disease and provides data to allow a rational approach to the optimum use of both techniques.

Cerebral perfusion as a diagnostic marker of early Alzheimer's disease.

Clinical diagnosis of Alzheimer's disease (AD) is not fully satisfactory, and laboratory markers of this disease are not yet established. We report substantial regional Cerebral Blood Flow (rCBF) abnormalities in patients with documented early stages of the disease, when differential diagnosis is most critical. Thirty-six patients with carefully documented clinical diagnosis of early AD (mean disease duration, 3.25 +/- 1.80 years) and 12 elderly healthy controls participated in rCBF studies using the 133Xe inhalation method. Whole-brain perfusion was significantly (p less than 0.001) lower in the AD group, and a characteristic perfusion deficit was consistently found in temporoparietal cortex of the AD patients. Discriminant analyses demonstrated over 90% correct classification of the two groups. Two subgroups of patients with mildest disease manifestations were equally well discriminated. The similarity of these findings to those in late stages, which have been validated neuropathologically, offers indirect confirmation of validity and specificity. These results suggest that rCBF procedures may provide an accurate and sensitive laboratory marker for early AD.

Correlation between computerized transaxial tomography and radionuclide cisternography in dementia.

A study of the findings on cisternograms and computerized transaxial tomography (CTT) of 144 patients showed good correlation between the two tests. Patients with a cisternographic pattern of communicating hydrocephalus tended to show more severe degrees of lateral ventricular dilation, with involvement of the third and fourth ventricles and relative sparing of the cerebral sulci. Patients with a cisternographic pattern of cerebral atrophy showed lesser degrees of lateral ventricular dilatation and more severe degrees of dilatation of the cerebral sulci. The statistical significance of the individual CTT findings in these patients is presented, and a cheme for interpretation is proposed. The study shows that CTT can replace pneumoencephalography in evaluating patients with dementia, while cisternography contributes complementary information.

A comparative evaluation of techniques for rapid and efficient in vivo labeling of red cells with [99mTc] pertechnetate.

Red blood cells (RBCs) labeled in vivo with 99mTcO4- have recently been recommended for blood-pool imaging, but the optimum conditions for in vivo labeling of RBCs have not been clearly defined. We therefore evaluated several stannous-ion preparations and stannous-ion concentrations to determine which provided the best labeling. The effect of the time interval between the Sn(II) and 99mTcO4- injections and the effect of carrier technetium on labeling efficiency were also studied. Maximal in vivo labeling efficiency was obtained using an intravenous dose of 10 microgram Sn(II)/kg followed 5-30 min later by an injection of 99mTcO4-. Neither the chelated form of stannous ion used in these studies nor the amount of carrier present had a significant effect on labeling efficiency. The biologic half-time of Tc-99m RBCs labeled in vivo was similar to that of Tc-99m RBCs labeled in vitro. In vivo labeling is a rapid and efficient method for the preparation of Tc-99m RBCs.

Effect of acute experimental pulmonary arterial occlusion on the deposition and clearance of technetium-99m-DTPA radioaerosols.

UNLABELLED: Canine models of autologous PE and balloon occlusion of the pulmonary vasculature were used to evaluate radioaerosol deposition and to quantify radioaerosol clearance in the immediate postembolic period. METHODS: A total of 28 animals were anesthetized, intubated and studied (central balloon occlusion = 4, peripheral balloon occlusion = 7, autologous PE = 5, various control groups = 12). A gamma camera computer system was used to monitor the distribution and clearance rate of inhaled DTPA radioaerosol. The perfusion defect distribution was determined after the radioaerosol study using 99mTc-MAA. RESULTS: A new radioaerosol deposition defect was seen in 3 of 16 animals in a zone of acute vascular occlusion by a balloon (n = 2) or PE (n = 1). In addition, radioaerosol clearance rates were altered substantially. Peripheral vascular occlusion and PE caused radioaerosol clearance rates to accelerate significantly (control clearance half-time = 33.6 +/- 4.6 min, post-balloon occlusion = 19.0 +/- 8.3 min, post-PE = 12.4 +/_ 3.7 min, both p < 0.05). In only one case did these clearance rate changes create a visible abnormality in the aerosol images. CONCLUSIONS: The pulmonary deposition patterns and clearance rates of 99mTc-DTPA radioaerosol can be altered by acute vascular occlusion or PE. These findings should be considered when interpreting radioaerosol images in patients with suspected PE.

The role of Ga-67 citrate imaging and diagnostic ultrasound in patients with suspected abdominal abscesses.

Fifty patients with suspected abdominal abscesses were examined by [67Ga[ Gallium citrate imaging and abdominal sonography. Fifteen of the patients had a proven intra-abdominal abscess; Gallium-67 images were positive in 13 (87%), while the sonogram detected the abscess in 11 (73%). Nineteen patients had true-negative radionuclide images and sonography, and one had a false-positive result by both procedures. The remaining 15 patients did not have abdominal abscesses, but did have other abnormalities (e.g., pyelonephritis, extra-abdominal sites of inflammation) which were detected by the nuclide study. Gallium-67 imaging and abdominal ultrasound have similar sensitivity for detection of abdominal abscesses. A significant advantage of Gallium imaging is its ability to detect other inflammatory foci (both within and outside the abdomen).