Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of 'development' and 'validation' cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

The prevalence of hazardous and harmful drinking in the UK Police Service, and their co-occurrence with job strain and mental health problems.

AIMS: Due to the stressful nature of policing, police employees are at risk of mental health problems and problematic alcohol use. We aim to determine the prevalence of hazardous and harmful alcohol use in the UK Police Service, and to explore the associations with job strain and mental health problems. METHODS: Cross-sectional data from the Airwave Health Monitoring Study (N = 40 986) included measures of alcohol consumption (total units in past week), mental health (depression, anxiety and post-traumatic stress disorder [PTSD]) and job strain. The associations between mental health and job strain with alcohol consumption (i.e. abstinence, low-risk [<14 units per week, reference group], hazardous [>14 to 35 units for women, >14 to 50 units for men], harmful [>35 units for women, >50 units for men]), were analysed using multinomial logistic regressions, adjusting for potential confounders (i.e. age, gender, ethnicity, marital status, children under 18, income and smoking status). RESULTS: A total of 32.6% of police employees reported hazardous drinking, with 3.0% drinking at harmful levels. Compared to those without a mental health problem, police employees with depression, anxiety or PTSD were twice as likely to be harmful drinkers and were also 1.3 times more likely to report abstinence. Those reporting low strain (reference group) were more likely to drink hazardously compared to those reporting high strain, which was statistically moderated by mental health. When the sample was stratified by mental health status, the association between low strain (compared to all other categories) and hazardous drinking, was significant only in those without a mental health problem. CONCLUSIONS: These findings indicate that police employees may be an occupational group at risk of alcohol harm, with one-third drinking hazardously. The J-shaped relationship between mental health and alcohol use highlights a need for an integration of mental health and alcohol services, tailored for the UK Police Service.

Activity of oxygen-versus sulfur-containing analogs of the Flex-Het anticancer agent SHetA2.

Five series of chromans with urea and thiourea linkers connecting a chroman unit (ring A) and a 4-substituted benzene unit (ring B) have been prepared and evaluated relative to SHetA2 (NSC 721689) for activity against the human A2780 ovarian cancer cell line. The lead compound SHetA2 had a sulfur in place of the oxygen in ring A and a thiourea linker to ring B. The 2-Me-4-Me series (two sets of geminal dimethyl groups at C2 and at C4 on the ring A unit) permitted direct comparison with SHetA2. Ring B in this series was evaluated with specific functional groups at C4 on the ring, including NO2, CO2Et, CF3, OCF3, CN and SO2NH2. The 2-H-4-Me series (only one geminal dimethyl group at the C4 position on ring A) permitted structure-activity relationship analysis to assess the importance of the hydrophobic geminal dimethyl groups on ring A to the activity of SHetA2. The remaining three series 2-Et-4-Me, 2-Me-4-Et and 2-Et-4-Et (ring A methyl groups replaced with ethyls at C2, at C4 and at both C2 and C4, respectively) offered the opportunity to modulate the hydrophobicity of the chroman moiety. Additionally, in all these series, the influence of a urea versus a thiourea linker was also investigated. The results of these modifications are summarized below. The exact analog of SHetA2 with oxygen substituted for sulfur in ring A (2a) showed comparable efficacy but a significantly lower IC50 against the ovarian cancer cell line. The urea linked analogs bearing CN, CF3 and OCF3 at C4 of ring B (3c,d and f) showed greater efficacy than SHetA2, but also had lower IC50 values. Removing the geminal dimethyl group at C2 (4a-c, 5a-c) caused a significant lowering of the efficacy and percent growth inhibition, indicating that the hydrophobic geminal dimethyl group at C2 in ring A is crucial for activity. Finally, replacing the geminal dimethyl groups with geminal diethyls on ring A in the urea derivatives gave 6b-c, 7c-d and 8b, all of which outperformed SHetA2 with respect to efficacy and IC50. The results for compounds 4-8 are in concurrence with modeling studies, which predicted that greater hydrophobicity in ring A would be beneficial. Binding energies were determined for compounds docked in silico to mortalin, the protein identified as a receptor of SHetA2. The urea linker promoted activity comparable to or, in some cases, greater than compounds with a thiourea linker. Several compounds achieved 94% efficacy and an IC50 of 2 µM, which were better than SHetA2 (84%, 3 µM).

Randomized clinical trial of the use of glyceryl trinitrate patches to aid arteriovenous fistula maturation.

BACKGROUND: Arteriovenous fistulas are critical for haemodialysis, but maturation rates remain poor. Experimental and anecdotal evidence has supported the use of transdermal glyceryl trinitrate (GTN) patches. The aim of this RCT was to determine whether use of a GTN patch aids arteriovenous fistula maturation. METHODS: Patients referred for arteriovenous fistula formation were eligible. The GTN or placebo patch was applied immediately after surgery and left in situ for 24 h. The primary outcome measure was the change in venous diameter at 6 weeks after fistula formation. The secondary outcome measure was clinical fistula patency at 6 weeks. RESULTS: Of 200 patients recruited (533 screened), 101 were randomized to the placebo group and 99 to the GTN group. Of these, 81 and 86 respectively completed surgery, and had follow-up data available at 6 weeks. Improvements in venous diameter were similar in the two groups: mean(s.d.) increase 2·3(1·9) mm in the placebo group compared with 2·2(1·8) mm in the GTN group (P = 0·704). The fistula failure rate did not differ significantly between the two groups: 23 per cent for placebo and 28 per cent for GTN (P = 0·596). CONCLUSION: GTN transdermal patches used for 24 h after surgery did not improve arteriovenous fistula maturation. REGISTRATION NUMBER: NCT01685710 (http://www.clinicaltrials.gov).

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer.

Selection of women for treatment-focused genetic testing (TFGT) following a new diagnosis of breast cancer is changing. Increasingly a patient's age and tumour characteristics rather than only their family history are driving access to TFGT, but little is known about the impact of receiving carrier-positive results in individuals with no family history of cancer. This study assesses the role of knowledge of a family history of cancer on psychosocial adjustment to TFGT in both women with and without mutation carrier-positive results. In-depth semistructured interviews were conducted with 20 women who had undergone TFGT, and who had been purposively sampled to represent women both family history and carrier status, and subjected to a rigorous qualitative analysis. It was found that mutation carriers without a family history reported difficulties in making surgical decisions quickly, while in carriers with a family history, a decision regarding surgery, electing for bilateral mastectomy (BM), had often already been made before receipt of their result. Long-term adjustment to a mutation-positive result was hindered by a sense of isolation not only by those without a family history but also those with a family history who lacked an affected relative with whom they could identify. Women with a family history who had no mutation identified and who had not elected BM reported a lack of closure following TFGT. These findings indicate support deficits hindering adjustment to positive TFGT results for women with and without a family history, particularly in regard to immediate decision-making about risk-reducing surgery.

Hand-assisted Laparoscopic Donor Nephrectomy and Cytokine Changes.

BACKGROUND: Laparoscopic living-donor nephrectomy (LDN) exerts systemic effects causing transaminitis and increased urinary neutrophil gelatinase-associated lipocalm (NGAL) excretion. Hand-assisted laparoscopic donor nephrectomy, which tends to be shorter with less pneumoperitoneum, may be hypothesized to produce less systemic stimulation than total laparoscopic LDN. METHODS: Serial urine and serum samples were collected from 15 patients undergoing HALDN. Samples were analyzed for NGAL and kidney injury molecule 1 (KIM-1) levels preoperatively and 24 hours post-surgery. Data relating to alanine aminotransferase, creatinine, and estimated glomerular filtration rate was also analyzed in 48 live donors preoperatively and at 24 hours and 48 hours post-surgery and compared to published data on LDN. RESULTS: Expected changes to creatinine and estimated glomerular filtration rates were observed in the donors. Compared to the preoperative levels, alanine aminotransferase levels showed a significant decrease at 24 hours (P = .004) and were not significantly different from baseline levels at 48 hours (P = .08). Serum KIM-1 and NGAL levels remained unchanged (P = .89 and P = .14, respectively) at 24 hours after donation. Similarly, urinary levels of KIM-1 and NGAL were not statistically significantly different after donation. Mean operating time for this cohort was 1 hour, 36 minutes. CONCLUSIONS: In contrast to other published data, our cohort did not exhibit changes to liver function tests or biomarker changes after donor nephrectomy. This could be because of the lower operative time (96 minutes vs. 216 minutes) or because of the intermittent release of the pneumoperitoneum in the hand-assisted method which may exert less of a systemic inflammatory response.

An apical left ventricular aneurysm rupture presenting as left breast mass 11 years after surgical repair.

Left ventricular (LV) pseudoaneurysm is a rare entity and, consequently, there is limited knowledge of the condition's natural history. The most frequent mode of presentation for LV pseudoaneurysm is heart failure with chest pain. However, the variable presentation of this condition requires a high index of suspicion for diagnosis. We report the case of a 75-year-old woman who had suffered an acute myocardial infarction 23 years previously, which resulted in a calcified LV apical aneurysm. Three weeks prior to being referred to our hospital, she was noted by her general practitioner to have a left-sided breast mass although mammography was negative. One week later, she attended the accident and emergency department; she was haemodynamically unstable but was resuscitated successfully. Contrast enhanced computed tomography showed a large haematoma located in the left chest wall communicating with the left ventricle. She underwent emergency cardiac surgical repair. On arrival at the intensive care unit following surgery, her haemodynamic status was unstable, and she deteriorated rapidly and died. With this report, we aim to raise the level of awareness for an apical LV pulsatile mass that could anatomically expand and present as a breast mass or tumour. An early diagnosis and timely surgical intervention is essential in order to achieve better outcomes and avoid detrimental complications.

Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models.

Accurate identification of sparse heterozygous single-nucleotide variants (SNVs) is a critical challenge for identifying the causative mutations in mouse genetic screens, human genetic diseases and cancer. When seeking to identify causal DNA variants that occur at such low rates, they are overwhelmed by false-positive calls that arise from a range of technical and biological sources. We describe a strategy using whole-exome capture, massively parallel DNA sequencing and computational analysis, which identifies with a low false-positive rate the majority of heterozygous and homozygous SNVs arising de novo with a frequency of one nucleotide substitution per megabase in progeny of N-ethyl-N-nitrosourea (ENU)-mutated C57BL/6j mice. We found that by applying a strategy of filtering raw SNV calls against known and platform-specific variants we could call true SNVs with a false-positive rate of 19.4 per cent and an estimated false-negative rate of 21.3 per cent. These error rates are small enough to enable calling a causative mutation from both homozygous and heterozygous candidate mutation lists with little or no further experimental validation. The efficacy of this approach is demonstrated by identifying the causative mutation in the Ptprc gene in a lymphocyte-deficient strain and in 11 other strains with immune disorders or obesity, without the need for meiotic mapping. Exome sequencing of first-generation mutant mice revealed hundreds of unphenotyped protein-changing mutations, 52 per cent of which are predicted to be deleterious, which now become available for breeding and experimental analysis. We show that exome sequencing data alone are sufficient to identify induced mutations. This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease.

Preoperative IABP in high risk patients undergoing CABG.

A recent international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care included intraoperative aortic balloon pump among the ancillary (i.e. non-surgical) drugs/techniques/strategies that might influence survival rates in patients undergoing cardiac surgery. The consensus conferences state that "Pre-operative intraoperative aortic balloon pump might reduce 30-day mortality in elective high risk patients undergoing coronary artery bypass surgery unless specifically contraindicated". The authors of this "expert opinion" presents their insights into the use of the preoperative intraoperative aortic balloon pump and conclude that based on available limited randomized controlled trials and clinical experience preoperative intraoperative aortic balloon pump saves lives in unstable patients.

Distal revascularisation with interval ligation (DRIL): an experience.

INTRODUCTION: The global increase of chronic renal failure has resulted in a growing number of patients on haemodialysis using arteriovenous fistulas (AVFs). By virtue of their very function, AVFs at times shunt blood away from regions distally, resulting in an ischaemic steal syndrome. Distal revascularisation with interval ligation (DRIL) has been described as a procedure to treat symptomatic ischaemic steal. We present our experience in the management of this complication. PATIENTS AND METHODS: Six patients with severe ischaemic steal were treated using a DRIL procedure between May 2004 and June 2007. There were three males and three females, all with elbow brachiocephalic AVFs. Symptoms ranged from severe rest pain to digital gangrene. Published results from international studies of 135 DRIL procedures were also reviewed. RESULTS: Vascular access was maintained along with the elimination of ischaemic symptoms in the six patients using an ipsilateral reversed basilic vein graft. Interval ligation of the distal brachial artery was performed at the same time. All patients showed immediate and sustained clinical improvement of symptoms with a demonstrable increase in digital pulse oximetry. CONCLUSIONS: DRIL is a beneficial treatment option that has proven successful at alleviating ischemic steal symptoms and preserving vascular access. This avoids placement of central lines, its associated risks, and the need to create an alternative sited fistula.

High glucose induced endothelial cell growth inhibition is associated with an increase in TGFbeta1 secretion and inhibition of Ras prenylation via suppression of the mevalonate pathway.

OBJECTIVE: Ras proteins are known to affect cellular growth and function. The influence of the prenylation status of Ras on the observed changes in endothelial cell growth under high glucose conditions has not previously been examined. METHODS: Human umbilical vein endothelial cells were exposed to normal or high glucose conditions for 72 h. They were then examined for proliferative and hypertrophic effects, transforming growth factor beta(1) (TGFbeta(1)) release, and phosphorylated p38 expression. The importance of prenylation was explored by the addition of mevalonate, isoprenoids or farnesyltransferase inhibitors to control the high glucose media and by measuring changes induced by high glucose and exogenous TGFbeta(1) in Ras prenylation and farnesyltransferase activity. Kidneys from diabetic rats treated with atorvastatin were also compared to specimens from untreated animals and the expression of the Ras effector p-Akt examined. RESULTS: High glucose conditions caused a reduction in cell number. This was reversed in the presence of mevalonate or farnesylpyrophosphate (FPP), suggesting that the cell growth abnormalities observed are due to high glucose induced inhibition of the mevalonate pathway and subsequent prenylation of proteins. Endothelial cells exposed to high glucose increased their secretion of TGFbeta(1) and the phosphorylation of p38 both of which were reversed by concurrent exposure to FPP. A reduction in farnesyltransferase activity was observed after exposure to both high glucose and TGFbeta(1). Exposure to a farnesyltransferase inhibitor in control conditions mimicked the growth response observed with high glucose exposure and prenylated Ras was reduced by exposure to both high glucose and TGFbeta(1). Finally, interruption of the mevalonate pathway with a statin reduced the expression of p-Akt in diabetic rat kidneys. CONCLUSION: This study demonstrates that high glucose induced significant alterations in endothelial cell growth by inhibition of the mevalonate pathway, which subsequently mediates the increase in TGFbeta(1) and inhibition of Ras prenylation.

A stuck hemodialysis central venous catheter.

BACKGROUND: A growing number of hemodialysis patients are dependent upon central venous catheters (CVCs) for long-term vascular access. Although many complications of CVCs have been documented, the phenomenon of the stuck catheter is described relatively infrequently. CASE REPORT: We describe a case where attempts to remove the line by exploration of the jugular insertion site in theater were unsuccessful and the line was internalized. DISCUSSION: The case is then discussed with all available cases in the literature to suggest principles of managing and preventing the stuck catheter phenomenon.

Do the affective properties of smoking-related cues influence attentional and approach biases in cigarette smokers?

Research indicates that drug-related cues elicit attention and approach biases in drug users. However, attentional biases are not unique to addiction (e.g., they are also found for emotional information). This study examined whether attentional and approach biases in cigarette smokers are mediated by the motivational salience of cues (relevance to drug-taking), rather than by their affective properties (subjective liking of the cues). Cues included pleasant and unpleasant smoking-related pictures. Attentional biases, approach tendencies and subjective evaluation of the cues were assessed on visual probe, stimulus-response compatibility and rating tasks, respectively. Compared with non-smokers, smokers showed a greater attentional bias for both pleasant and unpleasant smoking-related cues presented for 2000 ms, but not for 200 ms. Smokers showed a greater approach bias for unpleasant cues, although the groups did not differ significantly in approach bias for pleasant smoking-related cues. Smokers rated both pleasant and unpleasant smoking pictures more positively than did non-smokers. Results suggest that a bias to maintain attention on smoking-related cues in young adult smokers is primarily a function of drug-relevance, rather than affective properties, of the cues. In contrast, approach tendencies and pleasantness judgements were influenced by drug use, drug-relevance and the affective properties of the cues.

Relationships between personal, indoor, and outdoor exposures to trace elements in PM(2.5).

Twenty-four hour average fine particle concentrations of 23 trace elements (TEs) were measured concurrently in (a) ambient air in three urban neighborhoods (Battle Creek-BCK; East St. Paul-ESP; and Phillips-PHI), (b) air inside residences of participants, and (c) personal air near the breathing zone of healthy, non-smoking adults. The outdoor (O), indoor (I), and personal (P) samples were collected in the Minneapolis/St. Paul metropolitan area over three seasons (Spring, Summer, Fall) using either the federal reference (O) or inertial impactor (I,P) inlets to collect PM(2.5). In addition to descriptive statistics, a hierarchical, mixed-effects statistical model was used to estimate the mutually adjusted effects of monitor location, community, and season on mean differences between monitoring locations while accounting for within-subject and within-monitoring period correlation. The relationships among P, I, and O concentrations varied across TEs. The O concentrations were usually higher than P or I for elements like Ca and Al that originate mainly from entrained crustal material, while P concentrations were often highest for other elements with non-crustal sources. Unadjusted mixed model results demonstrated that O monitors more frequently underestimated than overestimated P TE exposures for elements associated with non-crustal sources. This finding was true even though the O TE measurements were taken in the same neighborhoods as the P and I measurements. Further adjustment for community or season effects in the mixed models reduced the number of significant O-P and O-I differences compared to unadjusted models, but still indicated a tendency for underestimation of personal and indoor TE exposures by central site monitors, particularly in the PHI community. These results indicate that community and season are important covariates for developing long term TE exposure estimates, and that personal exposure to trace elements in PM(2.5) is likely to be underestimated by outdoor central site monitors.

Quantification of the rat spinal microglial response to peripheral nerve injury as revealed by immunohistochemical image analysis and flow cytometry.

Microgliosis is implicated in the pathophysiology of several neurological disorders, including neuropathic pain. Consequently, perturbation of microgliosis is a mechanistic and drug development target in neuropathic pain, which highlights the requirement for specific, sensitive and reproducible methods of microgliosis measurement. In this study, we used the spinal microgliosis associated with L5 spinal nerve transection and minocycline-induced attenuation thereof to: (1) evaluate novel software based semi-quantitative image analysis paradigms for the assessment of immunohistochemical images. Microgliosis was revealed by immunoreactivity to OX42. Several image analysis paradigms were assessed and compared to a previously validated subjective categorical rating scale. This comparison revealed that grey scale measurement of the proportion of a defined area of spinal cord occupied by OX42 immunoreactive cells is a robust image analysis paradigm. (2) Develop and validate a flow cytometric approach for quantification of spinal microgliosis. The flow cytometric technique reliably quantified microgliosis in spinal cord cell suspensions, using OX42 and ED9 immunoreactivity to identify microglia. The results suggest that image analysis of immunohistochemical revelation of microgliosis reliably detects the spinal microgliosis in response to peripheral nerve injury and pharmacological attenuation thereof. In addition, flow cytometry provides an alternative approach for quantitative analysis of spinal microgliosis elicited by nerve injury.

Preoperative intra aortic balloon pumps in patients undergoing coronary artery bypass grafting.

BACKGROUND: The intra aortic balloon pump (IABP) is a mechanical assist device which improves cardiac function. The device has a well-established place in algorithms for managing low cardiac output following cardiac surgery. There is increasing evidence that certain cardiac surgery patients benefit from a period of preoperative augmentation with the intra aortic balloon pump. OBJECTIVES: To determine the effect of the preoperative intra aortic balloon pump on mortality and morbidity in a number of different patients groups undergoing coronary artery bypass grafting. SEARCH STRATEGY: Searches were performed of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1 2005), MEDLINE (2000-2005) and EMBASE (1998-2005). No language restrictions were applied. SELECTION CRITERIA: Randomised or controlled trials of any size or length were included. DATA COLLECTION AND ANALYSIS: Papers were assessed for inclusion by two reviewers independently. Differences were settled by consensus with a third reviewer. Data were extracted and entered into RevMan 4.1, through which a meta-analysis of the data was performed. MAIN RESULTS: Five randomised controlled trials were identified from a total of 765 studies (4 on-pump and 1 off-pump). Data from a total of 193 patients were included in the meta-analysis; all on-pump. Generally, the patients were designated as "high risk" . 105 patients were treated preoperatively with IABP and 88 patients served as controls. There were three hospital deaths in the intervention arm and 18 in the non-intervention arm (odds ratio (OR) 0.16; 95% confidence intervals (CI): 0.06 to 0.4; P<0.0001). Low cardiac index (<2.0 L/min/m2) was noted in 21 out of 105 patients in the treatment arm and 59 patients out of 88 in the non-treatment arm (OR 0.14; 95% CI: 0.08 to 0.25; P<0.00001). A large proportion of the control group had an IABP inserted postoperatively for low cardiac index (52 out of 88). An off-pump versus on-pump analysis was not possible due to the limited number of off-pump studies. However a single well-conducted randomised controlled trial suggested favourable effect of the preoperative IABP in off-pump patients. AUTHORS' CONCLUSIONS: Available evidence suggests the preoperative intra aortic balloon pump may have a beneficial effect on mortality and morbidity in specific high risk patient groups undergoing coronary artery bypass grafting, however, the randomised evidence is from a number of small trials, with a high proportion of unstable patients, recruited at a single institution.

True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is considered to be the gold standard alternative treatment for severe obesity. Weight loss after RYGB results primarily from decreased food intake. Inadequate calcium (Ca) intake and metabolic bone disease can occur after gastric bypass. To our knowledge, whether malabsorption of Ca contributes to an altered Ca metabolism in the RYGB patient has not been addressed previously. RESEARCH METHODS AND PROCEDURES: We recruited 25 extremely obese women in order to study true fractional Ca absorption (TFCA) before and 6 months after RYGB surgery, using a dual stable isotope method ((42)Ca and (43)Ca) and test load of Ca (200 mg). Hormones regulating Ca absorption and markers of bone turnover were also measured. RESULTS: In 21 women (BMI 52.7 +/- 8.3 kg/m(2), age 43.9 +/- 10.4 years) who successfully completed the study, TFCA decreased from 0.36 +/- 0.08 to 0.24 +/- 0.09 (p < 0.001) after RYGB. Bone turnover markers increased significantly (p < 0.01). TFCA correlated with estradiol levels (r = 0.512, p < 0.02) and tended to correlate with 1,25 (OH)(2)D (r = 0.427, p < 0.06) at final measurement. Stepwise linear regression indicated that estradiol explained 62% of the variance for TFCA at 6 months post-surgery (p < 0.01). DISCUSSION: TFCA decreases (0.12 +/- 0.08) after RYGB surgery but remains within normal range. Although only some patients were estimated to have low Ca absorption after surgery, all of the patients showed a dramatic increase in markers of bone resorption. The alteration in Ca metabolism after RYGB-induced weight loss appears to be regulated primarily by estradiol levels and might ultimately affect bone mass.