Overall readmissions and readmissions related to dehydration after creation of an ileostomy: a systematic review and meta-analysis.

BACKGROUND: Hospital readmissions after creation of an ileostomy are common and come with a high clinical and financial burden. The aim of this review with pooled analysis was to determine the incidence of dehydration-related and all-cause readmissions after formation of an ileostomy, and the associated costs. METHODS: A systematic literature search was conducted for studies reporting on dehydration-related and overall readmission rates after formation of a loop or end ileostomy between January 1990 and April 2021. Analyses were performed using R Statistical Software Version 3.6.1. RESULTS: The search yielded 71 studies (n = 82,451 patients). The pooled incidence of readmissions due to dehydration was 6% (95% CI 0.04-0.09) within 30 days, with an all-cause readmission rate of 20% (CI 95% 0.18-0.23). Duration of readmissions for dehydration ranged from 2.5 to 9 days. Average costs of dehydration-related readmission were between $2750 and $5924 per patient. Other indications for readmission within 30 days were specified in 15 studies, with a pooled incidence of 5% (95% CI 0.02-0.14) for dehydration, 4% (95% CI 0.02-0.08) for stoma outlet problems, and 4% (95% CI 0.02-0.09) for infections. CONCLUSIONS: One in five patients are readmitted with a stoma-related complication within 30 days of creation of an ileostomy. Dehydration is the leading cause for these readmissions, occurring in 6% of all patients within 30 days. This comes with high health care cost for a potentially avoidable cause. Better monitoring, patient awareness and preventive measures are required.

The Moondance Bowel Cancer Project schools initiative.

BACKGROUND: The 5-year survival rate for bowel cancer in Wales is poor and lags behind the rest of the UK. The aim of the pilot phase of the Moondance Schools Initiative was to develop, deliver and assess a bowel cancer learning module for secondary school students in South Wales. Ultimately, we aim to introduce this programme into the National Curriculum across Wales. METHODS: Two programmes regarding bowel cancer and screening were designed and delivered to a cohort of secondary school pupils in South Wales. This involved interactive teaching with patients and clinicians, practical sessions and live-streamed videos of bowel cancer surgery. Feedback regarding the events and bowel screening was collected from students and their families. RESULTS: The programmes were delivered to 185 secondary school students and feedback was extremely positive. The students delivered a live event at the end of the programme to demonstrate their learning to their families and invited guests. Feedback from family members revealed that 100% of respondents were more likely to take a bowel screening test as a result of attending the event. CONCLUSION: This project established that a pilot to create young bowel screening ambassadors is feasible and was positively received by students, their families and the local community. Future work will disseminate the programme further and correlate changes in bowel screening participation in the local area as a result of these events.

Impact of a defunctioning ileostomy and time to stoma closure on bowel function after low anterior resection for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Impaired bowel function after low anterior resection (LAR) for rectal cancer is a frequent problem with a major impact on quality of life. The aim of this study was to assess the impact of a defunctioning ileostomy, and time to ileostomy closure on bowel function after LAR for rectal cancer. METHODS: We performed a systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Comprehensive literature searches were conducted using PubMed, Embase and Cochrane databases for articles published from 1989 up to August 2019. Analysis was performed using Review Manager (version 5.3) using a random-effects model. RESULTS: The search yielded 11 studies (1400 patients) that reported on functional outcome after LAR with at least 1 year follow-up, except for one study. Five scales were used: the Low Anterior Resection Syndrome (LARS) score, the Wexner score, the Memorial Sloan Kettering Cancer Centre Bowel Function Instrument, the Fecal Incontinence Quality of Life scale, and the Hallbook questionnaire. Based on seven studies, major LARS occurred more often in the ileostomy group (OR 2.84, 95% CI, 1.70-4.75, p < 0.0001: I2 = 60%, X2 = 0.02). Based on six studies, a longer time to stoma closure increased the risk of major LARS with a mean difference in time to closure of 2.39 months (95% CI, 1.28-3.51, p < 0.0001: I2 = 21%, X2 = 0.28) in the major vs. no LARS group. Other scoring systems could not be pooled, but presence of an ileostomy predicted poorer bowel function except with the Hallbook questionnaire. CONCLUSIONS: The risk of developing major LARS seems higher with a defunctioning ileostomy. A prolonged time to ileostomy closure seems to reinforce the negative effect on bowel function; therefore, early reversal should be an important part of the patient pathway.

Where have all the appendicectomies gone?

INTRODUCTION: The COVID-19 pandemic stimulated a national lockdown in the UK. The public were advised to avoid unnecessary hospital attendances and health professionals were advised to avoid aerosol-generating procedures wherever possible. The authors hypothesised that these measures would result in a reduction in the number of patients presenting to hospital with acute appendicitis and alter treatment choices. METHODS: A multicentred, prospective observational study was undertaken during April 2020 to identify adults treated for acute appendicitis. Searches of operative and radiological records were performed to identify patients treated during April 2018 and April 2019 for comparison. RESULTS: A total of 190 patients were treated for acute appendicitis pre-lockdown compared with 64 patients treated during lockdown. Patients treated during the pandemic were more likely to have a higher American Society of Anesthesiology (ASA) score (p = 0.049) and to have delayed their presentation to hospital (2 versus 3 days, p = 0.03). During the lockdown, the use of computed tomography (CT) increased from 36.3% to 85.9% (p < 0.001), the use of an antibiotic-only approach increased from 6.2% to 40.6% (p < 0.001) and the rate of laparoscopic appendicectomy reduced from 85.3% to 17.2% (p < 0.001). The negative appendicectomy rate decreased from 21.7% to 7.1% during lockdown (p < 0.001). CONCLUSIONS: The COVID-19 lockdown was associated with a decreased incidence of acute appendicitis and a significant shift in the management approach. The increased use of CT allows the identification of simple appendicitis for conservative treatment and decreases the negative appendicectomy rate.

The management of adult appendicitis during the COVID-19 pandemic: an interim analysis of a UK cohort study.

BACKGROUND: Acute appendicitis (AA) is the most common general surgical emergency. Early laparoscopic appendicectomy is the gold-standard management. SARS-CoV-2 (COVID-19) brought concerns of increased perioperative mortality and spread of infection during aerosol generating procedures: as a consequence, conservative management was advised, and open appendicectomy recommended when surgery was unavoidable. This study describes the impact of the first weeks of the pandemic on the management of AA in the United Kingdom (UK). METHODS: Patients 18 years or older, diagnosed clinically and/or radiologically with AA were eligible for inclusion in this prospective, multicentre cohort study. Data was collected from 23rd March 2020 (beginning of the UK Government lockdown) to 1st May 2020 and included: patient demographics, COVID status; initial management (operative and conservative); length of stay; and 30-day complications. Analysis was performed on the first 500 cases with 30-day follow-up. RESULTS: The patient cohort consisted of 500 patients from 48 sites. The median age of this cohort was 35 [26-49.75] years and 233 (47%) of patients were female. Two hundred and seventy-one (54%) patients were initially treated conservatively; with only 26 (10%) cases progressing to an operation. Operative interventions were performed laparoscopically in 44% (93/211). Median length of hospital stay was significantly reduced in the conservatively managed group (2 [IQR 1-4] days vs. 3 [2-4], p < 0.001). At 30 days, complications were significantly higher in the operative group (p < 0.001), with no deaths in any group. Of the 159 (32%) patients tested for COVID-19 on admission, only 6 (4%) were positive. CONCLUSION: COVID-19 has changed the management of acute appendicitis in the UK, with non-operative management shown to be safe and effective in the short-term. Antibiotics should be considered as the first line during the pandemic and perhaps beyond.

Safe management of surgical smoke in the age of COVID-19.

BACKGROUND: The COVID-19 global pandemic has resulted in a plethora of guidance and opinion from surgical societies. A controversial area concerns the safety of surgically created smoke and the perceived potential higher risk in laparoscopic surgery. METHODS: The limited published evidence was analysed in combination with expert opinion. A review was undertaken of the novel coronavirus with regards to its hazards within surgical smoke and the procedures that could mitigate the potential risks to healthcare staff. RESULTS: Using existing knowledge of surgical smoke, a theoretical risk of virus transmission exists. Best practice should consider the operating room set-up, patient movement and operating theatre equipment when producing a COVID-19 operating protocol. The choice of energy device can affect the smoke produced, and surgeons should manage the pneumoperitoneum meticulously during laparoscopic surgery. Devices to remove surgical smoke, including extractors, filters and non-filter devices, are discussed in detail. CONCLUSION: There is not enough evidence to quantify the risks of COVID-19 transmission in surgical smoke. However, steps can be undertaken to manage the potential hazards. The advantages of minimally invasive surgery may not need to be sacrificed in the current crisis.

Psychological sequelae of colonic resections.

AIM: The prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population has been estimated to be 5.9%, 3.3% and 4.4% respectively. The aim of this study was to determine whether psychological problems are more prevalent following colorectal surgery. METHOD: Patients who had undergone colorectal resection in a 2-year period across four centres were asked to complete validated screening questionnaires for anxiety, depression and PTSD (GAD-7, PHQ-9, PCL-5) 12-48 months after surgery. Risk factors were identified using multiple linear regression analysis. RESULTS: After excluding those who had died or received palliative diagnoses, questionnaires were sent to 1150 patients. 371 responded (32.3% response rate); median age 67 (20-99) years; 51% were men. 58% of patients underwent surgery for cancer; 23% had emergency surgery. 28% of patients screened positive for at least one psychological condition, with 20% screening positive for anxiety, 22% for depression and 14% for PTSD. Patients who were younger, women, had surgery as an emergency, for benign conditions, had stomas and had critical care stay were more likely to have poorer psychological outcomes. Multiple linear regression found that only younger age (P = 0.000) and female gender (P = 0.048) were significant risk factors. CONCLUSION: The prevalence of anxiety, depression and PTSD appears to be high in patients who have undergone colorectal surgery. Younger patients and women are particularly at risk. Further work is needed to determine how best to prevent, detect and treat people with adverse psychological outcomes following colorectal surgery.

Altered N-methyl D-aspartate receptor subunit expression causes changes to the circadian clock and cell phenotype in osteoarthritic chondrocytes.

The chondrocyte circadian clock is altered in osteoarthritis. This change is implicated in the disease-associated changes in chondrocyte phenotype and cartilage loss. Why the clock is changed is unknown. N-methyl-D-aspartate receptors (NMDAR) are critical for regulating the hypothalamic clock. Chondrocytes also express NMDAR and the type of NMDAR subunits expressed changes in osteoarthritis. OBJECTIVE: To determine if NMDAR regulate the chondrocyte clock and phenotype. DESIGN: Chondrocytes isolated from macroscopically-normal (MN) and osteoarthritic human cartilage were treated with NMDAR antagonists or transfected with GRIN2A or GRIN2B-targetting siRNA. H5 chondrocytes were transfected with GluN2B-expression plasmids. Clock genes and chondrocyte phenotypic markers were measured by RT-qPCR. RESULTS: PER2 amplitude was higher and BMAL1 amplitude lower in osteoarthritic compared to MN chondrocytes. In osteoarthritic chondrocytes, NMDAR inhibition restored PER2 and BMAL1 expression to levels similar to MN chondrocytes, and resulted in reduced MMP13 and COL10A1. Paradoxically, NMDAR inhibition in MN chondrocytes resulted in increased PER2, decreased BMAL1 and increased MMP13 and COL10A1. Osteoarthritic, but not MN chondrocytes expressed GluN2B NMDAR subunits. GluN2B knockdown in osteoarthritic chondrocytes restored expression of circadian clock components and phenotypic markers to levels similar to MN chondrocytes. Ectopic expression of GluN2B resulted in reduced BMAL1, increased PER2 and altered SOX9, RUNX2 and MMP13 expression. Knockdown of PER2 mitigated the effects of GluN2B on SOX9 and MMP13. CONCLUSIONS: NMDAR regulate the chondrocyte clock and phenotype suggesting NMDAR may also regulate clocks in other peripheral tissues. GluN2B expression in osteoarthritis may contribute to pathology by altering the chondrocyte clock.

Acceptability and benefit of rectal irrigation in patients with Low Anterior Resection Syndrome: a qualitative study.

AIM: Low Anterior Resection Syndrome (LARS) following rectal cancer surgery impairs the patient's quality of life (QoL). Rectal Irrigation has been demonstrated to be effective for anterior resection syndrome but many surgeons do not suggest it as a treatment. This feasibility study aimed to explore treatment acceptability and the benefit of rectal irrigation in patients who developed LARS following an anterior resection for rectal cancer. METHODS: This was a qualitative study, involving semi-structured interviews. Twenty-one patients diagnosed with LARS following anterior resection for rectal cancer in a single tertiary centre were offered rectal irrigation as a treatment option. Qualitative interviews (n=17) were conducted at baseline to explore patient reported impact of LARS on QoL, treatment acceptability and factors influencing the decision to accept/decline treatment. Follow up interviews were carried out at six months for the treatment group only (n=12), to assess its practicality and impact on QoL. RESULTS: Qualitative interview findings suggest rectal irrigation is an acceptable method of treatment for LARS. Participants who perceived their symptoms to be more severe or poorly controlled were most likely to consider rectal irrigation as a treatment option. The patients who completed treatment reported improvements in their QoL, the ability to control the time of defaecation being the key benefit CONCLUSION: Clinicians should consider offering rectal irrigation as a treatment option to patients presenting with bowel dysfunction following anterior resection as it can improve symptoms. Patients who perceive that their symptoms are severe are more likely to consider treatment. This article is protected by copyright. All rights reserved.

Development of organic solvent-free micro-/nano-porous polymer scaffolds for musculoskeletal regeneration.

The use of biomaterial scaffolds has been an enormous field of research in tissue engineering, where the aim is to use graft materials for assisting the human body in recovering lost functions. Currently, there are many ways biomaterial scaffolds can be fabricated; however, many of these techniques involve the use of toxic organic solvents during the process. As biocompatibility is one of the mandatory requirements in designing a successful scaffold, there is an interest in fabricating scaffolds that are completely organic solvent-free. This paper describes the development and characterization of novel micro-/nano-fibrillar composites (MFC/NFC) that can produce scaffolds which are completely free from organic solvents. In this research, the cytocompatibility of these materials have been tested in vitro using mouse osteoblast-like cells and primary rat tenocytes, where cell numbers increase over the culture period, demonstrating the material viability. Gene expression analysis of primary rat tenocytes on MFC/NFC scaffolds demonstrate tenocytic behavior, and histology studies show an increase in cell formation on NFC scaffolds. This study establishes the potential of using the MFC/NFC technique to produce completely organic solvent-free scaffolds capable of hosting musculoskeletal cells, in the hope of providing a graft material for non-union skeletal fractures and rotator cuff repairs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1393-1404, 2017.

Hughes Abdominal Repair Trial (HART) - Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial.

BACKGROUND: Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. METHODS/DESIGN: This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. DISCUSSION: A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions. TRIAL REGISTRATION NUMBER: ISRCTN 25616490 . Registered on 1 January 2012.

Computer modelling integrated with micro-CT and material testing provides additional insight to evaluate bone treatments: Application to a beta-glycan derived whey protein mice model.

The primary aim of this study was to evaluate the influence of a whey protein diet on computationally predicted mechanical strength of murine bones in both trabecular and cortical regions of the femur. There was no significant influence on mechanical strength in cortical bone observed with increasing whey protein treatment, consistent with cortical tissue mineral density (TMD) and bone volume changes observed. Trabecular bone showed a significant decline in strength with increasing whey protein treatment when nanoindentation derived Young׳s moduli were used in the model. When microindentation, micro-CT phantom density or normalised Young׳s moduli were included in the model a non-significant decline in strength was exhibited. These results for trabecular bone were consistent with both trabecular bone mineral density (BMD) and micro-CT indices obtained independently. The secondary aim of this study was to characterise the influence of different sources of Young׳s moduli on computational prediction. This study aimed to quantify the predicted mechanical strength in 3D from these sources and evaluate if trends and conclusions remained consistent. For cortical bone, predicted mechanical strength behaviour was consistent across all sources of Young׳s moduli. There was no difference in treatment trend observed when Young׳s moduli were normalised. In contrast, trabecular strength due to whey protein treatment significantly reduced when material properties from nanoindentation were introduced. Other material property sources were not significant but emphasised the strength trend over normalised material properties. This shows strength at the trabecular level was attributed to both changes in bone architecture and material properties.

Chronic Methamphetamine Self-Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat.

The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant methamphetamine (METH). Recent findings have implicated the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in oxytocin modulation of acute METH reward and relapse to METH-seeking behaviour. Surprisingly, the oxytocin receptor (OTR) is only modestly involved in both regions in oxytocin attenuation of METH-primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant-induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NAc core and STh, as well as changes to oxytocin plasma levels, after chronic METH i.v. self-administration (IVSA) and after extinction of drug-taking. An additional aim was to examine whether changes to central corticotrophin-releasing factor (CRF) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress-regulatory mechanisms. Male Sprague-Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed-ratio 1 schedule or received yoked saline infusions during 2-h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA. Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NAc core and STh coronal sections. Rats that self-administered METH had higher oxytocin plasma levels, and decreased OTR-immunoreactive (-IR) fibres in the NAc core than yoked controls. In animals that self-administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR-IR fibre density increased in the STh, and a trend towards normalisation of OTR-IR fibre density was evident in the NAc core. CRF-IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally within the NAc core and STh, as well as peripherally through plasma measures, are dysregulated after METH abuse.

Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age.

OBJECTIVE: Bone marrow transplantation with total body irradiation (BMT/TBI) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH-IGF-I axis in relation to adiposity. DESIGN: Cross-sectional case control study. PATIENTS: BMT/TBI survivors (n = 22) and short stature control participants (n = 19), all GH-naïve or off GH treatment >3 months. MEASUREMENTS: Auxology, DEXA scans and GH-IGF-I axis investigation: (i) 12-h overnight GH profiles; (ii) insulin tolerance test (ITT); and (iii) IGF-I generation test. ANALYSIS: auto-deconvolution of GH profile data and comparison of quantitative parameters using ANOVA. RESULTS: Eighty-two percent of BMT/TBI survivors had growth hormone deficiency (GHD) using ITT. GH profile area-under-the-curve (GH-AUC) was reduced in BMT/TBI survivors vs short stature control participants [geometric mean (range) 209 (21-825) vs 428 (64-1400) mcg/l/12 h, respectively, P = 0·007]. GHD was more marked in those who had additional cranial irradiation (CRT) [ITT peak 1·4 (0·2-3·0) vs TBI only 4·1 (1·1-14·8) mcg/l, P = 0·036]. GHD was more marked at the end of growth in BMT/TBI survivors vs short stature control participants (GH-AUC 551 (64-2474) vs 1369 (192-4197) mcg/l/12 h, respectively, P = 0·011) and more prevalent (9/11 vs 1/9, respectively, P = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF-I generation tests were normal. BMT/TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat-adjusted mean difference for GH-AUC 90·9 mcg/l/12 h, P = 0·025). CONCLUSIONS: GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI.

Comparison of noradrenaline, dopamine and serotonin in mediating the tachycardic and thermogenic effects of methamphetamine in the ventral medial prefrontal cortex.

Methamphetamine (METH) is a psychostimulant that disrupts monoaminergic neurotransmission to evoke profound behavioral and physiological effects. Rapidly distributing to forebrain regions to increase synaptic concentrations of three monoamines (dopamine (DA), serotonin (5-HT) and noradrenaline (NA)), the medial prefrontal cortex (mPFC) is important in METH-altered behavioral and psychological profiles. Activation of the ventral mPFC can modify physiological variables, however, METH-evoked autonomic changes from this region are unknown. Therefore, the aim of this study was to characterize the respiratory, metabolic and cardiovascular effects of microinjection of METH, DA, 5-HT and NA into the ventral mPFC in urethane-anesthetized Sprague-Dawley rats. METH and NA microinjection evoked dose-related increases in heart rate, interscapular brown adipose tissue temperature and expired CO2, a pattern of response characteristic of non-shivering thermogenesis. NA and 5-HT microinjection elicited pressor and depressor responses, respectively, with matching baroreflex adjustments in sympathetic nerve activity while METH and DA evoked no change in vasomotor outflow. Low doses of METH and DA may evoke respiratory depression. These data suggest that METH's actions in the ventral mPFC, likely via adrenergic receptors, evoke non-shivering thermogenesis which may contribute to the increased body temperature and tachycardia seen in those that abuse METH.

Related hematopoietic cell donor care: is there a role for unrelated donor registries?

In almost half of allogeneic hematopoietic progenitor cell (HPC) transplants, a related donor (RD) is used, yet a lack of standardized guidelines means that their care is heterogeneous. Changes to regulatory standards aim to improve uniformity, but adherence to these regulations can prove logistically difficult for the transplant centers (TCs) managing RDs. Discussion has ensued around possible alternative models of related donor care and a session at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting in 2013 debated the question of whether a role exists for unrelated donor registries in the management of 'related' donors. In this overview, we discuss the issues raised at this debate and the pros and cons of donor registry involvement in various aspects of RD management. By examining existing models of related donor care that have been adopted by members of the World Marrow Donor Association (WMDA), we look for ways to enhance and homogenize RD care, while also enabling transplant centers to meet standards required for mandatory accreditation.

Correlation between microsatellite discrepancy scores and transplant outcome after haemopoietic SCT for pediatric ALL.

Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of ⩾1.8 had a risk of non-relapse mortality 4.9 times greater (P=0.025) and relapse risk three times greater (P=0.058) than those scoring <1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.

The orexin-1 receptor antagonist SB-334867 decreases anxiety-like behavior and c-Fos expression in the hypothalamus of rats exposed to cat odor.

Increasing evidence suggests that the orexin system is involved in modulating anxiety, and we have recently shown that cat odor-induced anxiety in rats is attenuated by the orexin receptor antagonist SB-334867. In the current experiment, c-Fos expression was used to map changes in neuronal activation following SB-334867 administration in the cat odor anxiety model. Male Wistar rats were exposed to cat odor with or without SB-334867 pre-treatment (10 mg/kg, i.p.). A naïve control group not exposed to cat odor was also used. Following cat odor exposure, brains were processed for c-Fos expression. Vehicle-treated rats showed an increase in anxiety-like behaviors (increased hiding and decreased approach toward the cat odor), and increased c-Fos expression in the posteroventral medial amygdala (MePV), paraventricular hypothalamus (PVN) and dorsal premammillary nucleus (PMd). In rats pretreated with SB-334867, approach scores increased and c-Fos expression decreased in the PVN and PMd. These results provide both behavioral and neuroanatomical evidence for the attenuation of cat odor-induced anxiety in rats via the orexin system.