Joint Inversion of GNSS and GRACE for Terrestrial Water Storage Change in California.

Global Navigation Satellite System (GNSS) vertical displacements measuring the elastic response of Earth's crust to changes in hydrologic mass have been used to produce terrestrial water storage change (∆TWS) estimates for studying both annual ∆TWS as well as multi-year trends. However, these estimates require a high observation station density and minimal contamination by nonhydrologic deformation sources. The Gravity Recovery and Climate Experiment (GRACE) is another satellite-based measurement system that can be used to measure regional TWS fluctuations. The satellites provide highly accurate ∆TWS estimates with global coverage but have a low spatial resolution of ∼400 km. Here, we put forward the mathematical framework for a joint inversion of GNSS vertical displacement time series with GRACE ∆TWS to produce more accurate spatiotemporal maps of ∆TWS, accounting for the observation errors, data gaps, and nonhydrologic signals. We aim to utilize the regional sensitivity to ∆TWS provided by GRACE mascon solutions with higher spatial resolution provided by GNSS observations. Our approach utilizes a continuous wavelet transform to decompose signals into their building blocks and separately invert for long-term and short-term mass variations. This allows us to preserve trends, annual, interannual, and multi-year changes in TWS that were previously challenging to capture by satellite-based measurement systems or hydrological models, alone. We focus our study in California, USA, which has a dense GNSS network and where recurrent, intense droughts put pressure on freshwater supplies. We highlight the advantages of our joint inversion results for a tectonically active study region by comparing them against inversion results that use only GNSS vertical deformation as well as with maps of ∆TWS from hydrological models and other GRACE solutions. We find that our joint inversion framework results in a solution that is regionally consistent with the GRACE ∆TWS solutions at different temporal scales but has an increased spatial resolution that allows us to differentiate between regions of high and low mass change better than using GRACE alone.

Seasonal and Long-Term Groundwater Unloading in the Central Valley Modifies Crustal Stress.

Changes in terrestrial water content cause elastic deformation of the Earth's crust. This deformation is thought to play a role in modulating crustal stress and seismicity in regions where large water storage fluctuations occur. Groundwater is an important component of total water storage change in California, helping to drive annual water storage fluctuations and loss during periods of drought. Here we use direct estimates of groundwater volume loss during the 2007-2010 drought in California's Central Valley obtained from high resolution Interferometric Synthetic Aperture Radar-based vertical land motion data to investigate the effect of groundwater volume change on the evolution of the stress field. We show that GPS-derived elastic load models may not capture the contribution of groundwater to terrestrial water loading, resulting in an underestimation of nontectonic crustal stress change. We find that groundwater unloading during the drought causes Coulomb stress change of up to 5.5 kPa and seasonal fluctuations of up to 2.6 kPa at seismogenic depth. We find that faults near the Valley show the largest stress change and the San Andreas fault experiences only ~40 Pa of Coulomb stress change over the course of a year from groundwater storage change. Annual Coulomb stress change peaks dominantly in the fall, when the groundwater level is low; however, some faults experience peak stress in the spring when groundwater levels are higher. Additionally, we find that periods of increased stress correlate with higher than average seismic moment release but are not correlated with an increase in the number of earthquakes. This indicates groundwater loading likely contributes to nontectonic loading of faults, especially near the Valley edge, but is not a dominant factor in modulation of seismicity in California because the amplitude of stress change declines rapidly with distance from the Valley. By carefully quantifying and spatially locating groundwater fluctuations, we will improve our understanding of what drives nontectonic stress and forces that modulate seismicity in California.

Cardiac biomarkers of disordered eating as a function of diagnostic subtypes.

OBJECTIVE: The purpose of this study was to identify cardiac biomarkers of disordered eating as a function of diagnostic subtype as assessed via self-report inventory. METHOD: Mean heart rate (HR), systolic and diastolic blood pressure, mean R wave amplitude (mV), mean T wave amplitude (mV), QTc interval (sec), Tpeak-Tend interval prolongation (sec), QTc interval prolongation (sec), QRS prolongation (sec), and spectral indicators of cardiac dysfunction (LF/HF spectral ratio, HF spectral power) were assessed via electrocardiography among women with no eating disorder symptoms (n = 32), subclinical eating disorder symptoms (n = 92), anorexia nervosa (n = 7), bulimia nervosa (n = 89), binge eating disorder (BED: n = 20), and other specified feeding and eating disorders (OSFED: n = 19). RESULTS: MANOVA results showed statistically significant group differences. Follow-up tests revealed significantly decreased mean R wave amplitude among participants with self-indicated clinical (bulimia nervosa, binge eating disorder) and subclinical forms of disordered eating compared to asymptomatic controls. DISCUSSION: Results suggest decreased mean R wave amplitude is a promising cardiac biomarker of disordered eating.

Pre-pubertal bipolar disorder: origins and current status of the controversy.

BACKGROUND: Evidence from epidemiological, clinical and high-risk studies has established that the peak period of risk for onset of bipolar disorder spans late adolescence and early adulthood. However, the proposal of the existence of a pre-pubertal form of bipolar disorder manifesting in early childhood created substantial debate. In this narrative review, the literature and contributing factors pertaining to the controversy surrounding the proposed pre-pubertal bipolar disorder subtype are discussed. The resolution of the debate and lessons learned are highlighted. MAIN BODY: In the mid 1990s US researchers proposed that chronic irritability and explosive temper in pre-pubertal children with pre-existing ADHD and/or other learning and developmental disorders might represent a variant of mania. A number of factors contributed to this proposal including severely ill children with no diagnostic home given changes in the ADHD DSM diagnostic criteria and over-reliance on symptoms and structured interviews rather than on a clinical assessment incorporating developmental history, social context and clinical course. Prospective studies of children at high familial risk did not support the proposed pre-pubertal bipolar phenotype; but rather provided convergent evidence that bipolar disorder onset in adolescence and early adulthood not uncommonly preceded by sleep and internalizing symptoms and most often debuting as depression in adolescence (after puberty). Epidemiological studies of population and hospital discharge data provided evidence that the pre-pubertal bipolar phenotype was largely a US driven phenomenon. CONCLUSIONS: Psychiatric diagnosis is particularly challenging given the current lack of objective biomarkers. However, validity and utility of clinical diagnoses can be strengthened if all available predictive information is used to formulate a diagnosis. As in other areas of medicine, critical information required to make a valid diagnosis includes developmental history, clinical course, family history and treatment response-weighed against the known trajectories of classical disorders. Moreover, given that psychiatric disorders are in evolution over childhood and adolescence and symptoms, in of themselves, are often non-specific, a thorough clinical assessment incorporating collateral history and psychosocial context is paramount. Such an approach might have avoided or at least brought a more timely resolution to the debate on pre-pubertal mania.

Home parenteral nutrition and the older adult: Experience from a national intestinal failure unit.

INTRODUCTION: The population in developed countries is getting older and with advancing age comes increasing co-morbidity and demand on health care services. The use of home parenteral nutrition (HPN) is also increasing in the UK and elsewhere. Age and co-morbidity need to be taken into consideration when HPN is contemplated because of the significant associated economic burden and clinical risk. However, there are minimal data on HPN outcomes specific to the elderly. METHOD: We performed an observational study of a prospectively maintained database of patients dependent on HPN managed at a national U.K. referral centre. Data were collected on the 31st March 2018. Charlson index was used to assess co-morbidity. Data included demographics, HPN requirements, underlying disease aetiology, mechanism of intestinal failure, and whether the patient, carer or home care nurses administered the PN. The main outcome was the occurrence of at least one catheter-related blood stream infection (CRBSI) during HPN, with putative predictors of CRBSI assessed by uni- and multi-variable logistic regression. RESULTS: Two hundred and seventy-seven patients were included in this study, 62% were female and the overall mean age of the entire cohort was 58 years (range 20-93). The mean duration of HPN was 1778 days (range 45-12,832). One hundred patients were aged 65 years or older. Patients aged 65 years or older had a higher Charlson index (1.8 vs 1.1, p = <0.0001), were more likely to require a home care nurse to administer PN (p = 0.01), and had the lowest risk of CRBSI (25% vs 39%; p = 0.01). Home care nurse administration was associated with the lowest risk of CRBSI, followed by carer and self-administration (P = 0.001). In multivariable analysis, duration of HPN and CVC care provider were the only independent predictors of CRBSI occurrence. There was no significant difference in unplanned intestinal failure-related hospital admissions between those under or above 65 years of age (p = 0.08). CONCLUSIONS: HPN can be safely used in patients over the age of 65, even with increased co-morbidity. In this large cohort study, increasing age was found to be protective against CRBSI. CVC care provider was an independent predictor of CRBSI, while age and co-morbidity were not, suggesting that the use of home care nurses for PN administration is the principal reason for the low CRBSI rate in the elderly. Hence, older age should not be seen as a contra-indication for HPN, but increased healthcare resource may be required as those aged over 65 are more likely to require nursing assistance for CVC care.

Management of colonic complications of type IV Ehlers-Danlos syndrome: a systematic review and evidence-based management strategy.

AIM: Type IV Ehlers Danlos Syndrome (EDS) is a connective tissue disorder affecting approximately 1 per 100,000-200,000 people. Life expectancy is reduced secondary to spontaneous vascular rupture or colonic perforation. Surgery carries significant morbidity and mortality. While strategies to manage colonic perforation include primary repair with or without a defunctioning stoma, Hartmann's procedure, total abdominal colectomy with end ileostomy and ileorectal anastomosis, evidence is contradictory and has not previously been evaluated in order to form a treatment strategy. We aim to review the published literature and identify outcome data relating to operative management of colonic perforation in type IV EDS. METHODS: Pubmed, EM-BASE, Cochrane library and Google Scholar were searched with the following details: Ehlers Danlos Syndrome AND colonic surgery. The main outcome measure was re-perforation rates following colonic surgery on patients with type IV EDS. If the nature of surgery and follow up were reported, data were recorded in a SPSS database according to PRISMA guidelines. RESULTS: One hundred and nine operations have been described in 51 patients in 44 case series. There were 26 visceral re-perforations, 2 affecting the small intestine and 24 colonic. Survival analysis favoured total abdominal colectomy compared with operations where the colon was left in situ. CONCLUSIONS: Total abdominal colectomy with end ileostomy or ileorectal anastomosis are the safest strategies after colonic perforation in type IV EDS. Anastomotic leak rates are high. End colostomy is high risk for colonic re-perforation and anastomotic leak rates are extremely high. Restoration of colonic continuity should be avoided.

Recurrent intestinal fistulation after porcine acellular dermal matrix reinforcement in enteric fistula takedown and simultaneous abdominal wall reconstruction.

PURPOSE: Porcine acellular dermal matrix (PADM) has been promoted as a suitable material for the reinforcement of the abdominal wall in Ventral Hernia Working Group (VHWG) Grade 3/4 wounds by Ventral Hernia Working Group et al. (Surgery 148(3):544-548). We describe our experience of, and assess the mechanisms for the failure of PADM (PermacolTM) in intestinal and abdominal wall reconstruction (AWR) for enterocutaneous fistulation (ECF). METHODS: All patients referred to our unit who had PADM used for AWR and ECF were studied from a prospectively maintained database. Follow-up data until 31/12/2018 were analysed. PADM was explanted at further surgery and examined histologically. RESULTS: 13 patients, (median age-58.5 years) underwent AWR with PADM reinforcement. Twelve of these (92%) patients had developed abdominal wall defects (AWD) and ECF following complications of previous surgery. Six patients underwent fistula takedown and AWR with PADM, of which 5(83%) refistulated. Seven patients referred to us had already undergone similar procedures in their referring hospitals and had also refistulated. Median (range) time to fistulation after AWR with PADM was 17 (7-240) days. In all cases, PADM had been used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, PADM was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that the PADM almost completely integrated with the seromuscular layer of the small intestine. CONCLUSION: PADM may become inseparable from serosa of the human small intestinal serosa when it is left in the abdomen during reconstructive surgery. This technique is associated with recurrent intestinal fistulation and intestinal failure and should be avoided if at all possible.

Avoiding, diagnosing and treating well leg compartment syndrome after pelvic surgery.

BACKGROUND: Patients undergoing prolonged pelvic surgery may develop compartment syndrome of one or both lower limbs in the absence of direct trauma or pre-existing vascular disease (well leg compartment syndrome). This condition may have devastating consequences for postoperative recovery, including loss of life or limb, and irreversible disability. METHODS: These guidelines represent the collaboration of a multidisciplinary group of colorectal, vascular and orthopaedic surgeons, acting on behalf of their specialty associations in the UK and Ireland. A systematic analysis of the available peer-reviewed literature was undertaken to provide an evidence base from which these guidelines were developed. RESULTS: These guidelines encompass the risk factors (both patient- and procedure-related), diagnosis and management of the condition. Key recommendations for the adoption of perioperative strategies to facilitate prevention and effective treatment of well leg compartment syndrome are presented. CONCLUSION: All surgeons who carry out abdominopelvic surgical procedures should be aware of well leg compartment syndrome, and instigate policies within their own institution to reduce the risk of this potentially life-changing complication.

Catheter-related infections in patients with acute type II intestinal failure admitted to a national centre: Incidence and outcomes.

INTRODUCTION: The management of intestinal failure (IF) requires safe and sustained delivery of parenteral nutrition (PN). The long-term maintenance of central venous catheter (CVC) access is therefore vital, with meticulous catheter care and salvage of infected CVCs being of prime importance. CVC-related infection and loss of intravenous access are important causes of morbidity and mortality in IF. Avoidance, prompt recognition and appropriate management of CVC-related infections are crucial components of IF care. However, there are few, if any, data on the occurrence of CVC-related infections in patients with acute, type 2, IF managed on a dedicated IF unit and no data on the salvage outcomes of infected CVCs in this group of patients. METHODS: This is a retrospective observational study conducted between January 2011 and July 2017. All patients with acute, type 2 IF newly admitted to a national U.K. IF unit (IFU) during these dates were included. All patients admitted to the unit with a CVC in place underwent immediate 'screening' paired central and peripheral blood cultures on arrival before the CVC was used for any infusate. A prospectively maintained database was used to record all confirmed catheter-related blood stream infections (BSI)/colonisations, demographic and clinical data. Diagnosis of catheter-related BSI/colonisation was based on quantitative and qualitative analysis of paired central and peripheral blood cultures. A standardized 10-14-day catheter salvage treatment protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration was used to salvage any infected or colonised CVCs, as appropriate. The CVC was not used for PN until successful salvage had been confirmed by negative blood cultures drawn 48 h after antibiotic completion. The development of a subsequent catheter-related BSI was recorded for all patients, both during the remaining in-patient stay on the IFU and after discharge home on PN. RESULTS: Of the 509 patients with type 2 IF admitted to the IFU during the study period, 341 (54% female; mean age 54.6 (range 16-86 years)) had an indwelling CVC that had been placed in the referring hospital. Surgical complications and mesenteric ischaemia were the most common underlying disease aetiologies. Sixty-five of 341 (19.1%) patients had an infected/colonised CVC on the initial screening set of blood cultures. A successful CVC salvage rate of 91% was achieved in this cohort after antibiotic therapy. The subsequent in-patient catheter-related BSI rate for those admitted with a CVC (n = 341) on the IFU was 0.042 per 1000 catheter days, over a total of 23,548 in-patient catheter days. Two hundred and seventy nine of 341 patients were discharged on home PN (HPN); with a subsequent catheter-related BSI rate on HPN of 0.22 per 1000 catheter days (mean duration of HPN = 778 catheter days (range:)) over a follow-up period of 216,944 out-patient catheter days. There was no increased risk of HPN-related catheter-related BSI (p = 0.09) or mortality (p = 0.4) in those admitted with an infected CVC. CONCLUSION: This is the first study to report catheter-related BSI/colonisation rates and salvage outcomes in patients with type 2 IF newly admitted to a dedicated IF Unit. We report that nearly one-fifth of all patients were referred with evidence of a catheter related BSI/colonisation; despite this, successful catheter salvage is possible and, with stringent CVC care, an extremely low subsequent catheter related BSI rates can be achieved and maintained during in-patient stay on a dedicated IF Unit and after discharge on HPN. These data provide novel evidence to support ESPEN recommendations that patients with type 2 IF are managed on a dedicated IF Unit.

Examining the pathophysiology of short bowel syndrome and glucagon-like peptide 2 analogue suitability in chronic intestinal failure: experience from a national intestinal failure unit.

INTRODUCTION: Short bowel syndrome (SBS) is a leading cause of intestinal failure (IF). Home parenteral nutrition (HPN) remains the standard treatment, with small intestinal transplantation reserved for cases with severe complications to HPN. There have recently been significant developments in growth factor therapy. We aimed to develop a greater contemporary understanding of our SBS-IF subset. METHOD: We performed a retrospective observational study of a prospectively maintained HPN audit database in October 2017. Intestinal anatomical details and parenteral requirements were recorded. Each case was assessed for eligibility for growth factor therapy using recently published trials. RESULTS: Of 273 patients receiving HPN, 152 (55.7%) had type three IF as a result of SBS (SBS-IF), with a mean duration of HPN of 61 months (range 4-416). Mean length of small intestine was 98 cm. Furthermore, 114 (41.8%) patients had an end jejunostomy (SBS-J), 18 (6.6%) had an end ileostomy, and 7.3% of patients had all or part of the colon-in-continuity. Crohn's disease was the most common underlying pathology. Univariate analysis for the whole HPN cohort demonstrated SBS-IF and a longer duration of HPN to be associated with higher PN energy requirements, p ≤ 0.0001. Of all, 73 (48%) patients with SBS-IF were deemed suitable for GLP-2 analogue therapy, with co-morbidity being the most frequent cause of non-suitability (29.1%). CONCLUSION: We describe a large U.K. HPN cohort using ESPEN pathophysiological and clinical severity classification. The majority of patients with SBS-IF had a jejunostomy and relatively few had colon-in-continuity. Co-morbidity is the most common contra-indication to GLP-2 analogue therapy. CLINICAL RELEVANCY: GLP-2 analogues are emerging as an important treatment for patients with short bowel syndrome. Our study explores patient suitability in a large HPN cohort managed in a national IF centre. Furthermore, the international variation in the pathophysiology of SBS-IF varies significantly, which can have a bearing on PN requirements and outcomes when GLP-2 analogues are used.

Outcome of open abdominal management following military trauma.

BACKGROUND: Temporary abdominal closure (TAC) is increasingly common after military and civilian major trauma. Primary fascial closure cannot be achieved after TAC in 30 per cent of civilian patients; subsequent abdominal wall reconstruction carries significant morbidity. This retrospective review aimed to determine this morbidity in a UK military cohort. METHODS: A prospectively maintained database of all injured personnel from the Iraq and Afghanistan conflicts was searched from 1 January 2003 to 31 December 2014 for all patients who had undergone laparotomy in a deployed military medical treatment facility. This database, the patients' hospital notes and their primary care records were searched. RESULTS: Laparotomy was performed in a total of 155 patients who survived to be repatriated to the UK; records were available for 150 of these patients. Seventy-seven patients (51·3 per cent) had fascial closure at first laparotomy, and 73 (48·7 per cent) had a period of TAC. Of the 73 who had TAC, two died before closure and two had significant abdominal wall loss from blast injury and were excluded from analysis. Of the 69 remaining patients, 65 (94 per cent) were able to undergo delayed primary fascial closure. The median duration of follow-up from injury was 1257 (range 1-4677) days for the whole cohort. Nine (12 per cent) of the 73 patients who underwent TAC subsequently developed an incisional hernia, compared with ten (13 per cent) of the 77 patients whose abdomen was closed at the primary laparotomy (P = 1·000). CONCLUSION: Rates of delayed primary closure of abdominal fascia after temporary abdominal closure appear high. Subsequent rates of incisional hernia formation were similar in patients undergoing delayed primary closure and those who had closure at the primary laparotomy.

Assessing the impact of quality improvement measures on catheter related blood stream infections and catheter salvage: Experience from a national intestinal failure unit.

BACKGROUND & AIMS: Prevention of catheter related blood stream infections (CRBSI) and salvage of infected central venous catheters (CVC) are vital to maintaining long term venous access in patients needing home parenteral nutrition (HPN). It remains unclear as to whether patients are best trained for catheter care at home or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC. Furthermore, there is minimal data on the longer term outcome following salvage of infected catheter and limited consensus on agreed protocols for catheter salvage. METHOD: We conducted a retrospective 5-year evaluation of CRBSI occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients were primarily trained to administer PN in hospital; thereafter, patients underwent training at home. RESULTS: A total of 134 CRBSI were recorded in 92 patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI) in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)), Klebsiella spp. (16/134 (11.9%)) and methicillin - sensitive Staphylococcus aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to methicillin - resistant (MRSA) infection (1/34), fungal infection (13/34) or clinical instability due to sepsis (20/34). Of the 100 cases where salvage was attempted, 67% were successful. 82.8% of CNS salvage attempts were successful; there was no difference in salvage rates between CNS CRBSIs salvaged with a 10-day (22/26) or 14-day protocol (7/9) (p = 0.4). CRBSI rate, in those cared for by trained home care nurses was the lowest at 0.270 (self care: 0.342 and non-medical carer (e.g. family member): 0.320) (p = 0.03). CONCLUSION: We previously reported a sustained very low CRBSI rate in a large cohort of HPN patients in a national unit; we now further report that this is not influenced by training patients at home rather than in hospital but is influenced by the individual managing the catheter at home. CNS remains the primary cause of CRBSIs and can be successfully salvaged with a reduced duration of antibiotic therapy compared to our previous experience.

Intravenous fluid and electrolyte administration in elective gastrointestinal surgery: mechanisms of excessive therapy.

INTRODUCTION While clinical guidelines stress the importance of the judicious perioperative intravenous fluid administration, data show that adherence to these protocols is poor. The reasons have not been identified. We therefore audited the magnitude and indications of fluid and electrolyte administration in a teaching hospital. We hypothesised that epidural analgesia is associated with excessive fluid therapy. MATERIALS AND METHODS Intravenous fluid and electrolyte administration during the day of surgery and the subsequent 2 days in consecutive patients undergoing elective gastrointestinal surgery between November 2013 and May 2014 were retrospectively audited. Timing, volumes and indications were recorded. RESULTS One hundred patients undergoing elective gastrointestinal resection were studied. Patients received 9030 ml ± 2860 ml (mean ± standard deviation) intravenous fluids containing a total of 1180 ml ± 420 mmol sodium and resulting in a cumulative fluid balance of +5120 ml ± 2510 ml; 44% ± 14% of total volumes were given in theatre. Nearly all fluid was given for maintenance, 100% (96-100%, interquartile range), with 17 patients only receiving replacement or resuscitation. Independent predictors of increased volumes included open surgery, upper gastrointestinal surgery, increased duration and epidural analgesia but not body weight. Postoperative fluid volume was the only independent predictor of postoperative complication grade (P = 0.0044). CONCLUSIONS Despite published guidelines, perioperative fluid and electrolyte administration were excessive and were associated with postoperative morbidity. Substantial volumes were administered in theatre. Nearly all administration was for maintenance, yet patients received approximately five times the amount of sodium required. Epidural analgesia was an independent predictor of fluid volumes but body weight was not.

Recent developments in the surgical management of complex intra-abdominal infection.

BACKGROUND: Current guidance on the management of sepsis often applies to infection originating from abdominal or pelvic sources, which presents specific challenges and opportunities for efficient and rapid source control. Advances made in the past decade are presented in this article. METHODS: A qualitative systematic review was undertaken by searching standard literature databases for English-language studies presenting original data on the clinical management of abdominal and pelvic complex infection in adults over the past 10 years. High-quality studies relevant to five topical themes that emerged during review were included. RESULTS: Important developments and promising preliminary work are presented, relating to: imaging and other diagnostic modalities; antimicrobial therapy and the importance of antimicrobial stewardship; the particular challenges posed by fungal sepsis; novel techniques in percutaneous and endoscopic source control; and current issues relating to surgical source control and managing the abdominal wound. Logistical challenges relating to rapid access to cross-sectional imaging, interventional radiology and operating theatres need to be addressed so that international benchmarks can be met. CONCLUSION: Important advances have been made in the diagnosis, non-operative and surgical control of abdominal or pelvic sources, which may improve outcomes in the future. Important areas for continued research include the diagnosis and therapy of fungal infection and the challenges of managing the open abdomen.

Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects.

Essentials Limited data on hemostatic benefits of platelet transfusion (PT) exist. 44 healthy subjects had a single dose of ticagrelor or clopidogrel ± autologous PT post-dosing. PT did not reverse ticagrelor's antiplatelet effects and had minimal impact post clopidogrel. Post-ticagrelor, PT is unlikely to be beneficial, and the benefits post-clopidogrel are unknown. SUMMARY: Background Antiplatelet agents increase bleeding risk. Few data on hemostatic benefits of platelet transfusion exist. Objective To assess the effect of autologous platelet transfusion on ticagrelor-mediated and clopidogrel-mediated platelet inhibition in a single-center, open-label, randomized, cross-over study (NCT01744288). Methods Forty-four healthy subjects received ticagrelor (180 mg) or clopidogrel (600 mg; two functional CYP2C19 alleles [*1 or *17] required) with or without platelet transfusion (14-day washout). Subjects received one autologous platelet apheresis unit (approximately six pooled donor platelet units) 24 h (n = 15) or 48 h (n = 13) after ticagrelor or 48 h after clopidogrel (n = 16). Platelet apheresis was conducted 72 h before transfusion. Aspirin (81 mg per day) was taken from after apheresis until 24 h before transfusion. P2Y12 reaction units (PRUs) and inhibition of platelet aggregation (IPA) induced by ADP were measured. Results Mean age and body mass index were 30 years (standard deviation [SD] 6 years) and 26.9 kg m-2 (SD 4.0 kg m-2 ), respectively; 98% of subjects were men, and 39 of 44 completed treatment. Platelet transfusion 24 h after ticagrelor had minimal effects on IPA or PRU values within 48 h after transfusion. Platelet transfusion 48 h after ticagrelor also had minimal effects on IPA or PRU values at most post-transfusion times. Platelet transfusion 48 h after clopidogrel, versus no transfusion, had a small reversing effect on IPA (24 h, 36 h, and 48 h) and PRU values (12 h, 24 h, and 36 h) after transfusion. Conclusions Autologous platelet transfusion is unlikely to be of clinical benefit in reversing the antiplatelet effects of ticagrelor. The clinical relevance of the small effects seen with clopidogrel is unknown.

Outcome of intestinal failure after bariatric surgery: experience from a national UK referral centre.

BACKGROUND/OBJECTIVES: Bariatric surgery for morbid obesity provides sustained weight loss. Complications of bariatric surgery include severe nutritional decline, but minimal data describing occurrence and outcome of intestinal failure (IF) exist. SUBJECTS/METHODS: All patients referred to one of the UK's National IF units (IFU) are prospectively entered onto a database; case notes were assessed for bariatric surgery details, IF onset, outcomes, resulting intestinal anatomy, mortality and catheter-related bloodstream infections (CRBSIs). RESULTS: A total of six patients (mean referral age 54.0 years; 95% confidence interval (CI): 44.6-63.4; 5 female) were identified with IF after bariatric surgery from 457 patients (total cohort) managed on home parenteral nutrition (HPN) at the IFU between 2008 and 2014. In all, 6/6 had Roux-en-Y gastric bypass bariatric surgery. Median (range) time from index bariatric surgery to IF development was 28.7 months (1.7-106). IF aetiology was internal herniation (4/6), ischaemia (1/6) and anastomotic leak (1/6); all patients required HPN for a median of 26.4 months (15.3-34.7). CRBSI occurred on 7 occasions in 3 patients, equivalent to 1.5/1000 catheter days in these 6 compared with 0.32/1000 in the 451 IFU HPN patients during this time period. In all, 0/6 patients died, 6/6 had continuity restored in a median of 16.5 months (6.5-32.5) after IF diagnosis and 3/6 (50%) were weaned from PN by a median of 2.2 months (0.6-12.8). CONCLUSIONS: Bariatric surgery, an increasingly common operation, can be associated with IF necessitating long-term HPN. The cohort presented had a higher CRBSI compared with other HPN patients; more stringent approaches to catheter care may be required in this patient group, although more collective data are required.

European Society of Coloproctology consensus on the surgical management of intestinal failure in adults.

Intestinal failure (IF) is a debilitating condition of inadequate nutrition due to an anatomical and/or physiological deficit of the intestine. Surgical management of patients with acute and chronic IF requires expertise to deal with technical challenges and make correct decisions. Dedicated IF units have expertise in patient selection, operative risk assessment and multidisciplinary support such as nutritional input and interventional radiology, which dramatically improve the morbidity and mortality of this complex condition and can beneficially affect the continuing dependence on parenteral nutritional support. Currently there is little guidance to bridge the gap between general surgeons and specialist IF surgeons. Fifteen European experts took part in a consensus process to develop guidance to support surgeons in the management of patients with IF. Based on a systematic literature review, statements were prepared for a modified Delphi process. The evidence for each statement was graded using Oxford Centre for Evidence-Based Medicine Levels of Evidence. The current paper contains the statements reflecting the position and practice of leading European experts in IF encompassing the general definition of IF surgery and organization of an IF unit, strategies to prevent IF, management of acute IF, management of wound, fistula and stoma, rehabilitation, intestinal and abdominal reconstruction, criteria for referral to a specialist unit and intestinal transplantation.

Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains.

Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later.

BACKGROUND: Little is known about the predictive validity of disruptive mood dysregulation disorder (DMDD). This longitudinal, community-based study examined associations of DMDD at the age of 6 years with psychiatric disorders, functional impairment, peer functioning and service use at the age of 9 years. METHOD: A total of 473 children were assessed at the ages of 6 and 9 years. Child psychopathology and functional impairment were assessed at the age of 6 years with the Preschool Age Psychiatric Assessment with parents and at the age of 9 years with the Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with parents and children. At the age of 9 years, mothers, fathers and youth completed the Child Depression Inventory (CDI) and the Screen for Child Anxiety Related Disorders, and teachers and K-SADS interviewers completed measures of peer functioning. Significant demographic covariates were included in all models. RESULTS: DMDD at the age of 6 years predicted a current diagnosis of DMDD at the age of 9 years. DMDD at the age of 6 years also predicted current and lifetime depressive disorder and attention-deficit/hyperactivity disorder (ADHD) at the age of 9 years, after controlling for all age 6 years psychiatric disorders. In addition, DMDD predicted depressive, ADHD and disruptive behavior disorder symptoms on the K-SADS, and maternal and paternal reports of depressive symptoms on the CDI, after controlling for the corresponding symptom scale at the age of 6 years. Last, DMDD at the age of 6 years predicted greater functional impairment, peer problems and educational support service use at the age of 9 years, after controlling for all psychiatric disorders at the age of 6 years. CONCLUSIONS: Children with DMDD are at high risk for impaired functioning across childhood, and this risk is not accounted for by co-morbid conditions.