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Objectives Short bowel syndrome (SBS) is a complex and rare condition (incidence 1200/ 100,000 live births) that requires a multidisciplinary team approach to management. In January 2019 the first European Reference Network on Rare and Inherited Congenital Anomalies (ERNICA) Intestinal Failure (IF) workshop was held. Several questions about the strategies used in managing IF associated with short bowel syndrome (SBS) were devised. The aim of our study was to collect data on the enteral feeding strategies adopted by the ERNICA centres. Methods A questionnaire (36 questions) about strategies used to introduce enteral nutrition post-operatively and start complementary food/solids in infants with SBS associated IF was developed and sent to 24 centres in 15 countries that participated in the ERNICA-IF workshop. The answers were collated and compared with the literature. Results There was 100% response rate. In infants enteral nutrition was introduced as soon as possible, ideally within 24-48 hours post-small intestinal surgical resection. In 10/24 centres, bolus feeding was used, in 9 continuous, and in 5 a combination of both. Twenty-three centres used mothers' own milk as the first choice of feed with extensively hydrolysed feed, amino acid based feed, donor human milk or standard preterm/term formula as second choice. Although twenty-two centres introduced complementary/solid food by 6 months of age, food choice varied greatly between centres and appeared to be culturally based. Conclusions There is diversity in post-surgical enteral feeding strategies among centres in Europe. Further multi-centre studies could help to increase evidence-based medicine and management on this topic.

Frailty has been defined as a state of increased vulnerability due to a decline in the reserve and function of multiple physiological systems. Initially conceived as a geriatric syndrome indicative of physiological aging, it is now apparent that frailty can also be observed as a manifestation of chronic disease states including heart failure. Estimates of the prevalence of frailty in heart failure vary according to the age of the study population and the frailty instrument used; however, multiple studies have identified frailty to be prevalent in patients with advanced heart failure including those who are referred for heart transplantation. Frailty is emerging as an independent predictor of mortality both before and after bridge-to-transplant ventricular assist device implantation and heart transplantation. Frailty is also predictive of prolonged hospitalization following these procedures. Heart failure-associated frailty is a dynamic state. While reversibility of frailty can be anticipated in younger heart failure patients, predicting the reversibility of frailty is more challenging in older patients who often have multiple comorbidities that may contribute to the frailty syndrome. Prehabilitation is a promising approach to both preventing and reversing frailty however more research is urgently needed to establish its effectiveness in mitigating the adverse impacts of frailty on postventricular assist device and posttransplant morbidity and mortality.

Background and Objectives: \ud Gastrectomy for gastric cancer is associated with significant infective postoperative complications. C-reactive protein (CRP) is a useful biomarker in the early detection of infective complications following major abdominal surgery. This single-centre retrospective study aimed to determine the relationship between postoperative CRP levels and development of postoperative infective complications after gastrectomy.\ud \ud Methods: \ud Daily postoperative CRP levels were analyzed to determine a CRP threshold associated with infective complications. ROC curve analysis was used to determine which postoperative day (POD) gave the optimal cutoff. Multivariate analysis was performed to determine significant factors associated with complications.\ud \ud Results: \ud One hundred and forty-four patients were included. A total of 61 patients (42%) had at least one infective complication. A CRP level of 220 mg/L was associated with the highest AUC (0.765) with a sensitivity of 70% and specificity of 76% (positive predictive value, 67%; negative predictive value, 78%). More patients with a CRP > 220 mg/L on POD 3 developed infective complications (67% vs. 21%, p

Emerging evidence highlights intraindividual variability (IIV) during executive function (EF) tasks as a reliable endophenotype of Attention Deficit/Hyperactivity Disorder (ADHD) and as contributing to motor dysregulation and hyperactive-impulsive behaviors. This study examined the relationship between EF and motor control in children with and without ADHD.Ninety-seven children (6-13 years) completed standardized and experimental tasks of executive and motor control. Primary caregivers completed a semi-structured interview, and behavioral rating forms for ADHD symptoms and EF.Children with ADHD demonstrated lower performance on motor dexterity and sequencing tasks, and greater IIV during EF tasks with lower cognitive demand. IIV accounted for ADHD symptoms of hyperactivity, beyond age and motor dexterity. IIV from EF measures with lower cognitive demand was also sensitive to ADHD symptoms.IIV metrics may tap into the motor regulation challenges associated with ADHD, as well as attentional lapsing at lower levels of cognitive demand.

Low flow and suction alarms are provided to alert caregivers of changes in left ventricular assist device pump function but may be reset in clinical practice. We investigated the incidence and underlying causes of these alarms as well as their prognostic significance. HeartWare ventricular assist device patients (n = 113) were divided into quartiles based on their frequency of low flow and suction alarms. Survival and adverse events (thrombus, stroke, bleeding, and right heart failure) were compared between quartiles. Low flow alarms peaked in the first few months of pump support before dropping down to near negligible levels. Suction alarm frequency remained relatively constant throughout pump support. Although pump speeds (p < 0.001) and flow (p = 0.01) decreased over time, there was an increase in suction alarm frequency (p = 0.018), with no changes in low flow alarms. Patients with smaller body size (p = 0.016) and lower pump flows (p = 0.008) had higher frequencies of low flow alarms on multiple regression (p < 0.001). Patients with the highest low flow alarm frequency demonstrated poorer survival (p = 0.026). There was no relationship between suction alarm frequency and survival. There was also no relationship between either low flow or suction alarm frequency with strokes, gastrointestinal bleeds, pump thrombus, or right ventricular failure. Duration of alarm and intervention in response to the alarm was not assessed in this study. Further studies examining alarm duration and responses may inform future pump alarm algorithms.

OBJECTIVES: This study aimed to determine the safety and efficacy of combined low-dose everolimus and low-dose tacrolimus compared with standard-dose tacrolimus in attenuating left ventricular hypertrophy (LVH) after orthotopic heart transplantation (OHT). BACKGROUND: Calcineurin inhibitors (CNIs) such as tactrolimus are important in preventing cardiac allograft rejection and reducing mortality after OHT. However CNIs are causatively linked to the development of LVH, and are associated with nephrotoxicity and vasculopathy. CNI-sparing agents such as everolimus have been hypothesized to inhibit adverse effects of CNIs. METHODS: In this prospective, randomized, open-label study, OHT recipients were randomized at 12 weeks after OHT to a combination of low-dose everolimus and tacrolimus (the RADTAC group) or standard-dose tacrolimus (the TAC group), with both groups coadministered mycophenolate and prednisolone. The primary endpoint was LVH indexed as the change in left ventricular mass (DeltaLVM) by cardiovascular magnetic resonance (CMR) imaging from 12 to 52 weeks. Secondary endpoints included CMR-based myocardial performance, T1 fibrosis mapping, blood pressure, and renal function. Safety endpoints included episodes of allograft rejection and infection. RESULTS: Forty stable OHT recipients were randomized. Recipients in the RADTAC group had significantly lower tacrolimus levels compared with the TAC group (6.5 +/- 3.5 mug/l vs. 8.6 +/- 2.8 mug/l; p = 0.02). The mean everolimus level in the RADTAC group was 4.2 +/- 1.7 mug/l. A significant reduction in LVM was observed in the RADTAC group compared with an increase in LVM in the TAC group (DeltaLVM = -13.0 +/- 16.8 g vs. 2.1 +/- 8.4 g; p < 0.001). Significant differences were also noted in secondary endpoints measuring function and fibrosis (Delta circumferential strain = -2.9 +/- 2.8 vs. 2.1 +/- 2.3; p < 0.001; DeltaT1 mapping values = -32.7 +/- 51.3 ms vs. 26.3 +/- 90.4 ms; p = 0.003). No significant differences were observed in blood pressure (Delta mean arterial pressure = 4.2 +/- 18.8 mm Hg vs. 2.8 +/- 13.8 mm Hg; p = 0.77), renal function (Delta creatinine = 3.1 +/- 19.9 mumol/l vs. 9 +/- 21.8 mumol/l; p = 0.31), frequency of rejection episodes (p = 0.69), or frequency of infections (p = 0.67) between groups. CONCLUSIONS: The combination of low-dose everolimus and tacrolimus compared with standard-dose tacrolimus safely attenuates LVH in the first year after cardiac transplantation with an observed reduction in CMR-measured fibrosis and an improvement in myocardial strain.

We present a case of recurrent isolated cardiac sarcoidosis, 3 years post-heart transplantation. The case highlights the scarcity of data on the utility of immunosuppression in cardiac sarcoidosis and, in particular, raises questions about the optimal immunosuppression regimen in transplant recipients. (Level of Difficulty: Advanced.), Graphical abstract

The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. However, the IAP has an estimated failure rate of 13% at 10 years post-procedure (Tulchinsky et al., Ann Surg 238(2):229–34, 2003), which can result in pouch excision (P.E.). This systematic review aims to synthesise all the available studies reporting post-operative outcomes of P.E. and its impact on patient quality of life (QoL), when available, which have not previously been summarised. PubMed, Embase, Medline and the Cochrane library databases were searched with terms ‘Pouch AND excision’ OR ‘Pouch AND removal’ OR ‘Pouch AND remove’ OR ‘IAP AND excision’. All studies reporting post-operative morbidity, mortality or functional outcomes in patients who had P.E. were included. Studies with

BACKGROUND Better tools are needed to diagnose and identify children at risk of clinical malnutrition. OBJECTIVES We aimed to compare body composition (BC) and malnutrition screening tools (MSTs) for detecting malnutrition on admission; and examine their ability to predict adverse clinical outcomes [increased length of stay (LOS) and complications] in complex pediatric patients. METHODS This was a prospective study in children 5-18 y old admitted to a tertiary pediatric hospital (n = 152). MSTs [Pediatric Yorkhill Malnutrition Score (PYMS), Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGkids)] were completed on admission. Weight, height, and BC [fat mass (FM) and lean mass (LM) by DXA] were measured (n = 118). Anthropometry/BC and MSTs were compared with each other and with clinical outcomes. RESULTS Subjects were significantly shorter with low LM compared to reference data. Depending on the diagnostic criteria used, 3%-17% were classified as malnourished. Agreement between BC/anthropometric parameters and MSTs was poor. STAMP and STRONGkids identified children with low weight, LM, and height. PYMS, and to a lesser degree STRONGkids, identified children with increased LOS, as did LM compared with weight or height. Patients with complications had lower mean ± SD LM SD scores (-1.38 ± 1.03 compared with -0.74 ± 1.40, P

The aim was to investigate whether an intensive lifestyle intervention, with high volumes of exercise, improves beta cell function and to explore the role of low-grade inflammation and body weight. This was a randomised, assessor-blinded, controlled trial. Ninety-eight individuals with type 2 diabetes (duration

PURPOSE: There is increasing clinical utilization of hearts from the donation after circulatory death (DCD) pathway with the aim of expanding the donor pool and mitigating the ever-present discrepancy between the inadequate availability of good quality donor hearts and the rising number of patients with end-stage heart failure. METHODS: This article reviews the rationale, practice, logistical factors, and 5-year experience of DCD heart transplantation at St Vincent’s Hospital, Sydney. FINDINGS: Between July 2014 and July 2019, 69 DCD donor retrievals were undertaken resulting in 49 hearts being instrumented on an ex situ normothermic cardiac perfusion device. Seventeen (35%) of these hearts were declined and the remaining 32 (65%) were used for orthotopic DCD heart transplantation. At 5 years of follow-up, the 1-, 3-, and 5-year survival was 96%, 94%, and 94% for DCD hearts compared with 89%, 83%, and 82% respectively for donation after brain death (DBD) hearts (n.s). The immediate post-implant requirement for temporary extra-corporeal membrane oxygenation (ECMO) support for delayed graft function was 31% with no difference in rejection rates when compared with the contemporaneous cohort of patients transplanted with standard criteria DBD hearts. SUMMARY: DCD heart transplantation has become routine and incorporated into standard clinical practice by a handful of pioneering clinical transplant centres. The Australian experience demonstrates that excellent medium-term outcomes are achievable from the use of DCD hearts. These outcomes are consistent across the other centres and consequently favour a more rapid and wider uptake of heart transplantation using DCD donor hearts, which would otherwise be discarded.

BACKGROUND Frailty is a clinically recognized syndrome of decreased physiological reserve and a key contributor to suboptimal clinical outcomes in various lung disease groups. Interstitial lung disease (ILD) is fast approaching chronic obstructive pulmonary disease as the number one indication for lung transplantation worldwide. Our aim was to assess whether frailty is a predictor of mortality in patients with ILD referred for lung transplantation in an Australian cohort. METHODS Consecutive patients with ILD referred or on the waiting list for lung transplantation from May 2013 to December 2017 underwent frailty assessment using the modified Fried's frailty phenotype. Frailty was defined as a positive response to ≥3 of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. RESULTS One hundred patients (82 male:18 female; age, 59 ± 7 y; range, 30-70) underwent frailty assessment. Twenty-four of 100 (24%) were assessed as frail. Frailty was associated with anemia, hypoalbuminemia, low creatinine, and the use of supplemental oxygen (all P < 0.05). Frailty was independent of age, gender, measures of pulmonary dysfunction (PaO2, forced vital capacity percentage predicted, total lung capacity, total lung capacity percentage predicted, DLCO, or DLCO percentage predicted), cognitive impairment, or depression. Frailty and DLCO % predicted were independent predictors of increased all-cause mortality: 1-year actuarial survival was 86 ± 4% in the nonfrail group compared with 58 ± 10% for the frail group (P = 0.002). CONCLUSIONS Frailty is common among patients referred for lung transplant with a diagnosis of ILD and is associated with a marked increase in mortality.

BACKGROUND Frailty is prevalent in patients with heart failure (HF) and associated with increased morbidity and mortality. Hence, there has been increased interest in the reversibility of frailty following treatment with medication or surgery. This systematic review aimed to assess the reversibility of frailty in patients with HF before and after surgical interventions aimed at treating the underlying cause of HF. It also aimed to assess the efficacy of cardiac rehabilitation and prehabilitation in reversing or preventing frailty in patients with HF.Methods and Results:Searches of PubMed, MEDLINE and Academic Search Ultimate identified studies with HF patients undergoing interventions to reverse frailty. Titles, abstracts and full texts were screened for eligibility based on the PRISMA guidelines and using predefined inclusion/exclusion criteria in relation to participants, intervention, control, outcome and study design. In total, 14 studies were included: 3 assessed the effect of surgery, 7 assessed the effect of rehabilitation programs, 2 assessed the effect of a prehabilitation program and 2 assessed the effect of program interruptions on HF patients. CONCLUSIONS Overall, it was found that frailty is at least partially reversible and potentially preventable in patients with HF. Interruption of rehabilitation programs resulted in deterioration of the frailty status. Future research should focus on the role of prehabilitation in mitigating frailty prior to surgical intervention.

Aim Effective, high-quality patient handovers between the surgical team are essential for safe transfer of responsibility for patient care whilst ensuring continued patient-safety and supporting good clinical governance. Weekend handovers provide a particular challenge, with error potential, when patients are cared for by multiple different healthcare professionals. This project aimed to improve the documentation of the weekend handover for the surgical inpatients of a busy UK teaching hospital. Method Quality Improvement project performed within a single General Surgical department between August and October 2020. An initial casenote audit on 3 consecutive Fridays compared available handover information against RCS guidance. A comprehensive surgical weekend handover sticker was designed and all members of the surgical team educated in its use. Following sticker introduction, handover quality was similarly re-audited. **=p Results 138 inpatient records were evaluated in cycle 1 and 135 in cycle 2, with the proportion containing a weekend handover increased post-intervention (96 vs. 82%,p=0.0004). Handover quality improved following sticker introduction with more frequent documentation of: diagnosis (96 vs. 21%**); need for imaging review (94 vs. 29%**); intravenous fluid plan (84 vs. 21%**); blood test requirements (94 vs. 24%**); mode of nutrition (90 vs. 24%**); antibiotics (90 vs. 30%**); drug monitoring (90 vs. 1%**); discharge planning (94 vs. 44%**) and escalation plan (87 vs. 0%**). Conclusion Introduction of a sticker has significantly improved the quality of documented handover available to the responsible on-call team. Future work will assess sticker impact on quality of care and clinical outcomes.

Background: Ischemia–reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function. Methods: We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell–derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents. Results: Analysis of human complex trait genetics indicates that variants in the ASIC1 genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using human induced pluripotent stem cell–derived cardiomyocytes in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacologic inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction and 2 models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as preconditioning or postconditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no effect on cardiac ion channels regulating baseline electromechanical coupling and physiologic performance. Conclusions: Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

IntroductionThe effects of lifestyle interventions in persons with type 2 diabetes (T2D) on health-related quality of life (HRQoL) and subjective well-being are ambiguous, and no studies have explored the effect of exercise interventions that meet or exceed current recommended exercise levels. We investigated whether a 1-year intensive lifestyle intervention is superior in improving HRQoL compared with standard care in T2D persons.Research design and methodsWe performed secondary analyses of a previously conducted randomized controlled trial (April 2015 to August 2016). Persons with non-insulin-dependent T2D (duration ≤10 years) were randomized to 1-year supervised exercise and individualized dietary counseling (ie, ‘U-TURN’), or standard care. The primary HRQoL outcome was change in the 36-item Short Form Health Survey (SF-36) physical component score (PCS) from baseline to 12 months of follow-up, and a key secondary outcome was changes in the SF-36 mental component score (MCS).ResultsWe included 98 participants (U-TURN group=64, standard care group=34) with a mean age of 54.6 years (SD 8.9). Between-group analyses at 12-month follow-up showed SF-36 PCS change of 0.8 (95% CI −0.7 to 2.3) in the U-TURN group and deterioration of 2.4 (95% CI −4.6 to −0.1) in the standard care group (difference of 3.2, 95% CI 0.5 to 5.9, p=0.02) while no changes were detected in SF-36 MCS. At 12 months, 19 participants (30%) in the U-TURN group and 6 participants (18%) in the standard care group achieved clinically significant improvement in SF-36 PCS score (adjusted risk ratio 2.6, 95% CI 1.0 to 4.5 corresponding to number needed to treat of 4, 95% CI 1.6 to infinite).ConclusionIn persons with T2D diagnosed for less than 10 years, intensive lifestyle intervention improved the physical component of HRQoL, but not the mental component of HRQoL after 1 year, compared with standard care.Trial registration numberNCT02417012.

AIMS: Metformin may have clinical benefits in dialysis patients; however, its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients. METHODS: MEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials and observational studies evaluating metformin use in dialysis patients. Three authors reviewed the studies and extracted data. The primary outcomes were mortality, occurrence of lactic acidosis and myocardial infarction (MI) in patients taking metformin during dialysis treatment for ≥12 months (long term). Risk of bias was assessed using Risk Of Bias In Nonrandomised Studies of Interventions (ROBINS‐1). Overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen observational studies were eligible; 7 were prospective observational studies and 8 were case reports/case series. No randomised controlled trials were identified. The 7 prospective observational studies (n = 194) reported on cautious metformin use in patients undergoing maintenance dialysis. Only 3 provided long‐term follow‐up data. In 2 long‐term studies of metformin therapy (≤1000 mg/d) in patients undergoing peritoneal dialysis (PD), 1 reported 6 deaths (6/83; 7%) due to major cardiovascular events (3 MI) and the other reported no deaths (0/35). One long‐term study of metformin therapy (250 mg to 500 mg thrice weekly) in patients undergoing haemodialysis reported 4 deaths (4/61; 7%) due to major cardiovascular events (2 MI). These findings provide very low‐quality evidence as they come from small observational studies. CONCLUSION: The evidence regarding the safety of metformin in people undergoing dialysis is inconclusive. Appropriately designed randomised controlled trials are needed to resolve this uncertainty.

Rates of dementia continue to increase along with life expectancy. As neither dementia’s causenor its cure is well understood from the perspective of medical science, further investigations ofcomplementary lifestyle and non-pharmaceutical interventions are imperative. Although arts-basedtherapies have been explored selectively, the significance of these interventions for persons withdementia (PwD) remains undervalued in both the general population and scientific literature. Thisstudy aims to examine one promising lifestyle intervention, the effect of intergenerational choirparticipation, on psychosocial and cognitive function for PwD. Participants (n = 32), in partnershipwith their family caregivers and local high school students, participated in an intergenerational choirfor as many as three choir seasons spanning up to 18 months of follow-up. Participants underwent anexpansive assessment of psychosocial, physiological, and cognitive function every four to six weeksas part of an intensive repeated measures design. Here, the potential benefits of choir for PwD wereexplored in relation to change for select cognitive (Mini-Mental State Examination: MMSE; TrailMaking Task A: TMT-A; Word Recall) and psychosocial (Patient Health Questionnaire: PHQ-9)indicators. Multilevel modelling was used to index initial levels (at baseline) and change (spanningup to eight follow-up assessments) in function for measures of global cognition, executive functioning,episodic memory, and depressive symptoms. Notably, no significant declines were observed for MMSEor TMT-A tasks. As expected, episodic memory function continued to decline, with a significantlessening of depressive symptoms and signs observed for the PHQ-9. These results suggest thatdespite the progressive nature of underlying neuropathology for dementia subtypes like Alzheimer’sDisease, preservation of select cognitive functions as well as mitigation of psychosocial comorbidities(depressive symptoms) is possible through participation in an intergenerational choir.

Background To determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN). Methods An prospective double-blind randomized controlled trial studying surgical infants receiving PN for at least 5 days for congenital or acquired intestinal anomalies (2009-2012) was used. Infants were randomized to receive either glutamine supplementation (parenteral plus enteral; total 400 mg/kg/d) or isonitrogenous control. The primary end point was microbial invasion evaluated after 5 days of supplementation and defined as: (i) positive conventional blood culture, (ii) evidence of microbial DNA in blood (polymerase chain reaction), (iii) plasma endotoxin level ≥50 pg/mL, or (iv) plasma level of lipopolysaccharide binding protein ≥50 ng/mL. Data are given as median (range) and compared by logistic regression. Results Sixty infants were randomized and reached the primary end point. Twenty-five patients had intestinal obstruction, 19 had abdominal wall defects, and 13 had necrotizing enterocolitis. Thirty-six infants showed evidence of microbial invasion during the study, and 17 of these were not detected by conventional blood culture. There was no significant difference between the 2 groups in the primary outcome; evidence of microbial invasion after 5 days was found in 9/31 (control group) and 8/29 (glutamine group) (odds ratio 0.83 [0.24-2.86; P = 0.77]). Conclusion More than half of surgical infants requiring PN showed evidence of microbial invasion. Approximately half of this was not detectable by conventional blood cultures. Parenteral plus enteral glutamine supplementation had no effect on incidence of microbial invasion.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. To appraise published studies on the use of supplemental oxygen in chronic heart failure. Chronic breathlessness is a characterizing symptom of symptomatic heart failure resulting in substantial disability and healthcare utilization and is the primary reason for emergency room visits and hospitalizations. In spite of the variable evidence, oxygen therapy is commonly administered both acutely and chronically. Moreover, the role of oxygen therapy to relieve chronic breathlessness in heart failure is not well described, particularly in normoxemic or mild or intermittent hypoxemic states. In fact, several studies have shown the detrimental effects of oxygen therapy with normal oxygen saturation levels. A systematic review using PRISMA guidelines. Four databases PubMed, Embase, CINAHL, and Web of Science were systematically searched from January 2001 to January 2019 investigating the use of oxygen in heart failure. Duplicate articles were removed from the review. Titles and abstracts were screened for inclusion and exclusion criteria. The remaining full-text articles were reviewed and hand-searched for additional references. The quality of the full-text articles was assessed using standardized critical appraisal instruments by the Joanna Briggs Institute. A total of 11 studies, including three intervention and eight non-interventions studies, were included in this review from 1072 non-duplicated records retrieved. Sample size ranged from 4 to 5862. In spite of common usage, this review suggests that there are scant data available to justify the use of oxygen in individuals with non-hypoxemic chronic heart failure and chronic breathlessness.

Objective: Attention and executive function (EF) deficits are ubiquitous in neurodevelopmental disorders including Attention Deficit/Hyperactivity Disorder (ADHD), as are high levels of intraindividual variability (IIV). Attention and EF are typically assessed using informant ratings and objective measures; however, discrepancies between different metrics often make it difficult to fully characterize a child's attention capabilities, and IIV has been proposed as a potentially useful discriminator. Our objective was to explore the relationship between IIV, using the residualized intraindividual standard deviation (rISD) method, and informant ratings of attention and EF in a mixed pediatric sample, to determine the potential utility of IIV for aiding attention diagnostics. Another commonly used, though controversial, IIV indicator, the coefficient of variation (ICV), was calculated for comparison purposes. Method: We assessed 51 children with varying degrees of attention and EF deficits. Measures included parent and teacher responses on the Comprehensive Executive Function Inventory (CEFI) and response times (RT) on a go/no-go task, which were used to estimate IIV. Results: Mean RT, rISD, and ICV were significantly related to parent and teacher ratings of attention, though ICV showed a relatively weaker association. rISD also showed associations with parent ratings of working memory and self-monitoring, as well as teacher ratings of working memory. Conclusion: The significant, and relatively stronger, relationship between rISD and parent and teacher ratings of attention supports the use of this metric, compared to mean RT and ICV. The rISD indicator of IIV thus shows potential utility as a unique and objective measure of attention in children across various neurodevelopmental disorders and, with additional research, may prove useful for diagnosis of attention problems.

Background Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice. Objectives The purpose of this study is to provide an update on the authors’ Australian clinical program and discuss lessons learned since performing the world’s first series of distantly procured DCD heart transplants. Methods The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent’s Hospital. Results Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function. Conclusions DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors.

© 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ) Background: Chronic heart failure is a complex and multifaceted syndrome characterised by an unpredictable trajectory, high symptom burden and reduced quality of life. Although palliative care is recommended, patient, provider and system factors limit access. Aim: To examine the knowledge, attitudes and perspectives of health care professionals towards end of life care and palliative care for patients with chronic heart failure. Design: This is an integrative review. Data sources: CINAHL, Academic Search Complete and SCOPUS were searched. Specific inclusion criteria and search terms were used. The integrative review method entailed analysing data from primary articles using the constant comparison method and then synthesising data. Results: Twenty-six (26) articles were selected that explored health care professionals’ perspectives towards end of life care and palliative care. The categories that emerged were grouped into patient, provider and system issues. Most health care professionals involved in providing care to heart failure patients have misperceptions of palliative care, often confusing it with end of life and hospice care. This hinders patients’ access to palliative care as determining the end of life period in heart failure is difficult. Conclusions: Exploring health care professionals’ perspectives towards the delivery of end of life care and palliative care is important for understanding how their practice influences the delivery of palliative care for heart failure patients. Emphasis on increasing awareness of the principles of palliative care in the health care community, as well as addressing organisational issues will improve the care delivered to these patients.

BackgroundThe study aimed to determine whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty (PF) is associated with the risk of lung transplant (LTX) waitlist mortality.MethodsSince March 2013, all patients referred for LTX evaluation underwent PF assessment. Cognition was assessed using the Montreal Cognitive Assessment and depression assessed using the Depression in Medical Illness questionnaire. We assessed the association of 4 composite frailty measures: PF ≥3 of 5 = frail, cognitive frailty (CogF ≥ 3 of 6 = frail), depressive frailty (DepF ≥ 3 of 6 = frail), and combined frailty (ComF ≥ 3 of 7 = frail) with waitlist mortality.ResultsThe prevalence of PF was 78 (22%), CogF 100 (28%), DepF 105 (29%), and ComF 124 (34%). Waitlist survival in the non-PF group was 94% ± 2% versus 71% ± 7% in the PF group (p < 0.001). Cox proportional hazards regression analysis demonstrated that PF (Adjusted HR, 4.88; 95% CI, 2.06 - 11.56), mild cognitive impairment (Adjusted HR, 3.03; 95% CI, 1.05 - 8.78) and hypoalbuminemia (Adjusted HR, 0.89; 95% CI, 0.82 - 0.97) were independent predictors of waitlist mortality. There was no significant difference in the area under the curve of the 4 frailty measures.ConclusionsThe addition of cognitive function and depression variables to the PF assessment increased the number of patients classified as frail. However, the addition of these variables, does not strengthen the association with LTX waitlist mortality compared to the PF measure.

BACKGROUND The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality. METHODS Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment (MOCA) to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality. RESULTS 313 patients (233 male, 80 female; age 53 ± 13 years) were assessed. Of these, 224 patients (72%) were nonfrail and 89 (28%) were frail using the PF. The cognitive frailty assessment identified an additional 30 patients as frail: 119 (38%). Frail patients had significantly increased mortality as compared to nonfrail patients. Ventricular assist device and heart transplant-censored survival at 12 months was 92 ± 2 % for nonfrail and 69 ± 5% for frail patients (p < 0.0001) using the CogF instrument. CONCLUSIONS This study validates our previously published findings that frailty is prevalent in patients with advanced heart failure referred for heart transplantation. Physical frailty predicts early mortality. The addition of cognitive assessment to the physical assessment of frailty identifies an additional cohort of patients with a similarly poor prognosis.

Purpose Hemolysis is an important complication of ventricular assist device (VAD) therapy. Several studies have postulated that chronic hemolysis may be a cause of adverse outcomes in patients with VADs, but consistent definitions and clinical outcome data are lacking. Methods We conducted a single-center retrospective cohort study examining survival to transplantation in patients who underwent VAD implantation from 2010-2020. Baseline demographics, renal function, echocardiographic, and cardiac catheterization data for the first 12 months of VAD therapy or until transplantation were collected. Additionally, all available lactate dehydrogenase (LDH) values were collected over this time frame and means were calculated for each patient. Results VADs were implanted in 166 patients, 19% female and 87% left-sided devices. Patients with mean LDH above the upper limit of normal for our laboratory's LDH assay of 440 units/liter (U/L) were more likely to die prior to transplantation compared to those with mean LDH Conclusion Mean LDH above the normal range was an independent and significant predictor of mortality in patients with VADs awaiting transplantation at our center over the last decade. While concomitant severe liver or RV dysfunction can raise LDH, chronic hemolysis is an important potential etiology for our observations. Further work is needed to define chronic hemolysis and its impact on outcomes in patients with VADs.

Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

In spite of growing evidence supporting the occurrence of complex interactions between Schistosoma and gut bacteria in mice and humans, no data is yet available on whether worm-mediated changes in microbiota composition are dependent on the baseline gut microbial profile of the vertebrate host. In addition, the impact of such changes on the susceptibility to, and pathophysiology of, schistosomiasis remains largely unexplored. In this study, mice colonized with gut microbial populations from a human donor (HMA mice), as well as microbiota-wild type (WT) animals, were infected with Schistosoma mansoni, and alterations of their gut microbial profiles at 50 days post-infection were compared to those occurring in uninfected HMA and WT rodents, respectively. Significantly higher worm and egg burdens, together with increased specific antibody responses to parasite antigens, were observed in HMA compared to WT mice. These differences were associated to extensive dissimilarities between the gut microbial profiles of each HMA and WT groups of mice at baseline; in particular, the gut microbiota of HMA animals was characterized by low microbial alpha diversity and expanded Proteobacteria, as well as by the absence of putative immunomodulatory bacteria (e.g. Lactobacillus). Furthermore, differences in infection-associated changes in gut microbiota composition were observed between HMA and WT mice. Altogether, our findings support the hypothesis that susceptibility to S.mansoni infection in mice is partially dependent on the composition of the host baseline microbiota. Moreover, this study highlights the applicability of HMA mouse models to address key biological questions on host-parasite-microbiota relationships in human helminthiases.

Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease – processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.

BACKGROUND Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93–100) and 95% (91–99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76–96) and 74% (60–84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4–10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N‐terminal pro‐B‐type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC‐HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure, Graphical representation of the GALACTIC‐HF trial design, enrolment and baseline characteristics. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; CRT, cardiac resynchronization therapy (biventricular pacemaker); CV, cardiovascular; EF, ejection fraction; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter defibrillator; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, Hew York Heart Association; SBP, systolic blood pressure.

IL-13 plays a key role during protective type 2 immune responses at mucosal sites, such as during infection with nematodes. However, dysregulation of IL-13 can also contribute to the pathogenesis of atopic and fibrotic diseases such as allergic asthma. Matrix remodelling is an important component of repair processes in the lung but also a hallmark of chronic conditions involving fibrosis. Hence, understanding the role of IL-13 in tissue remodelling has important clinical implications. Since IL-13 shares receptors and signalling pathways with IL-4, disentangling the relative contributions of these type 2 cytokines has been challenging. Additionally, little is known about the singular role of IL-13 following acute tissue injury. In this study, we used Nippostrongylus brasiliensis infection as a model of acute lung tissue damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. Importantly, we found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung following infection. Through proteomic and transcriptomic profiling, we identified IL-13-dependent changes in matrix and associated regulators. We further showed that IL-13 is required for the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 was heavily involved in the induction of cellular stress responses and regulation of lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, we propose that IL-13 has tissue-protective functions during lung injury and regulates epithelial cell responses during type 2 immunity in this acute setting.

Exposure to loud noise causes damage to the inner ear, including but not limited to outer and inner hair cells (OHCs and IHCs) and IHC ribbon synapses. This cochlear damage impairs auditory processing and increases audiometric thresholds (noise-induced hearing loss, NIHL). However, the exact relationship between the perceptual consequences of NIHL and its underlying cochlear pathology are poorly understood. This study used a nonhuman primate model of NIHL to relate changes in frequency selectivity and audiometric thresholds to indices of cochlear histopathology. Three macaques (one Macaca mulatta and two Macaca radiata) were trained to detect tones in quiet and in noises that were spectrally notched around the tone frequency. Audiograms were derived from tone thresholds in quiet; perceptual auditory filters were derived from tone thresholds in notched-noise maskers using the rounded-exponential fit. Data were obtained before and after a four-hour exposure to a 50-Hz noise centered at 2 kHz at 141 or 146 dB SPL. Noise exposure caused permanent audiometric threshold shifts and broadening of auditory filters at and above 2 kHz, with greater changes observed for the 146-dB-exposed monkeys. The normalized bandwidth of the perceptual auditory filters was strongly correlated with audiometric threshold at each tone frequency. While changes in audiometric threshold and perceptual auditory filter widths were primarily determined by the extent of OHC survival, additional variability was explained by including interactions among OHC, IHC, and ribbon synapse survival. This is the first study to provide within-subject comparisons of auditory filter bandwidths in an animal model of NIHL and correlate these NIHL-related perceptual changes with cochlear histopathology. These results expand the foundations for ongoing investigations of the neural correlates of NIHL-related perceptual changes.

The purpose of this study was to explore and identify factors that influence motivation for and barriers to adopting and maintaining lifestyle changes in patients with type 2 diabetes, following participation in an intensive multiple-lifestyle intervention. Participants were recruited from the U-TURN trial, a one-year, intensive lifestyle intervention for type 2 diabetes patients. This study was conducted over time, informants were interviewed twice after the trial ended with a six-month interval between interviews. The qualitative data from these individual interviews were analysed using systematic text condensation with an inductive approach. Five themes emerged: Social support and relatedness, Achievement of results, Support from healthcare professionals, Identification with and acceptance of the new lifestyle and Coping with ongoing challenges. These are all important for maintaining lifestyle changes and diabetes self-management. Changing one&rsquo, s lifestyle can be a constant, difficult struggle. For sustainable progress after an intensive intervention, the changes must be adopted and endorsed by patients and co-opted into their social setting. Belonging to an exercise group, confidence in managing the lifestyle adjustments and handling of challenges through continual support and professional diabetes treatment are crucial in maintaining and adhering to the new lifestyle.

Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival.Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis.We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry.A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis.AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

Objective: Everolimus, a mammalian target-ofrapamycin (mTOR) inhibitor, is increasingly used post-transplantation due to favorable effects on renal function and malignancy risk when compared to other immunosuppressive treatments such as calcineurin inhibitors. However, it can confer adverse effects such as dyslipidemia, which is not underpinned by any long-term screening and management of dyslipidemia in heart transplant recipients treated with everolimus. Methods: We report a case of severe hypertriglyceridemia which developed after commencement of everolimus in a heart transplant recipient with a background of Dunnigan-type familial partial lipodystrophy. Results: The patient is a 36-year-old woman who underwent heart transplantation for dilated cardiomyopathy. About 11 weeks following commencement of everolimus as part of her antirejection medication regime, serum triglyceride level concentration peaked at 5,093 mg/dL (normal, 0.0 to 177.2 mg/dL). There were no clinical complications with triglycerides at this elevated level and it improved substantially following cessation of everolimus and initiation of a high dose intravenous insulin-dextrose infusion. Conclusion: This case highlights dyslipidemia as a potential complication of everolimus treatment and that appropriate screening is important as lipid lowering medication can effectively control levels and minimize adverse outcomes. Abbreviations: FPLD familial partial lipodystrophy LPL lipoprotein lipase MMF mycophenolate mofetil mTOR mammalian target-of-rapamycin

Purpose The purpose of this prospective evaluation is to document in-hospital management and discharge trends of patients presented for acute heart failure. Design A prospective evaluation of the patients presented for heart failure exacerbation at eight sites over 1 month using the method of the New South Wales Heart Failure Snapshot. Methods Trained personnel situated at each of the study sites recruited eligible patients to the study and collected data on their sociodemographic characteristics, clinical presentation, self-care, frailty, and depression. Findings Eight sites, out of the 27 contacted, agreed to participate in this study. A total of 137 admissions were reported in the 1-month time window. Mean age was 72 (SD = 13) years and the majority were female (52%). More than half (n = 60%) had heart failure reduced ejection fraction with a mean ejection fraction of 41%. The mean Charlson Comorbidity Index score was four with hypertension (80%) and diabetes (56%) being the most frequent. The majority were frail (86%), self-care mean scores were low; self-care maintenance (29), self-care management (48) and self-care confidence (42). The mean depression score was 14 indicating major depression. In reference to international guidelines recommendations, hospital administered medications and discharge medications were suboptimal. Some items of the discharge education recommended by the international guidelines were provided to 84% of the patients but none of the patients received the complete items of the discharge education. Conclusions The snapshot revealed that patients admitted for acute heart failure were frail with high levels of illiteracy and low self-care scores. Despite these findings, these patients were not provided with complete discharge education in reference to the international guidelines. Additionally, when provided, discharge education was inconsistent across the study sites. This study highlights the need for enlisting complete education as part of the discharge process, in addition to abidance to the guidelines in prescribing medication. The study draws major implications for nursing practice, research and policy. Clinical relevance Literacy among patients with heart failure is low and should be addressed in educational intervention to improve outcomes. Discharge education is under practiced across the country and should be implemented in accordance with the international guidelines.

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer, anti-helminth responses and response to colonic inflammation, the Mbd2-expressing cell types that control these responses are incompletely defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2-/- mice displayed dramatically worse pathology than wild type controls during dextran sulphate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.

One hallmark of mesenchymal stem cells (MSCs) is the ability to differentiate into multiple tissue types which assists in tissue regeneration. Another hallmark of MSCs is their potent anti-inflammatory and immunomodulatory properties and the potential to treat inflammatory, immune-mediated, and ischemic conditions. In equine practice, MSCs have shown efficacy in the treatment of musculoskeletal disorders such as tendinopathy, meniscal tears and cartilage injury. However, there are many equine disease processes and conditions that may benefit from the immunomodulatory properties of MSCs. Examples include conditions associated with overwhelming acute inflammatory response such as systemic inflammatory response syndrome to chronic diseases characterized by a prolonged low level of inflammation such as equine asthma and recurrent uveitis. For the acute inflammatory response processes, there is often high morbidity and mortality with no effective immunomodulatory treatment to prevent the overwhelming synthesis of proinflammatory mediators. For chronic inflammatory disease processes, frequently long-term corticosteroid treatment is the therapeutic mainstay, with serious potential complications. Thus, there is an unmet need for alternative anti-inflammatory treatments for both acute and chronic illnesses in horses. While MSCs show promise for such conditions, much research is needed before a clinically safe and effective treatment will be available. Optimal MSC tissue source, patient vs. donor source (autologous vs. allogeneic) and cell growth conditions need to be determined for each problem. For immediate use, allogeneic MSC treatments is preferable, but immune tolerance and adequate safety require further study. MSC collection and cryopreservation from horses before they are injured or ill, whether from umbilical cord tissue, bone marrow or adipose might become more widespread. Once these fundamental approaches to treating specific diseases with MSCs are determined, the route of administration, dose and timing of administration also need to be studied. To provide a framework for development of MSC immunomodulatory treatments, this article reviews the current understanding of equine MSC anti-inflammatory and immunomodulatory properties and proposes how MSC therapy may be further developed to treat acute onset systemic inflammatory processes and chronic inflammatory diseases.

Aims The cancer burden among Circumpolar Inuit is high. Palliative radiotherapy is a mainstay treatment for controlling symptoms of advanced cancers, but Inuit are required to travel far distances to access this service. Access to palliative radiotherapy and time away from home communities have not been explored among this population. We sought to describe the time intervals from symptom onset to the start of palliative radiotherapy among Canadian Inuit patients treated at The Ottawa Hospital (TOH). Materials and methods A retrospective review of Inuit patients from Nunavut treated with radiotherapy between 2005 and 2014 at TOH. Results Of a total of 152 radiotherapy patients, 88 (58%) were treated palliatively. Of these, 61 (70%) had stage IV disease at diagnosis and 63 (72%) had lung cancer. The median time from referral for specialist care to the patient's first flight to Ottawa was 4 days (range 0–97). The median length of treatment was 7 days (range 0–27), but patients spent a median of 64.5 days (range 14–633) in Ottawa. The median survival from the date of pathological diagnosis was 5.2 months. Conclusions Most Inuit radiotherapy patients at TOH were treated palliatively. Patients were brought from Nunavut relatively quickly for specialist care, which is encouraging. However, patients spent over 2 months away from home, in the context of a median survival of less than 6 months. Opportunities for improvement include both provider and system-level changes, which may be applicable to other Circumpolar Inuit regions across Europe and North America.

Objective: To investigate whether a dose-response relationship exists between volume of exercise and discontinuation of glucose-lowering medication treatment in patients with type 2 diabetes. Patients and Methods: Secondary analyses of a randomized controlled exercise-based lifestyle intervention trial (April 29, 2015 to August 17, 2016). Patients with non–insulin-dependent type 2 diabetes were randomly assigned to an intensive lifestyle intervention (U-TURN) or standard-care group. Both groups received lifestyle advice and objective target-driven medical regulation. Additionally, the U-TURN group received supervised exercise and individualized dietary counseling. Of the 98 randomly assigned participants, 92 were included in the analysis (U-TURN, n=61, standard care, n=31). Participants in the U-TURN group were stratified into tertiles based on accumulated volumes of exercise completed during the 1-year intervention. Results: Median exercise levels of 178 (interquartile range [IQR], 121-213; lower tertile), 296 (IQR, 261-310; intermediate tertile), and 380 minutes per week (IQR, 355-446; upper tertile) were associated with higher odds of discontinuing treatment with glucose-lowering medication, with corresponding odds ratios of 12.1 (95% CI, 1.2-119; number needed to treat: 4), 30.2 (95% CI, 2.9-318.5; 3), and 34.4 (95% CI, 4.1-290.1; 2), respectively, when comparing with standard care. Cardiovascular risk factors such as glycated hemoglobin A1c levels, fitness, 2-hour glucose levels, and triglyceride levels were improved significantly in the intermediate and upper tertiles, but not the lower tertile, compared with the standard-care group. Conclusion: Exercise volume is associated with discontinuation of glucose-lowering medication treatment in a dose-dependent manner, as are important cardiovascular risk factors in well-treated participants with type 2 diabetes and disease duration less than 10 years. Further studies are needed to support these findings. Study Registration: ClinicalTrials.gov registration (NCT02417012).