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There is emerging evidence of increase in injuries to children associated with abuse or neglect during the lockdown in response to the COVID-19 pandemic.1 We report an increase in the numbers of children under 16 years, during the COVID-19 lockdown period, with safeguarding concerns, and who were admitted under neurosurgery for head/spinal injuries following falls from height. Retrospective analysis of referrals from our hospital to children’s social care (CSC) from 1 April to 30 June 2020 was compared with data from the same period in 2018 and 2019. Children admitted with neurosurgical trauma, including falls out of buildings during school closure, were analysed. Referral to CSC and multiagency strategy meetings were used as an indicator of verifiable safeguarding concerns, justified by established organisational processes for convening strategy meetings after individualised case review, when there is risk of significant harm. During …

Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB., info:eu-repo/semantics/published

En Belgique francophone, pendant la période mars à fin mai 2020, 284 patients en dialyse ont contracté le Covid-19, soit 7,9% de la population prévalente, qu’ils aient été diagnostiques par rt-PCT parce que symptomatiques ou dépistés par culture virale systématique alors qu’asymptomatiques. Cinquante-deux décès ont été observés soit 18% de la population atteinte. La toute grand majorité de ces patients (274) étaient traités par hémodialyse en centre, seuls 10 patients étaient en traitement à domicile. Leurs maladies rénales primitives étaient à plus de 50% des diabète et pathologies vasculaires hypertensives et leurs comorbidités essentielles, les pathologies cardiovasculaires ischémiques et congestives, les problèmes d’autonomie, les néoplasies et le tabagisme., Bulletin de la Dialyse à Domicile, Vol. 3 No 3 (2020): Bulletin de la Dialyse à Domicile

ObjectivesTo determine any change in referral patterns and outcomes in children (0-18) referred for child protection medical examination (CPME) during the covid-19 pandemic compared to previous years.DesignRetrospective observational study, analysing routinely collected clinical data from CPME reports in a rapid response to the pandemic lockdown.SettingBirmingham Community Healthcare NHS Trust, which provides all routine CPME for Birmingham, England, population 1.1 million including 288,000 children.ParticipantsChildren aged under 18 years attending CPME during an 18 week period from late February to late June during the years 2018, 2019, and 2020.Main Outcome MeasuresNumbers of referrals, source of disclosure and outcomes from CPMEResultsThere were 78 CPME referrals in 2018, 75 in 2019 and 47 in 2020, this was a 39.7% (95%CI 12.4-59.0) reduction in referrals from 2018 to 2020, and a 37.3% (95%CI 8.6-57.4) reduction from 2019 to 2020. There were fewer CPME referrals initiated by school staff in 2020, 12(26%) compared to 36 (47%) and 38 (52%) in 2018 and 2019 respectively. In all years 75.9% of children were known to social care prior to CPME, and 94% of CPME concluded that there were significant safeguarding concerns.ConclusionsSchool closure due to covid-19 may have harmed children as child abuse has remained hidden. There needs to be either mandatory attendance at schools in future or viable alternatives found. There may be a significant increase in safeguarding referrals when schools fully re-open as children disclose the abuse they have experienced at home.Article summary: Strengths and Limitations of the StudyThis is a highly robust study: we obtained CPME reports for 97% of CPME referrals during the study period.We ensured consistency of data extraction by double reviewing every report, with further consensus discussions for the few cases that raised uncertainties.The team extracting the data comprised highly experienced paediatricians with expertise in child abuse.One weakness is that we only considered minor injuries from outpatient CPME, excluding those admitted to hospital, so our findings do not include those with more serious NAI, however they would be taken to hospital for treatment due to the severity of their injuries.

ObjectiveTo describe a safeguarding decision pathway for the assessment of osteopenic fractures in non-ambulant children with cerebral palsy.MethodLiterature review and consensus practice of a child safeguarding team, including clinicians and social workers.ConclusionLow-energy fractures of the lower limb in non-ambulant children with cerebral palsy are relatively common and explained by the presence of reduced bone strength, in the absence of any other unexplained injuries or safeguarding concerns.

Data Availability Statement: The datasets generated for this study are available on request to the corresponding author. Copyright © 2020 Debelle, Harkness-Armstrong, Hadwin, Maganaris and O'Brien. Aim: Falls commonly occur from trips and slips while walking. Recovery strategies from trips and backward falling slips have been extensively studied. However, until recently, forward falling slips (FFSs) have been considered less dangerous and have been understudied. This study aimed first to create an application to realistically simulate FFSs using a split-belt instrumented treadmill and then to understand the biomechanical requirements for young adults to recover from an FFS. Methods: We developed a semi-automatic custom-made application on D-Flow that triggered FFSs by briefly and unexpectedly increasing the speed (a = 5 m·s−2) of the right belt during stance. To validate the protocol, we tested against criteria defined for an ecologically and experimentally valid FFS: unexpected occurrence of the slip, increased foot velocity, forward loss of balance during the slip and consistent perturbation timing. We evaluated the recovery strategies of 17 young adults by measuring dynamic stability, joint moments and ground reaction force (GRF) vector angles before, during and on 15 steps following the FFS. Results: The application successfully triggered FFSs, according to the criteria we defined. Participants' balance returned to normal for a minimum of three consecutive steps in 10.9 (7.0) steps. Recovery from the FFSs was characterised by larger hip flexor and knee extensor moments to support the centre of mass during the slip, and a longer first recovery step with large hip extensor moments to arrest the fall followed by large knee extensor moments to raise and advance the centre of mass into the next step (p < 0.001 compared with normal gait). Subsequent steps progressively returned to normal. Conclusion: This is the first study to experimentally simulate FFSs meeting the aforementioned criteria, and to measure their effects on the dynamic balance and kinetic parameters. The split-belt instrumented treadmill proved a promising tool to better study the mechanisms of falls and recovery. The required large hip and knee joint moments generally agree with findings on trips and backward falling slips and provide an indication of the functional capacities that should be targeted in fall-prevention interventions. These findings should be used to better understand and target the mechanisms of balance loss and falls in older adults following FFSs. Minerva Research Labs Ltd. (London, UK); Liverpool John Moores University.

Objectives Describe cases of female genital mutilation (FGM) presenting to consultant paediatricians and sexual assault referral centres (SARCs), including demographics, medical symptoms, examination findings and outcome. Design The well-established epidemiological surveillance study performed through the British Paediatric Surveillance Unit included FGM on the monthly returns. Setting All consultant paediatricians and relevant SARC leads across the UK and Ireland. Patients Under 16 years old with FGM. Interventions Data on cases from November 2015 to November 2017 and 12 months later meeting the case definition of FGM. Main outcome measures Returns included 146 cases, 103 (71%) had confirmed FGM and 43 (29%) did not meet the case definition. There were none from Northern Ireland. Results The mean reported age was 3 years. Using the WHO classification of FGM, 58% (n=60) had either type 1 or type 2, 8% (n=8) had type 3 and 21% (n=22) had type 4. 13% (n=13) of the cases were not classified and none had piercings or labiaplasty. The majority, 70% had FGM performed in Africa with others from Europe, Middle East and South-East Asia. There were few physical and mental health symptoms. Only one case resulted in a successful prosecution. Conclusions There were low numbers of children presenting with FGM and in the 2 years there was only one prosecution. The findings may be consistent with attitude changes in FGM practising communities and those at risk should be protected and supported by culturally competent national policies

Data Availability Statement: The datasets generated for this study are available on request to the corresponding author. Copyright © 2020 Harkness-Armstrong, Debelle, Maganaris, Walton, Wright, Bass, Baltzopoulos and O’Brien. Aim: To study the causes of locomotor dysfunction, estimate muscle forces, or understand the influence of altered sarcomere and muscle properties and behaviours on whole body function, it is necessary to examine the leverage with which contractile forces operate. At the ankle joint, current methods to quantify this leverage for the plantarflexors do not account for curvature of the Achilles tendon, and so may not be appropriate when studying equinus gait. Thus, novel methodologies need to be developed and implemented to quantify the Achilles tendon moment arm length during locomotion. Methods: Plantarflexor internal moment arm length and effective mechanical advantage of 11 typically developed young adults were calculated throughout stance, while heel-toe walking and voluntarily toe-walking on an instrumented treadmill. Achilles tendon moment arm was defined in two-ways: (1) assuming a straight tendon, defined between the gastrocnemius medialis myotendinous junction and Achilles tendon insertion point, and (2) accounting for tendon curvature, by tracking the initial path of the Achilles tendon from the calcaneal insertion. Results: When accounting for tendon curvature, Achilles tendon moment arm length and plantarflexor effective mechanical advantage did not differ between walking conditions (p > 0.05). In contrast, when assuming a straight tendon, Achilles tendon moment arm length (p = 0.043) and plantarflexor effective mechanical advantage (p = 0.007) were significantly greater when voluntary toe-walking than heel-toe walking in late stance. Discussion: Assuming a straight Achilles tendon led to a greater Achilles tendon moment arm length and plantarflexor effective mechanical advantage during late stance, compared to accounting for tendon curvature. Consequently, plantarflexor muscle force would appear smaller when assuming a straight tendon. This could lead to erroneous interpretations of muscular function and fascicle force-length-velocity behaviour in vivo, and potentially inappropriate and ineffective clinical interventions for equinus gait. Liverpool John Moores University Ph.D. scholarship.

The Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) has recently published what they purported to be a systematic review of the literature on ‘isolated traumatic shaking’ in infants, concluding that ‘there is limited evidence that the so-called triad (encephalopathy, subdural haemorrhage, retinal haemorrhage) and therefore its components can be associated with traumatic shaking’. This flawed report, from a national body, demands a robust response. The conclusions of the original report have the potential to undermine medico-legal practice. We have conducted a critique of the methodology used in the SBU review and have found it to be flawed, to the extent that children’s lives may be put at risk. Thus, we call on this review to be withdrawn or to be subjected to international scrutiny.

Supplemental Digital Content is available in the text., Cariprazine, a potent dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, is Food and Drug Administration approved for treating schizophrenia and manic or mixed episodes of bipolar I disorder. A post-hoc safety/tolerability analysis of data from the four acute trials in the cariprazine schizophrenia clinical development program (NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the overall safety population (all patients who received ≥1 dose of study drug) and modal daily dose subgroups (1.5–3, 4.5–6, and 9–12 mg/day). These exploratory findings were summarized using descriptive statistics. Cariprazine was generally well tolerated. The incidence of treatment-emergent adverse events versus placebo was similar for cariprazine 1.5–3 mg/day and higher for cariprazine 4.5–6 and 9–12 mg/day; a dose–response relationship was observed for akathisia, extrapyramidal symptoms, and diastolic blood pressure. The mean changes in metabolic parameters were generally similar in cariprazine-treated and placebo-treated patients. There was no prolactin level increase or QTc value greater than 500 ms; small increases in mean body weight (∼1to2 kg) versus placebo were observed. Within the Food and Drug Administration-approved dose range (1.5−6 mg/day), cariprazine was generally safe and well tolerated in patients with schizophrenia.

Atypical antipsychotics have broad-spectrum efficacy against core symptoms of acute mania/mixed states in bipolar disorder; however, they are associated with clinically significant adverse effects (AEs).This post hoc analysis evaluated the safety and tolerability of the atypical antipsychotic cariprazine in the treatment of adult patients with acute manic/mixed episodes of bipolar I disorder. Data were taken from three 3-week randomized, double-blind, placebo-controlled, flexible-dose trials of cariprazine 3-12mg/d. Patient subgroups categorized by modal daily dose (3-6mg/d; 9-12mg/d) were used to assess dose response.The pooled safety population comprised 1065 patients (placebo=442; cariprazine 3-6mg/d=263; cariprazine 9-12mg/d=360). More cariprazine- than placebo-treated patients reported double-blind treatment-emergent AEs; the overall AE incidence was similar among cariprazine-dose groups. AEs reported in ≥5% of cariprazine patients overall with at least twice the incidence of placebo were akathisia, extrapyramidal symptoms, restlessness, and vomiting. The incidence of SAEs was low and similar between the placebo- and cariprazine-treatment groups. Metabolic parameter changes were small and generally similar between cariprazine and placebo groups; mean increases in fasting glucose levels were greater with cariprazine (3-6mg/d=6.6mg/dL; 9-12mg/d=7.2mg/dL) than placebo (1.7mg/dL). Mean weight change was 0.54kg and 0.17kg for cariprazine and placebo, respectively; weight increase ≥7% was3% in all treatment groups. Cariprazine was not associated with clinically meaningful changes in electrocardiogram parameters.Post hoc analysis, flexible-dose design, short trial duration.Cariprazine was generally safe and well-tolerated in patients with manic/mixed episodes associated with bipolar I disorder.

Summary Background Although predominant negative symptoms of schizophrenia can be severe enough to cause persistent impairment, effective treatment options are lacking. We aimed to assess the new generation antipsychotic cariprazine in adult patients with predominant negative symptoms. Methods In this randomised, double-blind, phase 3b trial, we enrolled adults aged 18–65 years with long-term (>2 year), stable schizophrenia and predominant negative symptoms (>6 months) at 66 study centres (mainly hospitals and university clinics, with a small number of private practices) in 11 European countries. Patients were randomly assigned (1:1) by an interactive web response system to 26 weeks of monotherapy with fixed-dose oral cariprazine (3 mg, 4·5 mg [target dose], or 6 mg per day) or risperidone (3 mg, 4 mg [target dose], or 6 mg per day); previous medication was discontinued over 2 weeks. The primary outcome was change from baseline to week 26 or end of treatment on the Positive and Negative Syndrome Scale factor score for negative symptoms (PANSS-FSNS) analysed in a modified intention-to-treat population of patients who had follow-up assessments within 5 days after last receipt of study drugs with a mixed-effects model for repeated measures. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, number 2012-005485-36. Findings Between May 27, 2013, and Nov 17, 2014, 533 patients were screened and 461 (86%) patients were randomised to treatment (230 for cariprazine and 231 for risperidone); 460 were included in the safety population (one patient discontinued before study drug intake). 227 (99%) of 230 patients in the cariprazine group and 229 (99%) of 230 patients in the risperidone group were included in the modified intention-to-treat population (178 [77%] in each group completed 26 weeks of treatment). Mean daily doses were 4·2 mg (SD 0·6) for cariprazine and 3·8 mg (0·4) for risperidone. Treatment-emergent adverse events (eg, insomnia, akathisia, worsening of schizophrenia, headache, anxiety) were reported in 123 (54%) patients treated with cariprazine and 131 (57%) patients treated with risperidone. Use of cariprazine led to a greater least squares mean change in PANSS-FSNS from baseline to week 26 than did risperidone (−8·90 points for cariprazine vs −7·44 points for risperidone; least squares mean difference −1·46, 95% CI −2·39 to −0·53; p=0·0022; effect size 0·31). One patient in the risperidone group died of a cause regarded as unrelated to treatment. Interpretation Our results support the efficacy of cariprazine in the treatment of predominant negative symptoms of schizophrenia. Funding Gedeon Richter Plc.

Rationale & Objective Membranous nephropathy (MN) is characterized by the deposition of immune complexes along glomerular basement membranes. M-Type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), exostosin 1 and 2 (EXT1/2), and neural epidermal growth factor-like 1 protein (NELL-1) have been identified as established or potential podocyte antigens in MN. We investigated the association of podocyte antigen staining with MN clinical phenotype and outcomes. Study Design Multicenter retrospective cohort study. Setting & Participants 177 consecutive patients with MN unrelated to lupus erythematosus, identified after screening of 3,875 native kidney biopsies performed in the Belgian UCLouvain Kidney Disease Network from 2000 through 2018. Predictor Positive immunostaining for podocyte antigens on archived kidney biopsy samples. Outcomes Association with different phenotypes (baseline characteristics of patients and pathologic findings on kidney biopsy), time to cancer and to kidney failure. Analytical Approach Kaplan-Meier estimates and Cox regression analyses to assess time to cancer and kidney failure. Results 177 patients were followed up for a median of 4.0 (IQR, 1.3-8.0) years. Diagnosis of PLA2R-positive (PLA2R+), THSD7A+, and double-negative (PLA2R−/THSD7A−) MN was made in 117 (66.1%), 6 (3.4%), and 54 (30.5%) patients, respectively. Progression to kidney failure was similar in all groups. Although the number of patients with THSD7A+ MN was small, they showed a higher incidence (50%) and increased risk for developing cancer during follow-up (adjusted HR, 5.0 [95% CI, 1.4-17.9]; P = 0.01). 8% and 5% of patients with double-negative MN stained positively for EXT1/2 and NELL-1, respectively. Most patients with EXT1/2+ MN were women, had features of systemic autoimmunity, and showed glomerular C1q deposits. Limitations Retrospective design; small number of patients in the THSD7A group; lack of evaluation of immunoglobulin G subclasses deposition. Conclusions Our real-world data describe the relative prevalence of subgroups of MN and support the hypothesis that a novel classification of MN based on podocyte antigen staining may be clinically relevant.

There is now a strong evidence base for the characteristics of inflicted injury. Professionals within the multidisciplinary team and the courts are increasingly relying on other features such as the child's presentation to help determine whether child maltreatment has occurred. These features are somewhat subjective in nature, with little or no evidence to assist the clinician, particularly where there is uncertainty surrounding the possibility of child maltreatment. This paper will examine further evidence on the physical signs of child maltreatment, focussing on primary research on bruising, sentinel injuries, occult rib fractures and conditions that mimic physical injury such as the resurgence in the use of cupping as a remedy for childhood illness. It will also examine emerging evidence on a child's presentation, including history, response to injury and time to seek medical attention. If uncertainty surrounding the causation of an injury remains following advice and peer review, this must be acknowledged and stated unequivocally.

The optimal method to prepare endometrium before frozen embryo transfer (FET) is not yet established. We retrospectively studied 4496 FET and detailed pregnancy and miscarriage rates in three groups of patients according to the endometrium preparation they have followed before their successive FET: clomifene citrate (CC, group 1), artificial cycle (AC, group 2) or switch between CC and AC (group 3). The overall pregnancy rates per transfer were 24.3, 20.8 and 17.3% while the miscarriage rates reached 23.2, 29.8 and 42.5%, respectively. Group 1 experienced the highest ongoing pregnancy rate (18.6%), the lowest being observed in group 3 (10.0%, p

Child maltreatment and intentional injuries are major public health challenges, incurring huge costs for both individuals and society. Violence is an abuse of power comprising acts of commission and omission, and can have lasting consequences for survivors. It includes abuse in the home and collective violence, resulting in children being orphaned or abandoned, forced to become child soldiers, ‘street kids’ or trafficked for domestic work or sexual exploitation. In addition to physical violence, emotional abuse can involve bullying and seeing or hearing the ill treatment of another, such as a child witnessing intimate partner violence. Child maltreatment rates are higher in countries affected by war, famine, social inequality, and economic transition and in communities with marginalised indigenous and disabled groups. Comprehensive interventions, based on child rights principles, are needed that focus on prevention, detection, and intervention.

Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1β, and TGF-β), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.

Aims This study aims to describe the presentation, incidence and clinical management of children with FGM in the UK and Ireland. Methods Cases of FGM are reported using the established British Paediatric Surveillance Unit (BPSU) orange card system. The online data collection period is from November 2015–November 2016. The sexual referral centres (SARCS) have agreed to participate. The study also includes a 12 month follow up. Results Of the 55 cases reported to the BPSU, 29 (53%) had confirmed FGM of which we are awaiting outstanding information, 20 were reported in error, or were duplicates, six questionnaires are incomplete. The results presented are interim findings on the 29. Of the completed questionnaire items, at the time of diagnosis all children were older than four years (n=26), most children were diagnosed at 4–6 years (n=7) or 13–16 years (n=7), followed by 7–9 years (n=6) and 10–12 years (n=6). Almost all children were born outside of the UK, in African countries (n=25). For confidentiality purposes we cannot disclose the place of birth for those children born outside of African countries (n=2), the place of birth was unknown for two cases. Social care referred most children (66%, n=19), and health professionals the remainder (34%, n=10) with a history of FGM (83%, n=26) or suspected FGM (n= Conclusion The first year of reporting has shown that cases are being found and investigated. The reporting of clinical presentation and examination findings can be used to educate healthcare professionals and plan health services. The study extension will help to identify the true incidence, presentation and management of cases.

Bipolar I disorder is a chronic disorder characterized by episodic recurrences of mania, depression, and mixed affective states interspersed with periods of full or partial remission; subsyndromal residual symptoms between episodes are common and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Post-hoc analyses of pooled data from 3 positive trials were conducted to evaluate the effect of cariprazine 3–12mg/d on the symptoms of mania in inpatients (18–65 years) with bipolar I disorder and a current manic episode. Analyses were based on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608). Mean change from baseline to the end of treatment on individual Young Mania Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated measures (MMRM); categorical symptom severity shifts were analysed using logistic regression. Statistically significant improvement in mean change was seen for cariprazine versus placebo on all 11 YMRS items (p

Objectives - In line with a national policy to move care ‘closer to home’, a specialist children's hospital in the National Health Service in England introduced consultant-led ‘satellite’ clinics to two community settings for general paediatric outpatient services. Objectives were to reduce non-attendance at appointments by providing care in more accessible locations and to create new physical clinic capacity. This study evaluated these satellite clinics to inform further development and identify lessons for stakeholders. Methods - Impact of the satellite clinics was assessed by comparing community versus hospital-based clinics across the following measures: (1) non-attendance rates and associated factors (including patient characteristics and travel distance) using a logistic regression model; (2) percentage of appointments booked within local catchment area; (3) contribution to total clinic capacity; (4) time allocated to clinics and appointments; and (5) clinic efficiency, defined as the ratio of income to staff-related costs. Results - Satellite clinics did not increase attendance beyond their contribution to shorter travel distance, which was associated with higher attendance. Children living in the most-deprived areas were 1.8 times more likely to miss appointments compared with those from least-deprived areas. The satellite clinics’ contribution to activity in catchment areas and to total capacity was small. However, one of the two satellite clinics was efficient compared with most hospital-based clinics. Conclusions - Outpatient clinics were relocated in pragmatically chosen community settings using a ‘drag and drop’ service model. Such clinics have potential to improve access to specialist paediatric healthcare, but do not provide a panacea. Work is required to improve attendance as part of wider efforts to support vulnerable families. Satellite clinics highlight how improved management could contribute to better use of existing capacity.

Aristolochic acids (AA) are nephrotoxic and profibrotic agents, leading to chronic kidney disease. As some controversial studies have reported a nephroprotective effect of exogenous recombinant human bone morphogenetic protein (rhBMP)-7 in several models of renal fibrosis, we investigated the putative effect of rhBMP-7 to prevent progressive tubulointerstitial damage after AA intoxication in vitro and in vivo. In vitro, the toxicity of AA on renal tubular cells was demonstrated by an increase in vimentin as well as a decrease in β-catenin expressions, reflecting a dedifferentiation process. Increased fibronectin and interleukin-6 levels were measured in the supernatants. Enhanced α-SMA mRNA levels associated to decreased E-cadherin mRNA levels were also measured. Incubation with rhBMP-7 only prevented the increase in vimentin and the decrease in β-catenin expressions. In vivo, in a rat model of AA nephropathy, severe tubulointerstitial lesions induced by AA after 10 and 35 days (collagen IV deposition and tubular atrophy), were not prevented by the rhBMP-7 treatment. Similarly, rhBMP-7 did not ameliorate the significant increase in urinary concentrations of transforming growth factor-β. In summary, our in vitro data demonstrated a poor beneficial effect of rhBMP-7 to reverse cell toxicity while, in vivo, there was no beneficial effect of rhBMP-7. Therefore, further investigations are needed to confirm the exact role of BMP-7 in progressive chronic kidney disease. Copyright © 2015 John Wiley & Sons, Ltd.

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as >= 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on >= 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders

Setting: England, Wales and Scotland. Patients : 1958 birth cohort. Exposure : Experience of abuse during childhood, measured prospectively by parent and teacher interviews and retrospectively by self-report. Outcomes: Markers of socioeconomic function at 45–50 years. Follow-up period: 50 years from birth. Patient follow-up: Surveys sent out at 45 and 50 years of age. All forms of childhood maltreatment result in poorer socioeconomic outcomes at 50 years of age (summarised in table 1). Sexual abuse had the greatest effect, with neglect also having a significant impact. Adjusting for cognition …

We present data that raises questions about the need for routine CT head in infants aged 0–12 months old with suspected physical abuse. We performed an audit of our compliance with the Joint RCPCH and RCR guidelines 2008, which recommend that infants under the age of 12 months with suspected physical abuse undergo a CT head as part of their skeletal survey to exclude occult injury. Methods We performed a retrospective analysis of infants aged 1 year or less who were investigated for suspected physical abuse with a skeletal survey. We reviewed whether CT head was performed in every case, and from case notes whether their presentation was symptomatic of Non-Accidental Head injury. The period of study was December 2011 – January 2015. Cases of sudden unexpected death in infancy were excluded, as were infants who had skeletal surveys for other clinical reasons. Results We reviewed 111 skeletal survey reports, which revealed 16 occult skeletal injuries (14.4%). 100/111 patients underwent a CT head, achieving 90.1% concordance with the national guideline. 58/100 CT scans were normal, all infants were asymptomatic and had routine CT scans. 42/100 were abnormal, 39/42 were symptomatic infants, scans undertaken urgently for presenting features of abusive head trauma (acute encephalopathy 23, significant impact trauma 14, suspected raised ICP 2). 3/42 infants had intracranial abnormalities of uncertain significance related to their underlying condition and not to abusive head trauma. CT Head did not reveal any occult non-accidental head injury in the asymptomatic cohort. Conclusion Only 3/100 CT showed occult abnormality which were not felt to be suggestive of abusive head trauma. Although the total number of infants is low, the yield for occult head trauma in this retrospective case series was negligible, less than that previously reported for infants without neurological concerns at presentation. We suggest that a larger, prospective study is needed to clearly establish the role of routine CT head in excluding occult injuries in the potentially abused infant. The yield from skeletal survey was 14.4% is in line with other published studies, suggesting that this investigation has a role in medical assessment of suspected physical abuse.

Background Sexually transmitted infections in children ought to raise concerns about sexual abuse. It is not known how frequently they are identified in the UK and Ireland, nor how well they are investigated. Aims To measure the incidence, mode of presentation, investigations and child protection procedures among children under 13 years and over 12 months of age presenting with infections of Neisseria gonorrhoea , Treponema pallidum , Chlamydia trachomatis or Trichomonas vaginalis in the UK and Republic of Ireland. Methods National surveillance study over 25 months through the British Paediatric Surveillance Unit. All consultant paediatricians in the UK and Republic of Ireland reported laboratory confirmed infections followed by a confidential questionnaire covering clinical details, investigation results and child protection outcomes. Results Fifteen cases were reported, giving an overall incidence of these infections of 0.075 cases per 100 000 children per year. Most were identified because they presented with symptoms. Five cases presented with ophthalmic infection. Laboratory investigation and screening for other infections was adequate in most cases. Although only three cases of sexual abuse were confirmed in court or case conference, abuse was suspected in a further seven cases based on clinical factors, family or social history. Conclusions Sexually transmitted infections in children, although rare, are generally well investigated. The findings support current guidance on the management of sexually transmitted infection in young children and the need to maintain a high index of suspicion for sexual abuse. Isolated ophthalmic infection with N gonorrhoeae and C trachomatis occurs beyond infancy, but the mode of transmission is unclear.

I asked a 13-year-old girl whether she had been cut. She replied, “That's horrible isn't it”, a rhetorical question to which I nodded assent. She felt that it was an appropriate question to ask, given the clinical context. The next morning I read, “Cameron in crackdown on summer surge of FGM cases” (from The Observer , Sunday 14 June 2015). New laws aimed at preventing young girls being taken abroad to undergo what the prime minister described as the “cruel and barbaric practice” of female genital mutilation (FGM) were to be “fast-tracked within weeks, amid fears that the number of cases could soar during the summer holidays”. The headline and story is revealing in a number of respects: it is one of a number of articles, particularly in the lead up to the historic Girl Summit in London in July 2014, that reflect increasing community, professional and political concern over the practice of ‘FGM/cutting’. It signals government determination to eradicate this practice yet does so in a tone and language that might be construed as hostile to the very communities and their activists who put FGM onto the front pages in the first place. Later that week, I was sent a link to the West Midlands Police and Crime Panel press release, which announced that, between January and November 2014, 118 cases of FGM had been referred to the West Midlands Police, and that, while there had been “no reports to West Midlands Police of mutilation in the area”, there had been some intelligence to suggest girls “are brought to Birmingham to be cut”. Is there a ‘summer surge’ when at-risk children and young people from practising communities are more vulnerable? Is there a risk that some of those children will be sent to Birmingham to be cut? Are these …

Gastrointestinal stimulator implants have recently shown positive results in helping obese patients lose weight. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. Our team is aiming for a less invasive procedure to stimulate the stomach with a gastrostimulator. Attempts covered fully endoscopic implantation and, more recently, we have focussed on a single incision laparoscopic procedure. Whatever the chosen implantation solution, the electronic design of the implant system shares many challenges. This paper covers the work achieved to meet these.

There is a growing evidence-base for physical signs of child maltreatment. However, health professionals sometimes find themselves in situations that are not clear cut, particularly when there is one suspicious injury in an otherwise normal child in a family where there are no risk factors for maltreatment present. This paper highlights such situations and guides the clinician through uncertainty to a consideration of whether or not the explanation for an injury is reasonably possible. This will be done by discussing the location, configuration and patterns of injury arising from low level falls, stairway falls, climbing into the bathtub, pacifiers or bottles, and being bitten by another child; explanations often proffered for an injury. The location of bruising in disabled children and young people will also be discussed. If uncertainty surrounding the causation of an injury remains following advice and peer review, this must be acknowledged and stated unequivocally.

A case is presented of a child who was initially diagnosed with osteogenesis imperfecta following a skull fracture. However, she later presented with multiple fractures and soft tissue injuries which were considered to be due to non-accidental injury. It can be perplexing distinguishing accidental and non-accidental injury in children where a bone fragility disorder has been suspected. A combination of a careful review of the history, a thorough examination and expert review of the radiology is imperative. DNA testing can be helpful. Multidisciplinary case review, taking into account the social history and any concerns professionals have about the family, is invaluable in informing a difficult diagnosis. In this context, there is a definite role for other agencies in challenging the diagnosis or exclusion of non-accidental injury. Professionals should be willing to challenge the exclusion of non-accidental injury when such exclusion is not evidence based. Copyright © 2009 John Wiley & Sons, Ltd.

The advent of moderate dilatations in ascending aortas is often accompanied by structural modifications of the main components of the aortic tissue, elastin and collagen. In this study, we have undertaken an approach based on FTIR microscopy coupled to a curve-fitting procedure to analyze secondary structure modifications in these proteins in human normal and pathological aortic tissues. We found that the outcome of the aortic pathology is strongly influenced by these proteins, which are abundant in the media of the aortic wall, and that the advent of an aortic dilatation is generally accompanied by a decrease of parallel beta-sheet structures. Elastin, essentially composed of beta-sheet structures, seems to be directly related to these changes and therefore indicative of the elastic alteration of the aortic wall. Conventional microscopy and confocal fluorescence microscopy were used to compare FTIR microscopy results with the organization of the elastic fibers present in the tissues. This in-vitro study on 6 patients (three normal and three pathologic), suggests that such a spectroscopic marker, specific to aneurismal tissue characterization, could be important information for surgeons who face the dilemma of moderate aortic tissue dilatation of the ascending aortas.

Dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR) could help to improve arterial hypertension. We evaluated the impact of isonatric HFR (HFR-iso) on hypertension control compared to conventional HFR. Forty-seven hemodialysis patients were included and randomized (ratio 2/1) HFR-iso versus HFR during 24 dialysis sessions. In the HFR-iso group (32 patients, 768 dialysis sessions), the predialytic systolic blood pressure (BP) decreased from S1 to S24 of 9 ± 20 mm Hg and increased of 5 ± 24 mm Hg in the HFR group (15 patients, 360 dialysis sessions), variation that differed between the 2 groups (ΔS1-S24, p = 0.035; interaction group*time, p = 0.012). The diastolic BP (HFR-iso -3 ± 14 mm Hg vs. HFR 5 ± 13 mm Hg; p = 0.088), the DDD of antihypertensive treatment and the dry weight did not vary significantly during the study. Number of sessions complicated by symptomatic hypotension was similar in the 2 groups. HFR-iso improved BP control without increasing dialysis hypotension episodes. Short Summary: In this multicenter, open-label, controlled, randomized study, we evaluated the impact of dialysis biofeedback in HFR on arterial hypertension compared to conventional HFR. We observed that HFR-iso improved arterial BP control without increasing dialysis hypotension episodes.

To estimate the clinical and economic impact of using macrogol 3350 plus electrolytes (macrogol 3350; Movicol; Movicol Paediatric Plain) in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction.A chart review was undertaken to extract clinical outcomes and resource use from the case notes of a cohort of children aged 2-11 years with faecal impaction who initially received either macrogol 3350 (in an outpatient setting) or enemas and suppositories or manual evacuation for initial disimpaction. Five centres across England and Wales participated in the study. These data were used to inform a decision model which depicted the management of children during the disimpaction phase and for a period of 12 weeks following initial disimpaction. Unit resource costs at 2005/2006 prices were applied to the resource utilisation estimates within the model, enabling the incremental costs and consequences of using macrogol 3350 in an outpatient setting, compared to the other treatments, to be estimated.112 patients treated with macrogol 3350, 101 who received enemas and suppositories and 11 who underwent a manual evacuation were eligible for analysis. Ninety-seven per cent of children treated with macrogol 3350 were successfully disimpacted within 5 days, compared to 73% of those who received enemas and suppositories and 89% of those who underwent a manual evacuation (p0.001). There were no significant differences in reported adverse events between the different treatments for disimpaction, with the exception of vomiting which was significantly higher among those who underwent a manual evacuation (18% versus 2% with the other treatments; p0.01). There were no significant differences in the number of clinician outpatient visits between treatments. However, macrogol 3350-treated patients had significantly fewer hospital admissions than those who received the other interventions (0.1 versus 1.4 and 1.0 for enemas and suppositories and manual evacuation respectively; p0.05) and occupied fewer bed days. The total NHS cost of disimpaction and subsequent maintenance of children initially treated with macrogol 3350 was estimated to be 694 pounds sterling (95% CI: 496 pounds sterling; 892 pounds sterling). This compared with 2759 pounds sterling (95% CI: 1266 pounds sterling; 4252 pounds sterling) and 2333 pounds sterling (95% CI: 1609 pounds sterling; 3058 pounds sterling) for those who initially received enemas and suppositories or underwent a manual evacuation, respectively. Hence, using macrogol 3350 instead of enemas and suppositories and manual evacuation to disimpact the whole annual cohort of faecally impacted children aged 2-11 years in England could potentially reduce annual NHS expenditure on this condition by 59% (5 million pounds sterling) and reduce the annual number of paediatric hospital admissions for this condition by 92% (4330).Within the limitations of our model, macrogol 3350 affords the NHS a clinically effective and cost-effective treatment for the disimpaction of children suffering from faecal impaction compared to enemas and suppositories or a manual evacuation, and has the potential to release healthcare resources for alternative use within the system.

A case of paediatric hypopharyngeal perforation in a 7-month-old infant is reported. The diagnosis was delayed because it was not considered. It later transpired that the injury had been inflicted by one of the child's parents. Criminal proceedings were successfully brought against both parents and the child and his siblings were taken into foster care. A review of the available literature on paediatric hypopharyngeal perforation, excluding iatrogenic and external trauma mechanisms of injury suggests that non-accidental injury is by far the most common aetiology. Suspected child abuse remains one of the most sensitive and challenging areas in medicine. Awareness that non-iatrogenic paediatric hypopharyngeal perforation in the absence of external trauma is highly suggestive of a non-accidental injury is critical, and may save a child from subsequent abuse.

UNLABELLED In the 1970s several reports highlighted the long delay in diagnosis often experienced by children with Crohn's disease. In recent years this disorder has attracted much publicity, and many believe that the incidence has increased substantially. The aim of this investigation was to determine whether heightened awareness had shortened the interval to diagnosis, improved clinical management and reduced morbidity. A retrospective study was therefore carried out on 112 children with inflammatory bowel disease (64 Crohn's disease, 41 ulcerative colitis, 7 indeterminate colitis) referred to a paediatric gastroenterology department in the UK between 1994 and 1998. In Crohn's disease the median interval to diagnosis was 47 wk (maximum 7 y). In those without diarrhoea this was longer (66 vs 28 wk; p = 0.005). In ulcerative colitis the median interval was 20 wk (maximum 3 y). Even in severe colitis the median interval was 5.5 wk (range 3-9 wk) and 4 required urgent colectomy soon after referral. Many with unrecognized Crohn's disease had undergone inappropriate treatments, such as growth hormone or psychiatric therapy. Nineteen (17%) had undergone endoscopic investigations in adult units prior to referral. Malnutrition was equally common in Crohn's disease and ulcerative colitis (11%). Short stature was present in 19% with Crohn's disease, and 5% with ulcerative colitis, and was severe in 8% with Crohn's disease. There was a significant correlation between symptom duration and the degree of growth impairment present (r(s) = -0.4; p = 0.004). CONCLUSION This study suggests that late diagnosis and inappropriate investigation and management are still significant problems.

The renin-angiotensin system blockade does not prevent renal interstitial fibrosis induced by aristolochic acids.BackgroundExperimental aristolochic acid nephropathy (AAN), characterized by interstitial fibrosis, tubular atrophy, and chronic renal failure, was reported after 35-day injections of aristolochic acids (AA) to salt-depleted male Wistar rats. The link between renal fibrosis and the renin-angiotensin system (RAS) in this model remains unknown.MethodsWe investigated the impact of sodium diets (low and normal), of RAS inhibition with enalapril (ENA) alone, or combined with candesartan (CSN) for 35 days, and ENA + CSN for 65 days on AAN development. At the end of each observation period, blood pressure and renal angiotensin-converting enzyme activity were measured, as well as renal functional impairment (plasma creatinine increase, proteinuria) and histologic lesions (interstitial fibrosis, monocytes/macrophages infiltration, myofibroblasts collagens type I and IV, proliferating cells).ResultsSodium intake did not modify renal functional and morphologic impairment induced by AA. The RAS blockade by ENA or ENA + CSN in rats receiving AA did not result in any statistical difference in terms of renal failure, proteinuria, and interstitial fibrosis on day 35 or 65. On day 35, the monocytes/macrophages infiltration was significantly decreased by two-fold when ENA (P < 0.01) or ENA + CSN (P < 0.01) was given from day 0.ConclusionOur data demonstrate that RAS modulation by salt depletion and pharmacologic blockade do not influence renal failure and interstitial fibrosis in the rat model of AAN. We suggest that pathways of interstitial renal fibrosis may be independent of RAS at least in some conditions.

ObjectiveTo examine the effect of cariprazine, a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, on predominant negative symptoms of schizophrenia.MethodsSubjects with schizophrenia and PANSS factor score for negative symptoms (PANSS-FSNS) ≥ 24 and no pseudospecific factors (e.g. extrapyramidal symptoms, depression) were randomized to cariprazine 4.5 mg/d (dose range: 3-6 mg/d) or risperidone 4 mg/d (dose range: 3-6 mg/d) for 6 months.ResultsFour hundred and sixty-one patients were randomized 1:1 to double-blind risperidone (n = 231) or cariprazine (n = 230) treatment. Change from Baseline (CfB) at week 26 in the primary parameter, PANSS-FSNS, was larger in the cariprazine group than in the risperidone group (LSMD = −1.47; 95% CI: [−2.39, −0.53]; P = 0.002) significant from week 14 onwards. CfB at week 26 in the functional parameter, Personal and Social Performance (PSP) total score, showed similarly greater improvement with cariprazine than risperidone (LSMD = 4.63; 95% CI: [2.71, 6.56]; P < 0.001) significant from week 10 onward. Statistically significant differences in favor of cariprazine at week 26 were shown in the PSP areas of self-care, socially useful activities and personal and social relationships. Most patients tolerated the study treatment well, as reflected by low discontinuation rates due to adverse events (AEs). Adverse event profiles of cariprazine and risperidone were similar. The most common AEs during study treatment were insomnia (10.0%), and headache (10.4%), both in the risperidone group.Conclusion26-week cariprazine treatment, given as antipsychotic monotherapy, was significantly more effective on negative symptoms and on functioning than risperidone in patients with predominant negative symptoms of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

BackgroundIn response to a resurgence of symptomatic cases of vitamin D deficiency in a high-risk predominantly ethnic minority population, a programme of universal rather than targeted vitamin D supplementation was begun with a public awareness campaign about the importance of vitamin D.ObjectiveTo evaluate the effectiveness of this programme in reducing case numbers.MethodsCases of symptomatic vitamin D deficiency in children under 5 years resident in a primary care trust catchment area presenting at local hospitals were identified through laboratory records of low vitamin D levels which were cross-checked against medical records to confirm the diagnosis. Comparisons were made of the case incidence rate, level of public knowledge and vitamin supplement uptake rate at the onset of the programme in 2005 and 4 years later.ResultsThe number of cases of symptomatic vitamin D deficiency in those under 5 years fell by 59% (case incidence rate falling from 120/100 000 to 49/100 000) despite the supplement uptake rate rising only to 17%. Public awareness of vitamin D deficiency rose to near universal levels.ConclusionsA programme of universal rather than targeted Healthy Start vitamin D supplementation for pregnant and lactating women and young children has led to a substantial decrease in cases of symptomatic vitamin D deficiency in a high-risk population. Supplementation was also started at a younger age than in the national programme. This approach has implications for the delivery of vitamin D supplementation programmes in similar populations.

Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among glomerulopathies, membranous nephropathy is preferentially associated with respiratory and gastrointestinal tract adenocarcinomas, whereas minimal change disease is most often seen in haematological malignancies. Though breast cancer is one of the most frequent malignancies in women, paraneoplastic glomerular disease is rarely observed. We describe the case of a 79-year-old female patient who presented with nephrotic syndrome and renal failure. Breast cancer was found. Pathological studies of kidney and breast biopsy revealed a minimal change disease and an infiltrating ductal carcinoma, respectively.

Les maladies inflammatoires chroniques de l’intestin sont frequemment decouvertes au scanner, a l’heure actuelle. Il est important que radiologistes et gastro-enterologues se familiarisent avec les correlations anatomo-radiologiques dans ce domaine. Ils doivent comprendre les differences entre la maladie de Crohn (caracterisee par les signes macroscopiques d’inflammation transmurale et la tres importante proliferation fibro-graisseuse du mesentere) et la colite ulcereuse (epaississement parietal plus modere et extension continue du rectum au colon). L’analyse detaillee de la «stratification» parietale avec rehaussement iode peut apporter des informations utiles pour distinguer les poussees aigues et aider a optimiser les choix therapeutiques. Le diagnostic des complications pancreatiques et hepato-biliaires (cholangite sclerosante primitive, lithiase biliaire, pancreatites medicamenteuses, steatose hepatique focale, lithiase urinaire...) peut etre facilite par le scanner et plus encore par l’IRM.

Purpose: The fate of inhaled nitric oxide (NO) has not been precisely defined in critically ill patients. This study aimed at defining the effects of long-term NO inhalation on circulating NO byproduct levels. Material and Methods: During NO therapy, plasma and urine from 13 critically ill patients were sampled daily for determination of the stable byproducts of NO (nitrite [NO 2 − ] and nitrate [NO 3 − ]. Routine monitoring data included inhaled NO concentration, hemodynamic parameters, arterial blood gases, creatinine clearance, and C-reactive protein. Results: For the first 24 hours of NO inhalation (6.3 ± 1.1 ppm), NO 3 − plasma concentration increased (from 13.3 ± 5.4 to 52.3 ± 17.6 μmol/L), but NO 2 − plasma concentration was not affected. The NO 3 − plasma concentration was correlated with the C-reactive protein level, the inhaled NO concentration. Renal excretion of NO metabolites was unaltered by NO inhalation. The N0 3 concentrations returned to baseline when NO therapy was discontinued. Conclusion: Long-term NO inhalation was associated with a consistent increase in the NO 3 − plasma concentration. NO byproducts may be implicated in the systemic effects associated with this treatment.

In Belgium, the calcimimetic cinacalcet is initially reimbursed foror = 4 months in dialysis patients with secondary hyperparathyroidism (SHPT) and intact parathyroid hormone (iPTH)or = 800 pg/mL, or iPTH 300-800 pg/ mL and Ca x P55 mg 2/dL2 despiteor = 6 months' optimal treatment with vitamin D sterols and/or phosphate binders. The Belgian, multicentre, observational study ECHO-B evaluated cinacalcet in such patients. Patients who began cinacalcet treatment after March 1, 2007 were eligible. Data were collected retro/prospectively from 6 months before until 16 months after starting cinacalcet (whether or not cinacalcet was continued). Median iPTH was markedly elevated (816 [IQR 551-991] pg/mL) at baseline (the time of starting cinacalcet), but decreased continuously over the course of the study, reaching a value of 414 pg/mL (IQR 240-641; median change -41%) at 4 months, 335 pg/mL (IQR 159-616; -60%) at 12 months and 250 pg/mL (IQR 172-436; -64%) at 16 months. Reductions in serum calcium (-7%) and phosphorus (-13%) were already (near) maximal at 4 months. The primary outcome (iPTH 150-300 pg/mL and/or aor = 30% reduction within 4 months of starting cinacalcet; criterion for continued reimbursement in Belgium) was achieved in 65/81 patients (80%; 95% CI 72-89%). Results show that in dialysis patients with SHPT in real-life clinical practice, mineral metabolism improves after starting cinacalcet: our study findings suggest that PTH levels may continue decreasing after 12 months' treatment in this setting.

International audience; Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the b-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES.

International audience; Atherosclerosis is a progressive multifaceted inflammatory disease affecting large-and medium-sized arteries. Typical feature of this disease is the formation and build-up of atherosclerotic plaques characterized by vascular extracellular matrix degradation and remodeling. Many studies have documented degradation of native elastin, the main extracellular matrix protein responsible for resilience and elasticity of arteries, by local release of elastases, leading to the production of elastin-derived peptides (EDP). These peptides have been proposed to actively participate in the progression of the disease by accelerating different biological processes, such as LDL oxidation and calcification of the vascular wall. These pathophysiological effects are mediated by the binding of EDP on a peculiar heterotrimeric receptor named elastin receptor complex (ERC). In this article, we review the contribution of elastin in biological processes involved in atherosclerosis progression from its initial elastase-driven degradation to its ultimate cellular effects. Finally, we discuss the ERC and its derived signaling pathways as promising therapeutic targets.

Background: The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D-3 (25[OH] D) levels = 30 ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D. Measurements: Blood calcium and phosphate were measured weekly; iPTH, 25(OH) D, 1,25-dihydroxyvitamin D-3 (1,25[OH](2)D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39. Results: The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P = 30 ng/mL in patients issued from the placebo group. Limitations: Small size of the study population. Conclusions: Oral weekly administration of 25,000 IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)(2)D levels in hemodialysis patients. Further evaluation of clinical end points is suggested. (C) 2014 by the National Kidney Foundation, Inc.

The National Health Service (NHS) is embarking on significant changes. The new Health and Social Care Act comes into force on 1 April 2013 alongside increasing demographic challenges and capacity pressures. While costs are set to soar, finances are increasingly constrained so that the effective delivery of integrated out-of-hospital care coordinated around the needs of the child and family is vital. The case report1 illustrates how families’ lives are turned upside down when sustaining complex care at home. Adverse medical outcomes may partly reflect the difficulties connecting secondary health and social care. Previous failings in safeguarding show the dangers of a disconnected system and it is critical that the new commissioning arrangements should encourage integration. There has been a fourfold increase in young patients on Home Parenteral Nutrition (PN) since 1993 with a mean of 13.7 children per million.2 Young mothers are over-represented since teenage pregnancy is a risk factor for low birth weight and preterm delivery. Short bowel syndrome due to necrotising enterocolitis as a cause for intestinal failure has increased. Maternal age less than 20 years is also associated with gastroschisis and a near tripling of gastroschisis cases has led to more children requiring Home PN.3 Home PN requires technical competencies and strict adherence to daily routines. Recurrent catheter related blood steam infection with late presentation is a risk factor for intestinal failure associated liver disease. Intestinal transplantation is offered when PN has reached its limits due to life-threatening complications such as recurrent infections. Care routines continue to be demanding after transplantation. If parents are unable to maintain strict …