HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort

Granični poremećaj ličnosti je učestali psihički poremećaj koji se manifestira kroz simptome afektivne nestabilnosti, impulzivnog i nekontroliranog ponašanja, poremećaj identiteta, nestabilne interpersonalne odnose i moguće pogreške u testiranju realiteta uslijed kojih osoba može imati značajnih poteškoća u osobnom, roditeljskom, obiteljskom, socijalnom i radnom funkcioniranju. Svrha ovog istraživanja je dobiti uvid u iskustva rada stručnih djelatnika Odjela za zaštitu djece, obitelji i braka pri centru za socijalnu skrb, a ciljevi istraživanju su dobiti uvid u prepoznavanje simptoma graničnog poremećaja ličnosti , teškoće i potrebe stručnih djelatnika Odjela za zaštitu djece, obitelji i braka. Kvalitativno istraživanje provedeno je metodom polustrukturiranog intervjua s 12 stručnjaka zaposlenih na Odjelu za zaštitu djece, obitelji i braka pri centrima za socijalnu skrb na području grada Zagreba i Zagrebačke županije. U obradi podataka korištena je tematska analiza. Rezultati istraživanja pokazuju da stručnjaci prepoznaju različite simptome afektivne nestabilnost, impulzivnog i nekontroliranog ponašanja, smetnji identiteta, nestabilnih i intenzivnih interpersonalnih odnosa te teškoća testiranja realiteta. Simptomi graničnog poremećaja ličnosti roditelja najčešće dolaze do izražaja u situacijama prekida bračne ili izvanbračne zajednice koji često imaju obilježja visokonfliktnih razvoda, tijekom postupaka odlučivanja o roditeljskoj skrbi, obiteljskog i partnerskog nasilja te zlostavljanja i zanemarivanja djece zbog čega stručnjaci poduzimaju različite psihosocijalne intervencije i mjere obiteljsko pravne zaštite. Prema rezultatima istraživanja teškoće stručnjaka tijekom rada s roditeljima s dijagnozom i/ili simptomima graničnog poremećaja ličnosti proizlaze iz neposrednog rada s roditeljima, organizacije i uvjeta rada u centrima za socijalnu skrb te suradnje s drugim sustavima. Roditelji sa simptomima ovog poremećaja ličnosti prepoznati su kao nedobrovoljni korisnici skloni manipulaciji djetetom, drugim roditeljem, stručnjacima, policijom, pravosudnim, zdravstvenim i socijalnim sustavom. Rad stručnjaka otežavaju i dodatne teškoće kao što su preopterećenost količinom posla, nedovoljan broj stručnih djelatnika, neadekvatni prostorni uvjeti rada u centrima za socijalnu skrb i otežana suradanja s drugim sustavima. Nadalje, stručnjaci izvještavaju o izloženosti visokoj razini profesionalnog stresa i doživljenim simptomima sagorijevanja. U skladu s iskazanim teškoćama, stručnjaci ukazuju na nužnost unaprjeđenja suradnje s drugim sustavima, posebice s pravosudnim, zdravstvenim i obrazovnim sustavom, povećanja broja zaposlenih stručnih djelatnika, zapošljavanje psihijatra u centre za socijalnu skrb, uključenost u redovite edukacije i supervizije. Nadalje, stručnjaci iskazuju potrebu za dodatnim ovlastima kao što su mogućnost obveznog upućivanja korisnika na liječenje i konstatiranja nedostupnosti intervencijama socijalne službe.Borderline personality disorder is a frequent psychiatric disorder which manifests itself through several symptoms: affective instability, impulsive and disinhibited behaviour, disturbed sense of identity, unstable interpersonal relationships and possible stress-related reduction of contact with reality. The afflicted person may have significant difficulties in personal, parental, familial, social and work functioning. The purpose of this research was to gain insight into experiences of experts working in the Department for protection of children, family and marriage of the Social Welfare Centre. Qualitative research has been conducted using semi-structured interviews with 12 experts working in the Department for protection of children, family and marriage of Social Welfare Centres located in Zagreb and Zagreb County. Collected data was analysed using thematic analysis. Results have demonstrated that experts recognize various symptoms of affective instability, impulsive and disinhibited behaviour, identity disturbances, unstable and intense interpersonal relationships and reduction of contact with reality. Symptoms of parental borderline personality disorder most frequently appear after a divorce or separation which often have characteristics of high-conflict divorce, during procedures related to child custody, familial and domestic violence, as well as child abuse and neglect, forcing experts to do various psychosocial interventions and implement measures related to protection of the family. According to results of this research difficulties expressed by experts working eith parents with a diagnosis and/or symptoms of borderline personality disorder are the result of direct work with the parents, organisation and work conditions in Social Welfare Centres and cooperation with other systems. Symptomatic parents are recognized as involuntary clients prone to manipulation of children, other parent, experts, the police, the justice system, healthcare system and social system. There are additional difficulties for experts working with these parents, such as work overload, insufficient number of experts, inadequate working space in Social Welfare Centres and difficulties cooperating with other systems. Experts also report being exposed to high level of professional stress and experiencing symptoms of burn-out. Consistently with these difficulties, experts reported needing to improve cooperation with other systems, especially with the justice, healthcare and education systems, increase the number of hired experts, hire psychiatrists in Social Welfare Centres and taking part regularly in educations and supervisions. Experts also reported needing additional authorities, such as the possibility of mandatory reference to treatment of clients and the possibility of establishing the unavailability of social services interventions

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study

Background: Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant monitoring, but should be further explored in thoracic organ recipients. Methods: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by CO and blood was collected for analysis of C2 retrospectively. Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based on 2-week post-operative values (tertiles T1 to T3). Results: C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any rejections (p = 0.001) and time to first rejection (p = 0.03) between T1 and T3. C2 did not predict reduction in mGFR. Conclusions: C2 is a sensitive predictor for ACR in lung, but not heart, recipients, C2 was not predictive of a decline in mGFR. This study suggests that management of lung recipients by C2 may diminish the number of ACRs. J Heart Lung Transplant 2009; 28:919-26. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation

Three decades of heart transplantation in Scandinavia: long-term follow-up

Aim Heart transplantation (HTx) has become a standard treatment for patients with end-stage heart disease. The aim of this study was to report the long-term outcome after HTx in Scandinavia. Methods and results During the period, 1983-2009,2333 HTxs were performed in 2293 patients (mean age 45 +/- 16 years, range 0-70,78% mate). The main indications for HTx were non-ischaemic cardiomyopathy (50%), ischaemic cardiomyopathy (34%), valvular cardiomyopathy (3%), congenital heart disease (7%), retransplantation (2%), and miscellaneous (4%). The registry consists of pre-operative data from recipients and donors, data from pre-operative procedures, and long-term follow-up data. Mean follow-up was 7.8 +/- 6.6 years (median 6.9, interquartile range 2.5-12.3, interval 0-27) and no patients were lost to follow-up. Long-term survival for HTx patients was 85, 76, 61, 43, and 30% at 1, 5, 10, 15, and 20 years of follow-up, respectively. Ten-year survival in patients bridged with mechanical circulatory support, in children, after retransplantation, and after concomitant other organ transplantation was 56, 74, 38, and 43%, respectively. Older patients (age >55 years) had a significantly worse survival (P < 0.001). Patients transplanted more recently had a significantly better survival (P < 0.001). In a multivariate Cox regression analysis, independent predictors of long-term survival were recipient age (P < 0.001), donor age (P < 0.001), diagnosis (P = 0.001), and era of transplantation (P < 0.001). Conclusions HTx in Scandinavia proves to have a significantly better survival among patients transplanted in the last decade. HTxs from mechanical circulatory support, in children, after retransplantation, and with concomitant other organ transplantation were performed with acceptable results

Clamping of the Aortic Arch Vessels During Normothermic Regional Perfusion After Circulatory Death Prevents the Return of Brain Activity in a Porcine Model

Background. The cerebral effect of clamping following normothermic regional perfusion (NRP) in donation after circulatory death (DCD) remains unknown. We investigated the effect of cerebral reperfusion during NRP and the preventive effect of clamping on brain function in a porcine model. Methods. In 16 pigs, intracranial physiological parameters were recorded, including pressure, cerebral blood perfusion (CBF), temperature, and oxygen. Additionally, electroencephalography (EEG) and somatosensory evoked potentials (SSEPs) were used to assess brain function. The animals were cannulated for the heart-lung machine, and baseline measurements were performed before withdrawal from life support. After 8min of mechanical asystole, the animals were randomly allocated to clamp (n = 8) or nonclamp (n = 8) of the aortic arch vessels. After 30 min of NRP, the animals were monitored for 3 h after weaning (AW). Results. Intracranial measurements of CBF, oxygen, and temperature indicated successful occlusion of the arch vessels following NRP and AW in the clamp group versus the nonclamp group. In the clamp group, EEG was isoelectric and SSEPs were absent AW in all pigs. In the nonclamp group, EEG activity was observed in all 8 pigs, whereas SSEPs were observed in 6 of 8 pigs. Additionally, agonal respiratory movements in the form of gasping were observed in 6 of 8 pigs in the nonclamp group. Conclusions. Reperfusion of the brain during NRP led to a return of brain activity. Conversely, clamping of the arch vessels halted cerebral circulation, ensuring the permanent cessation of brain function and maintaining the determination of death in DCD

High Oxygenation During Normothermic Regional Perfusion After Circulatory Death Is Beneficial on Donor Cardiac Function in a Porcine Model

Background. Thoracoabdominal normothermic regional perfusion (NRP) is a new method for in situ reperfusion and reanimation of potential donor organs in donation after circulatory death by reperfusion of the thoracic and abdominal organs with oxygenated blood. We investigated effects of high oxygenation (HOX) versus low oxygenation (LOX) during NRP on donor heart function in a porcine model. Methods. Pigs (80 kg) underwent a 15-min anoxic cardiac arrest followed by cardiac reanimation on NRP using a heart-lung bypass machine with subsequent assessment 180 min post-NRP. The animals were randomized to HOX (FiO(2) 1.0) or LOX (FiO(2) 0.21 increased to 0.40 during NRP). Hemodynamic data were obtained by invasive blood pressure and biventricular pressure-volume measurements. Blood gases, biomarkers of inflammation, and oxidative stress were measured. Results. Eight of 9 animals in the HOX group and 7 of 10 in the LOX group were successfully weaned from NRP. Right ventricular end-systole elastance was significantly improved in the HOX group compared with the LOX group, whereas left ventricular end-systole elastance was preserved at baseline levels. Post-NRP cardiac output, mean arterial, central venous, and pulmonary capillary wedge pressure were all comparable to baseline. Creatinine kinaseMB increased more in the LOX group than the HOX group, whereas proinflammatory cytokines increased more in the HOX group than the LOX group. No difference was found in oxidative stress between groups. Conclusions. All hearts weaned from NRP showed acceptable hemodynamic function for transplantation. Hearts exposed to LOX showed more myocardial damage and showed poorer contractile performance than hearts reperfused with high oxygen

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained