Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

Hippocampal loss of the GABAA receptor α1 subunit in patients with chronic pharmacoresistant epilepsies

Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABA_A receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the ₁ subunit of the GABA_A receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABA_A receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABA_A receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABA_A receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABA_A receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.     

Intelligence and temperament as protective factors for mental health. A cross-sectional and prospective epidemiological study

The Sjöbring system of personality dimensions measuring intellectual capacity, activity, impulsivity and sociability was used to study possible salutogenic (i.e. causes of health) effects. The study comprised 590 subjects investigated in 1947, 1957, 1972 and 1988–1989 in the Lundby project, an epidemiological study in Sweden. Psychiatric diagnoses were made in 1947, 1957 and 1972. Mental health was estimated in 1988–1989 using the concept love well, work well, play well and expect well. The Sjöbring dimensions were clinically assessed in 1972. Both in the concurrent study in 1972 and in the prospective study in 1988–1989 super capacity (high intellectual function), super validity (high activity level) and super solidity (low impulsivity) were statistically associated with lower frequencies of certain psychiatric diagnoses and a higher frequency of positive mental health. These variables are proposed to increase coping capacity, and therefore increase stress resilience.     

Case Management

New roles for nurses are emerging as managed-care organisations continue to evolve. Many of these roles are new for nurses; others expand or redefine traditional roles in the diabetes disease management environment in integrated healthcare systems. It is important now to redefine these roles for nurses in a way which supports the organisations’s quality outcomes.Patient education, one of the cornerstones in diabetes disease management programmes, has been an important nursing role for decades. In the diabetes disease management environment, the challenge for nurses is to provide appropriate education to the diabetes population in a way which acknowledges the continuum of care, the course of the disease and the progression of patient learning needs. Much of the outcomes research studying the effectiveness of patient education programmes is related to traditional, hospital-based programmes. Simply adapting traditional diabetes education programmes may not be sufficient to address patient education needs for the entire diabetes population within the integrated healthcare system.Phased diabetes competency for nurses is built on the premise that both patients and nurses acquire diabetes expertise in a phased, progressive manner. This model matches the competency of nurses at each level with parallel competencies for patients with diabetes.     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Cognitive functioning in female patients with 21-hydroxylase deficiency

The cognitive functioning of 27 female patients with congenital adrenal hyperplasia (CAH) (aged 11–41 yrs) and 13 of their healthy sisters (13–31 yrs) was compared using short versions of age-appropriate Wechsler scales. In contrast to other studies, neither a higher than average IQ level for CAH patients (mean: 99.0) nor for their sisters (97.7) was found. Unexpectedly, and in contrast to other reports, the subgroup of salt-wasting (SW) patients>16 yrs (N=6; mean score: 111.5) differed from their sisters as well as from simple-virilizing (SV) patients in full IQ (p<0.05) and subtest scorings for Information, Similarities, and Picture Completion (p<0.05–<0.10). SW patients displayed more masculine behaviour (vs. SV patients and sisters) which, in turn, was related to differential prenatal hormonal influences. No clear-cut relationships between IQ/cognitive (subtest) findings and gender-role behaviour were found.

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Zusammenfassung 27 Patientinnen mit dem Adrenogenitalen Syndrom (AGS) (11–41 J.) und 13 ihrer Schwestern (13–31 J.) wurden hinsichtlich intellektueller Funktionen verglichen (Kurzformen von HAWIK, HAWIE). Im Unterschied zu den meisten früheren Untersuchungen wurden weder für Patientinnen (mean: 99.0) noch für Kontrollen (97.7) über dem Durchschnitt liegende IQ-Werte gefunden. Im Gegensatz zur Literatur unterschied sich die Teilgruppe der Salzverlust-Patientinnen (SW)>16 J. (N=6, mean: 111.5) von den Schwestern und den Patientinnen mit einfachem AGS (SV) im Gesamt-IQ (p<0.05) und in den Untertests Allgemeines Wissen, Gemeinsamkeiten und Bilderergänzen (p<0.05–<0.10). SW-Patientinnen hatten signifikant männlichere Verhaltensmuster gezeigt (vs. SV-Patientinnen und Schwestern), die auf differentielle Hormoneffekte pränatal bezogen worden waren. Es fanden sich aber keine klaren Zusammenhänge zwischen IQ-bzw. Untertest-Resultaten und Ergebnissen für Geschlechtsrollenverhalten.

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Résumé Le fonctionnement cognitif de 21 patientes avec une hyperplasie congénitale surrénale (âgée de 11 à 41 ans) et de 13 de leurs soeurs saines (13–31 ans) a été comparé au moyen de versions raccourcies de l'échelle de Wechsler appropriée à l'âge. En contraste avec d'autres études, il n'a été retrouvé un Q.I. plus haut que la moyenne ni pour les patientes (moyenne 99.0) ni pour leurs soeurs (moyenne 97.7). De façon inattendue, et en contraste avec d'autres études, le sous-groupe de patientes déprivées en sel (SW)>16 ans (N=6), moyenne score: 111.5) différait de leurs soeurs aussi bien en tant que patientes présentant des signes de virilsation (SV) pour le Q.I. complet (p<0.05) et les scores aux subtests d'information, de similarité et de complément d'images (p<0.05–0.10). Les patientes déprivées en sel (SW) montraient un comportement plus masculin (vs. SV et leurs soeurs) qui en retour était relié aux influences hormonales prénatales différentes. Il n'y avait pas de relation de différences nettes entre les résultats aux sous-tests cognitifs du Q.I. et le comportement de genre.