Obsessive–compulsive symptoms (OCS) are frequently reported in patients with schizophrenia and have been associated with subjective distress and higher impairment. Recent studies suggest fluctuation ...in co-occurring OCS and associations with the course of psychotic symptoms. Current evidence is limited by few studies with long assessments intervals and a sole focus on between-subject comparisons. The aim of this study was to specifically investigate co-variation of symptom domains over time within individuals. Patients with a psychotic disorder (
n
= 56) and un-affected siblings (
n
= 49) completed monthly assessments of clinical and subclinical symptoms over 6 months. Mixed-model multilevel analyses examined the variability and relationship between OCS and positive, negative, and depressive symptoms on the between- and within-subject level. Symptom domains were associated across subjects and assessment times, in patients and siblings, with the strongest association between OCS and (subclinical) positive symptoms. Within-subjects, substantial variability and co-variation of all symptom domains was found. Particularly, between-subject differences in positive symptoms and within-subject change in depressive symptoms predicted subsequent OCS in patients 1 months later. This is the first prospective study disaggregating between and within-subject associations between co-occurring OCS and symptom cluster of psychosis. Differences on these two levels suggest different underlying mechanisms. The association between depressive symptoms and subsequent increase/decrease of OCS within patients may have important treatment implications.
Calcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction.
A randomized ...multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001).
During 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization.
Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.
ABSTRACT
Background
Patients with chronic kidney disease (CKD) or kidney replacement therapy demonstrate lower antibody levels after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...vaccination compared with healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations.
Methods
Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained 1 month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination.
Results
Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared with patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared with KTR not using MMF 20 binding antibody unit (BAU)/mL (3–113) vs 340 BAU/mL (50–1492), P < .001. Seroconversion was observed in 35% of KTR using MMF, compared with 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 46% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared with BNT162b2 in all patient groups.
Conclusions
Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.
Graphical Abstract
Graphical Abstract
Intraoperative driving pressure (ΔP) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V
) is kept constant, ΔP may change according to positive ...end-expiratory pressure (PEEP)-induced changes in lung aeration. ΔP may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery.
The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged ≥ 18 years and with a body mass index ≤ 40 kg/m
, scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H
O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which ΔP is lowest. In both groups of the trial, V
is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events.
DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery.
Clinicaltrials.gov, NCT03884543. Registered on 21 March 2019.
Background: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because ...of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness. Methods: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (>50 ≤ 300 BAU/mL) or high-responder (>300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785). Findings: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11–4.78 and 4.22, IQR 3.67–4.67, p < 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported higher non-adherence. Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 0.51–0.91, p = 0.008 and OR 0.48 0.28–0.86, p = 0.010). Interpretation: Adherence decreased after SARS-CoV-2 vaccination and in KTRs who were aware of a subsequent antibody response compared with those without. Preventive measures in this vulnerable group seem to be effective, regardless of vaccination status. This study starts a debate on sharing antibody results with the patient and future studies should elucidate whether decreased adherence in antibody responders is justified, also in view of future pandemics. Funding: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.
The molecular basis for the control of iron absorption by the duodenum remains unknown; however, ferritin (Ft) and the iron status of enterocytes have been suggested as regulatory factors. We ...determined the iron and Ft status of duodenal enterocytes from mice with hypotransferrinaemia, a genetic defect leading to greatly enhanced iron absorption, and for comparison we also investigated mice with experimentally‐altered iron absorption. Duodenal enterocytes were isolated and analysed for Ft and non‐haem iron content and for transferrin binding (as a measure of transferrin receptor activity). RNA was extracted from the duodenal mucosa and examined for transferrin receptor and H‐ and L‐Ft mRNA levels by Northern hybridization analysis. Ft levels were elevated in enterocytes of hypotransferrinaemic mice, similar to that seen in iron dextran‐injected mice of the CD1‐strain. Enterocyte Ft levels were reduced in mice fed a diet diminished in iron, but unchanged in hypoxic mice enterocytes. Enterocytes of hypotransferrinaemic mice had normal non‐haem iron levels and transferrin binding; however, enterocytes from CD‐1 mice fed a low iron diet had increased transferrin binding and a decreased non‐haem iron content. Duodenal mRNA levels for transferrin receptor and H‐Ft were unchanged in hypotransferrinaemic mice, whereas L‐Ft was increased. We conclude from the Ft and non‐haem iron contents and transferrin binding that duodenal enterocytes from hypotransferrinaemic mice are not simply iron deficient, leading to increased expression of iron carriers proteins. Duodenal iron absorption can be enhanced in mice even when enterocyte Ft levels are raised or unchanged, suggesting that iron absorption is regulated by developmentally programmed expression of iron transporters by enterocytes.
Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. ...One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
During the years 1994–1997, the emulsion target of the CHORUS detector was exposed to the wide-band neutrino beam of the CERN SPS. In total about 100 000 charged-current neutrino interactions were ...located in the nuclear emulsion target and fully reconstructed. From this sample of events which was based on the data acquired by new automatic scanning systems, 1048 D
0 events were selected by a pattern recognition program. They were confirmed as neutral-particle decays through visual inspection. Fragmentation properties of deep-inelastic charm production were measured using these events. Distributions of the D
0 momentum, Feynman
x (
x
F
),
z and
tan
θ
out
, the transverse angle out of the leptonic plane defined by the muon and the neutrino, are presented. The mean value of
z was measured to be
〈
z
〉
=
0.63
±
0.03
(
stat
)
±
0.01
(
syst
)
. From fits to the
z distribution, values for the Peterson parameter
ε
P
=
0.108
±
0.017
(
stat
)
±
0.013
(
syst
)
and the Collins–Spiller parameter
ε
CS
=
0.21
−0.04
+0.05
(
stat
)
±
0.04
(
syst
)
are found. For the average value of
x
F
we find
〈
x
F
〉
=
0.38
±
0.04
(
stat
)
±
0.03
(
syst
)
and for the forward–backward asymmetry
A
=
0.79
±
0.14
(
stat
)
±
0.05
(
syst
)
. The distribution of
tan
θ
out
was measured with an average value
〈
tan
θ
out
〉
=
0.030
±
0.002
.
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