Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Allogeneic mesenchymal stromal/stem cell (MSC) infusions are a promising potential treatment for steroid-resistant aGvHD. Data from our institution and others demonstrate rescue of approximately 40-50% of aGvHD patients with MSCs in Phase I, II studies and minor side effects. Although promising, better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. METHODS: Single cell human small intestine organoids were embedded in Matrigel, grown for 5 days and treated with busulfan for 48 h. Organoids damaged by treatment with busulfan or control organoids were co-cultured with 5000, 10,000, and 50,000 MSCs for 24 h, 48 h or 7 days and the analyses such as surface area determination, proliferation and apoptosis assessment, RNA sequencing and proteomics were performed. RESULTS: Here, we developed a 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating epithelial to mesenchymal transition, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan-treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. CONCLUSIONS: Collectively, we demonstrate that our in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium. This could benefit further optimization of the use of MSCs in HSCT patients.

Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort.

PURPOSES: Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. METHODS: All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). RESULTS: Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6-24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. CONCLUSIONS: This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent 'cure' proportions of surgery for rHPT but stretches the importance of long-term follow-up.

Possible alleviation of symptoms and side effects through clinicians' nocebo information and empathy in an experimental video vignette study.

To alleviate anti-cancer treatment burden in advanced breast cancer, patient-clinician communication strategies based on nocebo-effect mechanisms are promising. We assessed distinct/combined effects on psychological outcomes (e.g. anxiety; main outcome) and side-effect expectations of (1) nocebo information about the (non)pharmacological origin of side effects, and (2) clinician-expressed empathy through reassurance of continuing support. Furthermore, we explored whether information and empathy effects on side-effect expectations were mediated by decreased anxiety. In a two-by-two experimental video-vignette design, 160 cancer patients/survivors and healthy women watched one of four videos differing in level of nocebo information (±) and empathy (±). Regression and mediation analysis were used to determine effects of information/empathy and explore anxiety's mediating role. Anxiety was not influenced by empathy or information (Stai-state: p = 0.295; p = 0.390, VAS p = 0.399; p = 0.823). Information improved (specific) side-effect coping expectations (p < 0.01). Empathy improved side-effect intensity expectations (p < 0.01 = specific; p < 0.05 = non-specific/partial) and specific side-effect probability expectations (p < 0.01), and increased satisfaction, trust, and self-efficacy (p < 0.001). No mediating effects were found of anxiety on expectations. Mainly empathy, but also nocebo information improved psychological outcomes and-mainly specific-side-effect expectations. Exploring the power of these communication elements in clinical practice is essential to diminish the anti-cancer treatment burden in advanced breast cancer.

Rift Valley fever virus detection in susceptible hosts with special emphasis in insects.

Rift Valley fever phlebovirus (RVFV, Phenuiviridae) is an emerging arbovirus that can cause potentially fatal disease in many host species including ruminants and humans. Thus, tools to detect this pathogen within tissue samples from routine diagnostic investigations or for research purposes are of major interest. This study compares the immunohistological usefulness of several mono- and polyclonal antibodies against RVFV epitopes in tissue samples derived from natural hosts of epidemiologic importance (sheep), potentially virus transmitting insect species (Culex quinquefasciatus, Aedes aegypti) as well as scientific infection models (mouse, Drosophila melanogaster, C6/36 cell pellet). While the nucleoprotein was the epitope most prominently detected in mammal and mosquito tissue samples, fruit fly tissues showed expression of glycoproteins only. Antibodies against non-structural proteins exhibited single cell reactions in salivary glands of mosquitoes and the C6/36 cell pellet. However, as single antibodies exhibited a cross reactivity of varying degree in non-infected specimens, a careful interpretation of positive reactions and consideration of adequate controls remains of critical importance. The results suggest that primary antibodies directed against viral nucleoproteins and glycoproteins can facilitate RVFV detection in mammals and insects, respectively, and therefore will allow RVFV detection for diagnostic and research purposes.

T cell-derived interferon-γ programs stem cell death in immune-mediated intestinal damage.

Despite the importance of intestinal stem cells (ISCs) for epithelial maintenance, there is limited understanding of how immune-mediated damage affects ISCs and their niche. We found that stem cell compartment injury is a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing ISCs and impairing their recovery in T cell-mediated injury models. Although imaging revealed few T cells near the stem cell compartment in healthy mice, donor T cells infiltrating the intestinal mucosa after allogeneic bone marrow transplantation (BMT) primarily localized to the crypt region lamina propria. Further modeling with ex vivo epithelial cultures indicated ISC depletion and impaired human as well as murine organoid survival upon coculture with activated T cells, and screening of effector pathways identified interferon-γ (IFNγ) as a principal mediator of ISC compartment damage. IFNγ induced JAK1- and STAT1-dependent toxicity, initiating a proapoptotic gene expression program and stem cell death. BMT with IFNγ-deficient donor T cells, with recipients lacking the IFNγ receptor (IFNγR) specifically in the intestinal epithelium, and with pharmacologic inhibition of JAK signaling all resulted in protection of the stem cell compartment. In addition, epithelial cultures with Paneth cell-deficient organoids, IFNγR-deficient Paneth cells, IFNγR-deficient ISCs, and purified stem cell colonies all indicated direct targeting of the ISCs that was not dependent on injury to the Paneth cell niche. Dysregulated T cell activation and IFNγ production are thus potent mediators of ISC injury, and blockade of JAK/STAT signaling within target tissue stem cells can prevent this T cell-mediated pathology.

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds.

Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage.A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters.Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described.Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery.

Effect of ephedrine on gastric conduit perfusion measured by laser speckle contrast imaging after esophagectomy: a prospective in vivo cohort study.

Compromised perfusion due to ligation of arteries and veins in esophagectomy with gastric tube reconstruction often (5-20%) results in necrosis and anastomotic leakage, which relate to high morbidity and mortality (3-4%). Ephedrine is used widely in anesthesia to treat intraoperative hypotension and may improve perfusion by the increase of cardiac output and mean arterial pressure (MAP). This study tests the effect of ephedrine on perfusion of the future anastomotic site of the gastric conduit, measured by laser speckle contrast imaging (LSCI). This prospective, observational, in vivo pilot study includes 26 patients undergoing esophagectomy with gastric tube reconstruction from October 2015 to June 2016 in the Academic Medical Center (Amsterdam). Perfusion of the gastric conduit was measured with LSCI directly after reconstruction and after an increase of MAP by ephedrine 5 mg. Perfusion was quantified in flux (laser speckle perfusion units, LSPU) in four perfusion locations, from good perfusion (base of the gastric tube) toward decreased perfusion (fundus). Intrapatient differences before and after ephedrine in terms flux were statistically tested for significance with a paired t-test. LSCI was feasible to image gastric microcirculation in all patients. Flux (LSPU) was significantly higher in the base of the gastric tube (791 ± 442) compared to the fundus (328 ± 187) (P < 0.001). After administration of ephedrine, flux increased significantly in the fundus (P < 0.05) measured intrapatients. Three patients developed anastomotic leakage. In these patients, the difference between measured flux in the fundus compared to the base of the gastric tube was high. This study presents the effect of ephedrine on perfusion of the gastric tissue measured with LSCI in terms of flux (LSPU) after esophagectomy with gastric tube reconstruction. We show a small but significant difference between flux measured before and after administration of ephedrine in the future anastomotic tissue (313 ± 178 vs. 397 ± 290). We also show a significant decrease of flux toward the fundus.

SNP g.1007A>G within the porcine DNAL4 gene affects sperm motility traits and percentage of midpiece abnormalities.

The flagellar beating of a spermatozoa's axoneme is caused by the varying activation and inactivation of dynein molecules. Dynein, axonemal, light chain 4 (DNAL4) is a functional candidate gene for sperm motility as it encodes a small subunit of the dyneins. We resequenced the porcine DNAL4 using three artificial insemination (AI) boars each with high (>68%) or low (<60%) motility, and detected 23 SNP. These were then genotyped for 82 AI boars. Using spermatological records, significantly negative genetic correlations between ejaculate volume (VOL) and the further spermatological parameters concentration (CONC) (r = -.43), motility of undiluted semen (MOTUD) (r = -.09), motility after 24 h (MOT1) (r = -.17) and after 48 hr (MOT2) (r = -.23) were estimated. Significantly positive correlations existed between CONC and MOT1 (r = .07) as well as MOT2 (r = .10), between MOTUD and MOT1 (r = .33), between MOTUD and MOT2 (r = .36), and finally between MOT1 and MOT2 (r = .70). Significantly negatively correlated were all motility traits with the parameters abnormal acrosome (AA) (MOTUD r = -.06; MOT1 r = -.08, and MOT2 r = -.1) and presence of cytoplasmic droplet (CD) (MOTUD r = -.07; MOT1 r = -.08; MOT2 r = -.07). Association analyses (single marker regression model; SMR) propose that SNP g.1007A>G, located in the second intron, reduces motility significantly (MOTUD -4.59%; MOT1 -10.33%; MOT2 -19.37%). According to the dominant-recessive model (DRM), genotype AA is always superior compared to genotypes AG and GG (i.e. MOTUD 67.67%, 64.16% and 53.91%; MOT1 54.17%, 43.75% and 28.44%; MOT2 44.12%, 24.91% and 4.97%). The average effect of gene substitution (g.1007A>G) on abnormal midpiece (AM) was 0.71%, the genotypic values-as expressed by LSmeans-were 0.1 (AA) and 0.81 (AG).

Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals.

BACKGROUND: Although there are many effective lifestyle interventions for type 2 diabetes (T2DM) prevention, insight into effective intervention pathways, especially of long-term interventions, is often lacking. This study aims to provide insight into the effective intervention pathways of the SLIMMER diabetes prevention intervention using mediation analyses. METHODS: In total, 240 participants at increased risk of T2DM were included in the analyses over 18 months. The intervention was a combined lifestyle intervention with a dietary and a physical activity (PA) component. The primary and secondary outcomes were change in fasting insulin (pmol/L) and change in body weight (kg) after 18 months, respectively. Firstly, in a multiple mediator model, we investigated whether significant changes in these outcomes were mediated by changes in dietary and PA behavior. Secondly, in multiple single mediator models, we investigated whether changes in dietary and PA behavior were mediated by changes in behavioral determinants and the participants' psychological profile. The mediation analyses used linear regression models, where significance of indirect effects was calculated with bootstrapping. RESULTS: The effect of the intervention on decreased fasting insulin was 40% mediated by change in dietary and PA behavior, where dietary behavior was an independent mediator of the association (34%). The effect of the intervention on decreased body weight was 20% mediated by change in dietary and PA behavior, where PA behavior was an independent mediator (17%). The intervention significantly changed intake of fruit, fat from bread spread, and fiber from bread. Change in fruit intake was mediated by change in action control (combination of consciousness, self-control, and effort), motivation, self-efficacy, intention, and skills. Change in fat intake was mediated by change in action control and psychological profile. No mediators could be identified for change in fiber intake. The change in PA behavior was mediated by change in action control, motivation, and psychological profile. CONCLUSION: The effect of the SLIMMER intervention on fasting insulin and body weight was mediated by changes in dietary and PA behavior, in distinct ways. These results indicate that changing dietary as well as PA behavior is important in T2DM prevention.

Effect and maintenance of the SLIMMER diabetes prevention lifestyle intervention in Dutch primary healthcare: a randomised controlled trial.

BACKGROUND/OBJECTIVES: To assess the effectiveness of the SLIMMER combined dietary and physical activity lifestyle intervention on clinical and metabolic risk factors, dietary intake, physical activity, and quality of life after 12 months, and to investigate whether effects sustained six months after the active intervention period ended. SUBJECTS/METHODS: SLIMMER was a randomised controlled intervention, implemented in Dutch primary healthcare. In total, 316 subjects aged 40-70 years with increased risk of type 2 diabetes were randomly allocated to the intervention group (10-month dietary and physical activity programme) or the control group (usual healthcare). All subjects underwent an oral glucose tolerance test and physical examination, and filled in questionnaires. Identical examinations were performed at baseline and after 12 and 18 months. Primary outcome was fasting insulin. RESULTS: The intervention group showed significantly greater improvements in anthropometry and glucose metabolism. After 12 and 18 months, differences between intervention and control group were -2.7 kg (95% confidence interval (CI): -3.7; -1.7) and -2.5 kg (95% CI: -3.6; -1.4) for weight, and -12.1 pmol l-1 (95% CI: -19.6; -4.6) and -8.0 pmol l-1 (95% CI: -14.7; -0.53) for fasting insulin. Furthermore, dietary intake, physical activity, and quality of life improved significantly more in the intervention group than in the control group. CONCLUSIONS: The Dutch SLIMMER lifestyle intervention is effective in the short and long term in improving clinical and metabolic risk factors, dietary intake, physical activity, and quality of life in subjects at high risk of diabetes.

Reliability of Eustachian tube function measurements in a hypobaric and hyperbaric pressure chamber.

OBJECTIVES: Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases-especially because more and more operative therapies are being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear. METHODS: Twenty-five participants (50 ears) were exposed to phases of compression and decompression in a hypo- and hyperbaric pressure chamber. The ET function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF)-were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test-retest reliability. RESULTS: ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altman graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases. CONCLUSIONS: We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.

Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

OBJECTIVE: Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. STUDY DESIGN/METHODS: The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. RESULTS: In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). CONCLUSION: Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A.

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism.

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD.

Hip arthroscopy in obese, a successful combination?

Discussion persists about the outcome and results of hip arthroscopy in obese patients. Hip arthroscopy gained popularity over time. A current discussion is if obese patients can reach similar results after surgery compared with non-obese. To our knowledge, this is the first systematic review of literature about hip arthroscopy and obesity. We searched the Pubmed/Medline databases for literature and included three studies that compared the outcome of hip arthroscopy between different BMI groups. We extracted and pooled the data. For continues data a weighted mean difference was calculated, for dichotomous variables a weighted odds ratio (OR) was calculated using Review Software Manager. Heterogeneity of the included studies was calculated using I(2) statistics. Data were extracted from two studies. In the Obese group, there was significant more conversion to total hip replacement or resurfacing hip replacement (OR = 2.21, 95% CI 1.07-4.56) and more re-arthroscopy (OR = 4.68, 95% CI 1.41-15.45). Any reoperation occurred more often in the obese group (OR = 2.87, 95% CI 1.53-5.38). In the Non Arthritic Hip Score obese scored lower than the non-Obese group [10.9 (-14,6 to 7.1)]. For the modified Harris Hip Score the score is - 6,6, according to the MCID this difference is clinically relevant. For both scores obese show lower outcomes but similar improvement after hip arthroscopy. Regarding a higher chance of needing a re-operation and lower subjective outcome scores obesity appears to have a negative influence on the outcome of hip arthroscopy.

In-Hospital Haloperidol Use and Perioperative Changes in QTc-Duration.

OBJECTIVES: Haloperidol may prolong ECG QTc-duration but is often prescribed perioperatively to hip-fracture patients. We aimed to determine (1) how QTc-duration changes perioperatively, (2) whether low-dose haloperidol-use influences these changes, and (3) which clinical variables are associated with potentially dangerous perioperative QTc-prolongation (PD-QTc; increase >50 ms or to >500 ms). DESIGN: Prospective cohort study. SETTING: Tertiary university teaching-hospital. PARTICIPANTS: Patients enrolled in a randomized controlled clinical trial of melatonin versus placebo on occurrence of delirium in hip-fracture patients. MEASUREMENTS: Data from ECGs made before and after hip surgery (1-3 days and/or 4-6 days post-surgery) were analyzed. QTc-duration was measured by hand, blinded for haloperidol and pre/post-surgery status. Clinical variables were measured at baseline. Mixed model analysis was used to estimate changes in QTc-duration. Risk-factors for PD-QTc were estimated by logistic regression analysis. RESULTS: We included 89 patients (mean age 84 years, 24% male); 39 were treated with haloperidol. Patients with normal pre-surgery QTc-duration (male ≤430 ms, female ≤450 ms) had a significant increase (mean 12 ms, SD 28) in QTc-duration. A significant decrease (mean 19 ms, SD 34) occurred in patients with prolonged pre-surgery QTc-duration (male >450ms, female >470 ms). Haloperidol-use did not influence the perioperative course of the QTc-interval (p=0.351). PD-QTc (n=8) was not associated with any of the measured risk-factors. CONCLUSION: QTc-duration changed differentially, increasing in patients with normal, but decreasing in patients with abnormal baseline QTc-duration. PD-QTc was not associated with haloperidol-use or other risk-factors. Low-dose oral haloperidol did not affect perioperative QTc-interval.

Electrocardiographic abnormalities in patients admitted for hip fracture.

BACKGROUND: Several risk factors for falls and hip fractures have been recognised, but controversy still exists regarding the importance of rhythm and conduction abnormalities as potentially modifiable risk factors for recurrent falls. The aim of this study was to determine the prevalence of clinically relevant ECG abnormalities in patients with a hip fracture versus controls. METHODS: The study was designed as a case-control study within consecutive hip surgery patients in an academic hospital. CASES: patients with traumatic hip fractures. CONTROLS: patients undergoing planned hip surgery (non-traumatic). CASES and controls were 1:1 matched for age and gender. INCLUSION CRITERIA: age ≥ 50 years. EXCLUSION CRITERIA: high-energy trauma, pathological and÷or previous hip fracture. ECGs were scored using predefined categories. Multivariate logistic regression was performed to calculate odds ratios (OR) and to correct for confounders. RESULTS: We included 888 patients (444 cases). Mean age was 70.9 years (SD 9.3), 70% were female. After correction for potential confounders we found the following associations between clinically relevant ECG abnormalities and hip fractures: atrial fibrillation OR 2.7 (95% CI 1.2-6.1), abnormal QTc prolongation OR 3.9 (2.2-6.8), sinus tachycardia OR 5.0 (2.1-11.8) and sinus bradycardia OR 0.3 (0.1-0.5). Univariately, several markers for decreased cardiac function were also associated with hip fractures. CONCLUSIONS: Hip fracture patients are at higher risk for ECG abnormalities than matched patients undergoing hip surgery for other indications. To potentially reduce the risk of future (injurious) falls, increased awareness of these ECG abnormalities is warranted to assess the need for further cardiovascular fall risk assessment.

Characterizing early contrast uptake of ductal carcinoma in situ with high temporal resolution dynamic contrast-enhanced MRI of the breast: a pilot study.

Improvements in the reliable diagnosis of preinvasive ductal carcinoma in situ (DCIS) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are needed. In this study, we present a new characterization of early contrast kinetics of DCIS using high temporal resolution (HiT) DCE-MRI and compare it with other breast lesions and normal parenchyma. Forty patients with mammographic calcifications suspicious for DCIS were selected for HiT imaging using T(1)-weighted DCE-MRI with ∼7 s temporal resolution for 90 s post-contrast injection. Pixel-based and whole-lesion kinetic curves were fit to an empirical mathematical model (EMM) and several secondary kinetic parameters derived. Using the EMM parameterized and fitted concentration time curve for subsequent analysis allowed for calculation of kinetic parameters that were less susceptible to fluctuations due to noise. The parameters' initial area under the curve (iAUC) and contrast concentration at 1 min (C(1 min)) provided the highest diagnostic accuracy in the task of distinguishing pathologically proven DCIS from normal tissue. There was a trend for DCIS lesions with solid architectural pattern to exhibit a negative slope at 1 min (i.e. increased washout rate) compared to those with a cribriform pattern (p < 0.04). This pilot study demonstrates the feasibility of quantitative analysis of early contrast kinetics at high temporal resolution and points to the potential for such an analysis to improve the characterization of DCIS.

Recommendations on end-of-life care for people with dementia.

OBJECTIVE: To establish, in collaboration with national Alzheimer Societies in Europe, practical and consensual recommendations for the end-of-life care of people with dementia. The aim of these recommendations is to provide a basis for understanding and action with regard to end-of-life care not only for family caregivers but also for professionals, policy makers and anyone with an interest in palliative care. DESIGN: A literature review was carried out by Alzheimer Europe in collaboration with a working group comprised of people from different backgrounds such as family caregivers, physicians, palliative care nurses and members of Alzheimer associations, who also prepared the draft recommendations during 4 sessions. These recommendations were then discussed with external experts and sent to Alzheimer Europe's member associations to be broadly discussed within their countries until a consensus was reached. SETTING: Alzheimer Europe is an umbrella association of European Alzheimer societies with 34 member associations in 30 different countries. SUBJECTS: Not applicable. METHODS: Literature review, workshops, dissemination by e-mail and during conferences, consensus finding. RESULTS: At the end of 2008, Alzheimer Europe prepared written recommendations on good end-of-life care for people with dementia. We are aware that this topic is challenging and that there is therefore a need for further discussion. CONCLUSION: In this article we aim to present these recommendations and to invite professionals to consider these important issues and to contribute towards a broader discussion.

Predictability of strabismus surgery in children with developmental disorders and/or psychomotor retardation.

BACKGROUND: Children with developmental disorders and/or psychomotor delay may respond differently to strabismus surgery than children who develop normally, but the literature is conflicting. METHODS: We studied 37 patients with spasm, trisomy 21, prematurity, epilepsy, psychomotor retardation, and/or hydrocephalus (study group) and 67 control patients, all between 14 months and 14 years of age. All received a recession of one or both medial rectus muscles (Rc-surgery) or a monocular recession-resection of medial-lateral rectus muscles (RcRs-surgery) for esotropia. Rc-surgery was performed in cases with convergence excess. Spectacles were prescribed prior to surgery for all hyperopia > 2D, all partly accommodative esotropia, and all myopia. RESULTS: (effect per mm of surgery): For Rc-surgery, after 2 months follow-up, at 2.5 m fixation distance, the effects (change of angle per millimeter of surgery, mean + or - SD) were 2.07 + or - 0.82 degrees /mm (study group) and 1.07 + or - 0.74 degrees /mm (control group) (P < 0.001). At 30 cm fixation distance, the effects were 2.42 + or - 0.79 degrees /mm (study group) and 1.53 + or - 1.00 degrees /mm (control group) (P < 0.001). Effects at infinity were similar to those at 2.5 m. Because of this larger effect on near angles, convergence excess decreased after surgery in both study and control groups. For RcRs-surgery, at 2.5 m fixation distance, the effects were 1.78 + or - 0.43 degrees /mm (study group) and 1.78 + or - 0.42 degrees /mm (control group) (P = 0.741). At 30 cm fixation distance, the effects were 1.82 + or - 0.39 degrees /mm (study group) and 1.84 + or - 0.58 degrees /mm (control group) (P = 0.918). At fixation distance infinity, results were similar to those at 2.5 m. For both Rc-surgery and RcRs-surgery, reported differences were similar after one year follow-up. Success of surgery: After 2 months of follow-up, esotropia between 0-6 degrees was present, for Rc-surgery in 64% in the study group (with adjusted dosages) and 93% in the control group; and for RcRs-surgery in 66% in the study group and 88% in the control group. CONCLUSIONS: Rc-surgery in children with developmental disorders and/or psychomotor delay has a larger effect per mm of surgery than in normal children. RcRs-surgery has a similar effect in delayed and normal children.