Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. ...We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator-initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter-ECG for up to 7 days in-hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady-/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all-cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued β-blocker medication. Discontinuation of β-blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 95% CI, 2.4-50.4;
=0.025 for interaction). Conclusions Systematic in-hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.
IntroductionProximal femoral fractures (PFF) are among the most frequent fractures in older people. However, the situation of people with a PFF after hospital discharge is poorly understood. Our aim ...is to (1) analyse healthcare provision, (2) examine clinical and patient-reported outcomes (PROs), (3) describe clinical and sociodemographic predictors of these and (4) develop an algorithm to identify subgroups with poor outcomes and a potential need for more intensive healthcare.Methods and analysisThis is a population-based prospective study based on individually linked survey and statutory health insurance (SHI) data. All people aged minimum 60 years who have been continuously insured with the AOK Rheinland/Hamburg and experience a PFF within 1 year will be consecutively included (SHI data analysis). Additionally, 700 people selected randomly from the study population will be consecutively invited to participate in the survey. Questionnaire data will be collected in the participants’ private surroundings at 3, 6 and 12 months after hospital discharge. If the insured person considers themselves to be only partially or not at all able to take part in the survey, a proxy person will be interviewed where possible. SHI variables include healthcare provision, healthcare costs and clinical outcomes. Questionnaire variables include information on PROs, lifestyle characteristics and socioeconomic status. We will use multiple regression models to estimate healthcare processes and outcomes including mortality and cost, investigate predictors, perform non-responder analysis and develop an algorithm to identify vulnerable subgroups.Ethics and disseminationThe study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (approval reference 6128R). All participants including proxies providing written and informed consent can withdraw from the study at any time. The study findings will be disseminated through scientific journals and public information.Trial registration numberDRKS00012554.
Zusammenfassung
Hintergrund
Nach der Veröffentlichung der American College of Surgeons Oncology Group Z0011-Studie (ACOSOG Z0011) ist die Analyse der intraoperativen Gefrierschnitte von ...Wächterlymphknoten zurückgegangen. Aber für Patientinnen, welche die ACOSOG Z0011-Kriterien nicht erfüllen, bleibt die Gefrierschnittanalyse ein wichtiges Instrument für die intraoperative Entscheidungsfindung im Hinblick auf eine Axilladissektion. Ziel dieser Studie war es, eine retrospektive Evaluierung der Vorteile und der diagnostischen Genauigkeit von Gefrierschnittanalysen bei Brustkrebspatientinnen durchzuführen, welche die Kriterien der Z0011-Studie erfüllten oder nicht erfüllten, und dabei mögliche prädiktive Faktoren für falsch negative Ergebnisse festzustellen.
Methoden
Zwischen 2008 und 2013 wurde eine intraoperative Gefrierschnittanalyse der Wächterlymphknoten bei 522 cT1-T3-Brustkrebspatientinnen durchgeführt. Die klinisch-pathologischen Merkmale wurden retrospektiv mithilfe der Krankenakten evaluiert.
Ergebnisse
Insgesamt betrug die Sensitivität und Spezifität für alle Gefrierschnittanalysen 67,8 % bzw. 100 %. Generell war die Sensitivität für Makrometastasen höher als für Mikrometastasen. Bei der Gruppe, welche die Kriterien der Z0011-Studie erfüllte, betrugen die Sensitivität und Spezifität 72,7 % bzw. 100 %, verglichen mit 62,1 % bzw. 100 % für die Gruppe, welche die Z0011-Kriterien nicht erfüllte. In der Gruppe, welche die Z0011-Kriterien erfüllte, wurde eine Untergruppenanalyse durchgeführt, und die Ergebnisse für ≤ 2 positiven Wächterlymphknoten wurden mit den Ergebnissen für > 2 verglichen. Bei beiden Untergruppen betrugen Spezifität und Sensitivität jeweils 100 %. In der Patientinnengruppe, welche die Z0011-Kriterien nicht erfüllte, waren mehrere klinisch-pathologische Faktoren mit einer höheren Rate an falsch positiven Ergebnissen assoziiert. Im Hinblick auf die intraoperative Entscheidungsfindung für eine Axilladissektion brachte die Durchführung einer intraoperativen Gefrierschnittanalyse Vorteile für 22,2 % der Patientinnen, welche die Z0011-Kriterien nicht erfüllten, aber nur für 0,6 % der Patientinnen, welche die Z0011-Kriterien erfüllten.
Schlussfolgerungen
Die Gefrierschnittanalyse ist besonders für die intraoperative Evaluierung von Wächterlymphknoten bei Patientinnen, welche die Z0011-Kriterien nicht erfüllen, vorteilhaft, da dadurch eine Zweitoperation zur Axilladissektion vermieden werden kann. Obwohl die Sensitivität der Gefrierschnittanalyse in der Gruppe, welche die Z0011-Kriterien erfüllte, insgesamt niedriger war, hat die Gefrierschnittanalyse in beiden Gruppen eine vergleichbar hohe Sensitivität und diagnostische Genauigkeit für Makrometastasen.
The cohesin subunit
has emerged as a recurrently inactivated tumor suppressor in human cancers. Using candidate approaches, recent studies have revealed a synthetic lethal interaction between
and its ...paralog
To systematically probe genetic vulnerabilities in the absence of STAG2, we have performed genome-wide CRISPR screens in isogenic cell lines and identified STAG1 as the most prominent and selective dependency of STAG2-deficient cells. Using an inducible degron system, we show that chemical genetic degradation of STAG1 protein results in the loss of sister chromatid cohesion and rapid cell death in STAG2-deficient cells, while sparing
-wild-type cells. Biochemical assays and X-ray crystallography identify STAG1 regions that interact with the RAD21 subunit of the cohesin complex. STAG1 mutations that abrogate this interaction selectively compromise the viability of
-deficient cells. Our work highlights the degradation of STAG1 and inhibition of its interaction with RAD21 as promising therapeutic strategies. These findings lay the groundwork for the development of STAG1-directed small molecules to exploit synthetic lethality in
-mutated tumors.
Abstract
Aim
The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of ...Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline.
Methods
This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40).
Recommendations
The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patientʼs personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.
Zusammenfassung
Ziel
Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) publiziert und zusammen mit der Deutschen Gesellschaft für Urologie (DGU) sowie Deutschen Gesellschaft für Reproduktionsmedizin (DGRM) koordiniert wurde, ist es, durch die Evaluation der relevanten Literatur konsensbasierte Handlungsempfehlungen für die Beratung und den Einsatz von fertilitätserhaltenden Maßnahmen bei präpubertären Mädchen und Jungen sowie für Patienten/-innen im reproduktiven Alter zu geben. Im Folgendem werden die Statements und Empfehlungen für Mädchen und Frauen dargestellt. Die Statements und Empfehlungen für Jungen und Männer sind nicht Inhalt dieser Publikation.
Methoden
Diese S2k-Leitlinie wurde durch einen strukturierten Konsens von repräsentativen Mitgliedern verschiedener Fachgesellschaften (n = 40) im Auftrag der Leitlinienkommission der DGGG, DGU und DGRM entwickelt.
Empfehlungen
Es werden Empfehlungen zur Beratung und dem Einsatz von fertilitätserhaltenden Maßnahmen bei Patientinnen unter Berücksichtigung der Lebensumstände, der geplanten onkologischen Therapie und des individuellen Risikoprofils dargestellt sowie über das Vorgehen bei ausgewählten Tumorentitäten.
In human albinism, part of the temporal retina projects abnormally to the contralateral hemisphere. This study was undertaken to test whether this abnormality can be identified with multifocal visual ...evoked potentials (mfVEPs) and whether it is evident in carriers of ocular albinism (OA1).
In 12 control subjects, 11 patients with albinism, and 5 female carriers of OA1 monocular pattern-reversal mfVEPs were recorded for 60 locations comprising a visual field of 44 degrees diameter (VERIS ver. 4.8; EDI, San Mateo, CA). For each eye and each stimulus location interhemispheric difference potentials were calculated and correlated with each other to assess the lateralization of the responses: positive and negative correlations indicate lateralization on same or opposite hemispheres, respectively. Misrouted optic nerves are expected to yield negative interocular correlations. Visual field locations without recordable responses were excluded from the analysis using a signal-to-noise threshold. The analysis also allowed assessment of the sensitivity and specificity of the detection of projection abnormalities.
Sizable mfVEPs were obtained in all control subjects, carriers, and the three patients with albinism who had negligible nystagmus and visual acuity>0.25. Ninety-seven percent and 99% of the visual field locations were identified as normal in control subjects and carriers, respectively. While this indicates a specificity of the procedure of 97%, the sensitivity was estimated as 75%. Finally, in albinism, 55% percent of the responses were abnormally represented.
In the absence of nystagmus mfVEPs are a powerful tool to identify, in a spatially resolved manner, abnormal visual field representations. No local representation abnormalities were evident in the female carriers of OA1.
Estimation of the Body Weight of Icelandic Horses Hoffmann, Gundula; Bentke, Annika; Rose-Meierhöfer, Sandra ...
Journal of equine veterinary science,
November 2013, 2013-11-00, Volume:
33, Issue:
11
Journal Article
Peer reviewed
The body weight of horses is an interesting variable for horse owners, as well as for veterinarians. It is useful to have methods of estimation like weight tape or formula, rather than visual ...estimation, when a weight scale is not available. Different methods of weight estimation exist for adult horses, but to date, there has been no validation of these methods in Icelandic horses. Therefore, three different methods of weight determination (weight scale, weight tape, and weight formula) were compared in this study to investigate whether it is possible to obtain reliable weight measurements of Icelandic horses by using an estimation method. Both the weight pursuant to weight tape and pursuant to weight formula showed no significant differences (P = 1.00 and P = 0.37, respectively) from the actual weight. The correlation between estimated and actual weights was r = 0.94 for weight tape and r = 0.93 for weight formula. However, the differences between the estimated and actual weights were smallest when estimated using an adjusted weight formula: weight (kg) = girth² × length (both in cm)/11,400. In conclusion, the body weight of Icelandic horses can be estimated from the measurements of body girth and length, and weight tape also seems to be a suitable method.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The comet assay (single cell gel electrophoresis) has become increasingly used in human biomonitoring. In its standard version at pH > 13, DNA lesions such as DNA double-strand breaks (DSB), DNA ...single strand breaks (SSB) and alkali-labile sites (ALS) lead to increased DNA migration. Besides DNA damage, strand break formation during excision repair can also increase DNA migration. Inhibitors of DNA repair have been shown to enhance the DNA effects of mutagens and the use of repair inhibitors has been proposed for human biomonitoring studies to increase the sensitivity of the comet assay. To further evaluate the usefulness of such an approach we performed an experimental study with human blood and tested the enhancing effect of aphidicolin (APC) on DNA effects induced by different mutagens. Our results clearly show that APC enhances the genotoxic effects of benzoapyrene diolepoxide (BPDE), bischloroethylnitrosurea (BCNU) and methyl methanesulfonate (MMS), but has no significant effect on gamma radiation-induced DNA effects. The enhancing effect is seen in unstimulated and PHA-stimulated blood, indicating repair activity under both conditions but the effect is stronger in stimulated blood. Our results indicate that APC can be used to increase the sensitivity of the comet assay towards a broad spectrum of induced primary DNA lesions and support the usefulness of this approach. However, for human biomonitoring, a sensitive protocol still has to be established.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A combined OMICS screening approach of human plasma and serum was used to characterize protein and metabolome signatures displaying association to severity of Community-acquired pneumonia (CAP). 240 ...serum and BD P100 EDTA plasma samples from patients diagnosed with CAP, collected during the day of enrolment to the hospital, were analyzed by a metabolomic and proteomic approach, respectively. Disease severity of CAP patients was stratified using the Sequential Organ Failure Assessment (SOFA) score. Quantitative proteome and metabolome data, derived by LC-MS/MS, were associated to SOFA and specific parameters of SOFA using linear regression models adjusted for age, BMI, sex, smoking and technical variables.
Both proteome and metabolome profiling revealed remarkable strong changes in plasma and serum composition in relation to severity of CAP. Proteins and metabolites displaying SOFA associated levels are involved in immune response, particularly in processes of lipid metabolism. Proteins, which show an association to SOFA score, are involved in acute phase response, coagulation, complement activation and inflammation. Many of these metabolites and proteins displayed not only associations to SOFA, but also to parameters of SOFA score, which likely reflect the strong influence of lung-, liver-, kidney- and heart-dysfunction on the metabolome and proteome patterns.
Community-acquired pneumonia is the most frequent infection disease with high morbidity and mortality. So far, only few studies focused on the identification of proteins or metabolites associated to severity of CAP, often based on smaller sample sets. A screening for new diagnostic markers requires extensive sample collections in combination with high quality clinical data. To characterize the proteomic and metabolomics pattern associated to severity of CAP we performed a combined metabolomics and proteomic approach of serum and plasma sample from a multi-center clinical study focused on patients with CAP, requiring hospitalization. The results of this association study of omics data to the SOFA score enable not only an interpretation of changes in molecular patterns with severity of CAP but also an assignment of altered molecules to dysfunctions of respiratory, renal, coagulation, cardiovascular systems as well as liver.
Display omitted
•Combined plasma proteome and serum metabolome profiling of CAP patients•Samples were obtained from a comprehensively phenotyped multi-center study.•Profiling revealed changes in plasma/serum composition in relation to CAP severity.•SOFA associated omics signatures are involved in immune response related processes.•Specific signatures may reflect strong influence on the extent of organ dysfunction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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