Einfluss der Fetalblutanalyse auf die Prozess- und Ergebnisqualität in der Perinatalmedizin

Fragestellung: Der klinische Nutzen des Einsatzes der Fetalblutanalyse wird national und international kritisch diskutiert. Kann dieses biochemische Verfahren, welches bei pathologischem Kardiotokogramm (CTG) durchgeführt wird, die ärztliche Entscheidung optimieren und somit Einfluss auf die Prozess- und Ergebnisqualität der geburtshilflichen Behandlung ausüben? Methode: Anhand von Daten der Hessischen Perinatalerhebung eines Kollektivs klinischer Geburten in Hessen der Jahre 1990-2003 wurde dieser Frage nachgegangen. Hierbei wurden nur Fälle eingeschlossen, bei denen ein kontinuierliches oder intermittierendes CTG durchgeführt und dieses als pathologisch dokumentiert wurde. Ausgeschlossen waren Geburten mit weiteren Geburtsrisiken. Von insgesamt 785.766 Geburten konnten 20.335 ausgewertet werden. Als Parameter der Prozessqualität wurde die Kaiserschnittrate verwendet, APGAR-Wert, Nabelarterien-pH, Verlegung in eine Kinderklinik sowie neonatale Mortalität wurden als Parameter der Ergebnisqualität betrachtet. Verglichen wurden diese Parameter für die Fälle mit und ohne durchgeführte Fetalblutanalyse sowie für deren Untergruppen, die per Sectio caesarea oder vaginal entbunden wurden. Neben der bivariaten Untersuchung wurde auch eine multivariate Analyse unter Berücksichtigung der Schwangerschaftsrisiken durchgeführt. Ergebnis: In 22,5 % der untersuchten Geburten mit pathologischem CTG wurde eine Fetalblutanalyse durchgeführt, 18.9% dieser Geburten wurden per Sectio caesarea beendet. Eine konsequente Durchführung der Fetalblutanalyse reduziert die Häufigkeit der sekundären Sectio caesarea bei Vorliegen eines pathologischen CTGŽs als ausschließliches Geburtsrisiko von 20.6% auf 13.1% (p< .05) und vermindert somit die Anzahl operativer Entbindungen. Die Anzahl der Neugeborenen mit relevanter Frühmorbidität (APGAR 5min < 7) wird ebenfalls reduziert (0.9% auf 0.5%, p< .05). Die Zahl der Kinder mit anhaltendem klinischem Depressionszustand (Nabelarterien pH < 7.0) sowie die Not-wendigkeit der postpartalen Verlegung in eine Kinderklinik wurde reduziert (0,6% auf 0,4% (n.s.), bzw. 7,4% auf 5,9% (p< .05). Dieser Unterschied ist bei den vaginal geborenen Kindern stärker ausgeprägt als bei den per Sectio caesarea geborenen. Schwangerschaftsrisiken haben auf das Ergebnis keinen Einfluss. Schlussfolgerung: Die konsequente zusätzliche Durchführung der Fetalblutanalyse im Falle eines pathologischen Herzfrequenzmusters beim Fetus verbessert die Qualität der geburtshilflichen Versorgung

Asymptomatic elevation of the hyperchromic red blood cell subpopulation is associated with decreased red cell deformability

Hyperchromasia of the red blood cells (RBC), defined as an elevation of the hyperchromic subpopulation, has been described for various medical conditions. However, neither the association of hyperchromasia with an altered RBC membrane nor with other medical conditions has been investigated in a systematic way so far. Since the percentage of hyperchromic RBC is measured on a routine basis by many hematologic laboratories, we evaluated the predictive value of this parameter for the detection of RBC disorders. An extensive workup of all patients undergoing standard hematogram during a period of 6months at our institution with a fraction of hyperchromic RBC larger than 10% was collected by reviewing the medical history and performing osmotic gradient ektacytometry on RBC from a part of these patients. Thirty-two thousand two hundred twenty-six individuals were screened; of which, 162 (0.5%) showed more than 10% hyperchromic RBC. All of the patients examined by ektacytometry featured abnormal membrane deformability. Hereditary spherocytosis was found in 19 out of these 32 patients, in most cases unknown to the patient and currently asymptomatic. Another 17.9% of the patients with an elevated subpopulation of hyperchromic RBC suffered from viral infection (human immunodeficiency virus, hepatitis). Our study shows that an elevated proportion of hyperchromic erythrocytes larger than 10% is associated with both hereditary and acquired RBC membrane disorders and further follow-up should be considere

Stability of gene rankings from RNAi screens

Motivation: Genome-wide RNA interference (RNAi) experiments are becoming a widely used approach for identifying intracellular molecular pathways of specific functions. However, detecting all relevant genes involved in a biological process is challenging, because typically only few samples per gene knock-down are available and readouts tend to be very noisy. We investigate the reliability of top scoring hit lists obtained from RNAi screens, compare the performance of different ranking methods, and propose a new ranking method to improve the reproducibility of gene selection. Results: The performance of different ranking methods is assessed by the size of the stable sets they produce, i.e. the subsets of genes which are estimated to be re-selected with high probability in independent validation experiments. Using stability selection, we also define a new ranking method, called stability ranking, to improve the stability of any given base ranking method. Ranking methods based on mean, median, t-test and rank-sum test, and their stability-augmented counterparts are compared in simulation studies and on three microscopy image RNAi datasets. We find that the rank-sum test offers the most favorable trade-off between ranking stability and accuracy and that stability ranking improves the reproducibility of all and the accuracy of several ranking methods. Availability: Stability ranking is freely available as the R/Bioconductor package staRank at http://www.cbg.ethz.ch/software/staRank. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Hyperlipidemic myeloma: review of 53 cases

Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2-6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literatur

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation

Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranulom

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases

Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications.Identifying risk factors for gallstones and kidney stones in IBD patients.Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses.Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001).The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD