Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients

Background. Hypernatraemia is common in critically ill patients and has been shown to be an independent predictor of mortality. Osmotic urea diuresis can cause hypernatraemia due to significant water losses but is often not diagnosed. Free water clearance (FWC) and electrolyte free water clearance (EFWC) were proposed to quantify renal water handling. We aimed to (i) identify patients with hypernatraemia due to osmotic urea diuresis and (ii) investigate whether FWC and EFWC are helpful in identifying renal loss of free water. Methods. In this retrospective study, we screened a registry for patients, who experienced intensive care unit (ICU)-acquired hypernatraemia. Among them, patients with hypernatraemia due to osmotic urea diuresis were detected by a case-by-case review. Total fluid and electrolyte balances together with FWC and EFWC were calculated for days of rising serum sodium and stable serum sodium. Results. We identified seven patients (10% of patients with ICU-acquired hypernatraemia) with osmotic diuresis due to urea. All patients were intubated during development of hypernatraemia and received enteral nutrition. The median highest serum sodium level of 153 mmol (Q1: 151-Q3: 155 mmol/L) was reached after a 5-day period of rise in serum sodium. During this period, FWC was −904 mL/day (Q1: −1574-Q3: −572), indicating renal water retention, while EFWC was 1419 mL/day (Q1: 1052-Q3: 1923), showing renal water loss. While FWC did not differ between time of stable serum sodium and development of hypernatraemia, EFWC was significantly higher during rise in serum sodium. Conclusion. Osmotic urea diuresis is a common cause of hypernatraemia in the ICU. EFWC was useful in the differential diagnosis of polyuria during rising serum sodium levels, while FWC was misleadin

Shearlet-based compressed sensing for fast 3D cardiac MR imaging using iterative reweighting

High-resolution three-dimensional (3D) cardiovascular magnetic resonance (CMR) is a valuable medical imaging technique, but its widespread application in clinical practice is hampered by long acquisition times. Here we present a novel compressed sensing (CS) reconstruction approach using shearlets as a sparsifying transform allowing for fast 3D CMR (3DShearCS). Shearlets are mathematically optimal for a simplified model of natural images and have been proven to be more efficient than classical systems such as wavelets. Data is acquired with a 3D Radial Phase Encoding (RPE) trajectory and an iterative reweighting scheme is used during image reconstruction to ensure fast convergence and high image quality. In our in-vivo cardiac MRI experiments we show that the proposed method 3DShearCS has lower relative errors and higher structural similarity compared to the other reconstruction techniques especially for high undersampling factors, i.e. short scan times. In this paper, we further show that 3DShearCS provides improved depiction of cardiac anatomy (measured by assessing the sharpness of coronary arteries) and two clinical experts qualitatively analyzed the image quality

Einfluss von Vitamin B1 auf den klinischen Verlauf kritisch kranker Kinder mit V.a. Meningoenzephalitis unklarer Genese in Bhutan

Since 2008, the opening year of the PICU at JDWNRH in Thimphu, there where a lot of patients with the assumed diagnosis „meningoencephalitis“. A common cause for the disease or an infectious organism was however not yet detected. Patients presented with minor symptoms of upper respiratory tract infection which resulted in severe neurological impairment such as seizures and/or apathy. They quickly developed respiratory failure, kidney failure and other „shock-like“ clinical signs. Neurological imaging like cCT showed hypodense basal ganglia regions. Most of this patients did not survive the following week. In July 2018 one patient with „meningoencephalitis“ also had metabolic acidosis and pulmonary hypertension. As an inborn error of metabolism was suspected, the patient was treated with several amino acids, vitamins, enzymes and coenzymes including a high dose of thiamin. That resulted in dramatic clinical improvement. This was the first patient for the subsequent clinical investigation. We collected all the data from patients admitted in 2018 which had the diagnosis „meningoencephalitis“. Patients from the first seven month where enrolled retrospectively and made up the group which did not receive thiamin. From august 2018 onwards every patient with the diagnosis „meningoencephalitis“ was given thiamin after protocol. We compared the clinical presentation on admission and during hospital stay by vital signs, blood samples, urinary output, cerebral spinal fluid, respiration (including mandatory ventilation), echocardiography, cCT and cMRI if done. In total fifty-one patients were enrolled in the study out of which 32 received thiamin and 19 did not receive thiamin. Mean age was 3 months (2-7 months), 51% where females and 74,5% where fully breastfed. On admission most common neurologic signs where irritability (56,9%), seizures (43,1%) and signs of decortication (41,2%). Lumbar puncture was performed in 70,6% and always came back negative. 64,7% of all patients received cCT of which 84,8% showed basal ganglia hypo intensities. During the course of hospital stay 49,0% showed signs of shock, 58,8% respiratory failure and 29,6% acute kidney failure. In 25,5% metabolic acidosis was seen (not every patient did get tested due to lack of availability), 35,3% showed anemia and 13,7% showed signs of liver involvement. 27,5% where diagnosed with pulmonary hypertension. Overall mortality was 27,5%. The mortality in the non-treated group was 73,7% and 0% in the Thiamin group. 57,9% in the non-treated group underwent cCT-Scan and 90,9% of them showed pathological findings in the area of the basal ganglia. Mortality of these patients was 54,5%. We could demonstrate a direct correlation with positive outcome for patients with „meningoencephalitis“ and thiamin administration, which makes thiamin deficiency the most likely cause of this disease despite missing blood level concentrations. The infantile form of severe thiamin deficiency presented here as Wernicke Encephalopathy and multiorgan failure. Unfortunately the evaluation of the thiamin concentrations before, during and after treatment was not possible because of low income settings and high costs to do so. Also, a formal ethical committee statement was not obtained, the change in management was initiated by the pediatric ICU team and implicated by the hospital representatives. More clinical investigation towards this etiology should be done including measurements of thiamin status of sick patients on admission, after administration of thiamin and even broad testing of the healthy population. Also, a long term follow-up of patients after discharge seems to be necessary to monitor any neurological sequalae in patients with Wernicke Encephalopathy. Broad Thiamine supplementation of the population at risk as well as broad education concerning this problem should decrease the number of cases on the PICU if not completely vanish the disease in the population of interest

Sensitivity analysis of a climate vulnerability index - a case study from Indian watershed development programmes

Background: This paper presents a detailed analysis of a composite Climate Vulnerability Index (CVI) to examine and compare climate change vulnerability and its dimensions adaptive capacity, sensitivity and exposure. Thereby, we are mainly interested on climate change vulnerability at community-level watershed development programmes and how the different implementing agencies could help to address the problems associated with climate change in future planning and implementation. Method: The primary data used for this study was obtained from household surveys (n=215) in three watershed communities of Kerala, India. We use bootstrap sampling and a leave-one-out sensitivity analysis to compare the climate vulnerability of the three examined watersheds in detail. By introducing the bootstrapping method and sensitivity analysis into the research field of climate vulnerability, the paper describes significant differences in CVI values and the influencing indicators to the overall vulnerability at the watershed community level. Results The results show that there are significant differences in the exposure and sensitivity dimensions of vulnerability even if the overall CVI shows less variability and no significant differences among the three watersheds. The sensitivity analysis emphasizes that Livelihood Strategies and SSocial Network are the most influencing major components of vulnerability. This suggests that implementing agencies should focus on these two major components in order to improve the watershed development programmes. Conclusion The bootstrapping approach is transferable to evaluate the degree of influence of indicators on a composite index like the CVI. Moreover, it allows us to evaluate the potential effectiveness of various other climate change programmes where the evaluation is commonly done by field surveys. This thereby helps to increase the credibility in the examination of the impacts of climate change at different scales in order to find key areas for better policy planning

Learning Description Logic Concepts: When can Positive and Negative Examples be Separated?

Learning description logic (DL) concepts from positive and negative examples given in the form of labeled data items in a KB has received significant attention in the literature. We study the fundamental question of when a separating DL concept exists and provide useful model-theoretic characterizations as well as complexity results for the associated decision problem. For expressive DLs such as ALC and ALCQI, our characterizations show a surprising link to the evaluation of ontology-mediated conjunctive queries. We exploit this to determine the combined complexity (between ExpTime and NExpTime) and data complexity (second level of the polynomial hierarchy) of separability. For the Horn DL EL, separability is ExpTime-complete both in combined and in data complexity while for its modest extension ELI it is even undecidable. Separability is also undecidable when the KB is formulated in ALC and the separating concept is required to be in EL or ELI.</jats:p

Rising serum sodium levels are associated with a concurrent development of metabolic alkalosis in critically ill patients

Purpose: Changes in electrolyte homeostasis are important causes of acid-base disorders. While the effects of chloride are well studied, only little is known of the potential contributions of sodium to metabolic acid-base state. Thus, we investigated the effects of intensive care unit (ICU)-acquired hypernatremia on acid-base state. Methods: We included critically ill patients who developed hypernatremia, defined as a serum sodium concentration exceeding 149mmol/L, after ICU admission in this retrospective study. Data on electrolyte and acid-base state in all included patients were gathered in order to analyze the effects of hypernatremia on metabolic acid-base state by use of the physical-chemical approach. Results: A total of 51 patients were included in the study. The time of rising serum sodium and hypernatremia was accompanied by metabolic alkalosis. A transient increase in total base excess (standard base excess from 0.1 to 5.5mmol/L) paralleled by a transient increase in the base excess due to sodium (base excess sodium from 0.7 to 4.1mmol/L) could be observed. The other determinants of metabolic acid-base state remained stable. The increase in base excess was accompanied by a slight increase in overall pH (from 7.392 to 7.429, standard base excess from 0.1 to 5.5mmol/L). Conclusions: Hypernatremia is accompanied by metabolic alkalosis and an increase in pH. Given the high prevalence of hypernatremia, especially in critically ill patients, hypernatremic alkalosis should be part of the differential diagnosis of metabolic acid-base disorder

Search for dark matter in the hidden-photon sector with a large spherical mirror

If dark matter consists of hidden-sector photons which kinetically mix with regular photons, a tiny oscillating electric-field component is present wherever we have dark matter. In the surface of conducting materials this induces a small probability to emit single photons almost perpendicular to the surface, with the corresponding photon frequency matching the mass of the hidden photons. We report on a construction of an experimental setup with a large ~14 m2 spherical metallic mirror that will allow for searches of hidden-photon dark matter in the eV and sub-eV range by application of different electromagnetic radiation detectors. We discuss sensitivity and accessible regions in the dark matter parameter space.Comment: 9 pages, proceeding of the 34th International Cosmic Ray Conference (ICRC), July 30 - August 6, 2015, The Hague, The Netherland

Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors

Inter-individual differences in antidepressant drug concentrations attained in blood may limit the efficacy of pharmacological treatment of depressive disorders. Therapeutic drug monitoring (TDM) enables to determine drug concentrations in blood and adjust antidepressant dosage accordingly. However, research on the underlying assumption of TDM, association between concentration and clinical effect, has yielded ambiguous results for antidepressants. It has been proposed that this ambiguity may be caused by methodological shortcomings in studies investigating the concentration-effect relationship. Guidelines recommend the use of TDM in antidepressant treatment as expert opinion. This reflects the lack of research, particularly systematic reviews and meta-analyses of randomized controlled trials, on the relationship between concentration and effect as well as on the benefits of the use of TDM in clinical practice. In this study, a systematic review and meta-analysis of randomized controlled trials has been performed to investigate the relationship between antidepressant concentration, efficacy, and side effects. It is the first meta-analytical approach to this subject and additionally considers methodological properties of primary studies as moderators of effect in quantitative analysis. Our results identified methodological shortcomings, namely the use of a flexible dose design and the exclusion of concentrations in lower- or subtherapeutic ranges, which significantly moderate the relationship between antidepressant concentration and efficacy. Such shortcomings obscure the evidence base of using TDM in clinical practice to guide antidepressant drug therapy. Further research should consider these findings to determine the relationship between concentration and efficacy and safety of antidepressant treatments, especially for newer antidepressants.Peer Reviewe

First Outbreak of Callitrichid Hepatitis in Germany: Genetic Characterization of the Causative Lymphocytic Choriomeningitis Virus Strains

AbstractCallitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were ≥99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains