Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement Therapy

Background and objectives Hypophosphatemia is commonly observed in patients receiving continuous KRT. Patients who develop hypophosphatemia may be at risk of respiratory and neuromuscular dysfunction and therefore subject to prolongation of ventilator support. We evaluated the association of phosphate-containing versus phosphate-free continuous KRT solutions with ventilator dependence in critically ill patients receiving continuous KRT. Design, setting, participants, & measurements Our study was a single-center, retrospective, pre-post cohort study of adult patients receiving continuous KRT and mechanical ventilation during their intensive care unit stay. Zeroinflated negative binomial regression with and without propensity score matching was used to model our primary outcome: ventilator-free days at 28 days. Intensive care unit and hospital lengths of stay as well as hospital mortality were analyzed with a t test or a chi-squared test, as appropriate. Results We identified 992 eligible patients, of whom 649 (65%) received phosphate-containing solutions and 343 (35%) received phosphate-free solutions. In multivariable models, patients receiving phosphate-containing continuous KRT solutions had 12% (95% confidence interval, 0.17 to 0.47) more ventilator-free days at 28 days. Patients exposed to phosphate-containing versus phosphate-free solutions had 17% (95% confidence interval, 20.08 to 20.30) fewer days in the intensive care unit and 20% (95% confidence interval, 2 0.12 to 20.32) fewer days in the hospital. Concordant results were observed for ventilator-free days at 28 days in the propensity score matched analysis. There was no difference in hospital mortality between the groups. Conclusions The use of phosphate-containing versus phosphate-free continuous KRT solutions was independently associated with fewer ventilator days and shorter stay in the intensive care unit

Magnesium lactate in the treatment of Gitelman syndrome: patient-reported outcomes.

BACKGROUND: Gitelman syndrome (GS) is a rare recessively inherited renal tubulopathy associated with renal potassium (K) and magnesium (Mg) loss. It requires lifelong K and Mg supplementation at high doses that are at best unpalatable and at worst, intolerable. In particular, gastrointestinal side effects often limit full therapeutic usage. METHODS: We report here the analysis of a cohort of 28 adult patients with genetically proven GS who attend our specialist tubular disorders clinic, in whom we initiated the use of a modified-release Mg preparation (slow-release Mg lactate) and who were surveyed by questionnaire. RESULTS: Twenty-five patients (89%) preferred the new treatment regimen. Of these 25, 17 (68%) regarded their symptom burden as improved and seven reported no worsening. Of the 25 who were not Mg-treatment naïve, 13 (59%) patients reported fewer side effects, 7 (32%) described them as the same and only 2 (9%) considered side effects to be worse. Five were able to increase their dose without ill-effect. Overall, biochemistry improved in 91% of the 23 patients switched from therapy with other preparations who chose to continue the modified-release Mg preparation. Eleven (48%) improved both their Mg and K mean levels, 3 (13%) improved Mg levels only and in 7 cases (30%), K levels alone rose. CONCLUSIONS: Patient-reported and biochemical outcomes using modified-release Mg supplements were very favourable, and patient choice should play a large part in choosing Mg supplements with GS patients.This work was supported by the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre, and contains data that were presented in abstract form at ASN Kidney week 2014.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/ndt/gfw01

Prototype wireless sensors for monitoring subsurface processes in snow and firn

The detection and monitoring of meltwater within firn presents a significant monitoring challenge. We explore the potential of small wireless sensors (ETracer+, ET+) to measure temperature, pressure, electrical conductivity and thus the presence or absence of meltwater within firn, through tests in the dry snow zone at the East Greenland Ice Core Project site. The tested sensor platforms are small, robust and low cost, and communicate data via a VHF radio link to surface receivers. The sensors were deployed in low-temperature firn at the centre and shear margins of an ice stream for 4 weeks, and a bucket experiment’ was used to test the detection of water within otherwise dry firn. The tests showed the ET+ could log subsurface temperatures and transmit the recorded data through up to 150 m dry firn. Two VHF receivers were tested: an autonomous phase-sensitive radio-echo sounder (ApRES) and a WinRadio. The ApRES can combine high-resolution imaging of the firn layers (by radio-echo sounding) with in situ measurements from the sensors, to build up a high spatial and temporal resolution picture of the subsurface. These results indicate that wireless sensors have great potential for long-term monitoring of firn processes

Frequency Characteristics of Visually Induced Motion Sickness

This article was published in the journal, Human Factors [Sage Publications / © Human Factors and Ergonomics Society.]. The definitive version is available at: http://dx.doi.org/10.1177/0018720812469046Objective: The aim of this study was to explore the frequency response of visually induced motion sickness (VIMS) for oscillating linear motion in the foreand- aft axis. Background: Simulators, virtual environments, and commercially available video games that create an illusion of self-motion are often reported to induce the symptoms seen in response to true motion. Often this human response can be the limiting factor in the acceptability and usability of such systems. Whereas motion sickness in physically moving environments is known to peak at an oscillation frequency around 0.2 Hz, it has recently been suggested that VIMS peaks at around 0.06 Hz following the proposal that the summed response of the visual and vestibular selfmotion systems is maximized at this frequency. Methods: We exposed 24 participants to random dot optical flow patterns simulating oscillating foreand- aft motion within the frequency range of 0.025 to 1.6 Hz. Before and after each 20-min exposure, VIMS was assessed with the Simulator Sickness Questionnaire. Also, a standard motion sickness scale was used to rate symptoms at 1-min intervals during each trial. Results: VIMS peaked between 0.2 and 0.4 Hz with a reducing effect at lower and higher frequencies. Conclusion: The numerical prediction of the “crossover frequency” hypothesis, and the design guidance curve previously proposed, cannot be accepted when the symptoms are purely visually induced. Application: In conditions in which stationary observers are exposed to optical flow that simulates oscillating fore-and-aft motion, frequencies around 0.2 to 0.4 Hz should be avoided

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications

This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

To study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney. LPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group. In our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenatio

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer

PURPOSE: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. METHODS AND MATERIALS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework. RESULTS: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. CONCLUSIONS: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice

Involvement of Cyclin K Posttranscriptional Regulation in the Formation of Artemia Diapause Cysts

Background: Artemia eggs tend to develop ovoviviparously to yield nauplius larvae in good rearing conditions; while under adverse situations, they tend to develop oviparously and encysted diapause embryos are formed instead. However, the intrinsic mechanisms regulating this process are not well understood. Principal Finding: This study has characterized the function of cyclin K, a regulatory subunit of the positive transcription elongation factor b (P-TEFb) in the two different developmental pathways of Artemia. In the diapause-destined embryo, Western blots showed that the cyclin K protein was down-regulated as the embryo entered dormancy and reverted to relatively high levels of expression once development resumed, consistent with the fluctuations in phosphorylation of position 2 serines (Ser2) in the C-terminal domain (CTD) of the largest subunit (Rpb1) of RNA polymerase II (RNAP II). Interestingly, the cyclin K transcript levels remained constant during this process. In vitro translation data indicated that the template activity of cyclin K mRNA stored in the postdiapause cyst was repressed. In addition, in vivo knockdown of cyclin K in developing embryos by RNA interference eliminated phosphorylation of the CTD Ser2 of RNAP II and induced apoptosis by inhibiting the extracellular signal-regulated kinase (ERK) survival signaling pathway. Conclusions/Significance: Taken together, these findings reveal a role for cyclin K in regulating RNAP II activity during diapause embryo development, which involves the post-transcriptional regulation of cyclin K. In addition, a further role wa

Predicting restoration of kidney function during CRRT-free intervals

<p>Abstract</p> <p>Background</p> <p>Renal failure is common in critically ill patients and frequently requires continuous renal replacement therapy (CRRT). CRRT is discontinued at regular intervals for routine changes of the disposable equipment or for replacing clogged filter membrane assemblies. The present study was conducted to determine if the necessity to continue CRRT could be predicted during the CRRT-free period.</p> <p>Materials and methods</p> <p>In the period from 2003 to 2006, 605 patients were treated with CRRT in our ICU. A total of 222 patients with 448 CRRT-free intervals had complete data sets and were used for analysis. Of the total CRRT-free periods, 225 served as an evaluation group. Twenty-nine parameters with an assumed influence on kidney function were analyzed with regard to their potential to predict the restoration of kidney function during the CRRT-free interval. Using univariate analysis and logistic regression, a prospective index was developed and validated in the remaining 223 CRRT-free periods to establish its prognostic strength.</p> <p>Results</p> <p>Only three parameters showed an independent influence on the restoration of kidney function during CRRT-free intervals: the number of previous CRRT cycles (medians in the two outcome groups: 1 vs. 2), the "Sequential Organ Failure Assessment"-score (means in the two outcome groups: 8.3 vs. 9.2) and urinary output after the cessation of CRRT (medians in two outcome groups: 66 ml/h vs. 10 ml/h). The prognostic index, which was calculated from these three variables, showed a satisfactory potential to predict the kidney function during the CRRT-free intervals; Receiver operating characteristic (ROC) analysis revealed an area under the curve of 0.798.</p> <p>Conclusion</p> <p>Restoration of kidney function during CRRT-free periods can be predicted with an index calculated from three variables. Prospective trials in other hospitals must clarify whether our results are generally transferable to other patient populations.</p