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Hashimoto, Mihoko, Tsuyoshi Endo, Gilles Peltier, Masao Tasaka, and Toshiharu Shikanai. "A nucleus-encoded factor, CRR2, is essential for the expression of chloroplastndhBinArabidopsis." Plant Journal 36, no. 4 (November 2003): 541–49. http://dx.doi.org/10.1046/j.1365-313x.2003.01900.x.
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Ruwe, Hannes, Bernard Gutmann, Christian Schmitz‐Linneweber, Ian Small, and Peter Kindgren. "The E domain of CRR2 participates in sequence‐specific recognition of RNA in plastids." New Phytologist 222, no. 1 (December 6, 2018): 218–29. http://dx.doi.org/10.1111/nph.15578.
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Waschbusch, Gerd, Andrea Rolle, and Johannes Biewer. "Die Neugestaltung des aufsichtsrechtlichen Handelsbuchs nach dem CRR2-Verordnungsvorschlag im Lichte des IFRS 9." Zeitschrift für das gesamte Bank- und Börsenwesen 66, no. 2 (2018): 103. http://dx.doi.org/10.47782/oeba201802010301.
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Hogendorf, Piotr, Anna Suska, Aleksander Skulimowski, Joanna Rut, Monika Grochowska, Aleksandra Wencel, Filip Dziwisz, et al. "Neutrophil-lymphocyte ratio and creatinine reduction ratio predict good early graft function among adult cadaveric donor renal transplant recipients. Single institution series." Polish Journal of Surgery 90, no. 2 (April 30, 2018): 28–33. http://dx.doi.org/10.5604/01.3001.0011.7499.
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Background Delayed graft function (DGF) is a common complication following kidney transplantation and is associated with ischemia-reperfusion injury (IRI). Lymphocytes contribute to the pathogenesis of IRI and ischemia-reperfusion related delayed graft function Materials and Methods 135 Caucasian patients received a kidney graft from deceased heart-beating organ donors. We divided patients into 2 groups- patients with the eGFR>=30 on the 21st day post-transplantation (n=36) and patients with the eGFR<30 on the 21st day post-transplantation (n=99) to assess kidney graft function. We measured the serum creatinine levels on 1st and 2nd post-transplant day and preoperative levels of monocytes, lymphocytes, platelets and neutrophils and their ratios. Results We have found statistically significant differences between the eGFR<30 and the eGFR>=30 groups in the average lnLymphocytes (0,36 +/-0,6 vs -0,016 +/-0,74 respectively p=0,004) lnNLR ( 1,27 +/-0,92 vs. 1,73+/-1,08 p=0,016) lnLMR (1,01 +/-0,57 vs. 0,73 +/-0,64 p=0,02), lnPLR (4,97 +/-0,55 vs. 5,26 +/- 0,67 p=0,023) and CCR2% (-20,20 +/- 21,55 vs. -4,29 +/- 29,62 p=0,004 . On univariate analysis, factors of lnLymphocytes >=0,22 (OR=0,331 95%CI 0,151-0,728 p=0,006), lnLMR>=1,4 (OR=0,255 95%CI 0,072-0,903 p=0,034) were associated with worse graft function while lnNLR>=1,05 (OR=2,653 95%CI 1,158-6,078 p=0,021), lnPLR>=5,15 (OR=2,536 95%CI 1,155-5,566 p=0,02) and CRR2 (OR=3,286 95% CI 1,359-7,944 p=0,008) indicated better graft function Conclusion Higher absolute lymphocyte count (lnLymphocytes) and lnLMR as well as lower lnNLR and lnPLR were associated with lower eGFR on the 21st day after kidney transplantation. On multivariate analysis CRR2 in combination with either lnLymphocytes, lnNLR or lnPLR improved the accuracy of detecting patients with poor graft function.
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Hosono, Naoko, Hideki Makishima, Bartlomiej P. Przychodzen, Andres Jerez, Chantana Polprasert, Yuichi Shiraishi, Kenichi Chiba, et al. "Whole Exome Sequencing (“mutatome”) Of Deletion 5q." Blood 122, no. 21 (November 15, 2013): 656. http://dx.doi.org/10.1182/blood.v122.21.656.656.
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Abstract Interstitial deletion of chromosome 5q (del(5q)) is one of the most common karyotypic abnormalities in MDS. While a relatively small fraction of patients with del(5q) and 5q- syndrome show a relatively uniform clinical phenotype and a low rate of progression, the majority of del(5q) myeloid neoplasms are more heterogeneous. Prognosis correlates with the size and location of the deletion, with large deletions spanning subtelomeric and/or subcentromeric region correlating with a poor prognosis. Survival differences may relate to still undefined pathogenetic mechanisms underlying del(5q), which may involve hemizygous mutations or haploinsufficiency. With the latter scenario, it is possible that heterozygous mutations of genes located on 5q may phenocopy the deletion. To further elucidate the molecular mechanisms underlying del(5q), we preformed a comprehensive analysis of myeloid neoplasms using single nucleotide polymorphism array (SNP-A) and next generation whole exome sequencing (NGS) of paired DNA samples (germline/tumor) from 55 cases characterized by del(5q) among a total 428 patients with MDS and related disorders; we focused on mutations located on 5q in both diploid and deletion cases. In the total cohort, we identified 243 somatic mutations in 158 genes on chr5q, including well-known NPM1 or novel recurrent DDX41 mutations; 147 mutations were heterozygous, 11 hemizygous (in del(5q)). No homozygous mutations were found. Applying SNP-A-based karyotyping, we defined the commonly deleted region (CDR) as between 5q32 and 5q33.2 (145299747-153828955). In patients with 5q- syndrome, the proximal and terminal regions of chr5q were always retained; therefore we defined commonly retained regions (CRR) as CRR1 (proximal, 5q11.1 to 5q14.2, 48400001-81634579) and CRR2 (distal, 5q34 to 5q35.3, 164213764-180915260). The deletions of CRRs consequently contributed to worse prognosis in the aggressive types of MDS with longer del(5q). First we focused our study on the genes located on CRRs. We identified 120 heterozygous alterations in CRRs, including CWC27 (5q12.3), MAP1B (n=2, 5q13.2), NPM (n=50, 5q35.1), C5orf25 (n=4, 5q35.2) and DDX41 (n=4, 5q35.3); these mutations occurred only in a heterozygous configuration. Interestingly, spliceosome-associated gene CWC27 and RNA helicase DDX41 showed haploinsufficient expression in haploid cases without mutation, suggesting that mutated genes located on CRRs can be pathogenic due to both haploinsufficiency of WT genes and heterozygous mutations. Furthermore, patients with decreased expression of these genes had a poor survival (CWC27; HR=2.48, DDX41; HR=1.98). In positions corresponding to CDR and its proximal regions, we found 123 heterozygous alterations in 97 genes (50% of all alterations on 5q found), including recurrently mutated genes (FAT2: n=4; G3BP1: n=2) and hemizygous mutations of KDM3B (n=3, 5q31.2) and MCC (n=1, 5q22.2). In GPR98, associated with Usher syndrome, we detected both recurrent heterozygous and hemizygous mutations (each n=1). Also, minor alleles (frequencies were .002 and .004) of non-synonymous variants of GPR98 were selectively retained and wild-type alleles were deleted in del(5q) cases (n=2). We also searched accessory genetic events observed on other chromosomes in del(5q) cases. By SNP-A, deletions of CRRs (longer del(5q)) were significantly more associated with additional chromosomal defects. Similarly, some specific genes, including the splicing machinery genes and IDH family genes, were uniquely observed in the longer del(5q) cohort. In conclusion, we detected multiple pathogenic mutations in whole chr5q which might stratify del(5q) patients at risk for disease progression, though no single mutations could explain a majority of cases. Decreased expression or mutation of CWC27 and DDX41, located on CRRs, may exemplify the common pathophysiology shared by heterozygous mutations and haploinsufficient expressions on chr5q. Consequently, it is possible that deletion alone, through decreased expression, may be pathogenic. Disclosures: Makishima: AA & MDS international foundation: Research Funding; Scott Hamilton CARES grant: Research Funding. Polprasert:MDS foundation: Research Funding. Maciejewski:NIH: Research Funding; Aplastic anemia&MDS International Foundation: Research Funding.
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Pfeifer, Lukáš, and Zdeněk Pikhart. "Leverage Ratio and its Potential For Enhancing the Effectiveness of Capital Regulation." Journal of Central Banking Theory and Practice 8, no. 2 (May 1, 2019): 129–46. http://dx.doi.org/10.2478/jcbtp-2019-0017.
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Abstract The article deals with the procyclical development of risk weights and hence the risk-weighted capital ratio. The leverage ratio should be included in the regulatory reform package (CRR2) as a (non-risk-weighted) prudential backstop. The article defines the complementary relationship of capital and leverage by describing their different responses to the cyclical development associated with the change in the quality of assets in the various phases of the financial cycle. The results of the panel regression on a sample of selected countries illustrate: (i) that the banking sectors with lower capital adequacy relatively more increased the capital ratio in the period of financial stress and more often changed the structure of the assets into less risky assets for the improvement of the capital ratio, with a negative impact on profit; (ii) significantly lower pro-cyclicality of the leverage ratio than the capital ratio.
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Cheng, Haiying, Ligang Zhou, Wanling Zhu, Ajin Wang, Chuyan Tang, Owen Chan, Robert S. Sherwin, and Rory J. McCrimmon. "Type 1 corticotropin-releasing factor receptors in the ventromedial hypothalamus promote hypoglycemia-induced hormonal counterregulation." American Journal of Physiology-Endocrinology and Metabolism 293, no. 3 (September 2007): E705—E712. http://dx.doi.org/10.1152/ajpendo.00136.2007.
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Type 2 corticotropin-releasing factor (CRF) receptors (CRFR2) within the ventromedial hypothalamus (VMH), a key glucose-sensing region, play a major role in regulating the hormonal counterregulatory responses (CRRs) to acute hypoglycemia. The VMH expresses both subtypes of CRF receptors, CRFR1 and CRFR2. The objective of this study was to examine the role of the CRFR1 receptor in the VMH in the regulation of the CRR to acute hypoglycemia. To compare the hormonal CRR to hypoglycemia, awake and unrestrained Sprague-Dawley rats were bilaterally microinjected to the VMH with either 1) aECF, 2) CRF (1 pmol/side), 3) CRFR1 antagonist Antalarmin (500 pmol/side), or 4) CRF + Antalarmin prior to undergoing a hyperinsulinemic hypoglycemic (2.8 mM) clamp. A second series of studies also incorporated an infusion of [3H]glucose to allow the calculation of glucose dynamics. In addition the effect of CRFR1 antagonism in the paraventricular nucleus (PVN) was studied. Activation of VMH CRFR1 increased, whereas inhibition of CRFR1 suppressed hypoglycemia-induced CRRs. Inhibition of VMH CRFR1 also increased peripheral glucose utilization and reduced endogenous glucose production during hypoglycemia, whereas VMH CRF reduced peripheral glucose utilization. In contrast CRFR1 inhibition in the PVN blunted corticosterone but not epinephrine or glucagon CRR to hypoglycemia. In contrast to CRFR2 activation, CRFR1 activation within the VMH amplifies CRRs to acute hypoglycemia. The balance between these two opposing CRFRs in this key glucose-sensing region may play an important role in determining the magnitude of CRRs to acute hypoglycemia.
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Thuraisingham, R., E. VIllar, M. Varagunam, and M. Yaqoob. "THE CREATININE REDUCTION RATIO BETWEEN DAYS ONE AND TWO (CRR2) IS AN EARLY INDEPENDENT PREDICTOR OF POOR LONG TERM RENAL GRAFT SURVIVAL." Transplantation 86, Supplement (July 2008): 462. http://dx.doi.org/10.1097/01.tp.0000331326.58792.e0.
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Curzytek, Katarzyna, and Monika Leśkiewicz. "Targeting the CCL2-CCR2 axis in depressive disorders." Pharmacological Reports 73, no. 4 (May 24, 2021): 1052–62. http://dx.doi.org/10.1007/s43440-021-00280-w.
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AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.
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Hosono, Naoko, Mahfouz Reda, Bartlomiej P. Przychodzen, Chantana Polprasert, Latifa Zekri, Michael J. Clemente, Jamal Tazi, et al. "Haploinsufficiency and Deletions of G3BP1 on Chromosome 5q Result in Induction of TP53." Blood 124, no. 21 (December 6, 2014): 784. http://dx.doi.org/10.1182/blood.v124.21.784.784.
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Abstract Interstitial deletion of the long arm of chromosome 5 (del(5q)) is the most common chromosomal abnormality in MDS. The extent of individual defects vary, which may account for observed clinical diversity. Del(5q) pathogenesis has been related to haploinsufficiency of genes contained in the common deleted regions (CDR), including RPS14, miR-145/146a and SPARC. Driver mutations or pathogenic microdeletions were not identified for these genes, suggesting that multiple genes must function in combination to promote clonal evolution and phenotypic heterogeneity. Hence, we performed a comprehensive analysis of somatic mutations in genes located on chromosome 5 (chr5), both in patients with diploid 5q and in those with del(5q), to clarify the role of germline and somatic mutations in disease pathogenesis. In parallel, expression analysis was performed to correlate haploinsufficiency with the frequency of mutational events, in particular for diploid 5q cases. Applying SNP-array karyotyping to samples from 146 patients with del(5q), the lesion was identified in 5q31.1q33.1. Two retained regions (CRRs) were also observed in q11.1q14.2 (CRR1) and q34qter (CRR2). Lower-risk MDS is frequently affected by CDR, while in higher-risk MDS and secondary AML CRR1/2 are commonly co-involved. Using whole exome sequencing, we identified 11 hemizygous mutations located within the deleted area in del(5q) (N=59), while in cases diploid for 5q (N=330), 243 heterozygous mutations were found. One of the mutations discovered on chr5q afflicted a gene G3BP1 (5q33.1), located within the CDR and present in 2 patients. Both were missense mutations (one heterozygous and the other homo/hemizygous). A mutant case showed good responses to lenalidomide even though diploid 5. In addition, other somatic mutations of driver genes including TET2, CUX1 and EZH2 were concomitantly observed. Whole transcriptome sequencing demonstrated hemizygous loss of G3BP1 resulting in haploinsufficiency. G3BP1 was haploinsufficient in 48% of RAEB as well as low-risk MDS cases with del(5q). Overall, defective G3BP1 is associated with shorter overall survival (P<.001) in AML, consistent with the reports that del(5q) is a worse prognostic factor in myeloid neoplasms with aggressive phenotype. G3BP1 is a nuclear RNA-binding protein and is ubiquitously expressed in bone marrow, CD34+ progenitors and leukemic cell lines. Furthermore, G3BP1 binds to TP53 and its expression leads to the redistribution of TP53 from the nucleus to the cytoplasm. Similar to RPS14, haploinsufficient of G3BP1 resulted in TP53 up-modulation. Moreover, low expression of G3BP1 in diploid 5q cases was indeed associated with higher TP53 expression. Next, we generated haploinsufficient G3BP1 cell lines using shRNA transduction. Decreased expression of G3BP1 led to growth inhibition and impaired colony formation by transduced cells lines and hematopoietic progenitor cells, respectively. Knockdown of G3BP1 in K562 cell line increased TP53 in the nucleus, and when treated with CPT11, DNA-damaged induced G1-arrest was more prominent in knockdown cells. Furthermore, after knockdown of G3BP1 in TP53-null HL60 cells, we observed increased aneuploidy, suggesting that the loss of function of G3BP1 and TP53 may result in chromosomal instability. Most significantly, G3bp1-/+ mice showed lower blood counts and defective, dysplastic hematopoiesis, similar to lower-risk MDS. As previously described, TP53 defects are associated with advanced disease but recently it became apparent that TP53 may be one of the most common somatic lesions found in the context of del(5q). We stipulate that loss of TP53 function might overcome TP53 tumor suppressor effects and induce leukemic evolution in the defective G3BP1 status. In our cohort, TP53 mutations were more frequently present in high-risk phenotype with G3BP1 haploinsufficient expression. In conclusion, novel somatic mutations of G3BP1 suggest that it could be a candidate gene associated with the clonal evolution of del(5q). Loss of function or low expression of G3BP1 has been shown to up-modulate TP53 and result in dysplasia and growth inhibition, hallmarks of early stages of MDS. Additional events constitute loss of function of TP53, resulting in chromosomal instability, which is associated with leukemogenesis. Disclosures Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees.
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Cheng, Yi-Hsiang, Tzu-Lung Lin, Yi-Tsung Lin, and Jin-Town Wang. "Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae." Antimicrobial Agents and Chemotherapy 60, no. 6 (April 11, 2016): 3709–16. http://dx.doi.org/10.1128/aac.00009-16.
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Colistin is a last-resort antibiotic for treatment of carbapenem-resistantKlebsiella pneumoniae. A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistantK. pneumoniaeclinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study,crrABsequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generatecrrBloci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. ThesecrrBmutants showed increased accumulation ofH239_3062,H239_3059,pmrA,pmrC, andpmrHtranscripts by quantitative reverse transcription (qRT)-PCR. Deletion ofH239_3062(but not that ofH239_3059) in the A4528crrB(N141I) strain attenuated resistance to colistin, andH239_3062was accordingly namedcrrC. Similarly, accumulation ofpmrA,pmrC, andpmrHtranscripts induced bycrrB(N141I) was significantly attenuated upon deletion ofcrrC. Complementation ofcrrCrestored resistance to colistin and accumulation ofpmrA,pmrC, andpmrHtranscripts in acrrB(N141I) ΔcrrCstrain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of thepmrHFIJKLMoperon andpmrC(an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.
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Li, Hui, and Amanda J. Page. "Activation of CRF2 receptor increases gastric vagal afferent mechanosensitivity." Journal of Neurophysiology 122, no. 6 (December 1, 2019): 2636–42. http://dx.doi.org/10.1152/jn.00619.2019.
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Gastric vagal afferent (GVA) sensing of food-related mechanical stimuli is a crucial mechanism in the control of feeding behavior and gastric function. Stress is an important factor contributing to eating disorders and gastric diseases. Chronic stress has been shown to increase the mechanosensitivity of GVAs in mice and to reduce food intake and body weight. Whether the mechanosensitivity of GVAs is modulated by stress hormones is not known. This study aimed to determine the effect of stress hormones on GVA mechanosensitivity. The expression of stress hormone receptors in GVA cell bodies was determined in 8-wk-old male C57BL/6 mice using quantitative RT-PCR combined with laser capture microdissection. The mechanosensitivity of GVAs was determined in the absence and presence of stress hormones using an in vitro single-fiber recording preparation. NR3C1 and CRHR2 (mRNA isoforms of glucocorticoid receptor and CRF2 receptor, respectively) were expressed in GVA neurons. The glucocorticoid receptor agonist corticosterone had no effect on the mechanosensitivity of either tension or mucosal GVAs. Activation of CRF2 receptor by its specific analog, urocortin 3, significantly increased the mechanosensitivity of both tension and mucosal GVAs, an effect prevented by the CRF2 receptor antagonist astressin 2B. In conclusion, activation of CRF2 receptor increases the mechanosensitivity of GVAs. This may contribute to the stress- and CRF2 receptor-associated changes in feeding behavior and gastric function, possibly contributing to the hypersensitivity of GVAs in chronic stress conditions. NEW & NOTEWORTHY Gastric vagal afferents (GVAs) relay food-related signals to the central nervous system, where they are processed, eventually leading to modulation of food intake and gastric function. GVA signaling can be modulated by an array of hormones. Stress has been shown to induce GVA hypersensitivity. This study demonstrates that GVA neurons express subtypes of stress hormone receptors, specifically CRF2. Furthermore, activation of CRF2 receptor increases GVA mechanosensitivity, which could have implications for food intake and gastric function.
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Rodríguez-Peña, José Manuel, Víctor J. Cid, Javier Arroyo, and César Nombela. "A Novel Family of Cell Wall-Related Proteins Regulated Differently during the Yeast Life Cycle." Molecular and Cellular Biology 20, no. 9 (May 1, 2000): 3245–55. http://dx.doi.org/10.1128/mcb.20.9.3245-3255.2000.
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ABSTRACT The Saccharomyces cerevisiae Ygr189c, Yel040w, and Ylr213c gene products show significant homologies among themselves and with various bacterial β-glucanases and eukaryotic endotransglycosidases. Deletion of the corresponding genes, either individually or in combination, did not produce a lethal phenotype. However, the removal of YGR189c and YEL040w, but not YLR213c, caused additive sensitivity to compounds that interfere with cell wall construction, such as Congo red and Calcofluor White, and overexpression of YEL040w led to resistance to these compounds. These genes were renamedCRH1 and CRH2, respectively, for Congo red hypersensitive. By site-directed mutagenesis we found that the putative glycosidase domain of CRH1 was critical for its function in complementing hypersensitivity to the inhibitors. The involvement ofCRH1 and CRH2 in the development of cell wall architecture was clearly shown, since the alkali-soluble glucan fraction in the crh1Δ crh2Δ strain was almost twice the level in the wild-type. Interestingly, the three genes were subject to different patterns of transcriptional regulation. CRH1 andYLR213c (renamed CRR1, for CRHrelated) were found to be cell cycle regulated and also expressed under sporulation conditions, whereas CRH2 expression did not vary during the mitotic cycle. Crh1 and Crh2 are localized at the cell surface, particularly in chitin-rich areas. Consistent with the observed expression patterns, Crh1–green fluorescent protein was found at the incipient bud site, around the septum area in later stages of budding, and in ascospore envelopes. Crh2 was found to localize mainly at the bud neck throughout the whole budding cycle, in mating projections and zygotes, but not in ascospores. These data suggest that the members of this family of putative glycosidases might exert a common role in cell wall organization at different stages of the yeast life cycle.
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Peng, Lianwei, Wenhe Cai, and Toshiharu Shikanai. "Chloroplast stromal proteins, CRR6 and CRR7, are required for assembly of the NAD(P)H dehydrogenase subcomplex A in Arabidopsis." Plant Journal 63, no. 2 (April 28, 2010): 203–11. http://dx.doi.org/10.1111/j.1365-313x.2010.04240.x.
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Zhou, Xing-Liang, Yan-He Chen, and Qing-Yun Wang. "A New Approach Combining Venoarterial Extracorporeal Membrane Oxygenation and CRRT for Adults: A Retrospective Study." International Journal of Artificial Organs 40, no. 7 (May 23, 2017): 345–49. http://dx.doi.org/10.5301/ijao.5000597.
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Purpose This study aimed to assess a new approach combining venoarterial (VA) extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) in adults, while monitoring CRRT circuit pressures. Methods The inlet and outlet of the CRRT circuit were connected to preoxygenator port and postoxygenator port, respectively. Then, complications and CRRT circuit pressures were evaluated. Results 7 patients underwent combined VA-ECMO and CRRT; 16 filters were used. CRRT blood flow ranged from 150 to 200 mL/min; the CRRT to ECMO blood flow ratio was <0.1. The CRRT pressures at treatment initiation were normal. No complications were reported. Conclusions This approach combining VA-ECMO and CRRT in adults did not compromise the accuracy of pressure monitoring systems for CRRT circuit function, and caused no complications. Hence, it may be a feasible method for performing combined VA-ECMO and CRRT in adults.
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Ciou, Huai-Syuan, Yu-Lun Tsai, and Chi-Chou Chiu. "Arabidopsis chloroplast J protein DJC75/CRRJ mediates nitrate-promoted seed germination in the dark." Annals of Botany 125, no. 7 (March 11, 2020): 1091–99. http://dx.doi.org/10.1093/aob/mcaa040.
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Abstract Background and Aims Nitrate can stimulate seed germination of many plant species in the absence of light; however, the molecular mechanism of nitrate-promoted seed germination in the dark remains largely unclear and no component of this pathway has been identified yet. Here, we show that a plastid J-domain protein, DJC75/CRRJ, in arabidopsis (Arabidopsis thaliana) is important for nitrate-promoted seed germination in the dark. Methods The expression of DJC75 during imbibition in the dark was investigated. The seed germination rate of mutants defective in DJC75 was determined in the presence of nitrate when light cues for seed germination were eliminated by the treatment of imbibed seeds with a pulse of far-red light to inactivate phytochrome B (phyB), or by assaying germination in the dark with seeds harbouring the phyB mutation. The germination rates of mutants defective in CRRL, a J-like protein related to DJC75, and in two chloroplast Hsp70s were also measured in the presence of nitrate in darkness. Key Results DJC75 was expressed during seed imbibition in the absence of light. Mutants defective in DJC75 showed seed germination defects in the presence of nitrate when light cues for seed germination were eliminated. Mutants defective in CRRL and in two chloroplast Hsp70s also exhibited similar seed germination defects. Upregulation of gibberellin biosynthetic gene GA3ox1 expression by nitrate in imbibed phyB mutant seeds was diminished when DJC75 was knocked out. Conclusions Our data suggest that plastid J-domain protein DJC75 regulates nitrate-promoted seed germination in the dark by upregulation of expression of the gibberellin biosynthetic gene GA3ox1 through an unknown mechanism and that DJC75 may work in concert with chloroplast Hsp70s to regulate nitrate-promoted seed germination. DJC75 is the first pathway component identified for nitrate-promoted seed germination in the dark.
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Sapp, Alex, Andrew Drahos, Madison Lashley, Amy Christie, and D. Benjamin Christie. "The Impact of Hemodynamic Transesophageal Echocardiography on Acute Kidney Injury Management and Use of Continuous Renal Replacement Therapy in Trauma." American Surgeon 86, no. 3 (March 2020): 190–94. http://dx.doi.org/10.1177/000313482008600326.
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Resuscitation of critically ill trauma patients can be precarious, and errors can cause acute kidney injuries. If renal failure develops, continuous renal replacement therapy (CRRT) may be necessary, but adds expense. Hemodynamic transesophageal echocardiography (hTEE) provides objective data to guide resuscitation. We hypothesized that hTEE use improved acute kidney injury (AKI) management, reserved CRRT use for more severe AKIs, and decreased cost and resource utilization. We retrospectively reviewed 2413 trauma patients admitted to a Level I trauma center's ICU between 2009 and 2015. Twenty-three patients required CRRT before standard hTEE use and 11 required CRRTafter; these are the “CRRT” and “CRRT/hTEE” groups, respectively. The hTEE group comprised 83 patients evaluated with hTEE, with AKI managed without CRRT. We compared the average creatinine, change in creatinine, and Acute Kidney Injury Network (AKIN) of “CRRT” with “CRRT/hTEE” and “hTEE.” We also analyzed several quality measures including ICU length of stay and cost. “CRRT” had a lower AKIN score (1.6) than “CRRT/hTEE” (2.9) ( P = 0.0003). “hTEE” had an AKIN score of 2.1 ( P = 0.0387). “CRRT” also had increased ICU days (25.1) compared with “CRRT/hTEE” (20.2) ( P = 0.014) and “hTEE” (16.8) ( P = 0.003). “CRRT” accrued on average $198,695.81 per patient compared with “CRRT/ hTEE” ($167,534.19) and “hTEE” ($53,929.01). hTEE provides valuable information to tailor resuscitation. At our institution, hTEE utilization reserved CRRT for worse AKIs and decreased hospital costs.
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Kee, Youn, Dahye Kim, Seung-Jung Kim, Duk-Hee Kang, Kyu Choi, Hyung Oh, and Dong-Ryeol Ryu. "Factors Associated with Early Mortality in Critically Ill Patients Following the Initiation of Continuous Renal Replacement Therapy." Journal of Clinical Medicine 7, no. 10 (October 8, 2018): 334. http://dx.doi.org/10.3390/jcm7100334.
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Continuous renal replacement therapy (CRRT) is an important modality to support critically ill patients, and the need for CRRT treatment has been increasing. However, CRRT management is costly, and the associated resources are limited. Thus, it remains challenging to identify patients that are likely to have a poor outcome, despite active treatment with CRRT. We sought to elucidate the factors associated with early mortality after CRRT initiation. We analyzed 240 patients who initiated CRRT at an academic medical center between September 2016 and January 2018. We compared baseline characteristics between patients who died within seven days of initiating CRRT (early mortality), and those that survived more than seven days beyond the initiation of CRRT. Of the patients assessed, 130 (54.2%) died within seven days of CRRT initiation. Multivariate logistic regression models revealed that low mean arterial pressure, low arterial pH, and high Sequential Organ Failure Assessment score before CRRT initiation were significantly associated with increased early mortality in patients requiring CRRT. In conclusion, the mortality within seven days following CRRT initiation was very high in this study. We identified several factors that are associated with early mortality in patients undergoing CRRT, which may be useful in predicting early outcomes, despite active treatment with CRRT.
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Beitland, Sigrid, Kjetil Sunde, Harald Moen, and Ingrid Os. "Variability in Uremic Control during Continuous Venovenous Hemodiafiltration in Trauma Patients." Critical Care Research and Practice 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/869237.
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Introduction. Acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT) is a severe complication in trauma patients (TP). We wanted to assess daily duration of CRRT and its impact on uremic control in TP.Material and Methods. We retrospectively reviewed adult TP, with or without rhabdomyolysis, with AKI undergoing CRRT. Data on daily CRRT duration and causes for temporary stops were collected from the first five CRRT days. Uremic control was assessed by daily changes in serum urea (Δurea) and creatinine (Δcreatinine) concentrations.Results. Thirty-six TP were included with a total of 150 CRRT days, 17 (43%) with rhabdomyolysis. The median (interquartile range (IQR)) time per day with CRRT was 19 (15–21) hours. There was a significant correlation between daily CRRT duration andΔurea (r=0.60,P≤0.001) andΔcreatinine (r=0.43;P=0.012). CRRT pauses were caused by filter clotting (54%), therapeutic interventions (25%), catheter related problems (10%), filter timeout (6%), and diagnostic procedures (6%). Rhabdomyolysis did not affect the CRRT data.Conclusions. TP undergoing CRRT had short daily CRRT duration causing reduced uremic control. Clinicians should modify their daily clinical practice to improve technical skills and achieve sufficient dialysis dose.
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Nishimi, Saeko, Hiroshi Sugawara, Chinatsu Onodera, Yukiko Toya, Hiromi Furukawa, Yu Konishi, Genichiro Sotodate, Atsushi Matsumoto, Ken Ishikawa, and Kotaro Oyama. "Complications During Continuous Renal Replacement Therapy in Critically Ill Neonates." Blood Purification 47, Suppl. 2 (2019): 74–80. http://dx.doi.org/10.1159/000496654.
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Background/ Aims: Owing to practical and technical developments, continuous renal replacement therapy (CRRT) has been administered even in critically ill neonates. In this study, the complications in CRRT for neonates were examined to establish a safe CRRT. Methods: This retrospective study reviewed the clinical records of neonates who underwent CRRT at our neonatal intensive care unit between 2009 and 2017. Results: Eight neonates with a body weight of 1,462–3,288 g were treated by 70 CRRT sessions with blood priming. Intradialytic hypotension (IDH) was observed in 39 sessions (55.7%), most of which occurred soon after the start of the CRRT. Body temperature decreased in 48 sessions (70.5%), and thrombocytopenia during CRRT occurred 30 times (42.9%). Conclusion: Complications during CRRT in neonates comprised IDH at the start of the CRRT, body temperature decline, and thrombocytopenia. These complications need to be analyzed for a safe neonatal CRRT.
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Nakamura, Toru M., Bettina A. Moser, Li-Lin Du, and Paul Russell. "Cooperative Control of Crb2 by ATM Family and Cdc2 Kinases Is Essential for the DNA Damage Checkpoint in Fission Yeast." Molecular and Cellular Biology 25, no. 24 (December 15, 2005): 10721–30. http://dx.doi.org/10.1128/mcb.25.24.10721-10730.2005.
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ABSTRACT The cellular responses to double-stranded breaks (DSBs) typically involve the extensive accumulation of checkpoint proteins in chromatin surrounding the damaged DNA. One well-characterized example involves the checkpoint protein Crb2 in the fission yeast Schizosaccharomyces pombe. The accumulation of Crb2 at DSBs requires the C-terminal phosphorylation of histone H2A (known as γ-H2A) by ATM family kinases in chromatin surrounding the break. It also requires the constitutive methylation of histone H4 on lysine-20 (K20). Interestingly, neither type of histone modification is essential for the Crb2-dependent checkpoint response. However, H4-K20 methylation is essential in a crb2-T215A strain that lacks a cyclin-dependent kinase phosphorylation site in Crb2. Here we explain this genetic interaction by describing a previously overlooked effect of the crb2-T215A mutation. We show that crb2-T215A cells are able to initiate but not sustain a checkpoint response. We also report that γ-H2A is essential for the DNA damage checkpoint in crb2-T215A cells. Importantly, we show that inactivation of Cdc2 in γ-H2A-defective cells impairs Crb2-dependent signaling to the checkpoint kinase Chk1. These findings demonstrate that full Crb2 activity requires phosphorylation of threonine-215 by Cdc2. This regulation of Crb2 is independent of the histone modifications that are required for the hyperaccumulation of Crb2 at DSBs.
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Bagshaw, Sean M., Madarasu Rajasekara Chakravarthi, Zaccaria Ricci, Ashita Tolwani, M. Neri, S. De Rosa, John A. Kellum, and Claudio Ronco. "Precision Continuous Renal Replacement Therapy and Solute Control." Blood Purification 42, no. 3 (2016): 238–47. http://dx.doi.org/10.1159/000448507.
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Continuous renal replacement therapy (CRRT) remains the dominant form of renal support among critically ill patients worldwide. Current clinical practice on CRRT prescription mostly relies on high quality studies suggesting no impact of CRRT dose on critically ill patients' outcomes. Recent clinical practice guidelines have been developed based on these studies recommending a static prescribed CRRT dose of 20-25 ml/kg/h. There is a rationale for renewed attention to CRRT prescription/practice based on the concept of dynamic solute control adapted to the changing clinical needs of critically ill patients. In response, Acute Disease Quality Initiative convened a 17th consensus meeting centered on re-evaluation of CRRT. This work group developed 4 themes focused specifically on CRRT dose prescription, delivery and solute control that were summarized in a series of consensus statements, along with the identification of critical knowledge gaps. CRRT dose prescription and delivery can be based on effluent flow rate. Delivered dose should be routinely monitored to ensure coherence with prescribed dose. CRRT dose should be dynamic, in recognition of between- and within-patient variation in targeted solute control or unintended solute clearance. Quality measures specific for monitoring delivered CRRT dose have been proposed that require further validation, prior to implementation, into the practice of guiding optimal CRRT dosage.
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Bullen, Heather A., and Simon J. Garrett. "CrO2 by XPS: Comparison of CrO2 Powder to CrO2 Films on TiO2(110) Single Crystal Surfaces." Surface Science Spectra 8, no. 3 (July 2001): 225–33. http://dx.doi.org/10.1116/11.20020308.
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Schell-Chaple, Hildy. "Continuous Renal Replacement Therapy Update: An Emphasis on Safe and High-Quality Care." AACN Advanced Critical Care 28, no. 1 (March 15, 2017): 31–40. http://dx.doi.org/10.4037/aacnacc2017816.
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Continuous renal replacement therapy (CRRT) was introduced more than 40 years ago as a renal support option for critically ill patients who had contraindications to intermittent hemodialysis and peritoneal dialysis. Despite being the most common renal support therapy used in intensive care units today, the tremendous variability in CRRT management challenges the interpretation of findings from CRRT outcome studies. The lack of standardization in practice and training of clinicians along with the high risk of CRRT-related adverse events has been the impetus for the recent expert consensus work on identifying quality indicators for CRRT programs. This article summarizes the potential complications that establish CRRT as a high-risk therapy and also the recently published best-practice recommendations for providing high-quality CRRT.
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Zhang, Jing, Yiming Li, and Zhiyong Peng. "Prognostic Factors and Efficacy for Continuous Renal Replacement Therapy in Critically Ill Patients: A Chinese Single-Center Retrospective Study." Blood Purification 45, no. 1-3 (December 7, 2017): 53–60. http://dx.doi.org/10.1159/000481769.
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Background: There is controversy about the efficacy and prognostic factors for continuous renal replacement therapy (CRRT) in China due to practice variation. Our aim is to investigate these questions. Method: A total of 613 adult patients receiving CRRT in last 3 years from one Chinese ICU were enrolled. The analysis of demographic data, vital signs, and laboratory tests prior to CRRT and outcomes were performed. The data between pre- and post-CRRT were compared for efficacy analysis. Results: Prior to CRRT, partial pressure of carbon dioxide (PCO2), systolic blood pressure (SBP), gender, age, bilirubin, cystatin C, and mechanical ventilation were correlated with in-hospital mortality. In a binary logistic regression, PCO2, SBP, age, and gender were significant in predicting mortality. Cox regression analysis demonstrated PCO2 independent association with mortality, and lower SBP worse mortality. CRRT could eliminate the fluid and metabolites. Conclusion: CO2 retention and low SBP prior to CRRT were associated with increased mortality. CRRT significantly improved hemeostasis.
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Hanafusa, Norio. "Application of Continuous Renal Replacement Therapy: What Should We Consider Based on Existing Evidence?" Blood Purification 40, no. 4 (2015): 312–19. http://dx.doi.org/10.1159/000441579.
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Background: Continuous renal replacement therapy (CRRT) is performed mainly in patients with acute kidney injury, severe sepsis, or septic shock. Evidence has emerged about the indications for and therapeutic conditions of CRRT. In this review, we focus on the evidence for CRRT to date. Summary: CRRT employs diffusion, convection and adsorption to remove solutes from plasma. Indications can be divided into renal and non-renal indications. Concrete renal indications have not yet been determined, except for life-threatening absolute indications. Modality selection is a point of debate. Intermittent renal replacement therapy is reportedly equivalent to CRRT in terms of overall survival. However, the selection of modality must consider individual circumstances. The optimal dosage of CRRT has proven to be lower than that previously recommended, and the dosage is almost the same as the one employed in the ‘real-world' setting. Patients treated by CRRT often have bleeding complications. In this situation, regional citrate anticoagulation can be used, but nafamostat is widely used in Japan. The right jugular vein is the most preferred vascular access site because it has the lowest likelihood of catheter malfunction. As for the complications of CRRT, hypophosphatemia and nutrient loss should be managed properly. When CRRT is no longer necessary, we should consider the appropriate timing of discontinuation. Key Messages: Even though CRRT is an established technique, several points remain under debate. Individualization of therapy should be considered in light of the changes in patient characteristics.
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Droege, Christopher A., Neil E. Ernst, Nicholas J. Messinger, Allison M. Burns, and Eric W. Mueller. "Evaluation of Thrombocytopenia in Critically Ill Patients Receiving Continuous Renal Replacement Therapy." Annals of Pharmacotherapy 52, no. 12 (June 5, 2018): 1204–10. http://dx.doi.org/10.1177/1060028018779200.
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Background: Continuous renal replacement therapy (CRRT) may be associated with thrombocytopenia in critically ill patients. A confounding factor is concomitant use of unfractionated heparin (UFH) and suspicion for heparin-induced thrombocytopenia (HIT). Objective: To determine the impact of CRRT on platelet count and development of thrombocytopenia. Methods: Retrospective analyses evaluated the intrapatient change in platelet count following CRRT initiation. Critically ill adult patients who received CRRT for at least 48 hours were included. The primary outcome was intrapatient change in platelet count from CRRT initiation through the first 5 days of therapy. Secondary outcomes included thrombocytopenia incidence, identification of concomitant factors associated with thrombocytopenia, and frequency of HIT. Results: 80 patients were included. Median platelet count at CRRT initiation (D0) was 128000/µL (81500-212500/µL), which was higher than those on subsequent post-CRRT days (D1: 104500/µL [63000-166750/µL]; D2: 88500/µL [53500-136750/µL]; D3: 91000/µL [49000-138000/µL]; D4: 93000/µL [46000-134000/µL]; and D5: 76000/µL [45500-151000/µL]; P < 0.05 for all). Twenty-five (35%) patients had thrombocytopenia on CRRT D0 compared with D2 (56.3%), D3 (58.7%), and D5 (59.1%); P < 0.05 for all. Controlling for potential confounders, Sequential Organ Failure Assessment score at the time of CRRT initiation was the only independent factor associated with thrombocytopenia. One (1.3%) patient had confirmed HIT. Conclusion and Relevance: This study is the first to demonstrate serial decreases in platelet count across multiple days after CRRT initiation. These data may provide additional insight to thrombocytopenia development in critically ill patients receiving heparin while on CRRT that is not associated with HIT.
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Spencer, Susan D., Francesco Di Marco, Jeff Hooley, Sharon Pitts-Meek, Michele Bauer, Anne M. Ryan, Bernard Sordat, Verna C. Gibbs, and Michel Aguet. "The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor." Journal of Experimental Medicine 187, no. 4 (February 16, 1998): 571–78. http://dx.doi.org/10.1084/jem.187.4.571.
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The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By ∼12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10–deficient mice. These findings suggest that CRF2-4 is essential for IL-10–mediated effects and is a subunit of the IL-10 receptor.
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Welte, René, Rudolph Beyer, Johannes Hotter, Astrid Broeker, Sebastian G. Wicha, Tiziana Gasperetti, Paul Ranke, et al. "Pharmacokinetics of trimethoprim/sulfametrole in critically ill patients on continuous renal replacement therapy." Journal of Antimicrobial Chemotherapy 75, no. 5 (January 28, 2020): 1237–41. http://dx.doi.org/10.1093/jac/dkz556.
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Abstract Objectives We investigated the effect of continuous renal replacement therapy (CRRT) on the pharmacokinetics of trimethoprim and sulfametrole. Patients and methods We enrolled critically ill adults undergoing CRRT and critically ill adults with normal or slightly impaired renal function (plasma creatinine concentration <1.5 mg/dL, control group). All patients received trimethoprim/sulfametrole at standard doses. Pharmacokinetics were determined after the first dose and at steady-state. In addition, a population pharmacokinetic model using plasma data was built. We also assessed the renal clearance (CLR) and the extracorporeal clearance in patients undergoing CRRT. Results Twelve patients were enrolled in the CRRT group and 12 patients in the control group. There was no statistically significant difference in trimethoprim pharmacokinetics between the two groups. In patients on CRRT, total plasma clearance (CLtot) and V of sulfametrole were significantly higher than in the control group. However, sulfametrole exposure was not significantly altered during CRRT. The population pharmacokinetic analysis indicated that neither CRRT intensity nor residual diuresis were significant covariates on trimethoprim or sulfametrole CL. Median CL by continuous venovenous haemofiltration accounted for about one-third of CLtot of trimethoprim and for about one-half of CLtot of sulfametrole. In patients on CRRT, CLR of trimethoprim and sulfametrole were <5% of CLtot. Conclusions During CRRT, standard doses of trimethoprim/sulfametrole appear to be adequate.
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Järvisalo, Mikko J., Tapio Hellman, and Panu Uusalo. "Mortality and associated risk factors in patients with blood culture positive sepsis and acute kidney injury requiring continuous renal replacement therapy—A retrospective study." PLOS ONE 16, no. 4 (April 5, 2021): e0249561. http://dx.doi.org/10.1371/journal.pone.0249561.
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Objectives Septic acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) carries a mortality risk nearing 50%. Risk factors associated with mortality in AKI patients undergoing CRRT with blood culture positive sepsis remain unclear as sepsis has been defined according to consensus criteria in previous studies. Methods Risk factors associated with intensive care unit (ICU), 90-day and overall mortality were studied in a retrospective cohort of 126 patients with blood culture positive sepsis and coincident severe AKI requiring CRRT. Comprehensive laboratory and clinical data were gathered at ICU admission and CRRT initiation. Results 38 different causative pathogens for sepsis and associated AKI were identified. ICU mortality was 30%, 90-day mortality 45% and one-year mortality 50%. Immunosuppression, history of heart failure, APACHE II and SAPS II scores, C-reactive protein and lactate at CRRT initiation were independently associated with mortality in multivariable Cox proportional hazards models. Blood lactate showed good predictive power for ICU mortality in receiver operating characteristic curve analyses with AUCs of 0.76 (95%CI 0.66–0.85) for lactate at ICU admission and 0.84 (95%CI 0.72–0.95) at CRRT initiation. Conclusions Our study shows for the first time that lactate measured at CRRT initiation is predictive of ICU mortality and independently associated with overall mortality in patients with blood culture positive sepsis and AKI requiring CRRT. Microbial etiology for septic AKI requiring CRRT is diverse.
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Griffin, Madison, Brett Howard, Sam Devictor, Josh Ferenczy, Frances Cobb, and D. Benjamin Christie. "The Impact of Hemodynamic Transesophageal Echocardiography on the Use of Continuous Renal Replacement Therapy in Trauma." American Surgeon 83, no. 8 (August 2017): 855–59. http://dx.doi.org/10.1177/000313481708300836.
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Post-traumatic fluid management is a widely debated topic. No best-practice consensus exists. Adverse outcomes such as acute kidney injury or volume overload are common. Continuous renal replacement therapy (CRRT) is an adjunct therapy for severe acute renal failure and volume overload, but is costly and not without risk. Hemodynamic transesophageal echocardiography (hTEE) is widely accepted as a reliable way to monitor volume status of intensive care unit (ICU) patients. Although data exist evaluating hTEE and CRRT independently, there is a lack of research mutually inclusive of the two. We hypothesized that the use of hTEE is associated with less need for CRRT. Retrospective review of a level I trauma center from 2009 to 2015 identified patients that required CRRT. In 2013, we implemented a protocol using hTEE in trauma patients with significant resuscitation needs. We compared CRRTuse before and after implementation of the protocol (pre- and post-hTEE). Multivariate analysis using two sample t tests and χ2 test of the odds ratio (O.R.) was completed on variables such as injury severity score (ISS), acute kidney injury network (AKIN), days of CRRT, ICU length of stay (LOS), and hospital LOS. A total of 5037 and 6699 trauma patients were evaluated in the pre- and post-hTEE groups, respectively. Mean ISS was 22 and 28 for pre- and post-hTEE, respectively (P value 0.19). Mean AKIN was 2.7 for both groups. Mean days on CRRT was eight before hTEE and seven after hTEE (P value 0.7); 23 patients required CRRT pre-hTEE, and 15 required CRRT post-hTEE (P value 0.01 O.R. 2.4). Given, the odds of CRRT pre-hTEE are more than twice that of CRRT post-hTEE; we conclude that the use of hTEE is associated with a reduction of CRRT.
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McConville, Thomas, Marla Giddins, Nenad Macesic, and Anne-Catrin Uhlemann. "707. Clarifying the Role of CrrB in Polymxyin-resistant Klebsiella pneumoniae Clinical Isolates Utilizing a Novel CRISPR-Cas9 System." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S254—S255. http://dx.doi.org/10.1093/ofid/ofy210.714.
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Abstract Background Polymyxin resistance (PR) threatens the mainstay of therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections. While mgrB disruption accounts for most cases of PR, missense mutations in crrB have been proposed as an alternative pathway for PR through PmrA/B/C upregulation of the pmrHFIJKLM operon. It remains unknown if CrrB acts as a positive or negative regulator on its downstream targets. Methods We assembled a CRISPR-Cas9 system for gene knockouts (KO) in CRE K. pneumoniae (CRKP) using zeocin as a selectable marker. We chose a polymyxin susceptible (PS) and a PR isolate with a missense mutation in crrB (L87V) (NR5337 and NR5083, respectively) for KO. Isolates were transformed with a crrB KO plasmid, grown with zeocin selection, induced with arabinose, and plated on low-salt LB-zeocin/arabinose. KOs were confirmed via PCR and Sanger sequencing. Polymyxin susceptibility was performed with broth-microdilution. Gene expression was determined by qRT-PCR of cDNA extracts. Results Colistin MIC following crrB KO of NR5337 (PS) remained unchanged. In contrast, crrB KO of NR5083 (PR), decreased polymyxin MIC (MIC >128 to 1.0 μg/mL). qRT-PCR of NR5083 did not show increased expression of pmrA/C, nor pmrK. NR5083 ^crrB showed a small decrease in phoQ expression, compared with NR5083, but similar expression of phoP, pmrA/C and pmrK (Table 1). Conclusion Polymyxin MIC decreased >128 fold after crrB KO in a PR isolate, but colistin MIC remained unchanged after KO in a PS isolate. CrrB mutations in PR isolates may confer a gain of function with CrrB acting as a positive regulator on its downstream targets. Contrary to previous literature, no upregulation of pmrA/C and pmrHFIJKLM was detected. Differences in crrB mutations or clonal background may explain this finding. CRISPR-Cas9 may serve as a reliable system for genetic manipulation of CRKP. Further data on the impact of individual crrB missense mutations are needed. Disclosures A. C. Uhlemann, Merck: Investigator, Grant recipient.
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Challener, Douglas W., Kianoush Kashani, and John C. O’Horo. "1340. The Effect of Continuous Renal Replacement Therapy on Body Temperature in Patients with and without Infection." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S485. http://dx.doi.org/10.1093/ofid/ofz360.1204.
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Abstract Background Sepsis frequently leads to acute kidney injury. In severe cases, patients may require continuous renal replacement therapy (CRRT) which involves placement of a dialysis catheter and an extracorporeal blood filtration circuit. CRRT is commonly considered to “mask” fever, though this phenomenon has not been investigated. Methods We queried an institutional database of all patients on CRRT from 2007 to 2015 for inpatient temperature data and antibiotic administration records. Receipts of piperacillin–tazobactam, a carbapenem, or a third or fourth-generation cephalosporin, indicating a serious infection, were considered intervention arm. We analyzed temperatures recorded in the intensive care unit before, during, and after CRRT. Patients were divided into groups that did not receive antibiotics as well as those who did. Temperature data were Winsorized to correct for outliers. We also performed descriptive statistics for each group. Results There were 237,988 temperature readings for 1,568 ICU patients on CRRT. 1,153 patients received broad-spectrum antibiotics in ICU. In patients who received antibiotics in ICU and were presumed to have an infection, the mean temperature was 37.2°C prior to initiation of CRRT, 36.8°C while on CRRT, and 37.2°C following discontinuation of CRRT. In the 415 patients who did not receive IV antibiotics, the mean temperature was 36.9°C prior to initiation of CRRT, 36.6°C while on CRRT, and 37.0°C following discontinuation of CRRT. During each of the periods before, during, and after CRRT, patients who received antibiotics had significantly higher temperatures than those who did not (P < 0.001). Patients receiving antibiotics were generally younger (mean 60 years vs. 64 years, P < 0.001), had longer ICU stays (mean 29 days vs. 12 days, P < 0.001) and spent more time being ventilated (mean 23 days vs. 7 days, P < 0.001). The mean SOFA score on day one was similar (mean 11.1 in the antibiotic group and 10.5 in the other group). Conclusion This investigation suggests that patients have slightly lower temperatures while on CRRT, by on average less than half a degree. A similar effect is seen in both patients with infections as well as those without. Further work will be needed to determine what constitutes a true febrile response in this population. Disclosures All authors: No reported disclosures.
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Misra, Ajay K. "Reaction of beta-phase Ni–Al alloys with CrB2." Journal of Materials Research 6, no. 8 (August 1991): 1664–72. http://dx.doi.org/10.1557/jmr.1991.1664.
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Reaction of Ni–Al alloys within the β-NiAl phase with CrB2 was studied at 1473 K as a function of Al concentration in the alloy. Reaction of 49–50 at. % Al alloys with CrB2 occurred by interdiffusion of Ni into CrB2 and Cr into the alloy without forming a new product phase. On the other hand, a new product phase, rich in Ni and B, formed by the reaction of alloys having Al concentrations 48 at. % or lower with CrB2. The reaction product was observed both at the CrB2/alloy interface and along the alloy grain boundaries.
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Kiely, B. E., M. A. Jenkins, J. M. McKinley, M. L. Friedlander, P. C. Weideman, R. Milne, S. McLachlan, J. L. Hopper, and K. Phillips. "Contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1509. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1509.
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1509 Background: Contralateral risk-reducing mastectomy (CRRM) reduces contralateral breast cancer (BC) risk by up to 97%. Few studies have examined the prevalence and predictors of CRRM in BC patients at high familial risk of a second primary BC. Methods: Participants were women with unilateral BC and a strong family history of the disease, including BRCA1 and BRCA2 mutation carriers. Data were collected by interview, self-administered questionnaire, and review of pathology and surgical reports. Associations between having CRRM and potential predictors were assessed using multivariate logistic regression. Results: Of 1018 study participants (median follow-up 5.5 years), 154 (15%) underwent CRRM. The median time from initial BC to CRRM was 1 year. More likely to undergo CRRM were women who were younger at the time of their BC diagnosis (odds ratio [OR] = 0.94 per year of age, p < 0.001), those diagnosed more recently (OR = 1.16 per calendar year, p < 0.001), those who underwent mastectomy rather than breast conservation as their initial definitive BC treatment (OR = 5.2, p < 0.001) and those who underwent risk-reducing salpingo-oophorectomy (OR = 3.4, p < 0.001). BRCA1/2 mutation status and tumor characteristics were not independently associated with CRRM uptake. A contralateral BC event occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. Conclusions: Younger women with more recently diagnosed BC treated with mastectomy were most likely to elect CRRM. BRCA1/2 mutation status and the competing risk of BC recurrence and death did not appear to influence decision making. No significant financial relationships to disclose.
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Nanda, Steven A., Patrick H. Roseboom, George A. Nash, James M. Speers, and Ned H. Kalin. "Characterization of the Human Corticotropin-Releasing Factor2(a) Receptor Promoter: Regulation by Glucocorticoids and the Cyclic Adenosine 5′-Monophosphate Pathway." Endocrinology 145, no. 12 (December 1, 2004): 5605–15. http://dx.doi.org/10.1210/en.2004-0907.
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Abstract Corticotropin-releasing factor (CRF) is a neurotransmitter and hormone believed to integrate responses to stress. Evidence suggests central CRF systems are overactive in some individuals suffering from depression and anxiety disorders. CRF receptor antagonism blocks stress-induced endocrine, autonomic, and behavioral effects in animal models, and studies have implicated the CRF2 receptor in anxiety-related behaviors. Greater understanding of the regulation of CRF2 expression may facilitate understanding mechanisms underlying anxiety. The present studies are the first to characterize the transcriptional regulation of the human CRF2(a), the predominant CRF2 isoform in brain. Four kilobase pairs of sequence immediately upstream of the first exon of CRF2(a) represented our full-length promoter region. Sequentially smaller fragments of the CRF2(a) promoter region were generated by PCR and cloned upstream of a luciferase reporter gene. Expression was monitored from these constructs within Chinese hamster ovary-K1 cells and within rat aortic A7R5 cells that express CRF2. Glucocorticoid treatment decreased expression and elevating intracellular cAMP increased expression from the human CRF2(a) promoter. The regions of the CRF2(a) promoter that regulate the inducible expression were determined, and the functional cAMP response element and glucocorticoid response element cis-regulatory elements within these regions were identified using a combination of site-directed mutagenesis and EMSAs. Given the possibility of species-specific differences in gene expression, interpretation of gene expression studies from rat and mouse model systems is difficult. Examination of expression from the human CRF2(a) promoter will provide insight into these model systems and may translate more readily to the development of therapeutics to treat human psychiatric illness.
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Sanders, Steven L., Ahmad R. Arida, and Funita P. Phan. "Requirement for the Phospho-H2AX Binding Module of Crb2 in Double-Strand Break Targeting and Checkpoint Activation." Molecular and Cellular Biology 30, no. 19 (August 2, 2010): 4722–31. http://dx.doi.org/10.1128/mcb.00404-10.
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ABSTRACT Activation of DNA damage checkpoints requires the rapid accumulation of numerous factors to sites of genomic lesions, and deciphering the mechanisms of this targeting is central to our understanding of DNA damage response. Histone modification has recently emerged as a critical element for the correct localization of damage response proteins, and one key player in this context is the fission yeast checkpoint mediator Crb2. Accumulation of Crb2 at ionizing irradiation-induced double-strand breaks (DSBs) requires two distinct histone marks, dimethylated H4 lysine 20 (H4K20me2) and phosphorylated H2AX (pH2AX). A tandem tudor motif in Crb2 directly binds H4K20me2, and this interaction is required for DSB targeting and checkpoint activation. Similarly, pH2AX is required for Crb2 localization to DSBs and checkpoint control. Crb2 can directly bind pH2AX through a pair of C-terminal BRCT repeats, but the functional significance of this binding has been unclear. Here we demonstrate that loss of its pH2AX-binding activity severely impairs the ability of Crb2 to accumulate at ionizing irradiation-induced DSBs, compromises checkpoint signaling, and disrupts checkpoint-mediated cell cycle arrest. These impairments are similar to that reported for abolition of pH2AX or mutation of the H4K20me2-binding tudor motif of Crb2. Intriguingly, a combined ablation of its two histone modification binding modules yields a strikingly additive reduction in Crb2 activity. These observations argue that binding of the Crb2 BRCT repeats to pH2AX is critical for checkpoint activity and provide new insight into the mechanisms of chromatin-mediated genome stability.
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Santiago, Maria J., Jesús López-Herce, Eva Vierge, Ana Castillo, Amaya Bustinza, Jose M. Bellón, Amelia Sánchez, and Sarah Fernández. "Infection in Critically Ill Pediatric Patients on Continuous Renal Replacement Therapy." International Journal of Artificial Organs 40, no. 5 (May 2017): 224–29. http://dx.doi.org/10.5301/ijao.5000587.
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Introduction Continuous renal replacement therapies (CRRT) are frequently used in critically ill children and may increase the risk of infection. However, the incidence, characteristics and prognosis of infection in critically ill children on CRRT have not been studied. Methods Data from a prospective, single-center register of critically ill children treated with CRRT was analyzed. Results 55 children (40% under 1 year of age) were treated with CRRT between June 2008 and January 2012; 43 patients (78.2%) presented 1 or more infections. The most common condition of patients requiring CRRT was heart disease (69%). Infection occurred a median of 11 days after the initiation of CRRT (IQ range: 4 to 21 days). A total of 21 patients (48.8 %) developed 1 infection, 7 (16.2%) developed 2 infections and 15 (34.9%) developed 3 or more infections. The most frequent infection was catheter-related bacteremia, with no differences in catheter location. CRRT duration longer than 4.5 days was the only risk factor for infection. Patients with infection had a longer length of stay (LOS) in the Pediatric Intensive Care Unit (PICU) than patients without it (37.8 vs. 17.6, p = 0.019), but there were no differences in mortality (30.2% vs. 33.3%; p = 0.84). Conclusions Infection rate is high in critically ill children treated with CRRT. More than 4 days of CRRT increases the risk of infection. Infection in these patients entails a longer stay in the PICU but did not increase mortality.
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Möller-Kerutt, Annika, Juan E. Rodriguez-Gatica, Karin Wacker, Rohan Bhatia, Jan-Peter Siebrasse, Nanda Boon, Veerle Van Marck, et al. "Crumbs2 Is an Essential Slit Diaphragm Protein of the Renal Filtration Barrier." Journal of the American Society of Nephrology 32, no. 5 (March 9, 2021): 1053–70. http://dx.doi.org/10.1681/asn.2020040501.
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BackgroundCrumbs2 is expressed at embryonic stages as well as in the retina, brain, and glomerular podocytes. Recent studies identified CRB2 mutations as a novel cause of steroid-resistant nephrotic syndrome (SRNS).MethodsTo study the function of Crb2 at the renal filtration barrier, mice lacking Crb2 exclusively in podocytes were generated. Gene expression and histologic studies as well as transmission and scanning electron microscopy were used to analyze these Crb2podKO knockout mice and their littermate controls. Furthermore, high-resolution expansion microscopy was used to investigate Crb2 distribution in murine glomeruli. For pull-down experiments, live cell imaging, and transcriptome analyses, cell lines were applied that inducibly express fluorescent protein–tagged CRB2 wild type and mutants.ResultsCrb2podKO mice developed proteinuria directly after birth that preceded a prominent development of disordered and effaced foot processes, upregulation of renal injury and inflammatory markers, and glomerulosclerosis. Pull-down assays revealed an interaction of CRB2 with Nephrin, mediated by their extracellular domains. Expansion microscopy showed that in mice glomeruli, Crb2 and Nephrin are organized in adjacent clusters. SRNS-associated CRB2 protein variants and a mutant that lacks a putative conserved O-glycosylation site were not transported to the cell surface. Instead, mutants accumulated in the ER, showed altered glycosylation pattern, and triggered an ER stress response.ConclusionsCrb2 is an essential component of the podocyte’s slit diaphragm, interacting with Nephrin. Loss of slit diaphragm targeting and increasing ER stress are pivotal factors for onset and progression of CRB2-related SRNS.
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Lee, Keum Hwa, In Suk Sol, Jung Tak Park, Ji Hong Kim, Jae Won Shin, Mi Rireu Park, Jae Hyun Lee, Yoon Hee Kim, Kyung Won Kim, and Jae Il Shin. "Continuous Renal Replacement Therapy (CRRT) in Children and the Specialized CRRT Team: A 14-Year Single-Center Study." Journal of Clinical Medicine 9, no. 1 (December 31, 2019): 110. http://dx.doi.org/10.3390/jcm9010110.
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Continuous renal replacement therapy (CRRT) has been used as an important intervention in critically ill children. Our center has the only specialized CRRT team (SCT) for children in Korea, which consists of pediatric intensivists, a pediatric nephrologist and CRRT-specialized-nurses. This study was a retrospective single-center analysis, including all pediatric patients admitted to the intensive care unit (ICU) of Severance hospital in Korea and received CRRT between 2003 and 2016, grouped as before SCT (group A, n = 51) and after SCT (group B, n = 212). We obtained the data for sex, age, weight, diagnosis, blood flow rate or type of CRRT machine used, administration of inotropic agents or anticoagulants, and ICU duration before CRRT (hours). A total of 263 patients were included. The age was significantly younger (p < 0.001) and blood flow rate was lower (p = 0.001) in group B than group A. Vasopressors (p < 0.001), continuous veno-venous hemodiafiltration (CVVHDF) (p < 0.001), nafamostat mesilate (p < 0.001), and extracorporeal membrane oxygenation (ECMO)-CRRT (p = 0.004) were more frequently used in group B. Based on our 14-year experience, we conclude that SCT operation could have played an important role in increasing the amount of CRRT utilization.
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Du, Hong, Jing Li, Hai-tao Yu, Wei Jiang, Ye Zhang, Jun-ning Wang, Ping-zhong Wang, and Xue-fan Bai. "A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome." Infection International 3, no. 2 (June 1, 2014): 71–76. http://dx.doi.org/10.1515/ii-2017-0078.
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Abstract Objective To observe the application of continuous renal replacement therapy (CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients (severe group) and 71 critical-type patients (critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group (P ＜ 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group (P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.
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Lee, Yunna, Elise L. Ma, Marisa Patel, Gayoung Kim, Cody Howe, Charalabos Pothoulakis, Yong Sung Kim, Eunok Im, and Sang Hoon Rhee. "Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer." International Journal of Molecular Sciences 22, no. 3 (January 21, 2021): 1043. http://dx.doi.org/10.3390/ijms22031043.
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The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.
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Akhoundi, Abbasali, Balwinder Singh, Myriam Vela, Sanjay Chaudhary, Myles Monaghan, Gregory A. Wilson, John J. Dillon, et al. "Incidence of Adverse Events during Continuous Renal Replacement Therapy." Blood Purification 39, no. 4 (2015): 333–39. http://dx.doi.org/10.1159/000380903.
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Background/Aims: The incidence of adverse events (AEs) in adults who receive continuous renal replacement therapy (CRRT) is unknown. We report the incidence of mechanical, metabolic, and hemodynamic CRRT AEs. Methods: This is a retrospective study of all consecutive adult patients (≥18 years) who underwent CRRT from January 1, 2007 to December 31, 2009. Results: Out of 595 patients who underwent CRRT, 366 (62%) were male and 500 (84%) were Caucasian. Regional citrate anticoagulation was used in 98.6% of all patients. The most common clinically significant electrolyte derangements were ionized hypocalcemia (22%), ionized hypercalcemia (23%), and hyperphosphatemia (44%). Almost all (97%) patients had at least one additional AE including new onset hypotension (within the first hour after CRRT initiation) (43%), hypothermia (44%), new onset arrhythmias (29%), new onset anemia (31%) and thrombocytopenia (40%). Conclusions: ICU patients who require CRRT have a high incidence of AEs. Although the extent to which these complications are attributable to CRRT is not known, clinicians need to be cautious and aware of their high prevalence in this patient population.
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Matsushita, Junichi, Kenji Shimao, Yoshiyuki Machida, Takumi Takao, Kiyokata Iizumi, Yutaka Sawada, and Kwang Bo Shim. "Sintering and Mechanical Properties of Chromium Boride - Chromium Carbide Composites." Materials Science Forum 534-536 (January 2007): 1077–80. http://dx.doi.org/10.4028/www.scientific.net/msf.534-536.1077.
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Several boride sintered bodies such as TiB2, ZrB2, and SiB6 were previously reported. In the present study, the sinterability and physical properties of chromium boride (CrB2) containing chromium carbide (Cr3C2) sintered bodies were investigated in order to determine its new advanced material. The samples were sintered at desired temperature for 1 hour in vacuum under a pressure by hot pressing. The relative density of sintered bodies was measured by Archimedes’ method. The relative densities of CrB2 addition of 0, 5, 10, 15 and 20 mass % Cr3C2 composites were 92 to 95 %. The Vickers hardness of the CrB2 with 10 and 15 mass % Cr3C2 composites were about 14 and 15 GPa at room temperature, respectively. The Vickers hardness at high temperature of the CrB2 addition of 10 mass % Cr3C2 composite decreased with increasing measurement temperature. The Vickers hardness at 1273 K of the sample was 6 GPa. The Vickers hardness of CrB2 addition of Cr3C2 composites was higher than monolithic CrB2 sintered body. The powder X-ray diffraction analysis detected CrB and B4C phases in CrB2 containing Cr3C2 composites.
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Kim, Jeong Yeon, Yeonhee Lee, and Heeyeon Cho. "Optimal Prescriptions of Continuous Renal Replacement Therapy in Neonates with Hyperammonemia." Blood Purification 47, no. 1-3 (September 14, 2018): 16–22. http://dx.doi.org/10.1159/000492660.
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Background/Aims: The aim of this study was to evaluate patients’ outcomes, determine the prescriptions of continuous renal replacement therapy (CRRT) that effectively reduce serum ammonia levels, and analyze the prognostic factors in neonates with hyperammonemia. Methods: The medical records of 12 Korean neonates with inborn error of metabolism (IEM) who underwent CRRT for hyperammonemia were retrospectively analyzed. Results: All patients received continuous venovenous hemodiafiltration. The median ultrafiltration rate (UFR) at the initiation of CRRT was 2,288.4 mL/h/1.73 m2. The median ammonia level at CRRT initiation was 1,320 µmol/L, and the median time to reduce the initial ammonia level by at least 50% was 12.8 h. The survival rate during hospitalization was 83.3%. There were significant differences between patients with neurologic sequelae and those without poor outcomes in peak serum ammonia level before CRRT and serum ammonia level at CRRT initiation. Conclusion: This study suggested that CRRT could be a therapeutic option for neonates with IEM. However, it is necessary to raise the UFR above 4,000 mL/h/1.73 m2 in patients with high initial ammonia level.
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Yetimakman, Ayse Filiz, Selman Kesici, Murat Tanyildiz, and Benan Bayrakci. "Continuous Renal Replacement Therapy for Treatment of Severe Attacks of Inborn Errors of Metabolism." Journal of Pediatric Intensive Care 08, no. 03 (March 27, 2019): 164–69. http://dx.doi.org/10.1055/s-0039-1683991.
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AbstractSevere metabolic crises in children with inborn errors of metabolism can result in mortality or severe morbidities where continuous renal replacement therapy (CRRT) can be lifesaving. Clinical data, the pediatric risk of mortality (PRISM) scores calculated in the first 24 hours, and pediatric logistic organ dysfunction (PELOD) scores calculated in the last 24 hours before CRRT, were studied. Overall, CRRT was successful in restoring metabolic balance in 72% of patients. PELOD scores before CRRT were lower in survivors (p = 0.02). Despite numerous comorbid factors, CRRT can be used effectively in management of metabolic crises. Early intervention with this therapy before occurrence of complications must be targeted.
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Erin K, Stenson, Brinton John T, Beil Liz, Soranno Danielle E, and Gist Katja M. "Modification of the Renal Angina Index for identifying the need for renal replacement therapy in critically ill pediatric patients." Journal of Clinical Nephrology 4, no. 3 (November 2, 2020): 070–76. http://dx.doi.org/10.29328/journal.jcn.1001062.
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Severe Acute Kidney Injury (AKI) is a common, serious problem affecting critically ill children that lacks effective treatment options. Currently, there are no treatment options for AKI other than supportive care. Continuous renal replacement therapy (CRRT) is employed to reduce Fluid Overload (FO) burden and treat metabolic disturbances in AKI. Identifying patients upon admission who may require CRRT has potential clinical care implications. The aim of this study was to determine if the RAI had diagnostic capabilities to identify patients who would require CRRT. The analytic cohort consisted of patients who required CRRT and illness severity score matched controls who did not require CRRT at a single center. Patients who required CRRT had higher mortality rates, length of stay, and use of ventilatory and inotropic support. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) assessed and compared the discriminatory accuracy of three scores: 1) the renal angina index (RAI), 2) serum-creatinine (sCr) based AKI on day 0 and 3) modified RAI created with an additional RAI injury tranche that corresponded to severe stage 3 AKI sCr elevation. Compared to Day0AKI (AUC 0.78, 0.70-0.87; sensitivity 0.63, 0.45-0.79; specificity 0.93, 0.870.97) and RAI (AUC 0.76, 0.69-0.82; sensitivity 0.94, 0.81-0.99; specificity 0.57, 0.47-0.66), the modified RAI had the highest AUC (0.79; 0.72-0.85) with a high sensitivity (0.91; 0.77-0.98) and moderate specificity (0.65; 0.56-0.75) for prediction of CRRT requirements. As a more accurate tool for discriminating patients in need of CRRT, a modified RAI has numerous potential implications. Identifying patients who ultimately require CRRT at an earlier timepoint may influence timing of CRRT initiation in an attempt to avoid further FO, or may influence nephrotoxin administration. The diagnostic capabilities of the modified RAI may be refined by the addition of urinary biomarkers. These findings should be validated in a larger cohort.
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Matsui, Tomohiro, Takafumi Nakagawa, Hitomi Kikuchi, Hiroyuki Horio, and Kazuhiko Hashimura. "The Effect of Continuous Renal Replacement Therapy with the AN69ST Membrane on Inflammatory Markers and the Level of Consciousness of Hemodialysis Patients with Stroke: Comparison with Hemodialysis with Low Blood Flow Rate." PRILOZI 39, no. 2-3 (December 1, 2018): 29–35. http://dx.doi.org/10.2478/prilozi-2018-0039.
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Abstract Introduction: Hemodialysis (HD) with low blood flow rate, continuous renal replacement therapy (CRRT), and peritoneal dialysis are recommended for patients with stroke complications to prevent intracranial hypertension because of the low diffusion capacity of the brain barrier. However, detailed guidelines are not currently available; thus, there is an urgent need to establish such guidelines. Material and Methods: We developed a novel protocol for performing CRRT with the AN69ST membrane, which has excellent adsorption capacity for various cytokines. The objective of this study was to compare the effect of the novel protocol with that of the current standard protocol, i.e. hemodialysis with low blood flow rate. To compare the effect of hemodialysis with low blood flow (HD group, n=27) and CRRT with AN69ST membrane (CRRT group, n=8), we measured the following consciousness and blood inflammatory parameters in patients with stroke complications at baseline and after 1 week of treatment: Glasgow Coma Scale (GCS) score, C-reactive protein (CRP) levels, and white blood cell (WBC) and platelet count. Results: After 1 week, the total GCS score did not improve in the HD group, but improved significantly in the CRRT group (HD group: 13.1±3.0 to 13.3±3.1, p=0.5508, CRRT group: 8.9±3.9 to 11.5±3.9, p=0.0313). Improvement in the CRRT group was significantly higher than in the HD group (p=0.0039). CRP levels did not change significantly in either the HD (3.8±5.5 to 5.3±4.3 n.s.) or CRRT groups (7.7±10.0 to 3.7±3.2 n.s.); however, they tended to increase in the HD group and decrease in the CRRT group. No significant changes were observed in WBC and platelet counts after 1 week of treatment in either group. Conclusion: CRRT with the AN69ST membrane might have a beneficial effect on the consciousness level and inflammation of patients with stroke.
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Warrillow, Stephen, Caleb Fisher, Heath Tibballs, Michael Bailey, Colin McArthur, Pia Lawson-Smith, Bheemasenachar Prasad, et al. "Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure." Critical Care and Resuscitation 22, no. 2 (June 1, 2020): 158–65. http://dx.doi.org/10.51893/2020.2.oa6.
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Objective: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. Design: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. Setting: All liver transplant ICUs across Australia and New Zealand. Participants: Sixty-two patients with ALF. Main outcome measures: Impact of CRRT on hyperammonaemia and patient outcomes. Results: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 mol/L (interquartile range [IQR], 91–172), median creatinine was 165 mol/L (IQR, 92–263) and median urea was 6.9 mmol/L (IQR, 3.1–12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2–12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 mol/L [IQR, 102–198] v 91 mol/L [IQR, 54–115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 mol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). Conclusion: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.
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Aygun, Fatih, Fatih Varol, Cigdem Aktuglu-Zeybek, Ertugrul Kiykim, and Halit Cam. "Continuous Renal Replacement Therapy with High Flow Rate Can Effectively, Safely, and Quickly Reduce Plasma Ammonia and Leucine Levels in Children." Children 6, no. 4 (April 4, 2019): 53. http://dx.doi.org/10.3390/children6040053.
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Introduction: Peritoneal dialysis and continuous renal replacement therapy (CRRT) are the most frequently used treatment modalities for acute kidney injury. CRRT is currently being used for the treatment of several non-renal indications, such as congenital metabolic diseases. CRRT can efficiently remove toxic metabolites and reverse the neurological symptoms quickly. However, there is not enough data for CRRT in children with metabolic diseases. Therefore, we aimed a retrospective study to describe the use of CRRT in metabolic diseases and its associated efficacy, complications, and outcomes. Materials and Methods: We performed a retrospective analysis of the records of all patients admitted in the pediatric intensive care unit (PICU) for CRRT treatment. Results: Between December 2014 and November 2018, 97 patients were eligible for the present study. The age distribution was between 2 days and 17 years, with a mean of 3.77 ± 4.71 years. There were 13 (36.1%) newborn with metabolic diseases. The patients were divided into two groups: CRRT for metabolic diseases and others. There was a significant relationship between the groups, including age (p ≤ 0.001), weight (p = 0.028), blood flow rate (p ≤ 0.001); dialysate rate (p ≤ 0.001), and replacement rate (p ≤ 0.001). The leucine reduction rate was 3.88 ± 3.65 (% per hour). The ammonia reduction rate was 4.94 ± 5.05 in the urea cycle disorder group and 5.02 ± 4.54 in the organic acidemia group. The overall survival rate was 88.9% in metabolic diseases with CRRT. Conclusion: In particularly hemodynamically unstable patients, CRRT can effectively and quickly reduce plasma ammonia and leucine.