Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy.

Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3⁻66.3) mL/min for Cockcroft Gault, 19.8 (9.8⁻47.0) mL/min/1.73 m² for MDRD and 20.5 (4.9⁻49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI

Design and implementation of a phase locked loop for high-speed serial links

Recent advances in the semiconductor industry and process technology scaling have increased the demand for fast, robust computing. The thirst for high-processing, low power ICs is ever increasing. This has pushed the demand for high data rates in wireless and wireline communication systems in the multi-Gbps range. With higher data rates, the I/O links need to scale proportionally. However, the I/O channel bandwidth has not scaled appropriately making it the biggest bottleneck in high-speed links. Parallel links have not been able to match this increasing system performance due to issues such as crosstalk, timing skew and packaging costs. Thus there is a need for high-speed serial links. For high-speed transmission of data, there arises a need for high-speed on chip clocking circuits making the use of Phase-Locked Loops (PLLs) imperative. This thesis includes an overview of high-speed links along with the need for PLLs. An in-depth understanding of PLL theory, loop dynamics and behavioral and transistor level simulation follows. Performance metrics such as phase noise, random jitter and deterministic jitter are discussed. Finally, this thesis concludes with an insight into All Digital Phase-Locked Loops (ADPLLs)

Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group

INTRODUCTION: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at ) CONCLUSION: Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology

Phenotype standardization for drug-induced kidney disease.

Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition

Sol-gel synthesized indium tin oxide as a transparent conducting oxide with solution-processed black phosphorus for its integration into solar-cells

This article describes the synthesis of indium tin oxide (ITO) thin films using solgel processing with a mixture of InCl₃, methanol, and SnCl₂, where the solutions were spin coated onto glass substrates. The combined architecture of black phosphorus on ITO thin films shows promise in its use for transparent electronics, which can also serve as a stepping stone for future solar cell platforms

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective, Randomized, Controlled Clinical Trial, and Clinical Experience from 19 Centers

Artificial liver support aims to prolong survival time of patients with liver failure by detoxification. Albumin as a molecular adsorbent in dialysis solution is capable of attracting even tightly albumin-bound toxins from blood into the dialysate if a specific dialysis membrane is used and if the albumin's binding sites are on-line-purified by a sorbent/dialysis-based recycling system (i.e., molecular adsorbents recycling system, or MARS). The MARS technology has been shown to remove water-soluble and albumin-bound toxins and to provide renal support in case of renal failure. Fourteen centers have reported that MARS treatment improved mental status of patients with liver failure and hepatic encephalopathy. In treating liver failure and cholestasis, MARS was associated with hemodynamic stabilization, improvement of hepatic and kidney function, and disappearance of pruritus. In hepatic failure and hepatorenal syndrome, a prospective, randomized, controlled trial of MARS treatment was able to prolong survival time significantly. MARS has been used in 26 patients with acute liver failure or primary graft dysfunction. Nineteen centers reporting on 103 patients have shown that MARS treatment is safe, easy to handle, feasible, and effective.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73869/1/j.1525-1594.2002.06822.x.pd

The effect of frequent hemodialysis on nutrition and body composition: frequent Hemodialysis Network Trial.

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition

Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI

Does intervertebral disc degeneration in adolescent idiopathic scoliosis correlate with patient-reported pain scores?:A review of 968 cases

PURPOSE: Report the rate and severity of degenerative disc disease (DDD) in non-surgical adolescent idiopathic scoliosis (AIS) patients and correlate these findings with patient-reported symptomatology scores. Additionally, to quantify the rate of concurrent pathological radiological findings in this group.METHODS: This was a retrospective chart review study at a single tertiary centre. AIS patients aged 10-16 who had received a whole spine MRI between September 2007 and January 2019 and who had not received surgical intervention to their spine were included. MRI scan reports were screened to extract those who had evidence of DDD. These were then reviewed by a blinded second reviewer who graded every disc using the Pfirrmann grading system. SRS-22 scores were extracted for patients when available.RESULTS: In total, 968 participants were included in the study. Of these, 93 (9.6%) had evidence of DDD, which was Pfirrmann grade ≥ 3 in 28 (2.9%). The most commonly affected level was L5/S1 (59.1% of DDD cases). A total of 55 patients (5.7%) had evidence of syringomyelia, 41 (3.4%) had evidence of spondylolisthesis (all L5/S1), 14 (1.4%) had bilateral L5 pars defects, and 5 (0.5%) had facet joint degeneration. Spondylolisthesis and bilateral pars defects were more common in patients with DDD identified on MRI scan (p &lt; 0.001 and p = 0.04, respectively). Function (p = 0.048) and pain (p = 0.046) scores were worse in patients with DDD.CONCLUSION: We present a baseline for the rate and severity of DDD in the non-operative AIS cohort. This should assist in decision-making and counselling of patients prior to surgery.LEVEL OF EVIDENCE: III.</p