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Black patients face disparities in cancer outcomes. Additionally, Black patients are more likely to be undertreated and underrepresented in clinical trials. The recent recommendation to remove race from the estimated glomerular filtration rate (eGFR) results in lower eGFR values for Black patients. The ramifications of this decision, both intended and unintended, are still being elucidated in the medical community. Here, the authors analyze the removal of race from eGFR for Black patients with cancer, specifically with respect to clinical trial eligibility.In a cohort of self-identified Black patients who underwent nephrectomy at a tertiary referral center from 2009 to 2021 (n = 459), eGFR was calculated with and without race in commonly used equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]). The distribution of patients and changes within chronic kidney disease stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated on the basis of the utilization of the race coefficient.The median eGFR from CKD-EPI was significantly higher with race (76 ml/min/1.73 mRace-free renal function equations may inadvertently result in increased exclusion of Black patients from clinical trials. This is especially concerning because of the underrepresentation and undertreatment that Black patients already experience.Black patients experience worse oncologic outcomes and are underrepresented in clinical trials. Kidney function, as estimated by glomerular filtration rate equations, is a factor in who can and cannot be in a clinical trial. Race is a variable in some of these equations. For Black patients, removing race from these equations leads to the calculation of lower kidney function. Lower estimated kidney function may result in more black patients being excluded from clinical trials. The inclusion of all races in clinical trials is important for offering best care to everyone and for making results from clinical trials applicable to everyone.

Background In critically ill patients receiving kidney replacement therapy (KRT), high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate current practices and evidence gaps related to fluid removal with KRT in critically ill patients. Methods This was a multinational, web-based survey distributed by 7 networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39 question survey about fluid-management practices on KRT. The survey was distributed from September 2021 to December 2021. Results There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5 to 2 L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods (i.e. ultrasound, hemodynamic markers, intra-abdominal pressure) while nephrologists were more likely to deploy co-interventions aimed at improving tolerance to fluid removal (i.e. osmotic agents, low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant. Conclusions We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. The majority of nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials.

Critically ill patients who develop severe acute kidney injury in the intensive care unit often require treatment with renal replacement therapies (RRTs). This complication is associated with severe morbidity and mortality and high costs, both during hospitalization and postdischarge. This article discusses the operational requirements to develop and conduct a RRT program, as well as the financial implications of this complex form of patient care. The management of these programs must occur in a context where a clear organizational and educational framework and a multidisciplinary team ensures safety, effectiveness, cost-control, and a clear quality control framework.

Amidst the pandemic, geographical boundaries presented challenges to those in need of higher levels of care from referral centers. Authors sought to evaluate potential predictors of treatment success; assess our transport and remote cannulation process; and identify transport associated complications. Retrospective series of critically ill adults with COVID-19 transferred by our Extracorporeal Membrane Oxygenation (ECMO) team 24 March 2020 through 8 June 2021. Descriptive statistics and associated interquartile ranges (IQR) were used to summarize the data. Sixty-three patients with COVID associated acute respiratory distress syndrome (ARDS) requiring ECMO support were admitted to our ECMO center. Mean age was 44 years old (SD 12; IQR 36–56). 59% ( n = 37) of patients were male. Average body mass index was 39.7 (SD 11.3; IQR 31–48.5). Majority of patients (77.8%; n = 35) had severe ARDS. Predictors of treatment success were not observed. Transport distances ranged from 2.2 to 236 miles (median 22.5 miles; IQR 8.3–79); round trip times from 18 to 476 min (median 83 min; IQR 44–194) . No transport associated complications occurred. Median duration of ECMO support was 17 days (IQR 9.5–34.5). Length of stay in the Intensive Care Unit (median 36 days; IQR 17–49) and hospital (median 39 days; IQR 25–57) varied. Amongst those discharged, 60% survived.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI., COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and is an independent risk factor for all-cause in-hospital death in patients with COVID-19. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI and for areas of future research, with the aim of improving understanding of the underlying processes and outcomes for patients with COVID-19 AKI.

611 Background: Race is no longer recommended in estimated glomerular filtration rate (eGFR) equations. The resulting lower eGFR may positively impact black patients, such as with earlier nephrology referral. However, the impact of race-free equations on black oncology patients–a cohort more likely to experience inferior cancer outcomes and underrepresentation in clinical trials–has not been fully examined. Here, we analyze removal of race from eGFR in black patients with cancer, specifically with regards to clinical trial eligibility. Methods: Self-identified black patients undergoing nephrectomy at a referral center from 2009-2021 were identified. Patients with end-stage renal disease were excluded. Using preoperative creatinine, height, and weight, eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with and without race (CKD-EPI-WithRace; CKD-EPI-WithoutRace, respectively), and the Modification of Diet in Renal Disease equation with and without race (MDRD-WithRace; MDRD-WithoutRace, respectively). Distribution of patients and changes within CKD stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated based on utilization of the race coefficient. Subgroup analysis was completed on patients with stage III-IV disease only. Results: 459 self-identified black patients that underwent nephrectomy at our institution were identified, 135 of which had stage III-IV disease. On average, eGFR decreased around 10-13ml/min/1.73m2 with removal of the race coefficient (Table). 13-22%, 6-12%, and 2-3% more black patients would fall under common clinical trial cutoffs of 60, 45, or 30ml/min cutoffs, respectively, depending on the equation used (Table). Subanalysis of stage III-IV patients only were similar. Conclusions: Race free renal function equations may inadvertently result in increased exclusion of black patients from clinical trials. [Table: see text]

Background COVID-19 associated hyperviscosity is a potential driver for the increased rates of thrombotic complications and multi-organ failure associated with severe COVID-19. Limited experience suggests a promising role for Therapeutic Plasma Exchange (TPE) in COVID-19 management based on the hypothesis that clinical benefit is derived from reduction in plasma viscosity. However, systematic study evaluating the safety and efficacy of TPE in these patients has not been done. Objective To evaluate the safety and efficacy of TPE in a subset of critically ill patients with COVID-19 and elevated blood viscosity in a randomized controlled trial (RCT). Study Design and Methods This study was conducted in the intensive care units (ICUs) of 3 hospitals in our health system, with a limited initial enrollment target of 20 patients. Participants included adult COVID-19 patients with moderate elevation in plasma viscosity (2.3-3.5 centipoise) or significant hyperfibrinogenemia (>800 mg/dL) that were not improving despite standard supportive care. Patients with bacterial or fungal coinfection or moribund patients were specifically excluded. Upon enrollment, patients were randomized 1:1 to the treatment group (1 plasma volume TPE with frozen plasma (FP) replacement on 2 consecutive days) or control group (continued standard of care (SOC)). Primary measures included the safety/tolerability of TPE and change in plasma viscosity levels after TPE versus SOC. Secondary measures included evaluation of various clinical and laboratory parameters, including fibrinogen and other coagulation-related markers, mortality, bleeding and thromboembolic complications, ICU length of stay and time to discharge after enrollment. Results Preliminary analysis of collected data demonstrates that TPE is safe and well-tolerated in these patients, with adverse events limited to one mild occurrence of tachycardia that improved upon decreasing the flow rate. There was significant decrease in plasma viscosity in the TPE treatment group, compared to the SOC control group. Secondary measures of select laboratory parameters also show a significant decrease in fibrinogen, von Willebrand factor (vWF), Factor VIII, and erythrocyte sedimentation rate in the TPE treatment group. No significant differences were seen in levels of fibrin monomer, total IgG, total IgM, total protein, or total albumin between the two groups. Data collection and analysis for clinical parameters are ongoing. Conclusions and Relevance Here we report preliminary results suggesting that TPE is safe and effective for normalizing plasma viscosity in critically ill COVID-19 patients. Concomitant removal of large plasma proteins (fibrinogen, vWF) hints at their role in driving the increased viscosity associated with severe disease, which may contribute to clotting and end-organ damage in COVID-19. Based on lack of change in total IgG/IgM levels, TPE is not anticipated to hinder the patient’s humoral immunity by removing existing anti-SARS-CoV-2 specific antibodies. These results warrant further studies on the utility of TPE to mitigate critical illness in COVID-19 patients.

Background Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID‐19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID‐19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID‐19‐associated hyperviscosity. Study Design and Methods Six critically ill COVID‐19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4‐1.8 cP) underwent daily TPE for 2‐3 treatments. Results TPE decreased plasma viscosity in all six patients (Pre‐TPE median 3.75 cP, range 2.6‐4.2 cP; Post‐TPE median 1.6 cP, range 1.5‐1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre‐TPE median 739 mg/dL, range 601‐1188 mg/dL; Post‐TPE median 359 mg/dL, range 235‐461 mg/dL); D‐dimer levels in all six patients (Pre‐TPE median 5921 ng/mL, range 1134‐60 000 ng/mL; Post‐TPE median 4893 ng/mL, range 620‐7518 ng/mL); and CRP levels in five of six patients (Pre‐TPE median 292 mg/L, range 136‐329 mg/L; Post‐TPE median 84 mg/L, range 31‐211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. Conclusions This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID‐19‐associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID‐19.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

As advances in Critical Care Medicine continue, critically ill patients are surviving despite the severity of their illness. The incidence of acute kidney injury (AKI) has increased, and its impact on clinical outcomes as well as medical expenditures has been established. The role, indications and technological advancements of renal replacement therapy (RRT) have evolved, allowing more effective therapies with less complications. With these changes, Critical Care Nephrology has become an established specialty, and ongoing collaborations between critical care physicians and nephrologist have improved education of multi-disciplinary team members and patient care in the ICU. Multidisciplinary programs to support these changes have been stablished in some hospitals to maximize the delivery of care, while other programs have continue to struggle in their ability to acquire the necessary resources to maximize outcomes, educate their staff, and develop quality initiatives to evaluate and drive improvements. Clearly, the role of the nephrologist in the ICU has evolved, and varies widely among institutions. This special article will provide insights that will hopefully optimize the role of the nephrologist as the leader of the acute care nephrology program, as clinician for critically ill patients, and as teacher for all members of the health care team.

For most American Society of Nephrology (ASN) Kidney Week attendees, case-based clinical nephrology talks are one of the most exciting venues. The Nephrology Quiz and Questionnaire (NQ&Q) is the essence of clinical nephrology and represents what drew all of us into the field of nephrology. This year

INTRODUCTION: Amongst COVID19 patients in the intensive care unit (ICU), acute kidney injury (AKI) occurs in 40-60% with 10-30% requiring renal replacement therapy (RRT) During any ICU surge situation, an increase in the total number of patients that will require RRT should be expected as the number of ICU patients increases This surge in RRT needs can quickly exhaust RRT machine availability During the pandemic, hospitals developed RRT surge contingency plans to maximize the number of patients who can receive RRT on a given day This may involve mixing modalities of therapy to include using CRRT machines to provide prolonged intermittent RRT (PIRRT) in a shift-based model However, implementing a machine allocation system to deploy RRT machines in the most efficient manner is a vexing challenge Automated strategies for machine allocation could aid staff in quickly developing daily RRT operational plans METHODS: Efficient routing of CRRT machines is analogous to an optimization routing problem, traditionally formulated with multiple vehicles picking up varying loads at each stop We reformulate the problem with CRRT machines as vehicles and patient needs as varying loads, with a maximum load of 24 patient-hours per day per machine, including transition time between patients RESULTS: Our solution, designed to be run daily, was written in Python 3 6 In conjunction with the primary team, nephrologists determine RRT durations based on patient need (6-12 hours vs 24 hours), generating a list of needs in the upcoming 24h period on a shared server If there is more RRT demand than capacity, nephrologists will be asked to reallocate required hours Next, we process CRRT machine locations with patient needs and locations The distance matrix preferentially routes machines between patients within units, then between closeby units, with preference given towards patients and units of similar COVID status to support cohorting The system then generates a sequence of patients that each machine should serve within minutes CONCLUSIONS: We report this as the first known implementation of automated scheduling for optimizing CRRT machine utilization given scarcity constraints from COVIDrelated surges Further characterization is necessary to quantify workload benefit and machine utilization

Background and objectives Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β -lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT. Design, setting, participants, & measurements We conducted an institutional review board–approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one– and two–compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μ g/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate. Results Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion. Conclusions Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.

The substantial burden of acute kidney injury and end-stage kidney disease among patients with critical illness highlights the importance and need for a specialized nephrologist in the intensive care unit. The last decade has seen a growing interest in a career focused on critical care nephrology. However, the scope of practice and job satisfaction of those who completed dual training in nephrology and critical care are largely unknown. This article discusses the current practice landscape of critical care nephrology and describes the educational tracks available to pursue this pathway and considerations to enhance the future of this field.

The use of extracorporeal membrane oxygenation (ECMO) is increasing rapidly. Patients on ECMO have a high risk of developing acute kidney injury (AKI) and needing renal replacement therapy (RRT). The aim of this review is to describe different strategies of combining RRT and ECMO and to outline their advantages and drawbacks.Fluid overload is the most common indication for RRT during ECMO, and continuous renal replacement therapy (CRRT) is the most commonly used modality. The optimal timing for initiation of CRRT should be individualized based on degree of fluid overload and severity of AKI-related metabolic derangements. In ECMO patients, CRRT can be provided via an integrated approach (i.e. in-line haemofilter or a fully integrated CRRT device) or a parallel system with separate ECMO and RRT circuits. In-depth knowledge of the resulting intra-circuit pressure changes, risks of air entrapment and haemolysis, and implications for ultrafiltration and solute clearance are essential. There is no evidence that the different methods of combining ECMO and CRRT impact mortality.In patients on ECMO, CRRT can be provided via an integrated approach or independently via parallel systems. An in-depth understanding of the advantages and drawbacks of the different techniques is required.

Continuous renal replacement therapy (CRRT) is a standard of care for critically ill patients according to the guidelines for Kidney Disease Improving Global Outcomes Clinical Practice. Within the CRRT dialysis instrument, blood requires anticoagulation with citrate with a goal to have ionized calcium (iCa) Method Twelve patient samples were drawn in triplicate and compared in the three different analyzers: RAPIDPoint, Nova Biomedical, and GEM4000 analyzers. One of the analyzers uses whole blood while the other two measure iCa in plasma. In one of the facilities, samples were spun, decapped, sent to the automated line outlet, and tested after having been exposed to air, and thus an experiment in another facility decapped the specimens for an hour and retested. Results Postfilter iCa measurements ranged from 0.18 to 0.64 mmol/L; however, range was different for each of the instruments: The Nova measurements averaged 0.55 mmol/L (range 0.42-0.64), the Rapid Point 0.36 (0.28-0.45), and the GEM 0.30 (0.18-0.39). The average difference between results of the Nova and GEM was 0.25 mmol/L, between Nova and RAPIDPoint 0.19 mmol/L, and GEM and RAPIDPoint 0.06 mmol/L. The differences between the values measured 1 hour after the sample had been decapped were negligible. Conclusion This study demonstrates inconsistency among instruments when measuring iCa in CRRT blood samples. The Nova analyzer tends to give higher results while the Rapid Point and GEM are lower and with values closer together. Currently, there is no reference material or reference method established for low iCa in CRRT samples. This study helped our clinicians understand the differences that occur between the different analyzers for low levels of iCa in CRRT blood samples.

Objective It was hypothesized that preoperative hyponatremia is associated with increased 30-day mortality after left ventricular assist device placement, and that large increases in sodium concentration are associated with adverse neurologic events and 30-day mortality. Design Data were collected retrospectively on all patients having continuous flow left ventricular assist device implantation between January 1, 2009 and March 31, 2013. Preoperative variables, operative variables, and perioperative sodium concentrations were recorded. Both 30-day mortality and 72-hour adverse neurologic events (stroke or seizure) were recorded as primary outcome variables. Preoperative sodium and Δ sodium (postoperative sodium-preoperative sodium) were analyzed as tests for 30-day mortality and adverse neurologic events using receiver operating characteristic curves. Both crude and adjusted logistic regression analyses were used to estimate odds ratios for the outcome variables. Setting Tertiary care academic medical center. Participants Patients having durable continuous flow left ventricular assist device placement. Interventions None. Measurements and Main Results Among 88 patients, 30-day mortality was 14% (12 of 88) and the rate of perioperative stroke or seizure was 9% (8 of 88). There were 3 strokes and 5 tonic-clonic seizures. Preoperative sodium was a poor discriminative test for 30-day mortality and stroke or seizure (AUC = 0.47 and 0.57, respectively). Δ sodium was a poor discriminative test for 30-day mortality, but a fair discriminative test for stroke or seizure (AUC = 0.55 and 0.78, respectively). Δ sodium was a good discriminative test for seizure alone (AUC = 0.82) and a fair discriminative test for stroke alone (AUC = 0.70). It also increased the odds of stroke or seizure significantly, even when adjusting for possible confounders. Conclusions Moderate-to-large increases in sodium concentration during left ventricular assist device placement appear to be associated with adverse postoperative neurologic events. Preoperative hyponatremia has no relationship with 30-day mortality or adverse perioperative neurologic events.

Continuous renal replacement therapy (CRRT) use continues to expand globally. Despite improving technology, CRRT remains a complex intervention. Delivery of high-quality CRRT requires close collaboration of a multidisciplinary team including members of the critical care medicine, nephrology, nursing, pharmacy, and nutrition support teams. While significant gaps in medical evidence regarding CRRT persist, the growing evidence base supports evolving best practice and consensus to define high-quality CRRT. Unfortunately, there is wide variability in CRRT operating characteristics and limited uptake of these best practices. This article will briefly review the current best practice on important aspects of CRRT delivery including CRRT dose, anticoagulation, dialysis vascular access, fluid management, and drug dosing in CRRT.

Extracorporeal membrane oxygenation (ECMO) is an established therapy in the management of patients with refractory cardiogenic shock or acute respiratory failure. In this report, we describe the rapid development and implementation of an organized ECMO program at a facility that previously provided ad hoc support. The program provides care for patients within the Emory Healthcare system and throughout the Southeastern United States. From September 2014 to February 2015, 16 patients were treated with either venovenous or venoarterial ECMO with a survival to decannulation of 53.3% and survival to intensive care unit discharge of 40%. Of the 16 patients, 10 were transfers from outside facilities of which 2 were remotely cannulated and initiated on ECMO support by our ECMO transport team. Complications included intracerebral hemorrhage, bleeding from other sites, and limb ischemia. The results suggest that a rapidly developed ECMO program can provide safe transport services and provide outcomes similar to those in the existing literature. Key components appear to be an institutional commitment, a physician champion, multidisciplinary leadership, and organized training. Further study is required to determine whether outcomes will continue to improve.

Summary Background and objectives Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions. Design,setting,participants,&measurementsAmulticenterprospectiveobservationalstudyintheintensivecare units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters. ResultsForty-twoof fifty-fivesubjectsenrolledhad complete sampling.Volumeofdistribution (median=0.38 L/kg, intraquartile range=0.20 L/kg)andeliminationrateconstants (median=0.104h 21 ,intraquartile range=0.052h 21 ) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokineticparameters.Probabilityoftargetattainmentforpiperacillinwas83%fortotaldrugbutonly77% when the unbound fraction was considered. ConclusionsThere is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy. Clin J Am Soc Nephrol 7: 452–457, 2012. doi: 10.2215/CJN.10741011

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome are increasingly recognized in both medical and surgical critically ill patients and are predictive of death and the development of acute kidney injury. Although there are many risk factors for the development of IAH, in the era of goal-directed therapy for shock, brisk volume resuscitation and volume overload are the most common contributors. Abdominal examination is an unreliable predictor of intra-abdominal pressure (IAP), but IAP can be easily measured in a reproducible and reliable manner by a number of simple bedside techniques. Prompt recognition and intervention to decrease IAP and improve vital organ perfusion are essential to minimize the negative effects of IAH on somatic and visceral organ functions.

Introduction: Advances in information technology offer new avenues for assembling data about diet and care regimens of diabetes patients “in the field.” This creates a challenge for their doctors and the diabetes care community—how to organize and use new data to produce better long-term outcomes for diabetes patients. Methods: iAbetics approaches the challenge as a quality management problem, drawing on total quality concepts, which in turn are grounded in application of the scientific method. We frame the diabetes patient's quality-of-care problem as an ongoing scientific investigation aimed at quantifying and predicting relationships between specific care-management actions and their outcomes for individual patients in their ordinary course of life. Results: Framing diabetes quality-of-care management as a scientific investigation leads to a seven-step model termed “adaptive empirical iteration.” Adaptive empirical iteration is a deliberate process to perfect the patient's choices, decisions, and actions in routine situations that make up most day-to-day life and to systematically adapt across differences in individual patients and/or changes in their physiology, diet, or environment. The architecture incorporates care-protocol management and version control, structured formats for data collection using mobile smart phones, statistical analysis on secure Web sites, tools for comparing alternative protocols, choice architecture technology to improve patient decisions, and information sharing for doctor review. Conclusions: Adaptive empirical iteration is a foundation for information architecture designed to systematically improve quality-of-care provided to diabetes patients who act as their own day-to-day care provider under supervision and with support from their doctor. The approach defines “must-have” capabilities for systems using new information technology to improve long-term outcomes for diabetes patients.

The Sierra Nevada Mountain range serves as an important source of drinking water for the State of California. However, summer cattle grazing on federal lands affects the overall water quality yield from this essential watershed as cattle manure is washed into the lakes and streams or directly deposited into these bodies of water. This organic pollution introduces harmful microorganisms and also provides nutrients such as nitrogen and phosphorus which increase algae growth causing eutrophication of otherwise naturally oligotrophic mountain lakes and streams. Disinfection and filtration of this water by municipal water districts after it flows downstream will become increasingly costly. This will be compounded by increasing surface water temperatures and the potential for toxins release by cyanobacteria blooms. With increasing demands for clean water for a state population approaching 40 million, steps need to be implemented to mitigate the impact of cattle on the Sierra Nevada watershed. Compared to lower elevations, high elevation grazing has the greatest impact on the watershed because of fragile unforgiving ecosystems. The societal costs from non-point pollution exceed the benefit achieved through grazing of relatively few cattle at the higher elevations. We propose limiting summer cattle grazing on public lands to lower elevations, with a final goal of allowing summer grazing on public lands only below 1,500 m elevation in the Central and Northern Sierra and 2,000 m elevation in the Southern Sierra.

In an attempt to resolve conflicting evidence from the literature concerning the existence of a paternal age effect in 46,X,i(Xq) Turner's syndrome, we have analysed data on all known cases ascertained in the main population centres of Scotland and on others ascertained in England, using population controls matched for year of birth. There was a significant (P = 0.02) increase of 2.3 years in the mean paternal age of the Scottish cases, and a smaller and non-significant increase in their mean maternal age. Logistic regression analysis confirmed that the primary association was with paternal, rather than maternal, age. For the English cases, however, there were small and non-significant decreases in their mean maternal and paternal ages. The differences between the two groups were also significant, but cannot be explained by any likely source of ascertainment bias. We therefore conclude that there is no evidence for a universal paternal age effect in this condition, but that at least one mechanism of origin, occurring with variable frequency, may be associated with increased paternal age. Using data from this and earlier published studies, we estimate the incidence of individuals with a 46,X,i(Xq) cell line to be between 3.3 and 13 per 10(5) female livebirths.

Ebola virus disease (EVD) is a severe illness primarily characterized by fever, fatigue, diarrhea, and vomiting. It was first identified in 1976 with several small, limited outbreaks occurring between 1976 and 2012 (1, 2). Since December 2013, a complex and wide-ranging outbreak of EVD centered in West Africa has primarily affected Guinea, Liberia, and Sierra Leone. As of March 11, 2015, the current outbreak has resulted in approximately 24,282 confirmed and suspected cases with 9,976 deaths globally (3). For the first time in history, there has been both local and distant spread of EVD in West Africa—to neighboring nations (including Mali, Nigeria, and Senegal)—and to resource-rich nations in Europe and North America through multiple mechanisms, including repatriation of infected healthcare workers (HCW), index cases traveling to resource-rich nations, and local spread through contacts with infected HCW (4). Limited laboratory and other resources in the affected West African nations have hampered a more detailed understanding of the clinical phenotypes of EVD. Several recently published case series demonstrate that there is a wide spectrum of severity of illness in EVD ranging from mild-to-moderate symptoms largely confined to the gastrointestinal system (copious watery diarrhea, vomiting, abdominal pain, and acute hepatitis) to the development of organ failure and death (5–7). Reported mortality rates in West Africa during the current outbreak have ranged from 40% to 70%, which is notably improved from previous outbreaks where mortality rates approached 90% (3, 8). With the arrival of EVD to resource-rich nations, a more detailed description of the natural history of both mild and severe EVD is beginning to emerge with several patients in the United States and Europe developing critical illness requiring advanced life support with mechanical ventilation and renal replacement therapy (RRT) (9–12). As in previous outbreaks, both severity of illness and mortality risk appear to be associated with both viral load at presentation and peak viral load (5, 13). Here, we report the spectrum of critical illness, organ failure, laboratory data, and interventions on three patients with severe EVD in the United States.

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori-negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsC1. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.

Based on preliminary reports, the use of chromoendoscopy and magnification endoscopy appears to be a valuable adjunct to standard endoscopy for the detection and classification of metaplastic and dysplastic lesions of the esophagus. Ideally, the use of this technique would enable the endoscopist to rule in or out the presence of intestinal metaplasia and dysplastic/cancerous epithelium by obtaining only a minimal number of targeted biopsy specimens--or potentially taking no biopsies at all, which could transform upper endoscopy into a much more effective screening and surveillance tool. There are several problems with the use of chromoendoscopy and magnification endoscopy in the esophagus. This technique is operator-dependent (ie, dependent on the skill and experience of the endoscopist). Studies reporting the accuracy of chromoendoscopy remain mixed, especially for Barrett's esophagus and dysplasia, which is likely explained by differences in techniques and materials used in the investigations. Staining within the esophagus is often patchy and uneven. Poor spraying technique can exaggerate irregular uptake by the mucosa. There is a high false-positive rate when staining gastric-type epithelium or in the setting of inflammation. Areas of dysplasia or cancer might take up stain in an irregular manner or might not stain at all. Magnification only allows the endoscopist to observe small areas of mucosa at a time, increasing the overall difficulty of the procedure and procedure length. Currently, the greatest body of literature exists concerning the use of Lugol's solution for the diagnosis of squamous cell dysplasia/carcinoma of the esophagus and methylene blue for diagnosing Barrett's esophagus. If used consistently by practicing physicians, the accuracy of biopsies could be improved. If endoscopic ablative therapy for high-grade dysplasia and early carcinoma (eg, photodynamic therapy and endoscopic mucosal resection) becomes accepted, sensitive methods of detecting residual metaplastic or dysplastic epithelium after ablation will be needed to help guide additional endoscopic therapy. Chromoendoscopy and magnification endoscopy could prove helpful in this setting. Further research in this field needs to be performed. As a first step, a uniform classification system for staining and magnification patterns should be devised. Future studies could then be performed using consistent terminologies. More controlled investigations with larger numbers of patients must be performed before tissue staining and magnification endoscopy become a part of day-to-day endoscopic practice. Lugol's chromoendoscopy is a simple technique for the detection of synchronous squamous dysplasia and cancer, but a substantial amount of work remains to be performed for the validation of chromoendoscopy for the detection of Barrett's esophagus and dysplasia. The ultimate aim of chromoendoscopy and magnification endoscopy in the esophagus is to show improved outcomes (ie, early detection of cancer and improved survival). These goals have not yet been realized and will require welldesigned studies in the future.

Continuous renal replacement therapy (CRRT) is commonly used to provide renal replacement therapy in the intensive care unit. Limited published data suggest that CRRT may lead to depletion of water-soluble vitamins and trace elements. The goal of this study was to identify the incidence of trace element and vitamin deficiencies in critically ill patients during CRRT.This study is based on a retrospective chart review of patients who were referred to Emory University Hospital's nutrition support services and had at least 1 serum micronutrient level measured during CRRT (thiamin, pyridoxine, ascorbic acid, folate, zinc, and copper) between April 1, 2009, and June 1, 2012.Seventy-five patients were included in the study. Nine of 56 patients (16%) had below-normal whole blood thiamin concentrations, and 38 of 57 patients (67%) had below-normal serum pyridoxine levels. Serum ascorbic acid and folate deficiencies were identified among 87% (13 of 15) and 33% (3 of 9) of the study patients, respectively. Nine of 24 patients had zinc deficiency (38%), and 41 of 68 patients had copper deficiency (60%). Of the 75 total subjects, 60 patients (80%) had below-normal levels of at least 1 of the micronutrients measured.The incidence of various micronutrient deficiencies in critically ill patients who required CRRT was higher than previously reported. Prospective studies are needed to determine the impact of CRRT on micronutrient status and the potential clinical and metabolic efficacy of supplementation in the intensive care unit setting.