Citations

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators.

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

ABSTRACT Few pooled analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction. Such information would be useful to assess new ARs or novel dosing regimens. In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, we analyzed individual-level data from 28,000 participants enrolled in 11 bisphosphonate (BP) and three selective estrogen receptor modulator (SERM) placebo-controlled fracture endpoint trials. Using BTM results for two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and pro-collagen I N-propeptide [PINP]) and two bone resorption markers (N-terminal and C-terminal telopeptide of type I collagen) and incident fracture outcome data, we performed a meta-regression relating the mean net effect of treatment on change in bone turnover (active minus placebo % difference after 3 to 12 months) to the log of study-wide fracture risk reduction, and used linear regression to plot the best fitting line. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 4 years of follow-up. Change in bone ALP and PINP were available for over 16,000 and 10,000 participants, respectively. For vertebral fracture, the results showed a strong relationship between treatment-related bone ALP or PINP changes and vertebral fracture risk reduction (r2 = 0.82 [p < 0.001] and r2 = 0.75 [p = 0.011], respectively) Relationships were weaker and no longer statistically significant for nonvertebral (r2 = 0.33 [p = 0.053] and r2 = 0.53 [p = 0.065], respectively) and hip fracture (r2 = 0.17 [p = 0.24] and r2 = 0.43 [p = 0.11], respectively) outcomes. Analyses limited to BP trials gave similar results. For all fracture types, relationships were weaker and nonsignificant for bone resorption markers. We conclude that short-term AR treatment-related changes in bone ALP and PINP strongly predict vertebral fracture treatment efficacy, but not nonvertebral or hip fracture treatment efficacy. Change in bone formation markers might be useful to predict the anti-vertebral fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs. © 2017 American Society for Bone and Mineral Research.

ABSTRACTIntroduction: Recessive mutations in the anoctamin‐5 gene (ANO5) cause a spectrum of clinical phenotypes, including limb‐girdle muscular dystrophy (LGMD 2L), distal myopathy, and asymptomatic hyperCKemia. Methods: In this report we describe our clinical, electrophysiological, pathological, and molecular findings in a subject with anoctaminopathy‐5. Results: A 49‐year‐old Arabic man from a consanguineous family presented with a 5‐year history of myalgias, hyperCKemia and an episode of unprovoked rhabdomyolysis. Muscle biopsy showed mild myopathic changes and interstitial amyloid deposition. ANO5 analysis detected a novel homozygous deletion of approximately 11.9 kb encompassing exons 13–17, predicted to be pathogenic. Conclusions: Anoctaminopathy‐5 can manifest with a phenotype reminiscent of metabolic myopathy and should be considered as a potential cause of myalgia and myoglobinuria. Amyloid deposition in the muscle biopsy is helpful for the diagnosis. A novel homozygous ANO5 deletion was identified, suggesting that screening for common mutations may have low yield in non‐European subjects. Muscle Nerve 50: 610–613, 2014

Epithelial–mesenchymal transition (EMT) is a form of epithelial plasticity implicated in fibrosis and tumor metastasis. Here we show that the mechanical rigidity of the microenvironment plays a pivotal role in the promotion of EMT by controlling the subcellular localization and downstream signaling of Rac GTPases. Soft substrata, with compliances comparable to that of normal mammary tissue, are protective against EMT, whereas stiffer substrata, with compliances characteristic of breast tumors, promote EMT. Rac1b, a highly activated splice variant of Rac1 found in tumors, localizes to the plasma membrane in cells cultured on stiff substrata or in collagen-rich regions of human breast tumors. At the membrane, Rac1b forms a complex with NADPH oxidase and promotes the production of reactive oxygen species, expression of Snail, and activation of the EMT program. In contrast, soft microenvironments inhibit the membrane localization of Rac1b and subsequent redox changes. These results reveal a novel mechanotransduction pathway in the regulation of epithelial plasticity via EMT.

BackgroundThe cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)‐42, total‐tau (T‐tau), and phosphorylated‐tau (P‐tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch‐to‐batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.MethodsThe program is open for laboratories using commercially available kits for Aβ, T‐tau, or P‐tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples.ResultsForty laboratories participated. Twenty‐six used INNOTEST enzyme‐linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO‐BIA AlzBio3 kit (both measure Aβ‐(1‐42), P‐tau(181P), and T‐tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN‐42, AβN‐40, and AβN‐38) or T‐tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within‐laboratory precisions differed considerably between biomarkers within individual laboratories.ConclusionsMeasurements of CSF AD biomarkers show large between‐laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.