Outcomes Following In-Hospital Cardiopulmonary Resuscitation in People Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis. STUDY DESIGN: Retrospective chart review. SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014. EXPOSURE: Initial in-hospital CPR. OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same hospitalization among initial survivors, predictors of discharge-to-home status. ANALYTICAL APPROACH: We provide descriptive statistics for the study variables and used t tests, χ2 tests, or Fisher exact tests to compare differences between the groups. We built multivariable logistic regression models to examine the CPR-related outcomes. RESULTS: A total of 184 patients received in-hospital CPR: 51 (28%) did not survive the initial CPR event, and 77 CPR survivors died (additional 42%) later during the same hospitalization (overall mortality 70%). Only 18 (10%) were discharged home, with the remaining 32 (17%) discharged to a rehabilitation facility or a nursing home. In the multivariable model, the only predictor of unsuccessful CPR was CPR duration (OR, 1.41; 95% CI, 1.24-1.61; P < 0.001). Predictors of death during the same hospitalization after surviving the initial CPR event were CPR duration (OR, 1.15; 95% CI 1.04-1.27; P = 0.007) and older age (OR, 1.64; 95% CI, 1.23-2.2; P < 0.001). Older people also had lower odds of discharge-to-home status (OR, 0.25; 95% CI, 0.11-0.54; P < 0.001). LIMITATIONS: Retrospective study design, single-center study, no information on functional status. CONCLUSIONS: Patients receiving maintenance dialysis experience high mortality following in-hospital CPR and only 10% are discharged home. These data may help clinicians provide useful prognostic information while engaging in goals of care conversations.

Long-Term Patency of Arteriovenous Fistulae Salvaged by Balloon Angioplasty with and without Accessory Vein Embolization: A Retrospective Study.

PURPOSE: To investigate whether accessory vein embolization (AVE) improves long-term performance of salvaged nonmaturing arteriovenous fistulae (AVFs). MATERIALS AND METHODS: This retrospective review included 72 patients who underwent percutaneous balloon angioplasty for salvage of nonmaturing AVFs between 2008 and 2014. AVE was performed on 32 patients between 2008 and 2011 (mean age, 59 y [range, 33-85 y]; men, n = 21; women, n = 11; upper arm, n = 17; forearm, n = 15), whereas the procedure was not performed on 40 patients after 2011 (mean age, 62 y [range, 28-85 y]; men, n = 26; women, n = 14; upper arm, n = 26; forearm, n = 14). Endpoints compared between groups included number of procedures required to achieve maturation, time to maturation, number of procedures required to maintain patency, and duration of primary and secondary patency after intervention. RESULTS: There was no statistically significant difference in number of procedures to achieve maturation (2.1 ± 1.4 vs 2.4 ± 1.2; P = .24) or time to maturation (26.1 d ± 56.2 vs 41.1 d ± 54.6; P = .072) between AVE and no embolization groups. Primary (P = .21) and secondary patency (P = .14) after intervention were not significantly different between groups. The number of procedures performed to maintain patency after maturation was significantly greater in the AVE group for patients with forearm AVFs (0.11 ± 0.098 vs 0.04 ± 0.064 per patient year; P = .039) but not for patients with upper arm AVFs. CONCLUSIONS: AVE of AVFs after balloon angioplasty does not lead to significantly improved long-term outcomes. Percutaneous salvage of nonmaturing AVFs in the forearm without AVE resulted in a decreased number of interventions to maintain patency.

Diamonds in the rough: a strong case for the inclusion of weak-intensity X-ray diffraction data.

Overwhelming evidence exists to show that the inclusion of weak-intensity, high-resolution X-ray diffraction data helps improve the refinement of atomic models by imposing strong constraints on individual and overall temperature B factors and thus the quality of crystal structures. Some researchers consider these data to be of little value and opt to discard them during data processing, particularly at medium and low resolution, at which individual B factors of atomic models cannot be refined. Here, new evidence is provided to show that the inclusion of these data helps to improve the quality of experimental phases by imposing proper constraints on electron-density models during noncrystallographic symmetry (NCS) averaging. Using electron-density correlation coefficients as criteria, the resolution of data has successfully been extended from 3.1 to 2.5 Å resolution with redundancy-independent merging R factors from below 100% to about 310%. It is further demonstrated that phase information can be fully extracted from observed amplitudes through de novo NCS averaging. Averaging starts with uniform density inside double-shelled spherical masks and NCS matrices that are derived from bound heavy-atom clusters at the vertices of cuboctahedrally symmetric protein particles.

Assisted maturation of native fistula in two patients with a continuous flow left ventricular assist device.

Patients who receive a left ventricular assist device (LVAD) are prone to develop end-stage renal disease. Primary arteriovenous fistula (AVF) maturation in these patients may be unsuccessful secondary to the nonpulsatile flow with an LVAD. Two patients with LVADs are described in whom assisted maturation aided long-term AVF patency.

The hexameric helicase DnaB adopts a nonplanar conformation during translocation.

DNA polymerases can only synthesize nascent DNA from single-stranded DNA (ssDNA) templates. In bacteria, the unwinding of parental duplex DNA is carried out by the replicative DNA helicase (DnaB) that couples NTP hydrolysis to 5' to 3' translocation. The crystal structure of the DnaB hexamer in complex with GDP-AlF(4) and ssDNA reported here reveals that DnaB adopts a closed spiral staircase quaternary structure around an A-form ssDNA with each C-terminal domain coordinating two nucleotides of ssDNA. The structure not only provides structural insights into the translocation mechanism of superfamily IV helicases but also suggests that members of this superfamily employ a translocation mechanism that is distinct from other helicase superfamilies. We propose a hand-over-hand mechanism in which sequential hydrolysis of NTP causes a sequential 5' to 3' movement of the subunits along the helical axis of the staircase, resulting in the unwinding of two nucleotides per subunit.

Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process.

Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis.

BACKGROUND: Optimal hydration measures to prevent contrast-induced nephropathy are controversial. STUDY DESIGN: We conducted a systematic review and meta-analysis using the MEDLINE database (1966 to January 2008), EMBASE (January 2008), and abstracts from conference proceedings. SETTING & POPULATION: Adult patients undergoing contrast procedures. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing intravenous hydration with sodium bicarbonate with hydration with intravenous normal saline for prevention of contrast-induced nephropathy. INTERVENTION: Hydration with intravenous sodium bicarbonate with or without N-acetylcysteine versus hydration with normal saline with or without N-acetylcysteine. OUTCOMES: Contrast-induced nephropathy, need for renal replacement therapy, and worsening of heart failure. RESULTS: Twelve trials (1,854 participants) were included. Sodium bicarbonate significantly decreased the risk of contrast-induced nephropathy (12 trials, 1,652 patients; odds ratio [OR], 0.46; 95% confidence interval [CI], 0.26 to 0.82; I2 = 55.9%) without a significant difference in need for renal replacement therapy (9 trials, 1,215 patients; OR, 0.50; 95% CI, 0.16 to 1.53; I2 = 0%), in-hospital mortality (11 trials, 1,640 patients; OR, 0.51; 95% CI, 0.15 to 1.69), or congestive heart failure compared with controls. Similar results were seen for the risk of contrast-induced nephropathy when sodium bicarbonate was compared with normal saline alone (OR, 0.39; 95% CI, 0.20 to 0.77), but not when sodium bicarbonate/N-acetylcysteine combination was compared with N-acetylcysteine/normal saline combination (OR, 0.68; 95% CI, 0.34 to 1.37). A subgroup analysis limited to published trials showed similar results (OR, 0.26; 95% CI, 0.10 to 0.64; I2 = 63.3%), whereas unpublished studies showed a nonsignificant decrease (OR, 0.85; 95% CI, 0.46 to 1.57; I2 = 25.9%) in risk of contrast-induced nephropathy. LIMITATION: Publication bias and heterogeneity. CONCLUSION: Hydration with sodium bicarbonate decreases the incidence of contrast-induced nephropathy in comparison to hydration with normal saline without a significant difference in need for renal replacement therapy and in-hospital mortality. Larger studies analyzing patient-centered outcomes are needed.

Insights into the replisome from the structure of a ternary complex of the DNA polymerase III alpha-subunit.

The crystal structure of the catalytic alpha-subunit of the DNA polymerase III (Pol IIIalpha) holoenzyme bound to primer-template DNA and an incoming deoxy-nucleoside 5'-triphosphate has been determined at 4.6-A resolution. The polymerase interacts with the sugar-phosphate backbone of the DNA across its minor groove, which is made possible by significant movements of the thumb, finger, and beta-binding domains relative to their orientations in the unliganded polymerase structure. Additionally, the DNA and incoming nucleotide are bound to the active site of Pol IIIalpha nearly identically as they are in their complex with DNA polymerase beta, thereby proving that the eubacterial replicating polymerase, but not the eukaryotic replicating polymerase, is homologous to DNA polymerase beta. Finally, superimposing a recent structure of the clamp bound to DNA on this Pol IIIalpha complex with DNA places a loop of the beta-binding domain into the appropriate clamp cleft and supports a mechanism of polymerase switching.

The structure of T. aquaticus DNA polymerase III is distinct from eukaryotic replicative DNA polymerases.

The crystal structure of Thermus aquaticus DNA polymerase III alpha subunit reveals that the structure of the catalytic domain of the eubacterial replicative polymerase is unrelated to that of the eukaryotic replicative polymerase but rather belongs to the Polbeta-like nucleotidyltransferase superfamily. A model of the polymerase complexed with both DNA and beta-sliding clamp interacting with a reoriented binding domain and internal beta binding site was constructed that is consistent with existing biochemical data. Within the crystal, two C-terminal domains are interacting through a surface that is larger than many dimer interfaces. Since replicative polymerases of eubacteria and eukaryotes/archaea are not homologous, the nature of the replicative polymerase in the last common ancestor is unknown. Although other possibilities have been proposed, the plausibility of a ribozyme DNA polymerase should be considered.

Microtubule-associated protein 2 (MAP2) associates with the NMDA receptor and is spatially redistributed within rat hippocampal neurons after oxygen-glucose deprivation.

MAP2 (microtubule-associated protein 2) is a cytoskeletal phosphoprotein that regulates the dynamic assembly characteristics of microtubules and appears to provide scaffolding for organelle distribution into the dendrites and for the localization of signal transduction apparatus in dendrites, particularly near spines. MAP2 is degraded after ischemia and other metabolic insults, but the time course and initial triggers of that breakdown are not fully understood. This study determined that MAP2 resides in a complex with the NMDA receptor, suggesting that spatially localized changes may be important in the mechanism of MAP2 redistribution and breakdown after oxygen-glucose deprivation (OGD). Using OGD in the adult rat hippocampal slice as a model system, this study demonstrated that MAP2 breakdown occurs very early after OGD, with the first statistical decrease in MAP2 levels within the first 30 min after the insult. There is a dramatic redistribution of MAP2 to the somata of pyramidal neurons, particularly neurons at the CA1-subiculum border. Free radicals and nitric oxide are not involved in the damage to MAP2. NMDA-receptor activation plays a prominent role in the MAP2 breakdown. In direct response to NMDA receptor activation, calcium influx, likely through the receptor ion channel complex, as well as release of calcium from the mitochondria through activation of the 2Na(+)-Ca(2+) exchanger of mitochondria, triggers MAP2 degradation. The proteolysis of MAP2 is limited by endogenous calpain activity, likely via the spatial access of calpain to MAP2.