D-dimer to Rule Out Pulmonary Embolism in Renal Insufficiency

BACKGROUND D-dimer levels are often elevated in renal insufficiency. The diagnostic accuracy of D-dimer to rule out pulmonary embolism in patients with renal insufficiency is unclear. METHODS We evaluated the data of patients presenting to our Emergency Department and receiving computed tomography angiography to rule out pulmonary embolism with measurement of D-dimer and creatinine. Glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. RESULTS There were 1305 patients included; 1067 (82%) had an estimated glomerular filtration rate (eGFR) exceeding 60 mL/min, 209 (16%) 30-60 mL/min, and 29 (2%) <30 mL/min. One hundred fifty-two patients (12%) had D-dimer below 500 μg/L. eGFR (R = -0.1122) correlated significantly with D-dimer (P <.0001). One hundred sixty-nine patients (13%) were found to have pulmonary embolism. Sensitivity of D-dimer for patients with an eGFR >60 mL/min was 96% (confidence interval [CI], 0.93-0.99) and 100% (CI, 100-100) for those with 30-60 mL/min, while specificity decreased significantly with impaired renal function. Area under the curve of the receiver operating characteristic for D-dimer was 0.734 in patients with an eGFR of >60 mL/min, and 0.673 for 30-60 mL/min. CONCLUSIONS D-dimer levels were elevated in patients with an eGFR <60 mL/min, but proved to be highly sensitive for the exclusion of pulmonary embolism. However, because almost all patients with impaired renal function had elevated D-dimer irrespective of the presence of pulmonary embolism, studies should be performed to determine renal function-adjusted D-dimer cutoffs.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

Interfaces, strings, and a soft mode in the square lattice quantum dimer model

The quantum dimer model on the square lattice is a U(1) gauge theory that addresses aspects of the physics of high-Tc superconductors. Using a quantum Monte Carlo method, we show that the theory exists in a confining columnar valence bond solid phase. The interfaces separating distinct columnar phases display plaquette order, which, however, is not realized as a bulk phase. Static “electric” charges are confined by flux tubes that consist of multiple strands, each carrying a fractionalized flux ¼. A soft pseudo-Goldstone mode (which becomes exactly massless at the Rokhsar-Kivelson point) extends deep into the columnar phase, with potential implications for high-Tc physics.

Clinical decision rules and D-Dimer in venous thromboembolism: current controversies and future research priorities

Venous thromboembolism (VTE) is a potentially lethal clinical condition that is suspected in patients with common clinical complaints, in many and varied, clinical care settings. Once VTE is diagnosed, optimal therapeutic management (thrombolysis, IVC filters, type and duration of anticoagulants) and ideal therapeutic management settings (outpatient, critical care) are also controversial. Clinical prediction tools, including clinical decision rules and D-Dimer, have been developed, and some validated, to assist clinical decision making along the diagnostic and therapeutic management paths for VTE. Despite these developments, practice variation is high and there remain many controversies in the use of the clinical prediction tools. In this narrative review, we highlight challenges and controversies in VTE diagnostic and therapeutic management with a focus on clinical decision rules and D-Dimer.

Excitonic Splitting, Delocalization, and Vibronic Quenching in the Benzonitrile Dimer

The excitonic S1/S2 state splitting and the localization/delocalization of the S1 and S2 electronic states are investigated in the benzonitrile dimer (BN)2 and its 13C and d5 isotopomers by mass-resolved two-color resonant two-photon ionization spectroscopy in a supersonic jet, complemented by calculations. The doubly hydrogen-bonded (BN-h5)2 and (BN-d5)2 dimers are C2h symmetric with equivalent BN moieties. Only the S0 → S2 electronic origin is observed, while the S0 → S1 excitonic component is electric-dipole forbidden. A single 12C/13C or 5-fold h5/d5 isotopic substitution reduce the dimer symmetry to Cs, so that the heteroisotopic dimers (BN)2-(h5 – h513C), (BN)2-(h5 – d5), and (BN)2-(h5 – h513C) exhibit both S0 → S1 and S0 → S2 origins. Isotope-dependent contributions Δiso to the excitonic splittings arise from the changes of the BN monomer zero-point vibrational energies; these range from Δiso(12C/13C) = 3.3 cm–1 to Δiso(h5/d5) = 155.6 cm–1. The analysis of the experimental S1/S2 splittings of six different isotopomeric dimers yields the S1/S2 exciton splitting Δexc = 2.1 ± 0.1 cm–1. Since Δiso(h5/d5) ≫ Δexc and Δiso(12C/13C) > Δexc, complete and near-complete exciton localization occurs upon 12C/13C and h5/d5 substitutions, respectively, as diagnosed by the relative S0 → S1 and S0 → S2 origin band intensities. The S1/S2 electronic energy gap of (BN)2 calculated by the spin-component scaled approximate second-order coupled-cluster (SCS-CC2) method is Δelcalc = 10 cm–1. This electronic splitting is reduced by the vibronic quenching factor Γ. The vibronically quenched exciton splitting Δelcalc·Γ = Δvibroncalc = 2.13 cm–1 is in excellent agreement with the observed splitting Δexc = 2.1 cm–1. The excitonic splittings can be converted to semiclassical exciton hopping times; the shortest hopping time is 8 ps for the homodimer (BN-h5)2, the longest is 600 ps for the (BN)2(h5 – d5) heterodimer.

Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

Sodium-proton antiporters rapidly exchange protons and sodium ions across the membrane to regulate intracellular pH, cell volume, and sodium concentration. How ion binding and release is coupled to the conformational changes associated with transport is not clear. Here, we report a crystal form of the prototypical sodium-proton antiporter NhaA from Escherichia coli in which the protein is seen as a dimer. In this new structure, we observe a salt bridge between an essential aspartic acid (Asp163) and a conserved lysine (Lys300). An equivalent salt bridge is present in the homologous transporter NapA, but not in the only other known crystal structure of NhaA, which provides the foundation of most existing structural models of electrogenic sodium-proton antiport. Molecular dynamics simulations show that the stability of the salt bridge is weakened by sodium ions binding to Asp164 and the neighboring Asp163. This suggests that the transport mechanism involves Asp163 switching between forming a salt bridge with Lys300 and interacting with the sodium ion. pKa calculations suggest that Asp163 is highly unlikely to be protonated when involved in the salt bridge. As it has been previously suggested that Asp163 is one of the two residues through which proton transport occurs, these results have clear implications to the current mechanistic models of sodium-proton antiport in NhaA.