Citations

When medically intractable epilepsy is multifocal or focal but poorly localized, neuromodulation can be useful therapy. One such technique is deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT). Unfortunately, the ANT is difficult to visualize in standard MRI sequences and its indirect targeting is difficult because of thalamic variability and atrophy in patients with epilepsy. The following study describes the novel use of the fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence to delineate the mammillothalamic tract for direct targeting of the ANT through visualizing the termination of the mammillothalamic tract in the ANT. The day prior to surgery in a 19-year-old, right-handed woman with a 5-year history of epilepsy, MRI was performed on a 3-T Siemens Prisma scanner (Siemens AG, Healthcare Sector) using a 64-channel head and neck coil. As part of the imaging protocol, noncontrast magnetization-prepared rapid gradient echo (MP-RAGE) and diffusion tensor imaging (DTI) sequences were obtained for targeting purposes. The ANT was directly targeted using the FGATIR sequence, and bilateral Medtronic 3389 leads were placed. At the last follow-up (2 months), the patient reported an approximate 75% decrease in seizure frequency, as well as a decrease in seizure severity.

Cardiac hemodynamic assessment during cardiopulmonary exercise testing (CPET) is proposed to play an important role in the clinical evaluation of individuals with cystic fibrosis (CF). Cardiac catheterization is not practical for routine clinical CPET. Use of oxygen pulse (O 2 pulse) as a noninvasive estimate of stroke volume (SV) has not been validated in CF. This study tested the hypothesis that peak exercise O 2 pulse is a valid estimate of SV in CF. Measurements of SV via the acetylene rebreathe technique were acquired at baseline and peak exercise in 17 mild-to-moderate severity adult CF and 25 age-matched healthy adults. We calculated [Formula: see text]. Baseline relationships between SV and O 2 pulse were significant in CF ( r = .80) and controls ( r = .40), persisting to peak exercise in CF ( r = .63) and controls ( r = .73). The standard error of estimate for O 2 pulse-predicted SV with respect to measured SV was similar at baseline (14.1 vs 20.1 mL) and peak exercise (18.2 vs 13.9 mL) for CF and controls, respectively. These data suggest that peak exercise O 2 pulse is a valid estimate of SV in CF. The ability to noninvasively estimate SV via O 2 pulse during routine clinical CPET can be used to improve test interpretation and advance our understanding of the impact cardiac dysfunction has on exercise intolerance in CF.

Abstract Background Iohexol is used for measurement of kidney glomerular filtration rate (GFR). Until recently, there have not been available proficiency standards to assist in calibrating a laboratory's results. In view of a shift in calibration at the University of Rochester Medical Center (URMC) laboratory, serving as Central Biochemistry Laboratory for the CKiD study, we performed a multicentered laboratory comparison. Methods Two batches of 30 fortified sera and patient samples from serum or heparinized plasma were sent for duplicate analysis to URMC, University of Minnesota (UMN), Mayo Clinic, and University of Lund. Five proficiency testing materials from Equalis AB were also provided. Iohexol calibration was performed using dilutions of OmnipaqueTM 300 and concentrations measured by HPLC or LC-MS/MS (Mayo). Results The 2 batches sent to UMN and University of Lund agreed well. URMC calibration was 11%–13% lower, and Mayo was 4%–8% lower for fortified samples. URMC corrected calibration was 3%–8% higher for these samples. When measured values were adjusted for the results of the Equalis samples, all laboratories agreed within 1%–2% on all iohexol concentrations. Conclusions For 12 URMC calibrator lots from November 2006 to March 2016, the factor quantifying the underestimation of measured to true iohexol concentration was 0.89. If each concentration was divided by 0.89, the calculated GFRs would be reduced by 10%–11%. GFR results for CKiD were adjusted for this shift in calibration. Regular examination of iohexol proficiency testing materials, free exchange of samples among laboratories, and standardized dilution of the stock iohexol for calibration would help to bring more universal agreement to this assay.

Abstract Rationale Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers are becoming increasingly important in patients with lung cancer to define targetable mutations suitable for personalized therapy, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species proto-oncogene (ROS1), and programmed death-ligand 1 (PD-L1). Objectives To evaluate the adequacy of EBUS-TBNA–derived tissue for molecular analysis. Methods We searched the MEDLINE, LILACS, www.clinicaltrials.gov, and Epistemonikos databases through January 2018. Data Extraction Two independent reviewers performed the data search, quality assessment, and data extraction. We included both prospective and retrospective studies; risk of bias was evaluated using the ROBINS-I tool. The primary outcome was the proportion of adequate samples obtained by EBUS-TBNA for molecular analysis. Data were pooled by using a binary random effects model. Finally, evidence was rated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results A total of 33 studies including 2,698 participants were analyzed. In 28 studies that evaluated EBUS-TBNA for the identification of EGFR mutations, the pooled probability of obtaining a sufficient sample was 94.5% (95% confidence interval CI], 93.2–96.4%). For identification of ALK mutations, the pooled probability was 94.9% (95% CI, 89.4–98.8%). Finally, the prevalence of EGFR mutation was 15.8% (95% CI, 12.1–19.4%), and the prevalence of ALK mutation was 2.77% (95% CI, 1.0–4.8%). Data for ROS1 and PD-L1 mutations were not suitable for meta-analysis. Conclusions EBUS-TBNA has a high yield for molecular analysis of both EGFR and ALK mutations. However, the suitability of TBNA samples for next-generation sequencing is uncertain and should be explored in further studies. Clinical trial registered with PROSPERO (CRD42017080008).

SummaryGermline mutations in patients with hemophilia B generally have arisen within the past 150 years. Evidence suggests that these germline mutations generally result from endogenous processes. However, a unique pattern would be expected if a population were exposed to a physiologically important germline mutagen since mutagens generally produce characteristic patterns, or “fingerprints”, of mutation. To determine the pattern of mutation in Mexican Hispanics, the regions of likely functional significance in the factor IX gene were screened by di-deoxy fingerprinting (ddF) in 31 families with hemophilia B. Mutations were found in 30 of these families. Haplotype analysis was performed on individuals with identical mutations to help distinguish independent, recurrent mutations from founder effects. Analysis of these 30 mutations, along with 7 mutations reported previously in Mexican Hispanic families, reveals a pattern of independent mutation that is similar to the pattern of mutation observed in 127 U. S. Caucasian families (p = 0.89). These results may reflect either an underlying pattern of germline mutation due to endogenous processes or the presence of an ubiquitous mutagen. Further analyses of the recurrent mutations revealed that two mutations, T296M and R248Q, accounted for 19% of the mutations found in the Mexicans. Haplotype data suggest that the multiple occurrences of T296M and R248Q are associated with founder effects and that screening for these mutations may allow rapid mutation detection and carrier diagnosis in a significant minority of Mexican families with hemophilia B. These two mutations also are associated with founder effects in the U. S. Caucasian population. However, the haplotypes are different in these two populations, indicating independent origins. The occurrence of identical founder mutations in distinct populations provides evidence for the previous hypothesis that the number of different mutations giving rise to mild or borderline mild/moderate hemophilia B is small compared to deleterious mutations causing more severe disease.

AbstractBackgroundShared decision making in the emergency department (ED) can increase patient engagement for patients presenting with chest pain. However, little is known regarding which factors are associated with actual patient involvement in decision making or patients’ desired involvement in emergency care decisions. We examined which factors were associated with patients’ actual and desired involvement in decision making among ED chest pain patients.MethodsThis is a secondary analysis of data from a randomized trial of a shared decision‐making intervention in ED patients with low‐risk chest pain. We evaluated the degree to which patients were involved in decision making using the OPTION‐12 (observing patient involvement) scale and patients’ reported desire for involvement in decision making using the Control Preferences Scale (CPS). We measured the associations of patient factors with OPTION‐12 and CPS scores using multivariable regression.ResultsOf the 898 patients enrolled, mean (±SD) age was 51.5 (±11.4) years and 59% were female. Multivariable analysis revealed that only two factors were significantly associated with OPTION‐12 scores: study site and use of the decision aid. OPTION‐12 scores were 10.3 (standard error = 0.6) points higher for patients randomized to the decision aid compared to usual care (p < 0.001). Higher health literacy was associated with lower scores on the CPS, indicating greater desire for involvement (odds ratio = 0.91, p < 0.001).ConclusionsPatients’ reported desire for involvement in decision making was higher among those with higher health literacy. After study site and other potential confounding factors were adjusted for, only use of the decision aid was associated with observed patient involvement in decision making. As the science and practice of shared decision making in the ED moves toward implementation, high‐fidelity integration of the decision aid into the flow of care will be necessary to realize desired outcomes.

Abstract Background and study aims Little consideration has been given to selection of endoscopic ultrasound-guided fiducials for proton radiotherapy and the resulting perturbations in the therapy dose and pattern. Our aim was to assess the impact of perturbations caused by six fiducials of different composition and dimensions in a phantom gel model. Materials and methods The phantom was submerged in a water bath and irradiated with a uniform 10 cm × 10 cm field of 119.7 MeV monoenergetic spot scanning protons delivered through a 45 mm range shifter. The proton “Bragg Peak” was evaluated. Results Dose perturbations manifesting as dose reductions up to 30 % were observed. A carbon composite (1 × 5 mm) and gold (0.4 × 10 mm) fiducial with backload potential rather than dedicated EUS pre-loaded gold fiducial needles had the best performance in terms of minimizing the dose perturbation. Conclusions Our data demonstrate that a carbon composite fiducial has a less untoward effect on proton therapy dose distribution than dedicated EUS pre-loaded gold fiducial needles. Such information is important to consider when selecting fiducials specifically for proton therapy.

Abstract BACKGROUND Head computerized tomography (CT) increases the risk of cancer in children and should be carefully prescribed to paediatric patients with head injury. The Pediatric Emergency Care Applied Network (PECARN) validated a rule to identify children at risk of a clinically important traumatic brain injury (TBI) needing a head CT. OBJECTIVES The objective was to evaluate adherence to the PECARN rule as a function of CT overuse (defined as a prescribed CT when not recommended by the rule) and underuse rates (no CT performed when recommended) in two Canadian emergency departments (EDs). DESIGN/METHODS We conducted a retrospective chart review of children under 17 years of age seen in 2016 in a paediatric Level I (site 1) and a general Level II (site 2) trauma center. We reviewed charts to determine the appropriateness of head CT use according to the PECARN rule in a random subset of children presenting with a head trauma. Mandatory inclusion criteria were (1) that the head trauma occurred in the 24 hours prior to arrival to the ED, (2) a GCS over 13 and (3) and at least one sign or symptom of minor TBI. Patients with a special condition that could have influenced the decision to order a head CT were automatically excluded. When a patient did not receive a head CT when recommended by the rule, we reviewed medical records to determine if the patient has returned to the ED after his discharge within the next 30 days. RESULTS 1546 eligible patients younger than 17 years consulted during the study period. Of the 203 randomly selected cases per setting, 16 (7.9%) and 24 (12%) respectively from sites 1 and 2 had a head CT performed. For the younger group (< 2), both overuse and underuse rates were below 3%. For the older group, overuse rates were higher in site 2 (9.3% (95%CI:4.8–17%) vs. 1.2% (95%CI:0.2–6.5%) (P=.03)) and there was no difference in underuse rates (22% (95%CI:6.3–55%) vs 39% (95%CI:18–65%) (P=.65)). For children who did not receive a head CT when recommended, none returned to the ED for a related complication. CONCLUSION Overall, even if there may be slightly more overuse of head CTs in the Level II trauma center, results showed an excellent agreement with the PECARN rule when CT was not recommended. However, results also showed a deviation when CT was recommended, where a higher portion of patients than expected did not receive a head CT. Reasons to explain this behaviour will need further exploration.

Improved methods are needed to risk stratify and predict outcomes in patients with primary sclerosing cholangitis (PSC). Therefore, we sought to derive and validate a prediction model and compare its performance to existing surrogate markers. The model was derived using 509 subjects from a multicenter North American cohort and validated in an international multicenter cohort (n = 278). Gradient boosting, a machine‐based learning technique, was used to create the model. The endpoint was hepatic decompensation (ascites, variceal hemorrhage, or encephalopathy). Subjects with advanced PSC or cholangiocarcinoma (CCA) at baseline were excluded. The PSC risk estimate tool (PREsTo) consists of nine variables: bilirubin, albumin, serum alkaline phosphatase (SAP) times the upper limit of normal (ULN), platelets, aspartate aminotransferase (AST), hemoglobin, sodium, patient age, and number of years since PSC was diagnosed. Validation in an independent cohort confirms that PREsTo accurately predicts decompensation (C‐statistic, 0.90; 95% confidence interval [CI], 0.84‐0.95) and performed well compared to Model for End‐Stage Liver Disease (MELD) score (C‐statistic, 0.72; 95% CI, 0.57‐0.84), Mayo PSC risk score (C‐statistic, 0.85; 95% CI, 0.77‐0.92), and SAP <1.5 × ULN (C‐statistic, 0.65; 95% CI, 0.55‐0.73). PREsTo continued to be accurate among individuals with a bilirubin <2.0 mg/dL (C‐statistic, 0.90; 95% CI, 0.82‐0.96) and when the score was reapplied at a later course in the disease (C‐statistic, 0.82; 95% CI, 0.64‐0.95). Conclusion: PREsTo accurately predicts hepatic decompensation (HD) in PSC and exceeds the performance among other widely available, noninvasive prognostic scoring systems.