Citations

Background: There is an ever-increasing demand for widespread implementation of patient-reported outcomes. However, adoption is slow owing to limitations in clinical infrastructure and resources within busy orthopaedic practices. Prior studies showed the single alpha-numeric evaluation (SANE) score to correlate at a single point in time with the American Shoulder and Elbow Surgeons (ASES) score. However, no study has validated the SANE in terms of test-retest reliability, responsiveness, or clinical utility. Purpose: To validate SANE with the ASES across a sample of patients with common orthopaedic shoulder diagnoses. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Patients undergoing rotator cuff repair (n = 77), total shoulder replacement (n = 55), or physical therapy (n = 80) for signs and symptoms of subacromial impingement syndrome (n = 61) or adhesive capsulitis (n = 19) were administered the SANE and ASES at baseline and again at their 3-month follow-up from initial care or surgery (N = 212, mean ± SD age = 52.6 ± 1.2 years, n = 145 women). Interclass correlation coefficient (ICC 2,1 ) and standard error of the measurement (SEm) were used to evaluate the test-retest reliability of the SANE and the validity between the SANE and ASES scores. Analysis of variance (treatment group × time) was used to evaluate the responsiveness to treatment, and a receiver operating characteristic curve was used to establish the minimal clinically important difference (MCID) for the SANE as compared with the ASES (α = .05). Floor and ceiling effects were evaluated as the percentage of patients who scored the highest or lowest score on each tool. Results: The SANE demonstrated good pretreatment reliability (ICC 2,1 = 0.84, SEM = 3.8), similar to the ASES (ICC 2,1 = 0.82, SEM = 3.4). The SANE also showed good agreement with the ASES before and after treatment across all treatment groups (rotator cuff repair, ICC 2,1 = 0.85, SEM = 3.4; total shoulder replacement, ICC 2,1 = 0.72, SEM = 5.2; physical therapy: ICC 2,1 = 0.82, SEM = 2.9). The SANE and ASES displayed similar responsiveness after treatment, with similar mean change and SD within each treatment group. The receiver operating characteristic curve revealed an area under the curve of 0.79 (SE, 0.62; P < .001) and a cutoff of 15% on the SANE, with a sensitivity of 85% to establish the MCID. Acceptable and similar floor and ceiling effects were observed for the ASES (4%) and SANE (9%). Conclusion: The study demonstrates that the SANE is valid for a range of common shoulder diagnoses to assess patient outcomes across operative and nonoperative treatment for shoulder complaints. The MCID of 15% is similar to that of the ASES (11%), suggesting that the SANE is a simple and efficient tool to assess treatment effects for shoulder disorders. Future studies are warranted to confirm these results and compare across other body parts and diagnoses.

Abstract The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval [CI], 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands’ blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.

Abstract Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. By the creation of a global PKD International Working Group in 2016, involving 24 experts from 20 Centers of Expertise we studied the current gaps in the diagnosis of PKD in order to establish diagnostic guidelines. By means of a detailed survey and subsequent discussions, multiple aspects of the diagnosis of PKD were evaluated and discussed by members of Expert Centers from Europe, USA, and Asia directly involved in diagnosis. Broad consensus was reached among the Centers on many clinical and technical aspects of the diagnosis of PKD. The results of this study are here presented as recommendations for the diagnosis of PKD and used to prepare a diagnostic algorithm. This information might be helpful for other Centers to deliver timely and appropriate diagnosis and to increase awareness in PKD.

Abstract Objectives Working Group 2 was convened to address topics relevant to prosthodontics and dental implants. Systematic reviews were developed according to focused questions addressing (a) the number of implants required to support fixed full‐arch restorations, (b) the influence of intentionally tilted implants compared to axial positioned implants when supporting fixed dental prostheses ( FDP s), (c) implant placement and loading protocols, (d) zirconia dental implants, (e) zirconia and metal ceramic implant supported single crowns and (f) zirconia and metal ceramic implant supported FDP s. Materials and methods Group 2 considered and discussed information gathered in six systematic reviews. Group participants discussed statements developed by the authors and developed consensus. The group developed and found consensus for clinical recommendations based on both the statements and the experience of the group. The consensus statements and clinical recommendations were presented to the plenary (gathering of all conference attendees) and discussed. Final versions were developed after consensus was reached. Results A total of 27 consensus statements were developed from the systematic reviews. Additionally, the group developed 24 clinical recommendations based on the combined expertise of the participants and the developed consensus statements. Conclusions The literature supports the use of various implant numbers to support full‐arch fixed prostheses. The use of intentionally tilted dental implants is indicated when appropriate conditions exist. Implant placement and loading protocols should be considered together when planning and treating patients. One‐piece zirconia dental implants can be recommended when appropriate clinical conditions exist although two‐piece zirconia implants should be used with caution as a result of insufficient data. Clinical performance of zirconia and metal ceramic single implant supported crowns is similar and each demonstrates significant, though different, complications. Zirconia ceramic FDP s are less reliable than metal ceramic. Implant supported monolithic zirconia prostheses may be a future option with more supporting evidence.

AbstractBACKGROUNDDroplet digital PCR (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, assay performance criteria must be established in a standardized manner to harness this potential. We reasoned that standard protocols used in clinical chemistry assay validation should be able to fill this need.METHODSWe validated KRAS, EGFR, and BRAF quantitative ddPCR assays based on the Clinical Laboratory Improvement Act regulations for laboratory-developed tests in clinical chemistry and the matching Clinical and Laboratory Standards Institute guidelines. This included evaluation of limit of the blank (LOB), limit of detection (LOD), limit of quantification (LOQ), intraassay and interassay imprecision, analytical range, dilution linearity, accuracy (including comparison with orthogonal platforms), reference range study, interference, and stability studies.RESULTSFor the ddPCR assays, the LOB was 4 mutant copies, LODs were 12 to 22 copies, and LOQs were 35 to 64 copies. The upper limit of the dynamic range was 30000 copies, and dilutions were linear down to the LOQs with good accuracy of spike recovery of Horizon reference material. Method comparisons with next-generation sequencing and an alternative ddPCR platform showed complete qualitative agreement and quantitative concordance, with slopes of 0.73 to 0.97 and R2s of 0.83 to 0.99. No substantial interferences were discovered. Wild-type copy numbers in plasma ranged from 462 to 6169/mL in healthy individuals.CONCLUSIONSStandard clinical chemistry assay validation protocols can be applied to quantitative ddPCR assays. This should facilitate comparison of the performance of different assays and allow establishment of minimal significant change thresholds in monitoring applications.