Precision or Pitfall? Evaluating the Accuracy of ICD-10 Coding for Cemented Total Hip Arthroplasty: A Multicenter Study.

BACKGROUND: The International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Procedure Coding System (ICD-10-PCS) was adopted in the U.S. in 2015. Proponents of the ICD-10-PCS have stated that its granularity allows for a more accurate representation of the types of procedures performed by including laterality, joint designation, and more detailed procedural data. However, other researchers have expressed concern that the increased number of codes adds further complexity that leads to inaccurate and inconsistent coding, rendering registry and research data based on ICD-10-PCS codes invalid and inaccurate. We aimed to determine the accuracy of the ICD-10-PCS for identifying cemented fixation in primary total hip arthroplasty (THA). METHODS: We retrospectively reviewed all cemented primary THAs performed at 4 geographically diverse, academic medical centers between October 2015 and October 2020. Cemented fixation was identified from the ICD-10-PCS coding for each procedure. The accuracy of an ICD-10-PCS code relative to the surgical record was determined by postoperative radiograph and chart review, and cross-referencing with institution-level coding published by the American Joint Replacement Registry (AJRR) was also performed. RESULTS: A total of 552 cemented THA cases were identified within the study period, of which 452 (81.9%) were correctly coded as cemented with the ICD-10-PCS. The proportion of cases that were correctly coded was 187 of 260 (72%) at Institution A, 158 of 185 (85%) at Institution B, 35 of 35 (100%) at Institution C, and 72 of 72 (100%) at Institution D. Of the 480 identified cemented THA cases at 3 of the 4 institutions, 403 (84%) were correctly reported as cemented to the AJRR (Institution A, 185 of 260 cases [71%]; Institution B, 185 of 185 [100%]; and Institution C, 33 of 35 [94%]). Lastly, of these 480 identified cemented THA cases, 317 (66%) were both correctly coded with the ICD-10-PCS and correctly reported as cemented to the AJRR. CONCLUSIONS: Our findings revealed existing discrepancies within multiple institutional data sets, which may lead to inaccurate reporting by the AJRR and other registries that rely on ICD-10-PCS coding. Caution should be exercised when utilizing ICD-10 procedural data to evaluate specific details from administrative claims databases as these inaccuracies present inherent challenges to data validity and interpretation.

Mono-2-ethylhexylphthalate (MEHP) is a potent agonist of human TRPA1 channel.

Phthalates are extensively used as plasticizers in diverse consumer care products but have been reported to cause adverse health effects in humans. A commonly used phthalate, di-2-ethylhexylphthalate (DEHP) causes developmental and reproductive toxicities in humans, but the associated molecular mechanisms are not fully understood. Mono-2-ethylhexylphthalate (MEHP), a hydrolytic product of DEHP generated by cellular esterases, is proposed to be the active toxicant. We conducted a screen for sensory irritants among compounds used in consumer care using an assay for human Transient Receptor Potential A1 (hTRPA1). We have identified MEHP as a potent agonist of hTRPA1. MEHP-induced hTRPA1 activation was blocked by the TRPA1 inhibitor A-967079. Patch clamp assays revealed that MEHP induced inward currents in cells expressing hTRPA1. In addition, the N855S mutation in hTRPA1 associated with familial episodic pain syndrome decreased MEHP-induced hTRPA1 activation. In summary, we report that MEHP is a potent agonist of hTRPA1 which generates new possible mechanisms for toxic effects of phthalates in humans.

Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex.

An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications.

Floating sphere assay: A rapid qualitative method for microvolume analysis of gelation.

A huge, unprecedented demand for gelatin coupled with its implications on global sustainability has resulted in the need to discover novel proteins with gelling attributes for applications in the food industry. Currently used gelation assays require large sample volumes and thus the screening for novel gelling proteins is a formidable technical challenge. In this paper, we report the 'Floating Sphere Assay' which is a simple, economical, and miniaturized assay to detect minimum gelling concentration with volumes as low as 50 µl. Results from the Floating Sphere Assay are consistent with currently used methods for gelation tests and accurately estimate the Minimum Gelling Concentrations (MGCs) of gelatin, κ-carrageenan and gellan gum. The assay was also able to differentiate the strengths of strong and weak gellan gum gels prepared at pH 3.5 and pH 7.0 respectively. The Floating Sphere Assay can be utilized in high-throughput screens for gelling proteins and can accelerate the discovery of gelatin substitutes.

Diethyl phthalate (DEP) perturbs nitrogen metabolism in Saccharomyces cerevisiae.

Phthalates are ubiquitously used as plasticizers in various consumer care products. Diethyl phthalate (DEP), one of the main phthalates, elicits developmental and reproductive toxicities but the underlying mechanisms are not fully understood. Chemogenomic profiling of DEP in S. cerevisiae revealed that two transcription factors Stp1 and Dal81 involved in the Ssy1-Ptr5-Ssy5 (SPS) amino acid-sensing pathway provide resistance to DEP. Growth inhibition of yeast cells by DEP was stronger in poor nitrogen medium in comparison to nitrogen-rich medium. Addition of amino acids to nitrogen-poor medium suppressed DEP toxicity. Catabolism of amino acids via the Ehrlich pathway is required for suppressing DEP toxicity. Targeted metabolite analyses showed that DEP treatment alters the amino acid profile of yeast cells. We propose that DEP inhibits the growth of yeast cells by affecting nitrogen metabolism and discuss the implications of our findings on DEP-mediated toxic effects in humans.