Self-reported Findings of the Korean Intermittent Exotropia Multicenter Study Questionnaire.

Purpose: To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. Methods: The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS) including 5385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS. Results: The mean age of symptom onset was 5.5 years of age. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery. Conclusions: The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.

Parental perspectives and concerns regarding exotropia surgery and comparison with clinicians' predictions.

PURPOSE: To evaluate parental perspectives and concerns regarding exotropia surgery and compare them with clinicians' predictions of parental responses in Korean pediatric patients with intermittent exotropia. METHODS: This survey study included the parents of pediatric patients with intermittent exotropia who underwent surgery and clinicians at five hospitals from June 2022 to February 2023, who participated in the Survey of Parental Attitude and Concerns of Exotropia surgery (SPACE) study 1. Parental attitudes and concern about exotropia surgery were assessed using a questionnaire. Clinicians' estimation of each item corresponding to the parental questionnaire was also assessed and compared with parental responses. RESULTS: A total of 266 parents and 41 clinicians were included. More parents responded that information about surgery was most helpful or most commonly received from clinicians than clinicians estimated (P = 0.001). More parents reported actively communicating with the child about surgery than clinicians estimated (P < 0.001). Parents showed a higher level of concern for general anesthesia and the hospital environment than clinicians thought they would (P = 0.002 and P < 0.001, resp.). In the postoperative follow-up items, parents showed high levels of concern regarding postoperative infection (P < 0.001), conjunctival redness (P = 0.040), persistent overcorrection (P < 0.001), and glasses wearing (P = 0.019). CONCLUSIONS: Parental perspectives and concerns regarding pediatric intermittent exotropia surgery differed from clinicians' estimations thereof. More parents obtain information on exotropia surgery from clinicians and actively talk about surgery with their child than estimated by clinicians. Parents had a higher level of concern regarding general anesthesia, hospital environment, postoperative infection, conjunctival redness, persistent overcorrection, and glasses wearing compared with clinician estimations.

Changes in ocular extorsion after horizontal muscle surgery in patients with intermittent exotropia coexisting with hypertropia and mild inferior oblique overaction.

PURPOSE: To investigate changes in vertical strabismus and extorsion in patients with intermittent exotropia and mild unilateral inferior oblique muscle overaction (IOOA) who underwent horizontal muscle surgery without vertical or oblique muscle surgery. METHODS: The medical records of 41 patients were retrospectively analyzed. The patients were followed up for at least 6 months after surgery. Fundus photography was performed before and after surgery, and the sum of the angles of torsion in both eyes was used to measure changes in extorsion using ImageJ software. The enrolled patients were divided into two groups according to the degree of IOOA: patients with grade 1 IOOA were placed in +1 IOOA group and those with grade 2 IOOA in +2 IOOA group. The pre- and postoperative angles of horizontal and vertical strabismus and extorsion were compared between the two groups. RESULTS: The +1 IOOA and +2 IOOA groups included 24 and 17 patients, respectively. The angle of preoperative exotropia did not differ significantly: 25.54 ± 5.68 prism diopters (PD) and 25.65 ± 8.11 PD in the +1 IOOA and +2 IOOA groups, respectively. In the +1 IOOA and +2 IOOA groups, hypertropia was 2.67 ± 1.52 PD and 2.82 ± 1.13 PD, respectively, and extorsion angles were 7.14 ± 2.77° and 7.94 ± 2.87°, respectively. As the IOOA degree increased, the extent of hypertropia and extorsion also increased. However, there were no significant differences between the two groups. Postoperative angles of hypertropia and extorsion significantly decreased in both groups (p < 0.001) after surgery. The degree of change in hypertropia and extorsion was not significantly different between the two groups (p = 0.563 and p = 0.354, respectively). CONCLUSIONS: Hypertropia and extorsion improved significantly after horizontal muscle surgery in patients with mild unilateral IOOA and intermittent exotropia. There was no significant difference in the improvement in hypertropia or extorsion between IOOA grades I and II.

A Clinical Incivility Management Module for Nursing Students: A Quasi-Experimental Study.

BACKGROUND: Incivility experienced by pre-licensure nursing students in clinical settings continues to grow. Interventions for clinical incivility to nursing students are needed. Our study aimed to examine the effects of a piloted two-hour interactive incivility management module on nursing students' perceived stress and general self-efficacy levels and preparedness for responding professionally to clinical incivility. METHODS: A quasi-experimental post-test-only non-equivalent comparison design with control and experimental groups was used. Senior nursing students enrolled in a Bachelor of Science in Nursing program from a nursing college located in Seoul, South Korea, were recruited. The control group (n = 94) completed a self-administered online survey without the clinical incivility management module. The experimental group (n = 93) completed the same survey after receiving the clinical incivility management module. The two groups' survey data were compared; qualitative data from the experimental group's post-module debriefing session were also analyzed. RESULTS: The prevalence of reported clinical incivility was 72.73% (n = 137 out of 187 participants). Clinical incivility experienced by the experimental group was significantly lower than that of the control group (z = -4.865, p < 0.001). However, there was no significant difference in stress levels and self-efficacy between the two groups. The mean score of the experimental group on preparedness for responding professionally to clinical incivility was statistically higher than the control group's mean score (z = -2.850, p = 0.004). CONCLUSIONS: Interventions to prepare students for the experience of clinical incivility are useful; they can positively affect the students' ability to respond professionally.

Plasma Antiretinal Autoantibody Profiling and Diagnostic Efficacy in Patients With Autoimmune Retinopathy.

PURPOSE: To evaluate plasma antiretinal autoantibody (ARA) profiling and diagnostic efficacy for autoimmune retinopathy (AIR). DESIGN: A multicenter, diagnostic evaluation study. METHODS: Forty-nine patients with a clinical diagnosis of AIR, disease controls including 20 patients with retinitis pigmentosa (RP), and 30 normal controls were included. Plasma samples from patients were analyzed for the presence of 6 ARAs, including recoverin, α-enolase, carbonic anhydrase II, heat shock protein 60, aldolase C, and cone-rod homeobox/cone-rod retinal dystrophy 2 using western blotting. RESULTS: Autoantibody detection rates against cone-rod homeobox/cone-rod retinal dystrophy 2, heat shock protein 60, and aldolase C in AIR were 67.3%, 40.8%, and 42.9%, respectively, which were higher than those in RP and normal controls (P < .001, P < .001, and P = .007, respectively), but recoverin, α-enolase, and carbonic anhydrase II were not different from other control groups (P = .117, P = .774, and P = .467, respectively). Among ARAs, antirecoverin antibody was the most specific, as it was found in 3 (6.1%) patients with AIR and none of the control groups. As the number of detected ARAs increased, the probability of AIR increased (odds ratio: 1.913; P < .001; 95% confidence interval: 1.456-2.785). The positive number of ARAs was significantly higher when photoreceptor disruption was observed on optical coherence tomography, or severe dysfunction was observed in electroretinography (P = .022 and P = .029, respectively). CONCLUSIONS: The profiles of ARAs in the AIR group were different from those in the RP and normal controls. The higher number of positive ARAs suggests a higher possibility of AIR diagnosis. ARAs should be used as adjunct tools for the clinical diagnosis of AIR.

Combined Model-Based Prediction for Non-Invasive Prenatal Screening.

The risk of chromosomal abnormalities in the child increases with increasing maternal age. Although non-invasive prenatal testing (NIPT) is a safe and effective prenatal screening method, the accuracy of the test results needs to be improved owing to various testing conditions. We attempted to achieve a more accurate and robust prediction of chromosomal abnormalities by combining multiple methods. Here, three different methods, namely standard Z-score, normalized chromosome value, and within-sample reference bin, were used for 1698 reference and 109 test samples of whole-genome sequencing. The logistic regression model combining the three methods achieved a higher accuracy than any single method. In conclusion, the proposed method offers a promising approach for increasing the reliability of NIPT.

Surgical outcomes of adjustment on recessed lateral rectus muscle versus resected medial rectus muscle for intermittent exotropia.

BACKGROUND: To evaluate the effectiveness of resected muscle adjustment compared with the recessed muscle adjustment in patients with intermittent exotropia. METHODS: This retrospective clinical investigation analyzed the data of patients who underwent strabismus surgery with adjustment. Patients who were followed-up for at least one and half year after adjustment were enrolled. They were divided into two groups; patients who underwent adjustment on recessed lateral rectus muscle (LR-Adj group) and adjustment on resected medial rectus muscle (MR-Adj group). Postoperative changes were compared. Surgical success was defined as horizontal deviation < 5 prism diopters (PD) esodeviation and < 10 PD exodeviation on distance measurement at 1.5 years postoperatively. RESULTS: Forty patients were included; LR-Adj group included 21 and MR-Adj group included 19 patients. The mean esodeviation at distance fixation immediately after adjustment was 8.1 ± 5.4 PD in the LR-Adj group and 8.4 ± 4.7 PD in the MR-Adj group (P = 0.843). Postoperative exodrift occurred in both groups, and amount of exodeviation after 1.5 year were not significantly different. For the comparison of the amount of exodrift at near measurement, the amount of exodrift within 1 month after surgery was smaller in the MR-Adj group than that in the LR-Adj group (P = 0.01). Surgical success rates were 81.0% in the LR-Adj group and 84.2% in the MR-Adj group (P = 0.559). CONCLUSIONS: The smaller amount of exodrift in the MR-Adj group may mean that the positional stability of the resected muscle is favorable in the early post-adjustment period. However, there was no significant difference groups in the final exodeviation and surgical success rate between the groups. Resected muscle adjustment was as effective as the conventional recessed muscle adjustment.

Spontaneous Recovery of Traumatic Unilateral Superior Oblique Palsy and Ocular Factors for Predicting Prognosis.

PURPOSE: This study evaluated the prognosis of patients with traumatic unilateral superior oblique palsy (SOP) and clinical factors associated with spontaneous resolution. METHODS: Medical records of patients with traumatic unilateral SOP who visited two hospitals (Yeungnam University Hospital and Daegu Catholic University Medical Center) between January 2015 and June 2020 were reviewed retrospectively. When traumatic unilateral SOP did not recover within at least 1 year of follow-up, no spontaneous resolution was considered. Both traumatic and ocular factors were evaluated to evaluate their association with spontaneous recovery. RESULTS: Fifty-nine patients (mean age, 52.6 years; 48 male patients) were enrolled in this study. The mean interval from trauma to initial presentation was 3.9 months. The mean vertical deviation at initial presentation was 6.34 ± 5.22 prism diopters (PD) (range, 0-25 PD). During the mean 24.1-month follow-up period, 28 patients (47.5%) achieved spontaneous resolution of SOP. Thirteen patients underwent surgical treatment for SOP. Vertical deviation <6 PD at the initial visit and low fundus torsion in the nonparetic eye and both eyes were significantly associated with spontaneous recovery (p < 0.05, logistic regression analysis). Traumatic factors, including the trauma type, presence of intracranial lesion, loss of consciousness, and Glasgow Coma Scale score, were not associated with spontaneous recovery. CONCLUSIONS: In this multicenter study, spontaneously recovery was achieved in 47.5% patients with traumatic unilateral SOP. Even mild head trauma can lead to permanent SOP. Ocular factors, including the angle of deviation and fundus torsion, may better predict spontaneous resolution than traumatic factors in patients with traumatic unilateral SOP.

Mediating effects of emotional intelligence and resilience on the relationship between type D personality and caring ability in nursing students: A cross-sectional study.

BACKGROUND: Nursing students must learn about the core values of nursing care. Thus, education designed to improve their caring ability should be included in nursing curricula. Nursing students' caring ability is reportedly affected by emotional intelligence and resilience. However, no studies have explored whether these qualities have mediating effects on the relationship between nursing students' type D personality and their caring ability. OBJECTIVES: To examine the mediating effects of emotional intelligence and resilience on the relationship between type D personality and caring ability in nursing students. DESIGN: A cross-sectional, descriptive survey study. SETTING: The study was conducted in South Korea. PARTICIPANTS: 278 nursing students. METHODS: Type D personality, emotional intelligence, resilience, and caring ability were measured using questionnaires. Data were analyzed using Pearson's correlations, regression analysis, and Hayes' Process Macro using the bootstrap method. RESULTS: Results indicated that type D personality significantly predicted emotional intelligence (B = -6.80, p < .001), resilience (B = -6.77, p < .001), and caring ability (B = -7.20, p = .001). Emotional intelligence mediated the relationship between type D personality and caring ability. CONCLUSION: Interventions to improve the caring ability of nursing students should include an evaluation of nursing students' emotional intelligence and strategies to promote their emotional intelligence.

Effects of Online Learning on Nursing Students in South Korea during COVID-19.

Daily life has changed due to COVID-19. This has affected nursing education and caused a shift in online learning. This study examined the effects of online learning on nursing students' knowledge, self-regulation, and learning flow. We used a quasi-experimental design on a sample comprising 164 senior nursing students. We compared pre- and post-test scores to examine the educational effects. The pre-test was conducted a week before the educational intervention, and the post-test was conducted a week after it. We found a significant increase in knowledge (t = -14.85, p < 0.001) and learning flow (t = -2.15, p = 0.033) in the post-test. We also found an increase in self-regulation (t = -1.57, p = 0.119) from the pre- to the post-test that was not statistically significant. The results could help instructors to provide additional information in online learning. They highlight the need to assess learners' readiness for online learning and to prepare the learning environment with systematic educational planning, design, development, and evaluation for improving the effectiveness of online learning outcomes.

[A Study on Dispatched Nursing during the Japanese Colonial Era].

PURPOSE: This study aimed to explore the characteristics of dispatched nursing, a type of private nursing called Hasutsu, during the Japanese colonial period in Korea. This specialized and professional nursing was a form of a dispatched nursing service provided by nurses associations. METHODS: This study reviewed a literature on visiting nursing, a literature on dispatched nursing, focusing on data collected during the Japanese colonial period from August 1910 to August 1945. Study design was a document research study of historical records. RESULTS: The dispatched nursing service was established by the Japanese nurses in Korea. More than 60 nurses associations operated to meet the demands in the modern Korean nursing period. It was found that some associations tried to raise the nursing fees. Also, the practice of employing visiting nurses who did not have a license was criticized severely in the newspapers. Considering that the data was limited in this study, the existence of Korean nurses association employing Korean visiting nurses has not been specifically identified. CONCLUSION: The findings reveal some aspects of dispatched nursing provided by the nurses associations in that era. The nurses associations developed their own specialized service independently by dispatching nurses to fulfill the needs of people not only with cheaper nursing fares than hospitals but with convenient nursing care services, including customized care for infectious diseases. A study of modern historical records of Korean nurses would facilitate deeper research into Korean nursing history.

Establishment of patient-derived three-dimensional organoid culture in renal cell carcinoma.

Purpose: Renal cell carcinoma is a heterogeneous kidney cancer, and over 403,000 cases were reported worldwide in 2018. Current methods for studying renal cell carcinoma are limited to two-dimensional (2D) culture of primary cell lines and patient-derived xenograft models. Numerous studies have suggested that 2D culture poorly represents the diversity, heterogeneity, and drug-resistance of primary tumors. The time and cost associated with patient-derived xenograft models poses a realistic barrier to their clinical utility. As a biomimetic model, patient-derived three-dimensional (3D) organoid culture can overcome these disadvantages and bridge the gap between in vitro cell culture and in vivo patient-derived xenograft models. Here, we establish a patient-derived 3D organoid culture system for clear cell renal cell carcinoma and demonstrate the biomimetic characteristics of our model with respect to both primary kidney cancer and conventional 2D culture. Materials and Methods: Normal renal tissues and tumor tissues were collected from patients with clear cell renal cell carcinoma. The dissociated cells were cultured as conventional 2D culture and 3D organoid culture. The biomimetic characteristic of the two cultures were compared. Results: Compared with 2D culture, the 3D organoid cultures retained the characteristic lipid-rich, clear cell morphology of clear cell renal cell carcinoma. Carbonic anhydrase 9 and vimentin were validated as biomarkers of renal cell carcinoma. Expression of the two validated biomarkers was more enhanced in 3D organoid culture. Conclusions: Patient-derived 3D organoid culture retains the characteristics of renal cell carcinoma with respect to morphology and biomarker expression.

Performance evaluation of commercial library construction kits for PCR-based targeted sequencing using a unique molecular identifier.

BACKGROUND: Target enrichment is a critical component of targeted deep next-generation sequencing for the cost-effective and sensitive detection of mutations, which is predominantly performed by either hybrid selection or PCR. Despite the advantages of efficient enrichment, PCR-based methods preclude the identification of PCR duplicates and their subsequent removal. Recently, this limitation was overcome by assigning a unique molecular identifier(UMI) to each template molecule. Currently, several commercial library construction kits based on PCR enrichment are available for UMIs, but there have been no systematic studies to compare their performances. In this study, we evaluated and compared the performances of five commercial library kits from four vendors: the Archer® Reveal ctDNA™ 28 Kit, NEBNext Direct® Cancer HotSpot Panel, Nugen Ovation® Custom Target Enrichment System, Qiagen Human Comprehensive Cancer Panel(HCCP), and Qiagen Human Actionable Solid Tumor Panel(HASTP). RESULTS: We evaluated and compared the performances of the five kits using 50 ng of genomic DNA for the library construction in terms of the library complexity, coverage uniformity, and errors in the UMIs. While the duplicate rates for all kits were dramatically decreased by identifying unique molecules with UMIs, the Qiagen HASTP achieved the highest library complexity based on the depth of unique coverage indicating superb library construction efficiency. Regarding the coverage uniformity, the kits from Nugen and NEB performed the best followed by the kits from Qiagen. We also analyzed the UMIs, including errors, which allowed us to adjust the depth of unique coverage and the length required for sufficient complexity. Based on these comparisons, we selected the Qiagen HASTP for further performance evaluations. The targeted deep sequencing method based on PCR target enrichment combined with UMI tagging sensitively detected mutations present at a frequency as low as 1% using 6.25 ng of human genomic DNA as the starting material. CONCLUSION: This study is the first systematic evaluation of commercial library construction kits for PCR-based targeted deep sequencing utilizing UMIs. Because the kits displayed significant variability in different quality metrics, our study offers a practical guideline for researchers to choose appropriate options for PCR-based targeted sequencing and useful benchmark data for evaluating new kits.

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients.

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Tubular organotypic culture model of human kidney.

Cell-culture methods that simplify the inherent complexities of the kidney have not sufficiently reproduced its true characteristics. Although reports indicate that organoid methodology surpasses traditional cell culture in terms of reproducing the nature of organs, the study of human kidney organoids have been confined to pluripotent stem cells. Furthermore, it has not yet progressed beyond the developmental state of embryonic kidney even after complicate additional differentiation processes. We here describe the kidney organotypic culture method that uses adult whole kidney tissues but mainly differentiates into tubular cells. This model was validated based on the retention of key kidney organotypic-specific features: 1) expression of Tamm-Horsfall protein; 2) dome-like organoid configurations, implying directed transport of solutes and water influx; and 3) organoid expression of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in response to nephrotoxic injury (i.e., gentamicin and cisplatin exposure). This 3D-structured organoid prototype of the human renal tubule may have applications in developing patient-specific treatments for kidney diseases.

High-Mobility Group Box 1-Induced Complement Activation Causes Sterile Inflammation.

High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.

Exogenous pentraxin-3 inhibits the reactive oxygen species-mitochondrial and apoptosis pathway in acute kidney injury.

Pentraxin-3 (PTX3) is a long-form member of the pentraxin family of proteins that has been studied in inflammatory diseases and in various organs. We found that PTX3 protects kidney cells during ischemia and proinflammatory acute kidney injury. The aim of this study was to develop an in vitro experimental model of acute kidney injury and to analyze the protective mechanism of exogenous recombinant PTX3. In this study, cells of the HK-2 renal tubular cell line were treated with a calcium ionophore (A23187), which induced injury by increasing intracellular calcium concentrations and inducing calpain activity and the generation of reactive oxygen species. Exposure of cells to PTX3 significantly attenuated these effects. In addition, the activity of caspase-3 and PARP-1 were decreased in ischemic cells exposed to exogenous recombinant PTX3. PTX3 stabilized the mitochondrial membrane potential and suppressed apoptosis, resulting in the protection of renal tubular cells from ischemic injury.

Clinical validation of serum endocan (ESM-1) as a potential biomarker in patients with renal cell carcinoma.

To determine the suitability of serum endocan (ESM-1) levels for diagnosing and monitoring renal cell carcinoma (RCC), we measure serum ESM-1 levels in 56 RCC patients who had undergone radical or partial nephrectomies and 56 age- and sex-matched healthy kidney donors. Measurements were made before and 1 month and 3 months after surgery. The areas under the curve (AUCs) were determined from receiver operating characteristic (ROC) analyses. RCC patients had higher mean serum ESM-1 levels than control subjects (0.59 ± 0.07 vs. 0.52 ± 0.08 ng/mL, P < 0.001), with an AUC of 0.721 (95% CI: 0.628-0.817). In patients with tumors larger than 2 cm (n = 40) and those with clear-cell histology (n = 44), the AUCs for ESM-1 were 0.771 and 0.721, respectively. In control subjects, serum ESM-1 levels were higher in older (>50 years) individuals (P < 0.001). Among the study cohort, the AUCs for ESM-1 were 0.813 in individuals 50 years of age or younger (n = 55) and 0.637 in individuals older than 50 years (n = 57). In RCC patients, serum ESM-1 levels were reduced 1 month (P = 0.047) and 3 months (P = 0.009) after surgery. These results suggest serum ESM-1 can serve as a serologic biomarker for diagnosing and monitoring RCC, particularly in patients younger than 50 years.

Prevalence and detection of low-allele-fraction variants in clinical cancer samples.

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay.