Change of joint line convergence angle and other coronal alignments after total hip arthroplasty.

BACKGROUND: The purpose of this study was to determine the unloading effect of total hip arthroplasty (THA) on the ipsilateral knee joint through the joint line convergence angle (JLCA) change and determine the changes in other coronal radiographic parameters after THA, and evaluate the sensitivity of JLCA. PATIENTS AND METHODS: We retrospectively assessed 70 patients who underwent unilateral THA. Hip parameters such as neck shaft angle (NSA), neck length, and femoral offset and coronal alignment parameters of the lower extremity such as hip-knee-ankle angle (HKA), femur length, mechanical lateral distal femoral angle (mLDFA), JLCA, medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), and plafond talus angle (PTA) were measured in the operative and non-operative sides. We compared all hip and coronal alignment parameters between before and 1 year after THA, and the amount of standardized changes (Δ) between all hip and coronal alignment parameters on the operative side, respectively. RESULTS: All mean hip and coronal alignment parameters on the operative side changed significantly 1-year after THA; however, those on the non-operative side did not. On the operative side, mean JLCA and PTA changed in the direction of closing the joint lateral space, from 1.81° and 0.47° to 1.22° and 0.11°, respectively (p<0.001 and 0.046, respectively). Mean NSA, HKA, and mLDFA changed in the valgus direction, from 129.39°, 2.62°, and 86.69° to 133.54°, 1.53°, and 85.91°, respectively (p<0.001). Mean femoral offset, neck length, and femur length increased from 36.45mm, 47.83mm, and 429.20mm to 39.85mm, 55.06mm, and 436.33mm, respectively (p<0.001). Mean MPTA and LDTA increased from 85.43° and 87.50° to 86.73° and 90.38, respectively (p<0.001). JLCA was more vulnerable to change than HKA, femur length, mLDFA, MPTA, and PTA (p<0.05). DISCUSSION: JLCA change on the operative side was more sensitive than changes of other coronal alignments after THA. According to the cohort, THA might have an unloading effect on the medial compartment of the knee joint. LEVEL OF EVIDENCE: IV; retrospective case-control and cohort studies.

Longer Operative Time and the Use of Anticoagulants Are Associated With Increased Blood Loss in Elderly Patients Undergoing Arthroscopic Rotator Cuff Repair.

Purpose: To study the effects of rotator cuff tear size, operation time, and the use of anticoagulant on blood loss in elderly patients undergoing arthroscopic rotator cuff surgery. Methods: Patients aged older than 65 years who underwent arthroscopic rotator cuff repair with subacromial decompression at our hospital from January 2015 to December 2021 were identified. We measured hemoglobin levels preoperatively, postoperatively, and 7 days after surgery. First, subjects were divided according to the operation time (group I, <90 minutes; group II, <120 minutes; group III <150 minutes; and group IV, >150 minutes). Second, we classified the subjects by the size of the rotator cuff tear (group A, <3 cm; group B, <5 cm; and group C, >5 cm). Lastly, we categorized the subjects into 2 groups according to the use of anticoagulant medication. Results: A total of 566 patients were included. The mean hemoglobin (Hgb) levels were 13.8 ± 1.4 g/dL preoperatively, 13.2 ± 1.4 g/dL postoperatively, and 12.8 ± 1.3 g/dL 7 days after surgery, and the differences among them were statistically significant (P < .001). The Hgb level changes 7 days after surgery showed a significant decrease in the group with a longer operation time, and the Hgb loss increased from group 1 to group 4 (P < .001). They did not show any difference in the Hgb levels among the groups according to the size of a cuff tear preoperatively, postoperatively, and 7 days after surgery. The subjects with anticoagulant use showed more decrease in Hgb levels between immediately after the surgery and 7 days after the surgery (P = .031). Still, both groups did not show a statistical difference in the Hgb level 7 days after surgery (P = .115). Conclusions: In this study, blood loss after arthroscopic rotator cuff repair in elderly patients was greater than expected. Bleeding increased in elderly patients who had longer surgical times or were taking anticoagulant medications after surgery. Tear size was not associated with a decrease in Hgb levels. Level of Evidence: Level III, retrospective comparative study.

Periprosthetic Occult Femoral Fracture: An Unknown Side Effect of Press-Fit Fixation in Primary Cementless Total Hip Arthroplasty.

Purpose: The objectives of this study were to examine the prevalence and risk factors for development of periprosthetic occult femoral fractures during primary cementless total hip arthroplasty (THA) and to assess the clinical consequences of these fractures. Materials and Methods: A total of 199 hips were examined. Periprosthetic occult femoral fractures were defined as fractures not detected intraoperatively and on postoperative radiographs, but only observed on postoperative computed tomography (CT). Clinical, surgical, and radiographic analysis of variables was performed for identification of risk factors for periprosthetic occult femoral fractures. A comparison of stem subsidence, stem alignment, and thigh pain between the occult fracture group and the non-fracture group was also performed. Results: Periprosthetic occult femoral fractures were detected during the operation in 21 (10.6%) of 199 hips. Of eight hips with periprosthetic occult femoral fractures that were detected around the lesser trochanter, concurrent periprosthetic occult femoral fractures located at different levels were detected in six hips (75.0%). Only the female sex showed significant association with an increased risk of periprosthetic occult femoral fractures (odds ratio for males, 0.38; 95% confidence interval, 0.15-1.01; P=0.04). A significant difference in the incidence of thigh pain was observed between the occult fracture group and the non-fracture group (P<0.05). Conclusion: Occurrence of periprosthetic occult femoral fractures is relatively common during primary THA using tapered wedge stems. We recommend CT referral for female patients who report unexplained early postoperative thigh pain or developed periprosthetic intraoperative femoral fractures around the lesser trochanter during primary THA using tapered wedge stems.

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing.

PURPOSE: Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. METHODS: A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. RESULTS: The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). CONCLUSION: Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

Development and Validation of Targeted Gene Sequencing Panel Based Companion Diagnostic for Korean Patients with Solid Tumors.

Recently, several panels using two representative targeting methods have been developed but they do not reflect racial specificity, especially for Asians. We have developed and analytically validated the Korean Pan-cancer Companion Diagnostic (CDX) Panel to apply targeted anticancer drugs to Korean patients based on the molecular characteristics of tumors using tumor samples without matched patient normal samples. The panel included 31 genes with reported single nucleotide variants, 9 genes with reported copy number variations, and 15 genes with predictive responses to targeted drugs under clinical testing, enabling the panel to be analyzed for the targets of 30 targeted anticancer drugs. It is cost-effective and optimized for cancer type-specific therapy in Korean cancer patients across solid cancer types while minimizing the limitations of existing approaches. In addition, the optimized filtering protocol for somatic variants from tumor-only samples enables researchers to use this panel without matched normal samples. To verify the panel, 241 frozen tumor tissues and 71 formalin-fixed paraffin-embedded (FFPE) samples from several institutes were registered. This gene screening method is expected to reduce test turnaround time and cost, making it a balanced approach to investigate solid cancer-related gene regions.

Paired comparisons of mutational profiles before and after brachytherapy in asian uveal melanoma patients.

Uveal melanoma(UM) is the most common primary intraocular malignancy in adults. However, the incidence of UM in Asia is 10 to 20 times less than in Western populations. Therefore, for the first time, we report our whole exome sequencing (WES) data analysis to discover differences in the molecular features of Asian and Western UM, and to determine the disparities between the primary tumor before brachytherapy and enucleated samples after brachytherapy. WES of 19 samples (13 primary tumors, 5 enucleation samples after brachytherapy, and 1 liver metastasis) from 13 patients diagnosed with UM and treated between 2007 and 2019 at the Yonsei University Health System (YUHS) were analyzed using bioinformatics pipelines. We identified significantly altered genes in Asian UM and changes in mutational profiles before and after brachytherapy using various algorithms. GNAQ, BAP1, GNA11, SF3B1 and CYSLTR2 were significantly mutated in Asian UM, which is similar that reported frequently in previous Western-based UM studies. There were also similar copy number alterations (M3, 1p loss, 6p gain, 8q gain) in both groups. In paired comparisons of the same patients, DICER1 and LRP1B were distinctly mutated only in tumor samples obtained after brachytherapy using rare-variant association tests (P = 0.01, 0.01, respectively). The mutational profiles of Asian UM were generally similar to the data from previous Western-based studies. DICER1 and LRP1B were newly mutated genes with statistical significance in the regrowth samples after brachytherapy compared to the primary tumors, which may be related to resistance to brachytherapy.

The effects of a single-dose subacromial injection of a nonsteroidal anti-inflammatory drug in geriatric patients with subacromial impingement syndrome: a randomized double-blind study.

BACKGROUND: As nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids have similar effects, steroids can be avoided to reduce adverse effects. This study aimed to compare the differences in symptom improvement after subacromial injection of steroids or NSAIDs. METHODS: Sixty patients with rotator cuff syndrome for at least 3 months were enrolled and divided into steroid and NSAID groups. The steroid group received a mixture of 1 mL of triamcinolone acetonide (40 mg/mL) and 1 mL of lidocaine hydrochloride 2%, while the NSAID group received a mixture of 1 mL of Ketorolac Tromethamine (30 mg/mL) and 1 mL of lidocaine hydrochloride 2%. The patients were assessed before and at 3, 6, and 12 weeks after the procedure. Shoulder scores from visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) were used for evaluation. RESULTS: Both groups showed improvements in the clinical outcomes. Overall VAS, ASES, and UCLA scores improved from 6.9, 32.7, and 16.0 before the procedure to 2.0, 1.2, and 1.1; 81.5, 87.6, and 88.5; and 29.7, 31.8, and 32.0 at weeks 3, 6, and 12 weeks after the procedure, respectively. Twenty-six patients (86.7%) in the steroid group and 28 (93.3%) in the NSAID group reported satisfactory treatment outcomes. There were no significant differences in the outcomes between the two groups (p=0.671). CONCLUSIONS: Subacromial injection of NSAIDs for rotator cuff tendinitis with shoulder pain had equivalent outcomes with those of steroid injection at the 12-week follow-up.

Comparison of stemless and conventional stemmed shoulder arthroplasties in shoulder arthropathy: A meta-analysis.

BACKGROUND: It is unclear whether stemless shoulder prosthesis lead to better clinical outcomes than conventional stemmed shoulder prosthesis. The purpose is to compare clinical outcomes and complication rates after surgery in patients with shoulder arthropathy treated with stemless or conventional stemmed shoulder prosthesis. METHOD: All studies comparing the constant score (CS), range of motion (ROM), and complication rates after surgery in patients with shoulder arthropathy treated with stemless or conventional stemmed shoulder prosthesis were included. The major databases MEDLINE, EMBASE, the Cochrane Library, Web of Science, and SCOPUS were searched for appropriate studies from the earliest available date of indexing through March 31, 2019. No restrictions were placed on language of publication. RESULTS: A total of 6 studies met the inclusion criteria and were analyzed in detail. Overall postoperative ROM (95% CI: 3.27 to 11.92; P < .01) was significantly greater for stemless prosthesis compared to conventional stemmed prosthesis. However, postoperative CS (95% CI: -2.98 to 7.13; P = .42) and complication rates (OR 1.22, 95% CI: 0.48-3.08; P = .68) were did not differ significantly between the 2 groups. CONCLUSION: This meta-analysis revealed that postoperative CS and complication rates did not differ significantly between the 2 treatment methods, stemless shoulder prosthesis and conventional stemmed shoulder prosthesis, for shoulder arthropathy. However, stemless shoulder prosthesis resulted in better outcomes than conventional stemmed shoulder prosthesis in terms of postoperative ROM. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Clinical Genome Data Model (cGDM) provides Interactive Clinical Decision Support for Precision Medicine.

In light of recent developments in genomic technology and the rapid accumulation of genomic information, a major transition toward precision medicine is anticipated. However, the clinical applications of genomic information remain limited. This lag can be attributed to several complex factors, including the knowledge gap between medical experts and bioinformaticians, the distance between bioinformatics workflows and clinical practice, and the unique characteristics of genomic data, which can make interpretation difficult. Here we present a novel genomic data model that allows for more interactive support in clinical decision-making. Informational modelling was used as a basis to design a communication scheme between sophisticated bioinformatics predictions and the representative data relevant to a clinical decision. This study was conducted by a multidisciplinary working group who carried out clinico-genomic workflow analysis and attribute extraction, through Failure Mode and Effects Analysis (FMEA). Based on those results, a clinical genome data model (cGDM) was developed with 8 entities and 46 attributes. The cGDM integrates reliability-related factors that enable clinicians to access the reliability problem of each individual genetic test result as clinical evidence. The proposed cGDM provides a data-layer infrastructure supporting the intellectual interplay between medical experts and informed decision-making.

Intracranial Ewing sarcoma with whole genome study.

INTRODUCTION: Ewing sarcoma (ES) as a primary intracranial tumor is very rare. Recently, CNS embryonal tumors with ES-like genomic change have been reported. Patients and methods We report a case of intracranial Ewing sarcoma in a 13-year-old girl who complained of headache and migraine. The tumor had developed in the right middle cranial fossa with a mass effect on the brain with impending transuncal herniation. RESULTS: Undifferentiated small round cell morphology with completely negative results for friend leukemia integration 1 transcription factor (Fli-1) and a nonspecific cytoplasmic CD99-positive staining pattern mislead the diagnosis as central nervous system (CNS) embryonal tumor, NOS. However, whole genome sequencing (WGS) revealed Ewing sarcoma (EWS)-Fli-1 gene fusion, which was confirmed by fluorescence in situ hybridization study and the diagnosis was revised to ES. CONCLUSIONS: This case is a true intracranial but extra-axial ES confirmed by WGS. We report this case of intracranial ES to demonstrate the importance of marker gene studies using FISH or NGS.

Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis.

Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by genomic database searching. We also analyzed a public microarray data to validate our results. Thirty-three ROS related genes were up-regulated in PTC with HT, whereas there were only nine genes in PTC without HT (Chi-square p-value < 0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and 0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data analysis, 12 of 32 ROS-related genes showed the same differential expression pattern with statistical significance. In gene ontology analysis, up-regulated ROS-related genes were related with ROS metabolism and apoptosis. Immune function-related and carcinogenesis-related gene sets were enriched only in HT group in Gene Set Enrichment Analysis. Our results suggested that ROS levels may be increased in PTC with HT. Increased levels of ROS may contribute to PTC development in patients with HT.

The strength of the rotator cuff before and after subacromial injection of lidocaine.

The purpose of this study was to evaluate the strength of the shoulder before and after the impingement test. This study included 153 cases of impingement syndrome, 20 cases of partial-thickness rotator cuff tear, and 60 cases of full-thickness rotator cuff tear. We divided each of the groups into 2 subgroups according to the mean percentage decrease in pain to evaluate the correlation between pain and muscle weakness. We also divided the impingement syndrome group into 2 groups based on stiffness. After the test, the subgroup with stiffness had a greater reduction in pain compared with the subgroup without stiffness. The results show no statistically significant difference in the strength of the shoulder, except for increased external rotation strength in patients with full-thickness rotator cuff tears and increased supraspinatus strength in patients with impingement syndrome with stiffness. In cases in which the continuity of the rotator cuff is maintained, pain is not an important factor in the cause of shoulder weakness. Preoperative muscle testing can be done despite pain, but if a full-thickness rotator cuff tear is confirmed, re-examination of external rotator strength is necessary. In patients with impingement syndrome, particularly with shoulder stiffness, supraspinatus strength can be decreased.