Differences in real-world outcomes by risk classification for localized prostate cancer patients after radiation therapy.

BACKGROUND: Limited real-world evidence exists on the long-term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high-risk LPC (HR-LPC) and low/intermediate-risk LPC (LIR-LPC) who received EBRT. METHODS: This retrospective study using Surveillance, Epidemiology, and End Results-Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis-free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan-Meier (KM) and adjusted Cox proportional hazard (PH) models. 5-year survival probabilities stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed. RESULTS: Of 11,313 eligible patients, 41% (n = 4600) had HR-LPC and 59% (n = 6713) had LIR-LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow-up time >40 months. More patients in the HR-LPC than LIR-LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR-LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR-LPC than LIR-LPC patients. Within 5 years after the initial EBRT treatment, 18%-26% of patients with HR-LPC are expected to have died or developed metastasis. The 5-year MFS rate in the HR-LPC group was lower than the LIR-LPC group across all racial/ethnic subgroups. NH Black patients with HR-LPC had the highest all-cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups. CONCLUSIONS: This real-world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR-LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR-LPC.

The Brassicaceae genome resource (TBGR): A comprehensive genome platform for Brassicaceae plants.

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae.

Combined transabdominal and transvaginal ultrasound-guided percutaneous microwave ablation of uterine myomas: an effective monitoring technique.

OBJECTIVE: This study compared the feasibility and efficacy of transabdominal ultrasound (TAU) and combined transabdominal and transvaginal ultrasound (TA/TV US)-guided percutaneous microwave ablation (PMWA) for uterine myoma (UM). METHOD: This study enrolled 73 patients with UM who underwent PMWA via the transabdominal ultrasound-guided (TA group) or the combined transabdominal and transvaginal ultrasound-guided (TA/TV group) approaches. The intraoperative supplementary ablation rates, postoperative immediate ablation rates, lesion reduction rates and other indicators three months postoperatively were compared between the groups. The display of the needle tip, endometrium, uterine serosa, rectum and myoma feeding vessels under the guidance of TAU, transvaginal ultrasound (TVU) and TA/TV US were evaluated in the TA/TV group. RESULTS: In the TA/TV group, the real-time position of the needle tip and the endometrium complete display rate of the same lesions with TVU guidance were significantly higher than those using TAU. TA/TV US guidance significantly improved the complete display rate of each indicator. The intraoperative supplementary ablation rate in the TA/TV group was lower than that in the TA group. Similarly, the postoperative immediate ablation and volume reduction rates of the lesions three months postoperatively were higher than those in the TA group, especially for lesions with a maximum diameter ≥6 cm. CONCLUSION: TA/TV US is an effective monitoring method that can be used to improve imaging display. Its use is recommended in patients with obesity, poor transabdominal ultrasound image quality and large myoma volumes.

Efficacy of Transabdominal Ultrasound-guided Percutaneous Microwave Ablation in the Treatment of Symptomatic Adenomyosis: A Retrospective Cohort Study.

STUDY OBJECTIVE: To evaluate and compare the clinical efficacy of transabdominal ultrasound-guided percutaneous microwave ablation (PMWA) in the treatment of symptomatic focal and nonfocal adenomyosis. DESIGN: Retrospective cohort study. SETTING: Longyan First Affiliated Hospital of Fujian Medical University. PATIENTS: From May 2019 to October 2021, 107 patients with symptomatic adenomyosis who refused hysterectomy received PMWA. INTERVENTIONS: Patients were divided into a focal group (n = 47, including 40 focal adenomyosis and 7 adenomyoma cases) and a nonfocal group (n = 60, including 36 diffuse and 24 mixed adenomyosis cases) according to the extent of lesion involvement. MEASUREMENTS AND MAIN RESULTS: We collected and analyzed preoperative baseline data on patient characteristics; postoperative efficacy measures at 3, 6, and 12 months; and intraoperative and postoperative complications. There was a significant post-treatment reduction in the uterine corpus volume and cancer antigen 125 levels, an increase in hemoglobin levels, and an improvement in the Uterine Fibroid Symptom and Health-related Quality of Life scores (consisting of the Symptom Severity Scale and the Health-related Quality of Life scale), dysmenorrhea visual analog scale, and menstrual volume score (MVS) (all p <.05). One patient had recurrence. Most adverse events (72.0%) were mild. Although the nonfocal group had significantly greater anemia severity, higher Symptom Severity Scale and MVS, lower Health-related Quality of Life scale, greater extent and severity of myometrial involvement, and larger uterine corpus volume, after treatment, the uterine corpus volume, uterine corpus reduction rate, cancer antigen 125 levels, hemoglobin levels, Uterine Fibroid Symptom and Health-related Quality of Life score, dysmenorrhea visual analog scale, MVS score, and clinical response rate were similar between the groups (p >.05). CONCLUSION: PMWA had good, similar, short-term efficacy for symptomatic focal and nonfocal adenomyosis.

Three-dimensional ultrasound VOCAL combined with contrast-enhanced ultrasound: an alternative to contrast-enhanced magnetic resonance imaging for evaluating ablation of benign uterine lesions.

OBJECTIVE: This study explores the feasibility and value of three-dimensional ultrasound virtual organ computer-aided analysis (3D-VOCAL) combined with contrast-enhanced ultrasound (CEUS) for measuring the non-perfused volume (NPV) after microwave ablation (MWA) of benign uterine lesions. METHODS: Fifty-six patients with uterine myoma (UM) and adenomyosis (AM) treated with MWA were enrolled. NPV measurements were obtained postoperatively using two-dimensional CEUS (2D-CEUS), 3D-VOCAL combined with CEUS and three-dimensional contrast-enhanced magnetic resonance imaging (3D-CEMRI). Bland-Altman analysis and intraclass correlation coefficient (ICC) values were used to analyze the agreement of NPV measurements obtained via 2D-CEUS and the combined method with 3D-CEMRI. The inter- and intra-observer agreements of the NPV values obtained with all three methods were also analyzed. RESULTS: Considering 3D-CEMRI as the standard, 3D-VOCAL showed greater agreement than 2D-CEUS and higher ICCs (ICC, 0.999 vs. 0.891) than 2D-CEUS for different lesion types and sizes of non-perfusion areas (p < 0.001 for all comparisons). NPV measurements obtained via 2 D-CEUS and 3 D-CEMRI differed significantly for AM and non-perfusion areas with maximum diameter ≥5 cm (p < 0.05) and showed no significant differences (p > 0.05) for UM and non-perfusion areas with maximum diameter <5 cm. The NPV measurements obtained via 3D-VOCAL and 3D-CEMRI did not differ significantly (p > 0.05). The intra- and inter-observer agreements of 3D-VOCAL measurements were better than those of 2D-CEUS and slightly lower than those of 3D-CEMRI. CONCLUSIONS: 3D-VOCAL combined with CEUS provides accurate estimates of NPV after MWA of benign uterine lesions, and offers a reliable, simple and efficient alternative to CEMRI.

Association of clinico-genomic characteristics with tumor mutational burden in small cell lung cancer patients.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

Association of depression symptom severity with short-term risk of an initial hospital encounter in adults with major depressive disorder.

BACKGROUND: Despite the availability of pharmacologic and nonpharmacologic treatment options, depression continues to be one of the leading causes of disability worldwide. This study evaluated whether depression symptom severity, as measured by PHQ-9 score, of patients diagnosed with MDD is associated with short-term risk of a hospital encounter (ER visit or inpatient stay). METHODS: Adults with ≥1 PHQ-9 assessment in an outpatient setting (index date) and ≥ 1 MDD diagnosis within 6 months prior were included from the de-identified Optum Electronic Health Record database (April 2016-June 2019). Patients were categorized by depression symptom severity based on PHQ-9 scores obtained by natural language processing. Crude rates, adjusted absolute risks, and adjusted relative risks of all-cause and MDD-related hospital encounters within 30 days following assessment of depression severity were determined. RESULTS: The study population consisted of 280,145 patients with MDD and ≥ 1 PHQ-9 assessment in an outpatient setting. Based on PHQ-9 scores, 26.9% of patients were categorized as having none/minimal depression symptom severity, 16.4% as mild, 24.7% as moderate, 19.6% as moderately severe, and 12.5% as severe. Among patients with none/minimal, mild, moderate, moderately severe, and severe depression, the adjusted absolute short-term risks of an initial all-cause hospital encounter were 4.1, 4.4, 4.8, 5.6, and 6.5%, respectively; MDD-related hospital encounter adjusted absolute risks were 0.8, 1.0, 1.3, 1.6, and 2.1%, respectively. Compared to patients with none/minimal depression symptom severity, the adjusted relative risks of an all-cause hospital encounter were 1.60 (95% CI 1.50-1.70) for those with severe, 1.36 (1.29-1.44) for those with moderately severe, 1.18 (1.12-1.25) for those with moderate, and 1.07 (1.00-1.13) for those with mild depression symptom severity. CONCLUSIONS: These study findings indicate that depression symptom severity is a key driver of short-term risk of hospital encounters, emphasizing the need for timely interventions that can ameliorate depression symptom severity.

Multifunctional co-loaded magnetic nanocapsules for enhancing targeted MR imaging and in vivo photodynamic therapy.

Drug delivery nanocarriers based on magnetic nanoparticles have attracted increasing attention due to their potential applications in magnetic resonance imaging, photodynamic therapy and targeted drug delivery. Herein, we have fabricated the multifunctional co-loaded magnetic nanocapsules (MNCPs) using a microemulsion process for enhancing targeted magnetic resonance imaging and in vivo photodynamic therapy. MNCPs were synthesized by co-loading Co@Mn magnetic nanoparticles and chlorin e6 into the matrix of an amphiphilic polymer, and further surface covalently coupled with target molecules. This work demonstrates that MNCPs have uniform sizes (dc: ~150 nm), favorable biocompatibility, long-term stability, excellent T2 relaxation values, and high drug loading efficiency. These advantages offer MNCPs successfully applied in targeted magnetic resonance imaging, real-time fluorescent labeling, and photodynamic therapy. The research results will contribute to rationally design novel nano-platform and provide a promising approach for further clinical integration of diagnosis and treatment in the near future.

Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: a nested case-control study using the healthcore integrated research database.

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

Rapid detection and quantification of tumor marker carbohydrate antigen 72-4 (CA72-4) using a superparamagnetic immunochromatographic strip.

Rapid and quantitative detection of biomarkers with high sensitivity and specificity has become a common practice in the clinical diagnosis and treatment of cancer. Herein, a quantitative lateral flow immunoassay (LFIA) based on superparamagnetic nanoparticles (SPMNPs) was developed for detection of carbohydrate antigen 72-4 (CA72-4) in human serum. This direct and rapid method did not involve any sample preparation and was accomplished using a test strip in which a sandwich reaction was performed. Probes on the conjugate pad were prepared by coupling monoclonal antibody CC49 specific to CA72-4 onto SPMNPs. Coupled monoclonal antibody B72.3 and goat anti-mouse IgG were loaded onto a nitrocellulose (NC) membrane, serving as the test and control lines, respectively. Initially, results were evaluated by macroscopic observation. Afterwards, the magnetic signal strength of the reaction area was quantified using a magnetic assay reader (MAR). Several parameters that may influence the detection sensitivity were studied and optimized. Under optimal conditions, the proposed method was capable of detecting as low as 0.38 IU/mL of CA72-4 in 20 min and had a wide detection linearity range (0-100 IU/mL). We evaluated 100 clinical samples (70 positive and 30 negative) to assess the validity of these test strips, which exhibited high sensitivity (99%) and specificity (97%). The results indicated a high rate of accuracy (98.4-102%) and a low relative standard deviation according to the average recovery test. In conclusion, the test strips based on SPMNP probes are a rapid, sensitive, and quantitative method for the detection of CA72-4 and possess great potential in point-of-care testing (POCT).

Identification of impaired fasting glucose, healthcare utilization and progression to diabetes in the UK using the Clinical Practice Research Datalink (CPRD).

PURPOSE: Few studies have examined patients with prediabetes in usual, "real-world" clinical practice settings. Among patients with impaired fasting glucose (IFG), we aimed to describe the rates of progression to diabetes and to examine the long-term reduction in diabetes risk associated with regression to normoglycemia at 1 year. METHODS: The UK-based study included 120 055 non-diabetic patients in Clinical Practice Research Datalink from 2001 to 2012 aged 25+ years and with ≥1 fasting plasma glucose (FPG) test between ≥6.1 and <7.0 mmol/l indicating IFG who were followed for progression to diabetes. In a subgroup of 45 167 patients with IFG with subsequent FPG results 1 year later, we assessed the 1-year glycemic status change and estimated the relative hazard of diabetes comparing patients with regression to normoglycemia (IFG-normoglycemia) to those who remained in IFG (IFG-IFG) using a multivariable Cox model. RESULTS: Among patients with IFG with over 414 649 person-years of follow-up, 52% received a subsequent FPG test, and 10% developed diabetes within 1 year after recognition of IFG. The incidence rate of diabetes was 5.86 (95% CI: 5.78 to 5.93) per 100 person-years. In the subgroup analysis, 31% of these patients remained in IFG, while 53% and 16% converted to normoglycemia or diabetes, respectively. The adjusted hazard ratio of developing diabetes was 0.33 (95% CI: 0.31 to 0.35) comparing IFG-normoglycemia to IFG-IFG. CONCLUSIONS: IFG is a high-risk state for diabetes. Regression to normoglycemia from IFG strongly reduces the long-term risk of developing diabetes. Our study also shows the feasibility of identifying patients with IFG in the Clinical Practice Research Datalink. Copyright © 2016 John Wiley & Sons, Ltd.

Synergetic effects of aqueous extracts of Fuzi (Radix Aconiti Lateralis Preparata) and Tubeimu (Rhizoma Bolbostemmatis) on MDA-MB-231 and SKBR3 cells.

OBJECTIVE: To test the synergistic effects of theaqueous extract of Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) on MDA-MB-231 and SKBR3 breast cancer cells. METHODS: A combined index was created for the effects of Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) extracts. Cell proliferation was performed by trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays. Flow cytometry was used to assess cell cycle distribution and apoptosis. Cell migration was determined by wound-healing and transwell assays. Confocal microscopy was used to detect E-cadherin and actin filaments. RESULTS: The aqueous extract from Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix AconitiLateralis Preparata) exerted synergetic effects on the growth of MDA-MB-231 cells and G1 phase arrest. When exposed to extracts at concentrations of 62.5 :62.5 and 62.5: 31.3 µg/mL, the combination index was 0.83 and 0.74, respectively. Interestingly, 62.5: 31.3 pg/mL of combined drugs enhanced the inhibitory effect of Tubeimu (Rhizoma Bolbostemmatis) on the migration of SKBR3 cells and reduced the stimulative effect of Fuzi (Radix Aconiti Lateralis Preparata) (P < 0.01), in which cells showed an increased expression of E-cadherin and reorganization of actin filaments (P < 0.001). 62.5:62.5 µg/mL extract also synergistically induced apoptosis of MDA-MB-231 cells (P < 0.05 and P < 0.001). Acting as the main active ingredients in the extract, tubeimoside I and acetylbenzoylaconine at 10: 10 µg/ mL and 5:2.5 µg/mL also produced inhibitory effects on the proliferation and migration of cells (P < 0.01). CONCLUSION: Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) extracts had synergic effects on MDA-MB-231 and SKBR3 cells.

Predicting Risk of 1-Year Hospitalization Among Patients with Pulmonary Arterial Hypertension.

INTRODUCTION: US claims-based analyses emphasize the substantial hospitalization burden of patients with pulmonary arterial hypertension (PAH) and the significant need for improved monitoring and more timely interventions. A claims-based predictive model may be useful to assist healthcare providers and payers in identifying patients with PAH at increased hospitalization risk. To address this aim, we constructed statistical models using baseline patient variables available in administrative healthcare claims to predict patients' risk for all-cause and PH-related hospitalization within 1 year of initiating ≥ 1 PAH indicated medication. METHODS: Adult patients with PAH who newly initiated ≥ 1 PAH indicated medication were selected from the MarketScan Commercial and Medicare Supplemental databases (January 1, 2009-January 31, 2019). Cox regression models were built with a randomly selected training set and evaluated using a validation set of remaining patients. Predictive variables for the models were selected in three steps: clinical knowledge, univariate analysis, and backward stepwise selection. RESULTS: Within 1 year of initiating ≥ 1 PAH indicated medication, 1502/3872 (38.8%) had an all-cause hospitalization and 950/3872 (24.5%) had a pulmonary hypertension (PH)-related hospitalization. Predictive risk factors for all-cause hospitalization were Quan-Charlson Comorbidity Index (CCI) score 2-3 [hazard ratio (HR) 1.229; P = 0.038] and ≥ 4 (HR 1.531; P < 0.001), claims-based frailty index (CFI) score > 1 (highest frailty level; HR 1.301; P = 0.018), hemoptysis (HR 1.254; P = 0.016), malaise/fatigue (HR 1.150; P = 0.037), history of PH-related hospitalization (HR 1.171; P = 0.011), non-PH-related ER visit (HR 1.713; P = 0.014), and higher non-PH-related outpatient visit cost (HR 1.069; P < 0.001). Predictive risk factors for PH-related hospitalization were female sex (HR 1.264; P = 0.004), Quan-CCI score ≥ 4 (HR 1.408; P = 0.008), portal hypertension (HR 1.565; P = 0.019), CFI score > 1 (HR 1.522; P = 0.002), dyspnea (HR 1.259; P = 0.023), and history of PH-related hospitalization (HR 1.273; P = 0.002). CONCLUSIONS: The US claims-based predictive models showed acceptable performance to predict 1-year hospitalization among patients with PAH.

Protective effect of FTY720 on several markers of liver injury induced by concanavalin a in mice.

BACKGROUND: 2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diol hydrochloride (FTY720) is a novel agent with protective effect on several markers of liver injury. It is a chemical substance derived by modifying myriocin from the ascomycete Isaria sinclairii. It has been reported that FTY720 is able to treat autoimmune encephalomyelitis, renal cancer, asthma, and multiple sclerosis. More potent clinical applications of FTY720 need to be investigated. OBJECTIVE: The aim of this study was to evaluate the protective effect of FTY720 on several markers of experimental liver injury and to investigate the possible mechanism of action. METHODS: Concanavalin A (Con A) at a dose of 15 mg/kg was intravenously. injected in mice, and 10 days before the Con A challenge, 1 mg/kg, 3 mg/kg, and 6 mg/kg of FTY720 were administered to mice. The liver injury was monitored biochemically by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and tumor necrosis factor-α (TNF-α) levels. TNF-α and nuclear factor-κB (NF-κB) in liver tissue were detected by Western blot analysis. RESULTS: FTY720, when administered intragastrically for 10 days in mice with Con A-induced liver injury, dose-dependently reduced serum ALT and AST and TNF-α levels. The differences were statistically significant (P ≤ 0.05). It was also found that FTY720 decreases TNF-α and NF-κB protein expression in liver tissue. CONCLUSIONS: FTY720 is able to improve several markers of Con A-induced liver injury in mice, including serum ALT, serum AST, TNF-α, and NF-κB, which might be at least in part related to its ability to reduce TNF-α/NF-κB cascade activity.

Real-World Patient Characteristics, Treatment Patterns, and Mutation Testing Patterns Among US Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations.

INTRODUCTION: Approximately 15% of patients with non-small cell lung cancer (NSCLC) harbor an epidermal growth factor receptor mutation (EGFRm). Mutation testing (including EGFRm) is recommended for patients with advanced NSCLC (aNSCLC) prior to initiating first-line therapy (L1) or after progression on targeted therapy. To elucidate current and future unmet needs, the present study characterized real-world EGFR testing patterns and treatment patterns in patients with aNSCLC. METHODS: This retrospective observational cohort study evaluated newly diagnosed adult patients with aNSCLC (stage IIIB or higher) from the Flatiron Health database. Eligible patients received at least L1 during 2015-2020 (testing cohorts) or 2011-2020 (treatment cohorts). Eligible patients for the treatment cohorts had an EGFR mutation. RESULTS: The testing cohort included 22,726 patients, 75.5% had at least one EGFR test and 15.2% of those tested were positive for EGFR mutation. From 2015 to 2020, the median time from sample collection to test results decreased substantially while the proportion of NGS EGFR tests and use of plasma samples increased. The treatment cohort included 3701 patients (95% common mutations [cEGFR], 5.0% exon 20 insertions [ex20ins]). Three or more lines of therapy (LOTs) were observed in approximately 30% of patients. For L1, most cEGFR patients received EGFR tyrosine kinase inhibitors (EGFR-TKI, 68.1%) or platinum-based chemotherapy (PBC, 24.8%); most ex20ins patients received PBC (66.1%) or EGFR-TKI (17.5%). The most common L2 was EGFR-TKI (54.1%) or PBC (22.8%) for cEGFR and immunotherapy (25.9%) or PBC (25.9%) for ex20ins. No predominant L3 was evident in either group. CONCLUSION: This real-world study, among the largest analyses of testing patterns for patients with aNSCLC, demonstrates a comprehensive view of treatment patterns for patients with EGFR mutations, including ex20ins. Despite recent improvement, increased use of EGFR testing, including advanced methods, is needed to optimize treatment pathways and outcomes. Additionally, the lack of a predominant therapy in later lines indicates a need for new therapies.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BACKGROUND: Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications. METHODS: This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1-4, 5-9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM). RESULTS: A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups. CONCLUSIONS: In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Healthcare Costs of Multiple Myeloma Patients with Four or More Prior Lines of Therapy, Including Triple-Class Exposure in the United States.

INTRODUCTION: The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). METHODS: Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012-30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti-CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. RESULTS: The study population included 68 patients with MM (63% men), with a mean age of 59.8 years. Mean duration from first-observed MM diagnosis until index date averaged 46.7 months. During a mean follow-up of 21.9 months, total all-cause healthcare costs averaged US$757,386 per patient (equivalent to US$34,610 per patient per month). MM-related healthcare costs (US$670,561 per patient) contributed on average 88.5% to the total all-cause healthcare costs; the majority (67.2%) of MM-related healthcare costs were attributed to drug and infusion costs (US$450,952 per patient). CONCLUSIONS: In this retrospective US claims-database study, patients with MM with ≥ 4 prior LOTs, including TCE, continued to experience high healthcare costs that were mostly attributable to anti-myeloma drugs and their administration.

Interleukin-17 and vascular endothelial growth factor: new biomarkers for the diagnosis of papillary thyroid carcinoma in patients with Hashimoto's thyroiditis.

OBJECTIVE: The incidences of papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) have shown increasing trends. Numerous studies have shown a close relationship between the two diseases, but the exact mechanism linking PTC with HT is still unclear. Interleukin-17 (IL-17) plays an important role in the development of malignant tumors. However, information on the association between IL-17 and thyroid disease is lacking. METHODS: Tissue samples were collected from patients with thyroid diseases admitted to the thyroid surgery department of our hospital between May 2015 and December 2017. The characteristics of the thyroid were observed by ultrasonography, hematoxylin-eosin staining, enzyme-linked immunosorbent assays, and immunohistochemistry. RESULTS: We found that HT with carcinoma (HTC) showed unique characteristics in two-dimensional ultrasound images. Moreover, IL-17 and vascular endothelial growth factor (VEGF) levels showed gradually increasing trends during the process of HT malignant transformation, with a significant positive correlation between the two cytokines. Serum IL-17 and VEGF levels could distinguish between HTC and HT with benign adenoma. CONCLUSION: Our data suggest that serum IL-17 and VEGF levels may represent novel biomarkers for the diagnosis of HT malignant nodules.

Evaluation of Different Anthropometric Indicators for Screening for Nonalcoholic Fatty Liver Disease in Elderly Individuals.

OBJECTIVE: To explore the anthropometric indicators suitable for screening for nonalcoholic fatty liver disease (NAFLD) in the elderly population. METHODS: This cross-sectional study screened subjects over 65 years, who had undergone a physical examination in 2019. Their height, weight, waist circumference, and fasting blood glucose and triglyceride levels were measured. Body mass index (BMI), waist circumstance (WC), waist-to-height ratio (WHtR), relative fat mass (RFM), ponderal index (PI), conicity index (CI), lipid accumulation product (LAP), and body shape index (ABSI) were calculated. Statistical analyses were performed using the Chi-square test, logistic regression, and receiver operating characteristic (ROC) curve. SUBJECTS: Of a total of 4985 subjects, 1173 diagnosed with NAFLD and 3812 without NAFLD were included. RESULTS: The NAFLD group had increased BMI, WC, WHtR, RFM, PI, CI, and LAP. ABSI was only significantly different in males between the groups. Logistic regression analysis showed that RFM was an effective prognostic factor for males with NAFLD, and LAP, BMI, and WC were effective prognostic factors for females. ROC curve analysis showed that LAP played a significant role in the prediction of NAFLD. CONCLUSION: LAP is closely related to the occurrence of NAFLD and could be an efficient screening and treatment tool for NAFLD in the elderly people. Lay Summary. We conducted a screening and study of nonalcoholic fatty liver disease in the elderly population by determining the association between obesity indexes and nonalcoholic fatty liver disease. We found that LAP is practical, easy-to-measure tool for screening and studying NAFLD in the high-risk community elderly population, making it a valuable indicator in research.

Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and diabetes.

AIMS: To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. METHODS: Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. RESULTS: A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09). CONCLUSIONS: In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.