Associations between first-trimester screening biomarkers and maternal characteristics with gestational diabetes mellitus in Chinese women.

Background: Gestational diabetes mellitus (GDM) can result in adverse maternal and neonatal outcomes. Predicting those at high risk of GDM and early interventions can reduce the development of GDM. The aim of this study was to examine the associations between first-trimester prenatal screening biomarkers and maternal characteristics in relation to GDM in Chinese women. Methods: We conducted a retrospective cohort study of singleton pregnant women who received first-trimester aneuploidy and preeclampsia screening between January 2019 and May 2021. First-trimester prenatal screening biomarkers, including pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, and placental growth factor (PLGF), along with maternal characteristics, were collected for analysis in relation to GDM. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate variables associated with GDM. Results: Of the 1452 pregnant women enrolled, 96 developed GDM. PAPP-A (5.01 vs. 5.73 IU/L, P < 0.001) and PLGF (39.88 vs. 41.81 pg/mL, P = 0.044) were significantly lower in the GDM group than in the non-GDM group. The area under the ROC curve of combined maternal characteristics and biomarkers was 0.73 (95% confidence interval [CI] 0.68-0.79, P < 0.001). The formula for predicting GDM was as follows: P = 1/[1 + exp (-8.148 + 0.057 x age + 0.011 x pregestational body mass index + 1.752 x previous GDM history + 0.95 x previous preeclampsia history + 0.756 x family history of diabetes + 0.025 x chronic hypertension + 0.036 x mean arterial pressure - 0.09 x PAPP-A - 0.001 x PLGF)]. Logistic regression analysis revealed that higher pregestational body mass index (adjusted odds ratio [aOR] 1.03, 95% CI 1.01 - 1.06, P = 0.012), previous GDM history (aOR 9.97, 95% CI 3.92 - 25.37, P < 0.001), family history of diabetes (aOR 2.36, 95% CI 1.39 - 4.02, P = 0.001), higher mean arterial pressure (aOR 1.17, 95% CI 1.07 - 1.27, P < 0.001), and lower PAPP-A level (aOR 0.91, 95% CI 0.83 - 1.00, P = 0.040) were independently associated with the development of GDM. The Hosmer-Lemeshow test demonstrated that the model exhibited an excellent discrimination ability (chi-square = 3.089, df = 8, P = 0.929). Conclusion: Downregulation of first-trimester PAPP-A and PLGF was associated with the development of GDM. Combining first-trimester biomarkers with maternal characteristics could be valuable for predicting the risk of GDM.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

Kelp as a biomonitor of persistent organic pollutants in coastal areas of China: Contamination levels and human health risk.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321-4.24 ng/g dry weight (dw), 0.255-25.5 ng/g dw and 3.00 × 10-3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.

Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer.

Background: Transmembrane E3 ubiquitin ligase (RNF43) mutations are present in approximately 6-18% of colorectal cancers (CRC) and could enhance Wnt/ß-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of RNF43-mutant CRC. Methods: A total of 78 patients with RNF43-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, clinical characteristics, treatment regimens used, and survival outcomes were collected and analyzed. Results: Our study uncovered that patients with RNF43 mutations in the N-terminal domain (NTD; n = 50) exhibited shorter overall survival (OS; median months, 50.80 versus not reached; p = 0.043) compared to those in the C-terminal domain (CTD; n = 17). Most RNF43 mutations in NTD had positive primary lymph node status, low tumor mutation burden (TMB-L), and correlated with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status. By contrast, RNF43 mutations in CTD were significantly enriched in deficient MMR (dMMR)/microsatellite instability (MSI-H) tumors with high TMB (TMB-H). N-terminal RNF43-mutated tumors harbored a hotspot variant (RNF43 R117fs), which independently predicted a significantly worse outcome in pMMR/MSS CRC with a median OS of 18.9 months. Patients with RNF43 mutations and the BRAF V600E alterations demonstrated sensitivity to BRAF/EGFR inhibitors. Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy. Conclusion: Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.

Disruption of redox balance in glutaminolytic triple negative breast cancer by inhibition of glutamate export and glutaminase.

In triple-negative breast cancer (TNBC) that relies on catabolism of amino acid glutamine, glutaminase (GLS) converts glutamine to glutamate, which facilitates glutathione synthesis by mediating the enrichment of intracellular cystine via xCT antiporter activity. To overcome chemo resistant TNBC, we have tested a strategy of disrupting cellular redox balance by inhibition of GLS and xCT by CB839 and Erastin, respectively. Key findings of our study include: 1. Dual metabolic inhibition (CB839+Erastin) led to significant increases of cellular superoxide level in both parent and chemo resistant TNBC cells, but superoxide level was distinctly lower in resistant cells. 2. Dual metabolic inhibition combined with doxorubicin or cisplatin induced significant apoptosis in TNBC cells and is associated with high degrees of GSH depletion. In vivo , dual metabolic inhibition plus cisplatin led to significant growth delay of chemo resistant human TNBC xenografts. 3. Ferroptosis is induced by doxorubicin (DOX) but not by cisplatin or paclitaxel. Addition of dual metabolic inhibition to DOX chemotherapy significantly enhanced ferroptotic cell death. 4. Significant changes in cellular metabolites concentration preceded transcriptome changes revealed by single cell RNA sequencing, underscoring the potential of capturing early changes in metabolites as pharmacodynamic markers of metabolic inhibitors. Here we demonstrated that 4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) PET detected xCT blockade by Erastin or its analog in mice bearing human TNBC xenografts. In summary, our study provides compelling evidence for the therapeutic benefit and feasibility of non-invasive monitoring of dual metabolic blockade as a translational strategy to sensitize chemo resistant TNBC to cytotoxic chemotherapy.

UPLC-Q-TOF-MS, network analysis, and molecular docking to investigate the effect and active ingredients of tea-seed oil against bacterial pathogens.

Object: This research intended to probe the antibacterial effect and pharmacodynamic substances of Tea-Seed Oil (TSO) through the use of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) analysis, network analysis, and molecular docking. Methods: The major chemical components in the methanol-extracted fractions of TSO were subjected to UPLC-Q-TOF-MS. Network pharmacology and molecular docking techniques were integrated to investigate the core components, targets, and potential mechanisms of action through which the TSO exert their antibacterial properties. To evaluate the inhibitory effects, the minimum inhibitory concentration and diameter of the bacteriostatic circle were calculated for the potential active ingredients and their equal ratios of combinatorial components (ERCC) against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Moreover, the quantification of the active constituents within TSO was achieved through the utilization of high-performance liquid chromatography (HPLC). Results: The methanol-extracted fractions contained a total of 47 chemical components, predominantly consisting of unsaturated fatty acids and phenolic compounds. The network pharmacology analysis and molecular docking analysis revealed that various components, including gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phlorizin, have the ability to interact with critical core targets such as serine/threonine protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), a monoclonal antibody to mitogen-activated protein kinase 14 (MAPK14), HSP90AA1, and estrogen receptor 1 (ESR1). Furthermore, these components can modulate the phosphatidylinositol-3-kinase protein kinase B (PI3K-AKT), estrogen, MAPK and interleukin 17 (IL-17) signaling pathways, hereby exerting antibacterial effects. In vitro validation trials have found that seven components, namely gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phloretin, displayed substantial inhibitory effects on E. coli, S. aureus, P. aeruginosa, and C. albicans, and are typically present in tea oil, with a total content ranging from 15.87∼24.91 µg·g-1. Conclusion: The outcomes of this investigation possess the possibility to expand our knowledge base concerning the utilization of TSO, furnish a theoretical framework for the exploration of antibacterial drugs and cosmetics derived from inherently occurring TSO, and establish a robust groundwork for the advancement and implementations of TOS products within clinical settings.

Infection of epithelioma papulosum cyprini (EPC) cells with spring viremia of carp virus (SVCV) induces autophagy and apoptosis through endoplasmic reticulum stress.

Spring viremia of carp virus (SVCV) is a lethal freshwater pathogen of cyprinid fish that has caused significant economic losses to aquaculture. To reduce the economic losses caused by SVCV, its pathogenic mechanism needs to be studied more thoroughly. Here, we report for the first time that SVCV infection of Epithelioma papulosum cyprini (EPC) cells can induce cellular autophagy and apoptosis through endoplasmic reticulum stress. The presence of autophagic vesicles in infected EPC cells was shown by transmission electron microscopy. Quantitative fluorescence PCR and Western blot results showed that p62 mRNA expression was decreased, and the expression of Beclin1 and LC3 mRNA was increased. The p62 protein was decreased, and the Beclin1 protein and LC3 were increased in the endoplasmic reticulum stress activation state. To further clarify the mode of death of SVCV-infected EPC cells, we examined caspase3, caspase9, BCL-2, and Bax mRNA, which showed that they were all increased. Apoptosis of SVCV-infected cells increased upon activation of endoplasmic reticulum stress. Our results suggest that endoplasmic reticulum stress can regulate SVCV infection-induced autophagy and apoptosis. The results of this study provide theoretical data for the pathogenesis of SVCV and lay the foundation for future drug development and vaccine construction.

Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.

Extracellular Vesicle Membrane Protein Profiling and Targeted Mass Spectrometry Unveil CD59 and Tetraspanin 9 as Novel Plasma Biomarkers for Detection of Colorectal Cancer.

Extracellular vesicles (EVs) are valuable sources for the discovery of useful cancer biomarkers. This study explores the potential usefulness of tumor cell-derived EV membrane proteins as plasma biomarkers for early detection of colorectal cancer (CRC). EVs were isolated from the culture supernatants of four CRC cell lines by ultracentrifugation, and their protein profiles were analyzed by LC-MS/MS. Bioinformatics analysis of identified proteins revealed 518 EV membrane proteins in common among at least three CRC cell lines. We next used accurate inclusion mass screening (AIMS) in parallel with iTRAQ-based quantitative proteomic analysis to highlight candidate proteins and validated their presence in pooled plasma-generated EVs from 30 healthy controls and 30 CRC patients. From these, we chose 14 potential EV-derived targets for further quantification by targeted MS assay in a separate individual cohort comprising of 73 CRC and 80 healthy subjects. Quantitative analyses revealed significant increases in ADAM10, CD59 and TSPAN9 levels (2.19- to 5.26-fold, p < 0.0001) in plasma EVs from CRC patients, with AUC values of 0.83, 0.95 and 0.87, respectively. Higher EV CD59 levels were significantly correlated with distant metastasis (p = 0.0475), and higher EV TSPAN9 levels were significantly associated with lymph node metastasis (p = 0.0011), distant metastasis at diagnosis (p = 0.0104) and higher TNM stage (p = 0.0065). A two-marker panel consisting of CD59 and TSPAN9 outperformed the conventional marker CEA in discriminating CRC and stage I/II CRC patients from healthy controls, with AUC values of 0.98 and 0.99, respectively. Our results identify EV membrane proteins in common among CRC cell lines and altered plasma EV protein profiles in CRC patients and suggest plasma EV CD59 and TSPAN9 as a novel biomarker panel for detecting early-stage CRC.

Two NPF transporters mediate iron long-distance transport and homeostasis in Arabidopsis.

Iron (Fe) transport and reallocation are essential to Fe homeostasis in plants, but it is unclear how Fe homeostasis is regulated, especially under stress. Here we report that NPF5.9 and its close homolog NPF5.8 redundantly regulate Fe transport and reallocation in Arabidopsis. NPF5.9 is highly upregulated in response to Fe deficiency. NPF5.9 expresses preferentially in vasculature tissues and localizes to the trans-Golgi network, and NPF5.8 showed a similar expression pattern. Long-distance Fe transport and allocation into aerial parts was significantly increased in NPF5.9-overexpressing lines. In the double mutant npf5.8 npf5.9, Fe loading in aerial parts and plant growth were decreased, which were partially rescued by Fe supplementation. Further analysis showed that expression of PYE, the negative regulator for Fe homeostasis, and its downstream target NAS4 were significantly altered in the double mutant. NPF5.9 and NPF5.8 were shown to also mediate nitrate uptake and transport, although nitrate and Fe application did not reciprocally affect each other. Our findings uncovered the novel function of NPF5.9 and NPF5.8 in long-distance Fe transport and homeostasis, and further indicated that they possibly mediate nitrate transport and Fe homeostasis independently in Arabidopsis.

[Research progress in establishment of N-methyl-N'-nitro-N-nitroso-guanidine-induced rat model of Precancerous lesion of gastric cancer].

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.

Identification of Fucosylated SERPINA1 as a Novel Plasma Marker for Pancreatic Cancer Using Lectin Affinity Capture Coupled with iTRAQ-Based Quantitative Glycoproteomics.

Pancreatic cancer (PC) is an aggressive cancer with a high mortality rate, necessitating the development of effective diagnostic, prognostic and predictive biomarkers for disease management. Aberrantly fucosylated proteins in PC are considered a valuable resource of clinically useful biomarkers. The main objective of the present study was to identify novel plasma glycobiomarkers of PC using the iTRAQ quantitative proteomics approach coupled with Aleuria aurantia lectin (AAL)-based glycopeptide enrichment and isotope-coded glycosylation site-specific tagging, with a view to analyzing the glycoproteome profiles of plasma samples from patients with non-metastatic and metastatic PC and gallstones (GS). As a result, 22 glycopeptides with significantly elevated levels in plasma samples of PC were identified. Fucosylated SERPINA1 (fuco-SERPINA1) was selected for further validation in 121 plasma samples (50 GS and 71 PC) using an AAL-based reverse lectin ELISA technique developed in-house. Our analyses revealed significantly higher plasma levels of fuco-SERPINA1 in PC than GS subjects (310.7 ng/mL v.s. 153.6 ng/mL, p = 0.0114). Elevated fuco-SERPINA1 levels were associated with higher TNM stage (p = 0.024) and poorer prognosis for overall survival (log-rank test, p = 0.0083). The increased plasma fuco-SERPINA1 levels support the utility of this protein as a novel prognosticator for PC.

Surgical Timing for Carpal Tunnel Syndrome: A Comparison of Health Care Delivery in the Veterans Administration and Private Sector.

PURPOSE: The U.S. Department of Veterans Affairs (VA) health care system monitors time from referral to specialist visit. We compared wait times for carpal tunnel release (CTR) at a VA hospital and its academic affiliate. METHODS: We selected patients who underwent CTR at a VA hospital and its academic affiliate (AA) (2010-2015). We analyzed time from primary care physician (PCP) referral to CTR, which was subdivided into PCP referral to surgical consultation and surgical consultation to CTR. Electrodiagnostic testing (EDS) was categorized in relation to surgical consultation (prereferral vs postreferral). Multivariable Cox proportional hazard models were used to examine associations between clinical variables and surgical location. RESULTS: Between 2010 and 2015, VA patients had a shorter median time from PCP referral to CTR (VA: 168 days; AA: 410 days), shorter time from PCP referral to surgical consultation (VA: 43 days; AA: 191 days), but longer time from surgical consultation to CTR (VA: 98 days; AA: 55 days). Using multivariable models, the VA was associated with a 35% shorter time to CTR (AA hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.52-0.82) and 75% shorter time to surgical consultation (AA HR, 0.25; 95% CI, 0.20-0.03). Receiving both prereferral and postreferral EDS was associated with almost a 2-fold prolonged time to CTR (AA HR, 0.49; 95% CI, 0.36-0.67). CONCLUSIONS: The VA was associated with shorter overall time to CTR compared with its AA. However, the VA policy of prioritizing time from referral to surgical consultation may not optimally incentivize time to surgery. Repeat EDS was associated with longer wait times in both systems. CLINICAL RELEVANCE: Given differences in where delays occur in each health care system, initiatives to improve efficiency will require targeting the appropriate sources of preoperative delay. Judicious use of EDS may be one avenue to decrease wait times in both systems.

Out-of-Pocket Spending for Thumb Carpometacarpal Arthritis: Capitation Matters.

Background: Patients are increasingly responsible for direct medical expenditures with a growth in out-of-pocket (OOP) expenses, which can impede access to care and affect treatment. This study aims to investigate the impact of capitation on OOP expenses for surgical and presurgical treatment for thumb carpometacarpal (CMC) joint arthritis. Methods: Patients with a diagnosis of thumb CMC arthritis who underwent surgery (2009-2016) comprised our study cohort. Sociodemographic data, total cost, and OOP expenses were collected at the time of surgery and 2 years prior. Patients were stratified by insurance type: fee-for-service (FFS), managed care (MC), Medicare-MC, and Medicare-FFS. Capitated plans were included in the MC and Medicare-MC groups. A generalized linear regression was performed to investigate the association between OOP expenses and insurance type. Results: Our cohort consisted of 7780 patients with FFS insurance, 953 with MC insurance, 2136 with Medicare-FFS, and 265 with Medicare-MC. There was no difference in total costs for FFS and MC (FFS $7281 vs. MC $7306, P = .73; Medicare-FFS $6663 vs. Medicare-MC $6183, P = .19). However, patients with FFS incurred significantly greater OOP costs (FFS $952 vs. MC $434, P < .01; Medicare-FFS $343 vs. Medicare-MC $232, P < .01). In the adjusted regression, MC, Medicare-FFS, and Medicare-MC had approximately 21% to 46% of the predicted OOP expenses of patients with FFS plans (P < .01). Conclusion: Despite similar total costs, OOP expenses were significantly greater for patients with FFS or Medicare-FFS insurance. With healthcare costs transitioning to patients, providers should consider cost sharing when conferring care to help alleviate the financial burden placed on patients.

The Association Between Electrodiagnostic Severity and Treatment Recommendations for Carpal Tunnel Syndrome.

PURPOSE: Our study aimed to evaluate the relationship between electrodiagnostic study (EDS) severity and utilization of treatments for carpal tunnel syndrome (CTS) as well as the duration of time between EDS and carpal tunnel release (CTR). METHODS: We conducted a retrospective medical chart review at a single tertiary hand center to evaluate CTS-related care that patients received after EDS. We recorded patient age, sex, race/ethnicity, insurance type, CTS-related surgical and nonsurgical healthcare utilization after EDS testing, and number of days between EDS and CTR. RESULTS: Among all patients with an eventual diagnosis of CTS who received EDS (n = 210), nearly half had normal or mild severity (23%, n = 48; and 28%, n = 58, respectively) and the other half had moderate or severe EDS findings (26%, n = 55; and 23%, n = 49, respectively). Patients with severe findings had the highest rate of receiving surgery (53%) compared with patients with mild and moderate findings (33% vs 46%, respectively). Among the patients who received CTR (n = 73), patients with severe EDS findings had the shortest time to CTR (59.5 days; interquartile range [IQR], 30-81), compared with mild severity (170 days; IQR, 87-415) and moderate severity (77 day; IQR, 42-292). Moderate and severe EDS findings were associated with significantly higher odds of receiving CTR in adjusted analyses (odds ratio, 2.48, 95% confidence interval, 1.04-5.93 and odds ratio 3.79, 95% confidence interval, 1.51-9.50, respectively) compared with patients with mild EDS findings. However, the odds of receiving steroid injection and hand therapy/orthosis were not significantly different based on severity. CONCLUSIONS: Electrodiagnostic study severity had a direct relationship to the probability of receiving surgery but did not correlate with use of nonsurgical treatment. The study findings signal a need to evaluate the value of nonsurgical treatments in patients with severe EDS findings. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Comparison of Safety and Insurance Payments for Minor Hand Procedures Across Operative Settings.

Importance: Surgical procedures can be performed in different settings, but the association between the operative setting and patient safety and cost to the patient and payer is unknown. Objective: To examine differences in complications, total payments, and out-of-pocket (OOP) spending for minor hand surgical procedures performed in office, ambulatory surgery center (ASC), and hospital outpatient department (HOPD) operative settings. Design, Setting, and Participants: A retrospective, population-based cohort study was conducted using deidentified claims data from private employer-sponsored health insurance from January 1, 2009, to December 31, 2017. Patients aged 18 years or older undergoing carpal tunnel release, trigger finger release, excision of wrist ganglion, and excision of small hand masses (N = 468 365) were included. Exposures: Operative setting, defined as procedures performed in the clinic setting, ASC, and HOPD. Main Outcomes and Measures: Complications during the 90-day postoperative period, total payments (total facility and payer reimbursement), and OOP spending. Results: Of the 468 365 patients, 296 378 women (63.3%) and 171 987 men (36.7%) underwent minor hand surgical procedures from 2009 to 2017, with 284 889 procedures (60.8%) performed in HOPDs, 158 659 procedures (33.9%) performed in ASCs, and 24 817 procedures (5.3%) performed in the office setting. Ninety-day complications occurred in 3.4% of procedures performed in HOPDs, 3.3% in ASCs, and 2.9% in office settings (P < .001). After controlling for patient characteristics, procedures performed outside of the office had higher odds of complications (HOPDs: odds ratio [OR], 1.32; 95% CI, 1.22-1.43; ASCs: OR, 1.24; 95% CI, 1.14-1.34). Compared with the office setting, procedures performed in HOPDs incurred an extra $1216 in total payments (95% CI, $1184-$1248) and $115 in OOP expenses (95% CI, $109-$121). Procedures performed in ASCs cost an additional $709 (95% CI, $676-$741) and $140 in OOP expenses (95% CI, $134-$146). Transitioning ASC and HOPD procedures to the office setting could have saved an estimated $6 million annually in OOP expenses during the study period. Conclusions and Relevance: The findings of this study suggest that minor hand surgery performed in the office setting is safe and less costly compared with ambulatory and hospital-based operations. Shifting minor surgical procedures to the office setting may lead to substantial cost savings for payers and patients without compromising care quality.

The Economic Burden of Out-of-Pocket Expenses for Plastic Surgery Procedures.

BACKGROUND: Health insurance reimbursement structure has evolved, with patients becoming increasingly responsible for their health care costs through rising out-of-pocket expenses. High levels of cost sharing can lead to delays in access to care, influence treatment decisions, and cause financial distress for patients. METHODS: Patients undergoing the most common outpatient reconstructive plastic surgery operations were identified using Truven MarketScan databases from 2009 to 2017. Total cost of the surgery paid to the insurer and out-of-pocket expenses, including deductible, copayment, and coinsurance, were calculated. Multivariable generalized linear modeling with log link and gamma distribution was used to predict adjusted total and out-of-pocket expenses. All costs were inflation-adjusted to 2017 dollars. RESULTS: The authors evaluated 3,165,913 outpatient plastic and reconstructive surgical procedures between 2009 and 2017. From 2009 to 2017, total costs had a significant increase of 25 percent, and out-of-pocket expenses had a significant increase of 54 percent. Using generalized linear modeling, procedures performed in outpatient hospitals conferred an additional $1999 in total costs (95 percent CI, $1978 to $2020) and $259 in out-of-pocket expenses (95 percent CI, $254 to $264) compared with office procedures. Ambulatory surgical center procedures conferred an additional $1698 in total costs (95 percent CI, $1677 to $1718) and $279 in out-of-pocket expenses (95 percent CI, $273 to $285) compared with office procedures. CONCLUSIONS: For outpatient plastic surgery procedures, out-of-pocket expenses are increasing at a faster rate than total costs, which may have implications for access to care and timing of surgery. Providers should realize the increasing burden of out-of-pocket expenses and the effect of surgical location on patients' costs when possible.

The Impact of Pre-Referral Advanced Diagnostic Testing on Wait Time to See a Hand Surgeon for Common Upper-Extremity Conditions.

PURPOSE: We sought to evaluate the use of pre- and post-referral advanced diagnostic testing among patients with 3 common hand conditions, rates of subsequent tests, and differences in wait time to see a hand surgeon. METHODS: We analyzed a single academic tertiary care center administrative database of encounters from 2006 to 2015 to identify adult patients who were referred to a hand surgeon for 3 conditions (carpal tunnel syndrome [CTS], soft tissue masses [STM], and joint pain [JP]). We recorded patient characteristics, use and timing of diagnostic tests, and wait time for the initial hand surgeon evaluation. RESULTS: Among patients who received advanced diagnostic tests before the surgeon evaluation, CTS patients had the highest rate of receiving pre-referral advanced testing (53.4%) compared with JP (10.6% ) and STM patients (5.8%). The CTS patients had the highest rates of repeat testing (19.5%) compared with patients with JP (1.4%) and STM (0%). Across all 3 conditions, patients who received pre-referral advanced testing waited an additional 19 to 94 days to see a surgeon, compared with patients who received only post-referral testing or no testing. CONCLUSIONS: Use of pre-referral advanced diagnostic tests is associated with an increased time to see a hand surgeon for common hand conditions. CLINICAL RELEVANCE: Hand surgeons should have a role in identifying patients who do or do not benefit from advanced testing before referral to ensure that tests ordered before consultation are useful to both patients and treating surgeons.

Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors.

For the development of novel anticancer agents, we designed and synthesized a total of 37 perimidine o-quinone derivatives containing the o-quinone group at the A or B ring and different substituents (alkyl groups, aryl groups or heterocycles) at the C ring of the compounds. The structure-activity relationships (SARs) were established based on the cytotoxicity data of compounds from the HL-60, Huh7, Hct116, and Hela cell lines. The cytotoxicity results showed that most compounds exhibited potent cytotoxicity. In particular, compound b-12 showed the best anti-proliferative activity (IC50 ≤ 1 µM) against four cancer cell lines and strong potency against the HL-60/MX2 (0.47 µM) cell line, which is resistant to Topo II poisons. Further studies showed that b-12 exhibited potent Topo IIα inhibitory activity (IC50 = 7.54 µM) compared with Topo I, which acted as a class of non-intercalative Topo IIα catalytic inhibitor by inhibiting the ATP binding site of Topo II. Cell apoptosis and cell cycle assays confirmed that b-12 could induce the apoptosis of Huh7 cells in a dose-dependent manner.