Search

Cardiac lymphoma is rare in children. Treatment typically includes chemotherapy, combination of radiotherapy, or surgery. We report a case of stage IV precursor B lymphoblastic lymphoma with secondary involvement of the heart in an 11-year-old girl who was treated with acute lymphoblastic leukemia-based chemotherapy. Also, we review the literature on this uncommon malignancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions. Both OncoTarget, which identifies high-affinity inhibitors of individual master regulator (MR) proteins, and OncoTreat, which identifies drugs that invert the transcriptional activity of hyperconnected MR modules, produced highly significant 30-day disease control rates (68% and 91%, respectively). Moreover, of 18 OncoTreat-predicted drugs, 15 induced the predicted MR-module activity inversion in vivo. Predicted drugs significantly outperformed antineoplastic drugs selected as unpredicted controls, suggesting these methods may substantively complement existing precision cancer medicine approaches, as also illustrated by a case study., Significance: Complementary precision cancer medicine paradigms are needed to broaden the clinical benefit realized through genetic profiling and immunotherapy. In this first-in-class application, we introduce two transcriptome-based tumor-agnostic systems biology tools to predict drug response in vivo. OncoTarget and OncoTreat are scalable for the design of basket and umbrella clinical trials. This article is highlighted in the In This Issue feature, p. 1275., (©2023 American Association for Cancer Research.)

Background: Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking., Methods: This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline., Discussion: The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery., Trial Registration: This study has been registered on ClinicalTrials.gov (NCT04734418)., (© 2023. The Author(s).)

The n-BuOH extract from the herb of Solanum lyratum Thunb. (Solanaceae) was purified by various chromatographic methods, which led to the isolation of seven undescribed alkaloids ((-)-(7'S)-N-feruloyltyramine A, (+)-(7'R)-N-feruloyltyramine A, (+)-(7'S)-N-solanamide A, (-)-(7'R)-N-solanamide A, 7'S-perillascens, solanpyrrole A, and (Z)-asmurratetra A) and 13 known alkaloids, including four pairs of enantiomers. Extensive spectroscopic data and electronic circular dichroism (ECD) calculations were applied to determine the structures of the undescribed compounds. In in vitro biological activity assays, (-)-(7'S)-N-feruloyltyramine A and (+)-(7'R)-N-feruloyltyramine A exhibited pronounced neuroprotective effects against SH-SY5Y cell damage with survival rates of 75.98% and 76.61%, respectively, at 50 μM. Additionally, (-)-(7'S)-N-feruloyltyramine A and N-cis-feruloyl-3'-methoxy-tyramine displayed acetylcholinesterase (AChE) inhibitory effects with IC 50 values of 7.41 ± 1.76 μM and 9.21 ± 0.89 μM, respectively. Molecular docking simulations revealed that (-)-(7'S)-N-feruloyltyramine A had a binding site for AChE. These findings reveal the structural diversity of the bioactive compounds in S. lyratum and provides insights into the use of this information for the production of functional components in the pharmaceutical industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia., Methods: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed., Results: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD., Conclusion: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy., Competing Interests: Financial Disclosure Yukio Suzuki reports receiving payment from The Japan Society for Menopause and Women's Health (JMWH Bayer Grant 2022) and from Honjo (JMSA Scholarship 2022). They received a Honjo-JMSA Scholarship and a JMWH Bayer Grant from the Japan Society for Menopause and Women's Health. Jason D. Wright has received royalties from UpToDate and research support from Merck. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Dengzhan Shengmai (DZSM), a traditional Chinese medicine formulation, has been administered extensively to elderly individuals with cognitive impairment (CI). However, the underlying mechanisms by which Dengzhan Shengmai improves cognitive impairment remains unknown. This study aimed to elucidate the underlying mechanism of the effect of Dengzhan Shengmai on aging-associated cognitive impairment via a comprehensive combination of transcriptomics and microbiota assessment. Dengzhan Shengmai was orally administered to a D-galactose-induced aging mouse model, and evaluation with an open field task (OFT), Morris water maze (MWM), and histopathological staining was performed. Transcriptomics and 16S rDNA sequencing were applied to elucidate the mechanism of Dengzhan Shengmai in alleviating cognitive deficits, and enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (PCR), and immunofluorescence were employed to verify the results. The results first confirmed the therapeutic effects of Dengzhan Shengmai against cognitive defects; specifically, Dengzhan Shengmai improved learning and impairment, suppressed neuro loss, and increased Nissl body morphology repair. Comprehensive integrated transcriptomics and microbiota analysis indicated that chemokine CXC motif receptor 4 (CXCR4) and its ligand CXC chemokine ligand 12 (CXCL12) were targets for improving cognitive impairments with Dengzhan Shengmai and also indirectly suppressed the intestinal flora composition. Furthermore, in vivo results confirmed that Dengzhan Shengmai suppressed the expression of CXC motif receptor 4, CXC chemokine ligand 12, and inflammatory cytokines. This suggested that Dengzhan Shengmai inhibited CXC chemokine ligand 12/CXC motif receptor 4 expression and modulated intestinal microbiome composition by influencing inflammatory factors. Thus, Dengzhan Shengmai improves aging-related cognitive impairment effects via decreased CXC chemokine ligand 12/CXC motif receptor 4 and inflammatory factor modulation to improve gut microbiota composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hou, Xu, Cao, Tian, Wang, Zhu, Zhang and Yang.)

The most frequent operation for anterior shoulder instability is the arthroscopic Bankart repair, which has a positive outcome and a low rate of complications. A variety of restoration procedures have been reported to reconstruct labral height and reproduce a dynamic concavity-compression reaction. The longitude-latitude loop is a knotless high-strength suture method that simultaneously tightens the joint capsule in the warp and weft direction and resists tearing. The suture method is safe and reproducible. This study aimed to present a longitude-latitude loop suture for joint capsule labral complex repair during Bankart arthroscopy surgery., (© 2023 The Authors.)

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.

Phosphofurin Acidic Cluster Sorting Protein 2 (PACS2) -related early infantile developmental and epileptic encephalopathy (EIDEE) is a rare neurodevelopmental disorder. EIDEE is characterized by seizures that begin during the first three months of life and are accompanied by developmental impairment over time. In this article, we present three patients with EIDEE who experienced neonatal-onset seizures that developed into intractable seizures during infancy. Whole exome sequencing revealed a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene. We conducted a literature review and found 29 cases to characterize the seizure patterns, neuroimaging features, the usage of anticonvulsants, and the clinical neurodevelopmental outcomes of PACS2 -related EIDEE. The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. Neuroimaging abnormalities were observed in the posterior fossa region, including mega cisterna magna, cerebellar dysplasia, and vermian hypoplasia. The long-term prognosis ranges from low-average intelligence to severe developmental retardation, emphasizing the importance of early recognition and accurate diagnosis by pediatric neurologists to provide personalized patient management.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

Background: Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply., Methods: Liquid chromatography-tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot., Results: DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4 + T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4 + T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4 + T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG., Conclusions: This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury., (© 2023. The Author(s).)

Peroxiredoxin-6 (PRDX6), a member of the peroxiredoxin family, has progressively emerged as a possible therapeutic target for a variety of brain diseases, particularly Alzheimer's disease and ischemic stroke. However, the role of PRDX6 in neurons under ischemic conditions has remained elusive. Here, we found that astrocytes could release PRDX6 extracellularly after OGD/R, and that PRDX6 release actually worsened neuroapoptosis under OGD/R. We discovered a unique PRDX6/RAGE/JNK signaling pathway that contributes to the effect of neuroapoptosis. We applied a specific inhibitor of the RAGE signaling pathway in a mouse MCAO model and observed significant alterations in animal behavior. Considered together, our findings show the crucial role of the astrocyte-released PRDX6 in the process of neuroapoptosis caused by OGD/R, and could provide novel insights for investigating the molecular mechanism of protecting brain function from ischemia-reperfusion injury., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hou, Liu, Kuo, Liu, Lin, Hsieh, Hung, Cheng, Su, Wang, Chou and Lin.)

Objective: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials., Methods: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens., Results: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology., Conclusions: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results., Competing Interests: Declaration of Competing Interest Dr. Wright received research support from Merck and honoraria from UpToDate., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with an elevated danger of metastasis and a short survival rate. Vibsane-type diterpenoids with novel structures possess marked antitumor activities against multiple cancer cells. However, the exact mechanism is poorly unclear., Purpose: To assess the antitumor mechanism of vibsane-type diterpenoids derived from Viburnum odoratissimum (V. odoratissimum) against HCC cells in vitro and in vivo., Methods: The main constituents in the ethyl acetate extract of V. odoratissimum (EAVO) were identified by LC-MS/MS. The antiproliferative activity of EAVO in vitro was evaluated by MTT assays. Annexin V-FITC/PI, AO/EB, and Hoechst 33,258 staining were employed to detect apoptosis. JC-1 fluorescence dye was used to detect the mitochondrial membrane potential (MMP). The levels of intracellular ROS and mitochondrial superoxides were assessed by H 2 DCF-DA and MitoSox staining, respectively. The levels of oxidative stress were determined by ROS Green™ H 2 O 2 probe, hydroxyphenyl fluorescein (HPF), and the C11 BODIPY 581/591 fluorescent probe. Transcriptomics was performed to investigate the antitumor mechanism of EAVO in HCC. The molecular mechanism by which EAVO suppressed HCC cells was verified by Western blot, RT-PCR, and HTRF® KinEASE™-STK S3 kits. The efficacy and safety of EAVO in vivo were evaluated using Hep3B xenograft models., Results: Vibsane-type diterpenoids were the main constituents of EAVO by LC-MS/MS. EAVO suppressed proliferation, aggravated oxidative stress, and promoted apoptosis in HCC cells. Moreover, EAVO dramatically inhibited tumor growth in Hep3B xenograft models. Transcriptomics results indicated that EAVO inhibited HCC cell proliferation by regulating the PI3K/AKT pathway. Vibsanin B, vibsanol I, and vibsanin S isolated from EAVO was used to further verify the antitumor activity of vibsane-type diterpenoids subsequently. Interestingly, the kinase results showed that vibsanin B and vibsanol I exhibited vital AKT kinase inhibitory activities., Conclusions: Collectively, this study provided a comprehensive mechanism overview of vibsane-type diterpenoids against HCC cells in vitro and in vivo. It also laid a foundation for further antitumor investigation of vibsane-type diterpenoids in V. odoratissimum., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Objective: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy., Design: Cost-effectiveness study., Population: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer., Methods: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values., Main Outcome Measures: The primary outcome was the incremental cost-effectiveness ratio (ICER)., Results: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses., Conclusions: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle., (© 2022 John Wiley & Sons Ltd.)

Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD)., Methods: Sympathetic nerve and its neurotransmitter NE, β-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of β2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics., Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, β2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of β2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, β2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of β2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9., Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of β2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression., Competing Interests: The authors declare no competing interests. Additional informationSupplementary content related to this article has been published online at https://doi.org/10.1016/j.heliyon.2022.e12468., (© 2022 The Author(s).)

Background: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan., Methods: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed., Results: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS., Conclusions: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns., (© 2022 American Cancer Society.)

Context: Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries., Objective: This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice., Materials and Methods: BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways., Results: QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 10 5 /mL to (4.01 ± 0.11) × 10 5 /mL, accompanied by the neutrophil from (1.41 ± 0.19) × 10 5 /mL to (0.77 ± 0.10) × 10 5 /mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway., Conclusions: This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

Investigation of the whole plant of Daphne gemmata E. Pritz. ex Diels (Thymelaeaceae) using molecular networking coupled to Network Annotation Propagation (NAP) and unsupervised substructure annotation (MS2LDA) led to the discovery of five tigliane diterpenoids, 14 guaiane sesquiterpenoids, one rhamnofolane diterpenoid and three carotene sesquiterpenoids. The structures of the eight undescribed compounds, daphnorbol A and daphnegemmatoids A-G, were characterized by detailed spectroscopic analyses, NMR and ECD calculations, application of Snatzke's method and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cytotoxic activities against HepG2, A549, and MCF-7 cells by MTT assay. Daphnorbol A exhibited significant cytotoxic activity against HepG2 and A549 cells with IC 50 values of 4.06 μM and 6.35 μM, respectively. Prostratin showed potent cytotoxic activity against HepG2 and A549 cells with IC 50 values of 6.06 μM and 5.45 μM, respectively. Further Hoechst 33,258 and AO-EB staining assays indicated that daphnorbol A and prostratin could induce apoptosis in HepG2 and A549 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No potential conflict of interest was reported by the authors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale: Extraosseous Ewing's sarcoma is a rare tumor which is aggressive with poor prognosis; it can occur anywhere in the body, but scantily in the pancreas. Pancreatic Ewing's sarcoma is not reported commonly, with inconsistent clinical manifestations. In this regard, early recognition of this disease is very important for the patient's sake., Patient Concerns: A 16-year-old boy presented with left lower quadrant abdominal pain for 2 months, and left flank pain with dysuria for 1 month., Diagnosis: Abdominal and renal ultrasonography found a mass between the spleen and left kidney as well as left renal pelvic dilatation. Abdominal computed tomography found a heterogenous mass derived from the tail of the pancreas. Serial examinations revealed that the mass was a pancreatic Ewing's sarcoma. Furthermore, no metastasis was documented., Interventions: The tumor was totally excised after 6 months of chemotherapy, which included 10 courses of neoadjuvant chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide. The patient completed consolidation chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide for 5 courses. Radiotherapy was applied to the tumor-involved region and tumor bed., Outcomes: To date, the malignancy has not recurred since the treatment was completed 4 years ago. There are no complications from the treatment for the patient., Lessons: The pancreas is a very rare extraosseous location for Ewing's sarcoma. Pancreatic extraosseous Ewing's sarcoma should be regarded as a differential diagnosis of non-urinary originated left flank pain with dysuria in adolescents., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

Objective: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance., Methods: Plasma samples were collected from patients with stage I-IV EOC. Cohort A included patients with pre-surgical samples (N = 44, median follow-up: 2.7 years), cohort B and C included: patients with serially collected post-surgically (N = 12) and, during surveillance (N = 13), respectively (median follow-up: 2 years). Plasma samples were analyzed using a tumor-informed, personalized multiplex-PCR NGS assay; ctDNA status and CA-125 levels were correlated with clinical features and outcomes., Results: Genomic profiling was performed on the entire cohort and was consistent with that seen in TCGA. In cohort A, ctDNA-positivity was observed in 73% (32/44) of presurgical samples and was higher in high nuclear grade disease. In cohort B and C, ctDNA was only detected in patients who relapsed (100% sensitivity and specificity) and preceded radiological findings by an average of 10 months. The presence of ctDNA at a single timepoint after completion of surgery +/- adjuvant chemotherapy and serially during surveillance was a strong predictor of relapse (HR:17.6, p = 0.001 and p < 0.0001, respectively), while CA-125 positivity was not (p = 0.113 and p = 0.056)., Conclusions: The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Four new terpenoids, solanoids F - I (1-4), together with eleven known compounds (5-15), were isolated from the whole herb of Solanum lyratum. The chemical structures were characterized by spectroscopic techniques, and electronic circular dichroism (ECD) data analysis was adopted to confirm the absolute configurations of 1-4. Compounds 1-6, 8 and 12-15 exhibited neuroprotective effects against H 2 O 2 -induced oxidative damage of human SH-SY5Y cells. Additionally, this study also combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the potential targets and signaling pathways of active terpenoids components in intervening Alzheimer's disease (AD)., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background/aims: Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism of DZW in middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury., Methods: The mice were divided into five groups: the sham group, I/R group, I/R + Ginaton group, I/R+DZW-L group, and I/R+DZW-H group. Neurological deficit scores and regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) and Nissl staining results were evaluated. Transcriptomics analysis and metabolomics analysis were applied to identify the key genes and metabolites, and qRT-PCR, ELISA, and immunofluorescence were applied to verify the key targets., Results: DZW significantly decreased the infarction size and neurological deficit scores, increased the rCBF percentage and neuronal number and improved neuronal morphology after MCAO. Transcriptomics and metabolomics analysis revealed that C3 and C5ar1 were core targets of DZW and indirectly regulated downstream purine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism-associated pathways via inflammatory cells. Moreover, ELISA, qRT-PCR, and immunofluorescence further confirmed that DZW significantly decreased the expression of C3, C5ar1, C5 and downstream inflammatory cytokines, including IL-6, IL-1β and MMP-9, at the gene and protein levels, suggesting that DZW decreased neuroinflammation and inhibited related metabolic pathways., Conclusion: C3 and C5 play important roles in the neuroprotective and antineuroinflammatory effects of DZW in protecting against cerebral I/R. This study provides novel insights into the neuroprotective effects of DZW and its clinical application., Competing Interests: Conflicts of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interest: The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The shoulders with critical shoulder angle (CSA) of greater than 33-35° are associated with rotator cuff tears, whereas a CSA of less than 30° is likely to be osteoarthritic. However, anterior acromioplasty or lateral acromioplasty could not reduce high CSAs to the desired range (30-33°), with satisfactory accuracy and efficacy. Thus, we introduce a computer image-guided precise acromioplasty (CIG-PAP) technique, an individualized treatment based on three-dimensional planning. We believe that the introduction of this technique will provide an alternative approach to reduce a large CSA to the desired range (30-33°)., (© 2022 The Authors.)

Cassava starch is a widely used raw material for industrial production. South Chinese cassava cultivar 8 ( Manihot esculenta Crantz cv. SC8) is one of the main locally planted cultivars. In this study, an efficient transformation system for cassava SC8 mediated with Agrobacterium strain LBA4404 was presented for the first time. Cassava friable embryogenic calli (FECs) were transformed through the binary vector pCAMBIA1304 harboring GUS- and GFP- fused genes driven by the CaMV35S promoter. The transformation efficiency was increased in the conditions of Agrobacterium strain cell infection density (OD 600 = 0.65), 250 µM acetosyringone induction, and agro -cultivation with wet FECs for 3 days in dark. Based on the optimized transformation protocol, approximately 120-140 independent transgenic lines per mL settled cell volume (SCV) of FECs were created by gene transformation in approximately 5 months, and 45.83% homozygous mono-allelic mutations of the MePDS gene with a YAO promoter-driven CRISPR/Cas9 system were generated. This study will open a more functional avenue for the genetic improvement of cassava SC8.

The cardiac function reserve is crucial for the successful weaning of V-A ECMO. During the V-A ECMO weaning phase, the gradual reduction in pump flow converts the blood flow originally driven by the pump to native cardiac output and also transforms afterload (caused by retrograde flow) into ventricular preload, thus introducing a "flow challenge" to the native heart. In this perspective, we propose to use this flow challenge as a test to simulate the preload-to-afterload conversion to assess cardiac functional reserve quantitatively. With this short article we offer the hemodynamic and clinical aspects regarding the flow challenge test., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Zhang, Hou, Luo, Liu, Tu and Luo.)

Objective: To estimate trends in use of laparoscopic power morcellators in women undergoing minimally invasive hysterectomy and to examine use of containment systems in these patients in relation to safety guidance from the U.S. Food and Drug Administration (FDA)., Methods: We examined data that were recorded in the Premier Healthcare Database from patients who underwent laparoscopic supracervical hysterectomy from 2010 to 2018. Patients were stratified based on use of laparoscopic power morcellators. The cohort was further stratified as either pre-FDA guidance (2010 quarter 1-2014 quarter 1) or post-FDA guidance (2014 quarter 2-2018 quarter 2). Interrupted time series analyses were performed to determine the effect of FDA guidance on the use of laparoscopic power morcellators and containment bags., Results: Among 67,115 patients, laparoscopic power morcellator use decreased from 66.7% in 2013 quarter 4 to 13.3% by 2018 quarter 2. The likelihood of laparoscopic power morcellator use decreased by 9.5% for each quarter elapsed in the post-FDA warning period (risk ratio [RR] 0.91, 95% CI 0.90-0.91). Containment bag use rose from 5.2% in 2013 quarter 4 to 15.2% by 2018 quarter 2. The likelihood of containment bag use increased by 3% for each quarter elapsed in the post-FDA warning period (RR 1.03, 95% CI 1.02-1.05). Among women who had laparoscopic power morcellator use, uterine cancers or sarcomas were identified in 54 (0.17%) before the FDA guidance compared with seven (0.12%) after the guidance ( P =.45). Containment bags were used in 11.1% of women with uterine cancers or sarcomas before the FDA guidance compared with 14.3% after the guidance ( P =.12). The perioperative complication rate was 3.3% among women who had laparoscopic power morcellator use without a containment bag compared with 4.5% ( P =.001) in those with a containment bag (aRR 1.35, 95% CI 1.12-1.64)., Conclusion: Use of laparoscopic power morcellators has decreased over time. Containment bag use increased after the FDA's 2014 guidance; however, most procedures employing laparoscopic power morcellators are still performed without a containment bag., Competing Interests: Financial Disclosure Dr. Wright has received royalties from UpToDate and received research support from Merck. Dr. Hou has served as a consultant for Foundation Medicine and Natera. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the effects of deferoxamine on macrophage polarization and wound healing in mice with deep tissue injury (DTI) and its mechanism. Methods: The experimental research methods were adopted. Fifty-four male C57BL/6J mice of 6-8 weeks old were divided into DTI control group, 2 mg/mL deferoxamine group, and 20 mg/mL deferoxamine group according to random number table, with 18 mice in each group. DTI was established on the back of mice by magnet compression method. From post injury day (PID) 1, mice were injected subcutaneously with 100 µL normal saline or the corresponding mass concentration of deferoxamine solution every other day at the wound edge until the samples were collected. Another 6 mice without any treatment were selected as normal control group. Six mice in each of the three DTI groups were collected on PID 3, 7, and 14 to observe the wound changes and calculate the wound healing rate. Normal skin tissue of mice in normal control group was collected on PID 3 in other groups (the same below) and wound tissue of mice in the other three groups on PID 7 and 14 was collected for hematoxylin-eosin (HE) staining to observe the tissue morphology. Normal skin tissue of mice in normal control group and wound tissue of mice in the other three groups on PID 7 were collected, and the percentages of CD206 and CD11c positive area were observed and measured by immunohistochemical staining, and the mRNA and protein expressions of CD206, CD11c, and inducible nitric oxide synthase (iNOS) were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Normal skin tissue of mice in normal control group and wound tissue of mice in DTI control group and 20 mg/mL deferoxamine group were collected on PID 3, 7, and 14, and the protein expressions of signal transducer and activator of transcription 3 (STAT3) and interleukin-10 (IL-10) were detected by Western blotting. The sample number in each group at each time point in the above experiments. The RAW264.7 cells were divided into 50 μmol/L deferoxamine group, 100 μmol/L deferoxamine group, 200 μmol/L deferoxamine group, and blank control group, which were treated correspondingly, with 3 wells in each group. The positive cell percentages of CD206 and CD86 after 48 h of culture were detected by flow cytometry. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and least significant difference test. Results: On PID 7, the wound healing rates of mice in 2 mg/mL and 20 mg/mL deferoamine groups were (17.7±3.7)% and (21.5±5.0)%, respectively, which were significantly higher than (5.1±2.3)% in DTI control group ( P <0.01). On PID 14, the wound healing rates of mice in 2 mg/mL and 20 mg/mL deferoamine groups were (51.1±3.8)% and (57.4±4.4)%, respectively, which were significantly higher than (25.2±3.8)% in DTI control group ( P <0.01). HE staining showed that the normal skin tissue layer of mice in normal control group was clear, the epidermis thickness was uniform, and skin appendages such as hair follicles and sweat glands were visible in the dermis. On PID 7, inflammation in wound tissue was obvious, the epidermis was incomplete, and blood vessels and skin appendages were rare in mice in DTI control group; inflammatory cells in wound tissue were reduced in mice in 2 mg/mL and 20 mg/mL deferoxamine groups, and a few of blood vessels and skin appendages could be seen. On PID 14, inflammation was significantly alleviated and blood vessels and skin appendages were increased in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoxamine groups compared with those in DTI control group. On PID 7, the percentages of CD206 positive area in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoxamine groups were significantly higher than that in DTI control group ( P <0.01), the percentage of CD206 positive area in wound tissue of mice in DTI control group was significantly lower than that in normal skin tissue of mice in normal control group ( P <0.01), the percentage of CD206 positive area in wound tissue of mice in 20 mg/mL deferoxamine group was significantly higher than that in normal skin tissue of mice in normal control group ( P <0.01). The percentages of CD11c positive area in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoxamine groups were significantly lower than those in DTI control group and normal skin tissue in normal control group ( P <0.05 or P <0.01), and the percentage of CD11c positive area in normal skin tissue of mice in normal control group was significantly higher than that in DTI control group ( P <0.05). On PID 7, the CD206 mRNA expressions in the wound tissue of mice in 2 mg/mL and 20 mg/mL deferoxamine groups were significantly higher than that in DTI control group ( P <0.01), but significantly lower than that in normal skin tissue in normal control group ( P <0.01); the CD206 mRNA expression in wound tissue of mice in DTI control group was significantly lower than that in normal skin tissue in normal control group ( P <0.01). The mRNA expressions of CD11c and iNOS in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoamine groups were significantly lower than those in DTI control group ( P <0.01). The mRNA expressions of CD11c in the wound tissue of mice in DTI control group, 2 mg/mL and 20 mg/mL deferoamine groups were significantly higher than that in normal skin tissue in normal control group ( P <0.01). Compared with that in normal skin tissue in normal control group, the mRNA expressions of iNOS in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoamine groups were significantly decreased ( P <0.01), and the mRNA expression of iNOS in wound tissue of mice in DTI control group was significantly increased ( P <0.01). On PID 7, the protein expressions of CD206 in the wound tissue of mice in 2 mg/mL and 20 mg/mL deferoamine groups were significantly higher than those in DTI control group and normal skin tissue in normal control group ( P <0.01), and the protein expression of CD206 in wound tissue of mice in DTI control group was significantly lower than that in normal skin tissue in normal control group ( P <0.01). The protein expressions of CD11c and iNOS in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoamine groups were significantly lower than those in DTI control group ( P <0.01). The protein expressions of CD11c and iNOS in wound tissue of mice in DTI control group were significantly higher than those in normal skin tissue in normal control group ( P <0.01). The CD11c protein expressions in wound tissue of mice in 2 mg/mL and 20 mg/mL deferoamine groups were significantly higher than those in normal skin tissue in normal control group ( P <0.05 or P <0.01). The protein expression of iNOS in wound tissue of mice in 2 mg/mL deferoamine group was significantly lower than that in 20 mg/mL deferoamine group and normal skin tissue in normal control group ( P <0.05). On PID 3, 7, and 14, the protein expressions of STAT3 and IL-10 in wound tissue of mice in 20 mg/mL deferoxamine group were significantly higher than those in DTI control group ( P <0.05 or P <0.01), and the protein expressions of STAT3 were significantly higher than those in normal skin tissue in normal control group ( P <0.05 or P <0.01). On PID 7 and 14, the protein expressions of IL-10 in wound tissue of mice in 20 mg/mL deferoxamine group were significantly higher than those in normal skin tissue in normal control group ( P <0.01). On PID 3, 7, and 14, the protein expressions of IL-10 in wound tissue of mice in DTI control group were significantly lower than those in normal skin tissue in normal control group ( P <0.05 or P <0.01). After 48 h of culture, compared with those in blank control group, the CD206 positive cell percentages in 100 μmol/L and 200 μmol/L deferoamine groups were significantly increased ( P <0.01), while the CD86 positive cell percentages in 100 μmol/L and 200 μmol/L deferoamine groups were significantly decreased ( P <0.01). Conclusions: Deferoxamine can promote the polarization of macrophages toward the anti-inflammatory M2 phenotype and improve wound healing by enhancing the STAT3/IL-10 signaling pathway in DTI mice.

Hierarchical porous heteroatom-doped carbon composites were developed by carbonization followed by KOH activation process, with natural silkworm cocoon and chemical exfoliated graphene sheets as starting materials. The introduction of graphene sheets offers more hierarchical micro/meso porosities, a low charge-transfer resistance, and a large BET surface area of ∼1281.8 m 2 g -1 , which are responsible for the fast charge/discharge kinetics and the high rate capability compared with those of single silk fibroins-derived carbon materials. The silk fiber provides a high level of heteroatom functionalities (∼2.54% N and ∼21.3% O), which are desirable for high faradaic pseudocapacitance. The as-prepared carbon composite exhibited a high specific capacitance of 290 F g -1 with good rate capability and cycling stability. The symmetric supercapacitors yielded a high value of energy density of 12.9 W h kg -1 at a power density of 95 W kg -1 with a 1.45 V voltage range in 1 M KOH aqueous electrolytes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: The optimal adjuvant therapy for uterine leiomyosarcoma (uLMS) remains uncertain. We analyzed the utilization of adjuvant chemotherapy and radiation therapy for stage II and III uLMS and explored the association between use of adjuvant therapy and survival., Methods: Patients with stage II or III uLMS treated from 2004 to 2016 and recorded in the National Cancer Database were identified. Multivariable regression models were fit to estimate predictors of use of either adjuvant radiation therapy or chemotherapy. To analyze the impact of chemotherapy on all-cause mortality, an inverse probability of treatment weighted (IPTW) propensity score method was used to account for measured confounders, and the receipt of radiation therapy was adjusted in the outcome model. The process was repeated to analyze the impact of radiation therapy on all-cause mortality by using an IPTW propensity score method and adjusting for the receipt of adjuvant chemotherapy., Results: A total of 890 patients were identified. Adjuvant chemotherapy use increased from 62.2% in 2010 to 70.4% in 2016, whereas radiation usage decreased from 26.7% in 2010 to 10.4% in 2016. Patients with stage III (vs. stage II) disease were less likely to receive radiation therapy. After propensity score weighting, chemotherapy was associated with a 30% decreased risk of all-cause mortality in stage III patients (HR 0.70, 95% CI 0.45-0.98) but had no effect on mortality for stage II patients (HR 0.93, 95% CI 0.70-1.20). Radiation therapy was associated with a 26% decreased risk of mortality for stage II tumors (HR 0.74; 95% CI, 0.53-0.99) and a 57% decrease in mortality for stage III disease (HR 0.43, 95% CI 0.18-0.99)., Conclusions: Among women with stage II-III uLMS, use of chemotherapy is increasing while use of radiation therapy is decreasing. Radiation therapy is associated with improved survival in both stage II and III disease, while there was no association between use of adjuvant chemotherapy and survival in stage II patients., Competing Interests: Declaration of Competing Interest Dr. Wright has received royalties from UpToDate and received research funding from Merck. Dr. Hou has served as a consultant for Foundation Medicine and Natera., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Recombinant human brain natriuretic peptide (rh-BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh-BNP on cardiac output and venous return function in post-cardiotomy patients with congestive heart failure (CHF)., Methods and Results: Twenty-four post-cardiotomy heart failure patients were enrolled and received a standard loading dose of rh-BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh-BNP. The cardiac output and venous return functions were estimated by depicting Frank-Starling and Guyton curves. After rh-BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m 2 /L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [-13% (-22% to -8%)] and VRRI [-12% (-25% to -5%)] was much greater than that in the systemic vascular resistance index [-7% (-14% to 0%)]. In the subgroup analysis of reduced ejection fraction (<40%) patients, the aforementioned changes were more significant., Conclusions: rh-BNP might ameliorate venous return rather than cardiac output function in post-cardiotomy CHF patients., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer., Design: Retrospective cohort study., Setting: United States inpatient and outpatient hospital services., Population: Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy., Methods: The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost., Main Outcome Measures: Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping., Results: Among 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001)., Conclusions: The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone., Tweetable Abstract: SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity., (© 2021 John Wiley & Sons Ltd.)

Objective: To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures., Methods: Women aged 18-64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation., Results: From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2., Conclusion: Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level., Competing Interests: Financial Disclosure: Jason D. Wright has received royalties from UpToDate and received research support from Merck. June Y. Hou has served as a consultant for Foundation Medicine and Natera. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Long head of the biceps tendinopathy is a common shoulder problem that is difficult to diagnose and treat. Biceps tenodesis is an effective surgical approach target for long head of the biceps tendon lesions. This article describes an all-arthroscopic proximal biceps tenodesis technique. This technique uses a high-strength suture to construct a tear-resistant loop; fixation is achieved with a suture anchor at the proximal aspect of the intertubercular groove or the greater tuberosity. This tenodesis fixation is simple, with no neurovascular injury or humeral fracture risk. In addition, our technique is cost-effective, with no need for specialty sutures., (© 2022 The Authors.)

Background: The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Objective: We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC. Patients and Methods: A total of 41 patients with advanced HCC who did not respond to sorafenib and followed a regorafenib regimen were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), radiological responses, and adverse events (AEs) were evaluated. Survival curves were compared by using the log-rank test and constructed with the Kaplan-Meier method. Results: The median PFS with regorafenib was 6.6 months (range: 5.0-8.2 months), and the median OS with regorafenib was not reached. The 1-year OS rate of regorafenib was 66.4%. The median OS of sequential sorafenib to regorafenib treatment was 35.3 months [95% confidence interval (CI), 24.3-46.3], and the 2-year OS rate of sequential sorafenib to regorafenib treatment was 74.4%. The most common AEs of regorafenib treatment were elevated aspartate aminotransferase [17/41 patients (41.5%)], elevated alanine aminotransferase [16/41 patients (39%)] and hand-foot syndrome [14/41 patients (34.1%)]. Conclusion: Regorafenib appears to be safe and clinically effective in patients with advanced HCC who progressed on first-line sorafenib., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hou, Xiao, Huang, Jiang, Jiang, Li, Xu and Chen.)

Diabetic ulcer is a challenging complication of diabetes mellitus but current treatments cannot achieve satisfactory results. In this study, the effect of Huangbai liniment (HB) and berberine on the wound healing in high fat diet/streptozotocin injection induced diabetic rats was investigated by RNA-seq technology. HB topical treatment promoted wound healing in the diabetic patients and diabetic rats, and it affected multiple processes, of which IL-17 signalling pathway was of importance. Inhibiting IL-17a by its inhibitor or antibody remarkably facilitated wound healing and HB significantly repressed the high IL-17 expression and its downstream targets, including Cxcl1, Ccl2, Mmp3, Mmp9, G-CSF, IL1B and IL6, in diabetic wounds, promoted T-AOC, SOD activity and GSH levels; decreased the levels of nitrotyrosine and 8-OHdG; enhanced angiogenesis-related CD31, PDGF-BB and ANG1 expression; inhibited cleaved caspase-3 levels and promoted TIMP1 and TGFB1. Moreover, berberine (a major component in HB) repressed the IL-17 signalling pathway, and promoted wound healing in diabetes mellitus. This study highlights the strategy of targeting IL-17a in diabetic wounds, deepens the understanding of wound healing in diabetes mellitus in a dynamic way and reveals the characteristics of HB and berberine in promoting wound healing of type 2 diabetes mellitus., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Knotted suture bridge repair (KSBR) has been widely proven to be an effective method for rotator cuff repairs. However, the occurrence of type 2 failure after suture bridge repair remains a frequent problem because of the stress concentration and disturbance of tendon perfusion in the medial row. The authors have developed the H-loop knotless double-row repair (HLDR) to counteract these problems., Purpose: To compare the biomechanical and histological outcomes of HLDR and KSBR for rotator cuff tear in the rabbit model., Study Design: Controlled laboratory study., Methods: Acute bilateral supraspinatus tears were created on the shoulders of 46 New Zealand White rabbits. HLDR and KSBR were randomly performed on the left side or right side. Thirteen animals each were sacrificed at 2, 4, and 8 weeks after surgery (n = 39), with 6 rabbits used for histological evaluation and the other 7 rabbits for biomechanical testing. The remaining 7 animals from the original 46 were only used for initial biomechanical evaluation at week 0., Results: Macroscopically, all repaired tendons were connected to their footprint on the greater tuberosity without postoperative complications at 8 weeks after surgery. The HLDR group had significantly better histological bone-to-tendon integration compared with the KSBR group in terms of fibrocartilage regeneration, collagen composition, and fiber organization. The biomechanical outcomes in the HLDR group were demonstrated to be better than those of the KSBR group at time 0 and 8 weeks after surgery., Conclusion: Both repair techniques were effective for rotator cuff tears in a rabbit rotator cuff tear model; however, HLDR demonstrated more advantages in improving biomechanical properties and histological tendon-to-bone healing compared with KSBR., Clinical Relevance: This animal study suggested that HLDR might be an alternative choice for rotator cuff tears in humans to increase tendon-to-bone healing and reduce the rate of failure to heal.

Objective: Cervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30-65 years. We examined the use of cervical cancer screening among average-risk Medicaid beneficiaries., Design: Retrospective cohort study., Population: Women age 30-64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co-testing or primary HPV testing from 2013 to 2016., Methods: The IBM Watson Health Multi-State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined., Main Outcome Measure: The rate of repeat cervical cancer screening was analysed using a cumulative incidence function., Results: A total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co-testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24-36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3., Conclusion: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination., Tweetable Abstract: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused., (© 2021 John Wiley & Sons Ltd.)

Objective: To examine the use of estrogen therapy (ET) and patterns of follow-up evaluation for sequelae of estrogen deprivation among women who were premenopausal who underwent bilateral salpingo-oophorectomy (BSO) for benign gynecologic diseases., Methods: The IBM Watson Health MarketScan Research Databases were used to identify women between age 18 and 50 years who underwent BSO from 2008 to 2019. Estrogen therapy was defined as any prescription of estrogen filled from 6 weeks before BSO to 36 months after BSO. Patterns of follow-up testing including bone mineral density and lipid testing were examined., Results: We identified a total of 61,980 women who underwent BSO for benign indications. Overall, 64.5% (95% CI 64.1-64.9%) of women received ET. The rate of ET use within 36 months of surgery declined from a peak of 69.5% in 2008 to 58.2% in 2016. The median duration of continuous ET was 5.3 months. Estrogen therapy use declined with increasing age. The cumulative rate of ET use at 36 months after surgery was 79.1% (95% CI 76.9-81.1) in those aged 18-29 years, 75.9% (95% CI 74.5-77.3%) in those aged 30-34 years, 70.2% (95% CI 69.1-71.2%) in those aged 35-39 years, 66.1% (95% CI 65.3-66.9%) in those aged 40-44 years, and 60.0% (95% CI 59.4-60.6%) in those aged 45-50 years. In a multivariable model, women who underwent surgery more recently and those with medical comorbidities were less likely to receive ET, whereas younger women, those with Medicaid insurance, those outside of the northeast, and those who underwent concurrent hysterectomy were more likely to receive ET., Conclusion: Estrogen therapy use in women who are premenopausal who underwent BSO for benign gynecologic diseases has declined substantially over the past decade., Competing Interests: Financial Disclosure Dr. Wright has received royalties from UpToDate and research support from Merck. Dr. Hou has served as a consultant for Foundation Medicine. The other authors did not disclose any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A prediction model of the welding process of Ti-6Al-4V titanium alloy was established by using the finite element method, which was used to evaluate the phase composition, residual stress and deformation of the welded joints of Ti-6Al-4V sheets with different processes (including tungsten inert gas welding, TIG, and laser beam welding, LBW). The Ti-6Al-4V structures of TIG welding and LBW are widely used in marine engineering. In order to quantitatively study the effects of different welding processes (including TIG welding and LBW) on the microstructure evolution, macro residual stress and deformation of Ti6Al4V titanium alloy sheets during welding, a unified prediction model considering solid-state phase transformation was established based on the ABAQUS subroutine. In this paper, LBW and TIG welding experiments of 1.6 mm thick Ti-6Al-4V titanium alloy sheets were designed. The microstructure distribution of the welded joints observed in the experiment was consistent with the phase composition predicted by the model, and the hardness measurement experiment could also verify the phase composition and proportion. From the residual stress measured by experiment and the residual stress and deformation calculated by finite element simulation of LBW and TIG weldments, it is concluded that the effect of phase transformation on residual stress is mainly in the weld area, which has an effect on the distribution of tensile and compressive stress in the weld area. The overall deformation of the welded joint is mainly related to the welding process, and the phase transformation only affects the local volume change of the weld seam. Importantly, the phase composition and residual stress, which are scalar fields, calculated by the established model can be introduced into the numerical analysis of structural fracture failure as input influence factors.

Objectives: To compare the patterns of care and outcomes of Asian-Americans/Pacific Islanders (AAPI) to non-Hispanic White (NHW) women with uterine cancer, and examine differences across Asian country of origin., Methods: National Cancer Database was used to identify AAPI and NHW women with uterine cancer diagnosed from 2004 to 2017. Marginal multivariable log-linear regression models and Cox proportional-hazards models were developed to estimate differences in quality-of-care and all-cause mortality between AAPI and NHW women and across AAPI ethnic groups., Results: We identified 13,454 AAPI and 354,693 NHW women. Compared to NHW women, AAPI patients were younger at diagnosis (median age 57 vs. 62 years), had fewer comorbidities, more often had serous or sarcoma histologic subtypes and stage III/IV cancer. AAPI women had a slightly higher rate of receiving pelvic lymphadenectomy for deeply invasive or high-grade tumors (77.6% vs. 74.3%), and a lower rate of undergoing minimally invasive surgery (70.4% vs. 74.8%) for stage I-IIIC tumors. Among patients undergoing hysterectomy, AAPI women had a lower mortality compared with NHW women for cancer stage I/II/III, and a 28% reduction for type I (grade 1 or 2 endometrioid cancers) disease (aHR = 0.72; 95% CI, 0.64-0.81). Among AAPI subgroups, Pacific Islanders had the worst survival across different cancer stage and disease type., Conclusion: AAPI women are diagnosed with uterine cancer at a younger age and have more aggressive histologic subtypes and advanced stage than their White counterparts. They have a similar level of quality-of-care as NHW women, and an improved survival for early stage and type I disease., Competing Interests: Declaration of Competing Interest Dr. Wright has served as a consultant for and Clovis Oncology, received royalties from UpToDate, and received research funding from Merck. Dr. Hou has served as a consultant for Foundation Medicine and Natera. Dr. Neugut has consulted for Otsuka, Eisai, GlaxoSmithKline, Hospira, and United Biosource Corp, and received grant funding from Otsuka. He serves on the medical advisory board of EHE Intl. No other authors have any conflicts of interest or disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alkaline/neutral invertase (A/N-INV) is an invertase that irreversibly decomposes sucrose into fructose as well as glucose and plays a role in plant growth and development, starch synthesis, abiotic stress, and other plant-life activities. Cassava is an economically important starch crop in tropical regions. During the development of cassava tuber roots, A/N-INV activity is relatively high, which indicates that it may participate in sucrose metabolism and starch synthesis. In this study, MeNINV1 was confirmed to function as invertase to catalyze sucrose decomposition in yeast. The optimal enzymatic properties of MeNINV1 were a pH of 6.5, a reaction temperature of 40 °C, and sucrose as its specific catalytic substrate. VB 6 , Zn 2+ , and Pb 2+ at low concentrations as well as EDTA, DTT, Tris, Mg 2+ , and fructose inhibited A/N-INV enzymic activity. In cassava, the MeNINV1 gene was mainly expressed in the fibrous roots and the tuber root phloem, and its expression decreased as the tuber root grew. MeNINV1 was confirmed to localize in chloroplasts. In Arabidopsis , MeNINV1 -overexpressing Arabidopsis had higher A/N-INV activity, and the increased glucose, fructose, and starch content in the leaves promoted plant growth and delayed flowering time but did not change its resistance to abiotic stress. Our results provide new insights into the biological function of MeNINV1.

Background: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD., Methods: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments., Results: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells., Conclusions: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line choices regarding the treatment of chronic hepatits B. The impact of the two antiviral agents on prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection remains to be explored. We aimed to assess the effect of antiviral therapy with ETV or TDF after curative resection on the prognosis of patients with HBV-related HCC., Methods: A total of 1173 consecutive patients who were treated with ETV or TDF after curative liver resection for HCC were enrolled in the study. HCC recurrence, overall survival, postoperative liver function reserve, and early virologic (VR) and biochemical responses (BR) of patients were compared between the ETV and TDF groups by propensity score matching (PSM) from the date of liver resection for HCC., Results: No difference was observed with recurrence-free survival between TDF and ETV in the PSM cohort (hazard ratio [HR], 0.91; 95% confidence interval [CI] 0.70-1.17; P = 0.45). No difference was observed with early VR and BR between TDF and ETV in the PSM cohort. Compared with ETV, TDF therapy was associated with significantly better protection of liver function and higher overall survival rates in the PSM cohort (HR, 0.37; 95% CI 0.20-0.71; P = 0.002). After PSM, 69 (40.8%) patients in the ETV group and 63 (57.3%) patients in the TDF group had single tumor recurrence, while the TDF group had significantly more patients with single tumor recurrence in the PSM cohort (P = 0.007)., Conclusions: For patients who underwent curative resection for HBV-related HCC, TDF treatment had a significantly better overall survival and better protection of liver function, but no difference in the incidences of HCC recurrence than ETV treatment., (© 2022. Japanese Society of Gastroenterology.)

Introduction: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment., Aim: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment., Methods: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM ® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens., Results: A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL., Conclusion: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered., (© 2022 John Wiley & Sons Ltd.)

Objective: Utilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS., Methods: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed., Results: A total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7-30.7) and 24.3 months (95% CI 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71-1.14)., Conclusions: Among women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival., Competing Interests: Declaration of Competing Interest Dr. Wright has served as a consultant for and Clovis Oncology, received royalties from UpToDate, and received research funding from Merck. No other authors have any conflicts of interest or disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)