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Qi-Feng Chen,1,* Xiong-Ying Jiang,1,2,* Yue Hu,1,* Song Chen,1 Jun-Zhe Yi,1 Sui-Xing Zhong,1 Jiong-Liang Wang,1 Ning Lyu,1 Ming Zhao1 1Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510210, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Zhao, Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +862087343272, Email zhaoming@mail.sysu.edu.cnPurpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers.Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results.Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters.Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.Keywords: HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness

Introduction: An optimal follow-up schedule for small (≤3-cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA., Methods: In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US], and α-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life year. Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER., Results: In a base case analysis, the dominant strategy was CT every 3 months during an initial 2 years, followed by semiannual CT, and then switch to biannual the combination of US screening and AFP testing after 5 years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared with the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a willingness-to-pay threshold., Discussion: For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every 3 months for the first 2 years, every 6 months thereafter, and transition to biannual the combination of US screening and AFP testing after 5 years., (Copyright © 2024 by The American College of Gastroenterology.)

Competing Interests: Conflicts of interest Dr Enos has previously served as a consultant on an advisory board for UCB and Amgen, is an investigator for Amgen and Castle Biosciences, and has previously received research funding from the ASA/Arcutis Biotherapeutics. Authors McLean, Sima, and Eckmann are employed by CorEvitas, LLC. Dr Van Voorhees has received grant/research support from Celgene, Lilly, and AbbVie and is a consultant for Amgen, Boehringer Ingelheim, BMS, UCB, and Novartis. Dr Yi and Vera have no conflicts of interest to declare.

Aim: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents., Methods: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed., Results: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed., Conclusions: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment., (© 2023 Japan Society of Hepatology.)

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management., (© 2023. Asian Pacific Association for the Study of the Liver.)

Rosacea is a chronic inflammatory skin condition that is associated with multiple systemic comorbidities, with the strongest evidence linking rosacea to hypertension, dyslipidemia, inflammatory bowel disease, and anxiety and depression. To assess dermatologists' awareness of and screening practices for rosacea comorbidities, we developed a survey that was distributed to attendings and residents across four academic dermatology departments in Massachusetts. A total of 73 dermatologists with varying experience participated in the study. Findings demonstrated significant knowledge and practice gaps among academic dermatologists in managing systemic comorbidities in rosacea. In addition, dermatologists' awareness of rosacea comorbidities was negatively correlated with number of years out of residency training, highlighting the need to address this knowledge gap through increased continuing medical education. Importantly, we observed a low screening frequency despite a high awareness of the association between rosacea and ocular comorbidities, suggesting that additional financial, institutional, or practice barriers likely contribute to the low screening rate., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest Dr Enos has served as a consultant on an advisory board for UCB and Amgen; Dr McLean, Sima, Kohl, and Eckmann are employees at CorEvitas, LLC; Dr Van Voorhees reports grant/research support from Celgene, Lilly, and AbbVie and is a consultant for Amgen, Boehringer Ingelheim, BMS, UCB, Novartis; author Yi has no conflicts of interest to declare.

Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with a poor prognosis. Individualized survival prediction tool is useful for this population. We constructed the predicted nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) using the data identified from the Surveillance, Epidemiology, and End Results database. The Concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC) and the calibration curves were used for the discrimination and calibration of the nomograms in the training and validation cohorts, respectively. 1962 mTNBC patients with a median follow-up was 13 months (interquartile range, 6-22 months), 1639 (83.54%) cases died of any cause, and 1469 (74.87%) died of breast cancer. Nine and ten independent prognostic factors for BCSS and OS were identified and integrated to construct the nomograms, respectively. The C-indexes of the nomogram for BCSS and OS were 0.694 (95% CI 0.676-0.712) and 0.699 (95% CI 0.679-0.715) in the training cohort, and 0.699 (95% CI 0.686-0.712) and 0.697 (95% CI 0.679-0.715) in the validation cohort, respectively. The AUC values of the nomograms to predict 1-, 2-, and 3-year BCSS and OS indicated good specificity and sensitivity in internal and external validation. The calibration curves showed a favorable consistency between the actual and the predicted survival in the training and validation cohorts. These nomograms based on clinicopathological factors and treatment could reliably predict the survival of mTNBC patient. This may be a useful tool for individualized healthcare decision-making., (© 2022. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer globally and is currently the third leading cause of cancer-related deaths. Recently, immunotherapy using immune checkpoint inhibitors (ICIs) has been shown with encouraging anticancer activity and safety in clinical trials. To reverse the phenomenon of tumours evading immune response, ICIs can be used to stimulate the natural antitumour potential of cancer cells by blocking the relevant checkpoints to activate T cells. However, the components and functions of the immune system may undergo a series of changes with ageing, known as 'immunosenescence,' potentially affecting the antitumour effect and safety of immunotherapy. In the current phase III clinical trials of ICIs including nivolumab, pembrolizumab and atezolizumab, the proportion of patients with HCC older than 65 years in CheckMate 459, KEYNOTE-240 and IMbrave150 is 51%, 58% and 50%, respectively, which is less than 70%-73% of epidemiological investigation. Therefore, the elderly population recruited in clinical trials may not accurately represent the real-world elderly patients with HCC, which affects the extrapolation of the efficacy and safety profile obtained in clinical trials to the elderly population in the real world. This review provides the latest advances in ICIs immuno-treatment available for HCC and relevant information about their therapeutic effects and safety on elderly patients. We discuss the benefits of ICIs for older HCC patients, and relevant recommendations about conducting further clinical trials are proposed for more complete answers to this clinical issue., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: The authors declare no conflicts of interest.

An estimated 1 million North Americans live with ostomies, with up to 80% of ostomy patients developing stoma-related skin morbidities. While ostomy nurses are often the first line of management, dermatologists may be involved in the care of ostomy patients with complex or persistent peristomal skin complications. Therefore, an understanding of the ostomy apparatus and possible peristomal skin conditions that may arise allows dermatologists to identify skin complications early and work effectively with a multidisciplinary team. In this article, we aim to review the ostomy apparatus, discuss the differential diagnoses, and provide practical guidelines for the management of peristomal skin conditions. Pubmed, Ovid Medline, and Google Scholar were searched for relevant articles assessing peristomal skin complications and their management. Peristomal skin complications may be local (e.g., contact dermatitis, infection, fistula, and mechanical trauma) or secondary to systemic disease (e.g., inflammatory bowel disease, pyoderma gangrenosum, and psoriasis). Ensuring appropriate ostomy fit and proper use of ostomy accessory products helps to reduce effluent leakage and prevent damage to the peristomal skin. For persistent peristomal skin conditions, corticosteroid sprays, systemic therapies, and surgical interventions may be warranted., (© 2021 Wiley Periodicals LLC.)

Epigenetic modifications include DNA methylation, histone modification and the action of microRNAs. These mechanisms coordinate in complex networks to control gene expression, thereby regulating key physiological processes in the skin and immune system. Recently, researchers have turned to the epigenome to understand the pathogenesis of inflammatory skin diseases. In psoriasis and atopic dermatitis, epigenetic modifications contribute to key pathogenic events such as immune activation, T-cell polarization and keratinocyte dysfunction. These discoveries have introduced new possibilities for the treatment of skin diseases; unlike genetics, epigenetic alterations are readily modifiable and potentially reversible. In this viewpoint essay, we summarize the current state of epigenetic research in inflammatory skin diseases and propose that targeting the histone machinery is a promising avenue for the development of new therapies for psoriasis and atopic dermatitis. Expanding on the progress that has already been made in the field of cancer epigenetics, we discuss existing epigenetic-modifying tools that can be applied to the treatment of inflammatory skin diseases and consider future directions for investigation in order to allow for the widespread clinical application of such therapies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Since the COVID-19 outbreak, teledermatology services have become an integral part of our daily practice. In this study, we compared three practice models of an academic department in an urban setting: 1) in-person only, 2) teledermatology only, and 3) hybrid of in-person and teledermatology. Our study demonstrated that older patients prefer in-person visits over teledermatology visits, while non-English-speaking patients prefer teledermatology visits over in-person visits. In addition, teledermatology services can be better utilized for evaluation of acne and psoriasis, as these diagnoses do not require in-person reevaluation, unlike the evaluation of concerning lesions. Considering these findings, our study highlights the need to continuously examine our practice models to understand patient preferences, overcome practice-driven barriers, and ensure the sound allocation of limited health care resources., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

5-Fluorouracil (5-FU) is an antineoplastic agent that is used topically to treat actinic keratoses. Although topical 5-FU frequently causes irritant contact dermatitis at the site of application, distant skin reactions are rare and could relate to accidental transfer or systemic absorption of the drug. We present a patient who developed a painful scrotal dermatitis after applying the topical cream to actinic keratoses on his chest. Upon discontinuation of topical 5-FU, the reaction resolved over a four-week period with oral prednisone and topical betamethasone ointment. The patient was re-challenged with topical 5-FU one year later and again developed scrotal pain and erythema similar to the initial reaction. Scrotal dermatitis is a rare adverse effect of topical 5-FU therapy that can be associated with significant distress and disruption of daily activities.

As a soluble cellulose derivative, methylcellulose (MC), can be used to construct thermosensitive hydrogels. However, a pure MC gel is generally considered an inert material that is inadequate for cell survival. We adopted an environmentally friendly method to fabricate a nano-hydroxyapatite (nHA) hybrid MC hydrogel. Rheology results showed that the addition of nHA increased the gelation temperature. Furthermore, the live/dead assay confirmed that the addition of nHA improved the survival of bone marrow-derived mesenchymal stem cells (BMSCs) inside the gel. In addition, ARS staining indicated that the presence of nHA stimulated osteogenic differentiation. Finally, in vivo cranial defect experiments showed improved remediation efficiency when using the nHA hybrid MC hydrogel to carry BMSCs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Though curcumin has potential treatment value for most chronic diseases, it exerts little potency in the clinic because of its low aqueous solubility, high chemical instability and poor pharmacokinetics. To enhance its potency, we developed a zein-based micelle as a nanocarrier to encapsulate curcumin. Herein, superhydrophilic zwitterionic polymers, poly(sulfobetaine methacrylate) (PSBMA), were conjugated to zein to obtain an amphiphilic zein-PSBMA conjugate. These conjugates could self-assemble into micelles composed of antifouling PSBMA shells and zein cores. The results from the cytokine secretion assay showed that the micelles induced a low level of macrophage activation. Moreover, the results from the in vivo fluorescence imaging experiment confirmed their long-circulating property, exceeding 72 h in mice. In comparison with native curcumin, micelle-encapsulated curcumin had a 230-fold increase in stability in vitro, and its half-life was 22-fold longer, according to a pharmacokinetic study on mice. Overall, this work presents a zein-PSBMA micelle with a long circulation time as a useful nanocarrier for effective curcumin delivery., 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 © 2020 Elsevier B.V. All rights reserved.)

We investigate the effects of interferon (IFN)-γ on human placenta-derived mesenchymal stromal cells (hPMSCs), in particular, their adhesion, proliferation and migration and modulatory effects on the CD4 + CXCR5 + Foxp3 + Treg subset. And we compared hPMSCs ability to induce the generation of different Treg subsets in response to treatment with IFN-γ. We found that IFN-γ suppressed the proliferation and migration for hPMSCs. The ability of hPMSCs to induce the generation of CD4 + CXCR5 + Foxp3 + Treg subset was enhanced by IFN-γ. And maximal effectiveness of IFN-γ treated hPMSCs upon inducing the generation of Treg subsets was for CD4 + CXCR5 + Foxp3 + Treg subset as compared with that of CD4 + CD25 + Foxp3 + , CD8 + CD25 + Foxp3 + , CD4 + IL-10 + and CD8 + IL-10 + Treg subsets. These results have important implications for the development and application of hPMSCs in clinical use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate the postoperative outcomes of preserving the left colonic artery during laparoscopic anterior resection for rectal cancer., Methods: The clinicopathologic data of 91 rectal cancer patients (pathologic Stage II) undergoing laparoscopic anterior resection was retrospectively analyzed. During the surgeries, the left colonic artery was preserved in 40 patients (preserved group) and ligated in 51 patients (unpreserved group). The operating time, intraoperative blood loss, time to first flatus and defecation, duration of postoperative abdominal distension and pain, number of retrieved lymph nodes, ileum fistulation and anatomical leakage rate were compared between the two groups., Results: The surgeries were completed in all the 91 patients laparoscopically without conversion. There was no intraoperative complications including rectal perforation, injury to vessel or ureter in either group. The operating time, blood loss and number of retrieved lymph nodes were similar between the groups (P>0.05). Three patients in preserved group and 5 in ligation group received preventive ileum fistulation due to low rectal cancer. Anatomical leakage occurred in three patients of unpreserved group. The average duration of postoperative abdominal distension and pain was 2.14∓0.35 days in preserved group and 3.15∓0.42 days in ligation group. The time to first flatus and defecation was 37.15∓12.62 h and 3.16∓0.52 days in preserved group and 62.25∓11.75 h and 4.25∓0.75 days in ligation group. Postoperative hospital stay was 4.54∓0.42 days in preserved group and 6.23∓0.51 days in ligation group. Total hospitalization cost in the two groups was 34 525.32∓1206.36 Yuan and 41 215∓1051.32 Yuan, respectively. Significant differences were found the in duration of postoperative abdominal distension and pain, postoperative hospital stay, and total cost between the two groups (P<0.05)., Conclusion: During laparoscopic anterior resection for rectal cancer, preserving the left colonic artery effectively ensures the blood supply to the anastomosis and the remaining descending colon to promote the recovery of the patients after surgery.

Monocyte/macrophage scavenger receptor CD163 plays an important role in porcine reproductive and respiratory syndrome virus (PRRSV) infection. To identify the domains of CD163 involved in PRRSV infection, CD163 fragments P1 (1-798 bp), P2 (790-2046 bp), P3 (2023-3345 bp), Y-P1 (160-798 bp), Y-P2 (790-2046 bp) and Y-P3 (2143-3084 bp) were expressed by eukaryotic and prokaryotic expression systems, respectively. Infection experiments revealed that non-permissive BHK-21 cells transfected with pCD163 could be infected by PRRSV. However, cells with truncated CD163 (P1, P2, or P3) were not susceptible to PRRSV. Meanwhile, Y-P1, Y-P2, and Y-P3 were expressed in E. coli and antisera to these peptides were prepared in mice. A virus blocking test showed that Y-P2 protein and anti-Y-P2 mouse serum could block PRRSV infection in a dose-dependent manner, while Y-P3 protein could improve virus infection.

A series of novel sodium humate/poly(N-isopropylacrylamide) (SH/PNIPA) hydrogels were synthesized by solution polymerization. The swelling and decoloring properties of SH/PNIPA hydrogels were also examined. Experiment results show that there exist hydrogen-bonding interactions between SH and PNIPA in the SH/PNIPA hydrogels network, which are not strong enough to disrupt the aggregation of dehydrated PNIPA chains at phase transition temperature, leading to the same volume phase transition temperature as pure PNIPA hydrogel. The adsorption and desorption of methylene blue (MB) for the hydrogels were influenced by temperature, initial MB concentration and SH amount. Low temperature favors the adsorption and desorption of MB. Appropriate SH amount of the hydrogels is crucial for the adsorption and desorption of MB. The maximum adsorption capacity was 10.8 mg MB per gram of SH/PNIPA gel.

A type of novel hybrid hydrogels from sodium humate (SH), polyacrylamide (PAM), and hydrophilic laponite clay were prepared using potassium persulfate (KPS) as the initiator and N,N'-methylenebisacrylamide (MBA) as the cross-linker. The morphology of the hydrogels was characterized by field emission scanning electron microscope (FESEM). The adsorption-desorption kinetics of methylene blue (MB) were also investigated. It was shown that SH/PAM/clay hydrogels exhibited excellent performance in MB adsorption. The maximum absorption concentration of MB was 800 mg/l/g of hydrogel. The adsorption concentration of hydrogels increased with increasing SH or clay content. Less MB were desorbed with increasing SH content, while the clay content had no significant influence on the amount of MB desorbed. This effect was attributed to the formation of a ionic complex between the imine groups of MB and the ionized carboxylic groups of SH. MB diffusion process was dominant in MB desorption.

In this study, two DNA fragments encoding amino acid (141-160)-(21-140)-(141-160) of the VP1 of FMDV (foot-and-mouth disease virus) serotype O and (138-160)-(21-40)-(138-160) of the serotype A FMDV were chemically synthesized. These two tandem-repeat fragments were ligated and transfected into prokaryotic expression vector pTrcHis A to construct pTH-O-A. The other vector called pTH-O-scIgG-A was constructed similarly only that the two tandem-repeat DNA fragments were linked by the bovine-IgG heavy chain coding sequence. Guinea pigs immunized with the two bivalent vaccines pTH-O-A and pTH-O-scIgG-A showed both specific antibody activity and T cell proliferation responses. FMDV challenge tests showed that 85% and 70% of guinea pigs vaccinated twice with 200 mg of the fusion protein of pTH-O-A were protected from FMDV serotype O and serotype A infection respectively. 70% and 57% of the guinea pigs immunized with the fusion protein of pTH-O-scIgG-A were protected from FMDV serotype O and serotype A infection respectively.