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Aims/Introduction To investigate the national trend in the prescription of first‐line non‐insulin antidiabetic agents and total medical costs (TMCs) after prescribing the drug in Japanese patients with type 2 diabetes. Materials and Methods Using the National Database of Health Insurance Claims and Specific Health Check‐ups of Japan covering almost the entire Japanese population, we calculated the proportion of each antidiabetic drug from 2014 to 2017, and determined the factors associated with drug selection. The TMCs in the first year after starting the drugs were calculated, and factors associated with the costs were also determined. Results Among 1,136,723 new users of antidiabetic agents, dipeptidyl peptidase‐4 inhibitors were the most prescribed (65.1%), followed by biguanides (15.9%) and sodium–glucose cotransporter 2 inhibitors (7.6%). Sodium–glucose cotransporter 2 inhibitor and biguanide use increased during 2014–2017 (2.2%–11.4% and 13.7%–17.2%, respectively), whereas the others decreased. Biguanides were not prescribed at all in 38.2% of non‐Japan Diabetes Society‐certified facilities. The TMCs were the lowest among those who started with biguanides. Fiscal year, age, sex, facility, number of beds and comorbidities were associated with drug choice and TMCs. There were wide regional variations in the drug choice, but not in the TMCs. Conclusions Unlike in the USA and Europe, dipeptidyl peptidase‐4 inhibitor is the most prescribed first‐line medication for type 2 diabetes patients in Japan, while there is a wide variation in the drug choice by facility‐type and prefecture. In this large‐scale, nationwide study of Japanese patients with type 2 diabetes, dipeptidyl peptidase‐4 inhibitors were the most prescribed followed by biguanides, with a wide variation in the drug choice by facility and prefecture. The total medical costs were the lowest among patients who started with biguanides.

Background Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti‐angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first‐line treatment of advanced ESCC. Methods In this single‐arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m2, and nedaplatin 50 mg/m2 on day 1, and apatinib 250 mg on days 1‐14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. Results We enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow‐up was 24.98 months (95% confidence interval [CI]: 23.05‐26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%‐92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%‐99.9%). The median PFS was 6.85 months (95% CI: 4.46‐14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months – not reached). The most common grade 3‐4 treatment‐related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment‐related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment‐related deaths occurred. Conclusions Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first‐line treatment demonstrated feasible anti‐tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted. Trial registration This trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).

PurposeManagement of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments.Materials and methodsMultiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible.ResultsSix studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73–0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75–0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76–0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74–0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib.ConclusionPembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy–tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs.

Xiuli Zhu,1,* Xiaoli Fang,2,* Qiaomin Wang,1 Ming Li,2 Kaiguang Zhang,1 Li Xie,1 Xiaoping Niu,3,4 Song Wang5 1Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230002, People’s Republic of China; 2Department of Anorectal Surgery, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230031, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 4Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 5Digestive Endoscopic Center, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Wang, Email drwangsong@163.com Xiaoping Niu, Email 47440311@qq.comBackground: There are few data on ustekinumab treatment for Crohn’s disease (CD) in a Chinese population. Our study is a real-world retrospective multicenter study aimed at exploring the effectiveness of ustekinumab in CD patients and comparing the effectiveness of first line and second line treatments.Methods: Laboratory indicators, CD activity index (CDAI) and simple endoscopic score for CD (SES-CD) scores of patients at the 8th, 16th and 24th weeks of treatment were collected, and the clinical remission rate, clinical response rate, endoscopic remission rate and endoscopic response rate were calculated, and the patients were divided into first line group and second line group for comparison.Results: A total of 102 patients were treated with ustekinumab, and 56 patients with a clinical data integrity rate greater than 70% were ultimately included. The clinical remission rate of the patients gradually increased at the 8th, 16th and 24th weeks of treatment, which were 34 cases (60.7%), 37 cases (66.1%) and 49 cases (87.5%), respectively. The clinical response rates for 8th, 16th and 24th weeks were 38 (67.8%), 42 (0.75%) and 51 (91.1%), respectively, and the endoscopic remission rate was 4% (2/50) at the 24th week. The clinical response rates of the first line group were higher than those of the second line group at the 16th and 24th weeks, with statistically significant differences. The clinical response time of patients receiving first line or second line treatment with ustekinumab was different, and the first line treatment group achieved clinical response more quickly.Conclusion: Ustekinumab is effective in the short-term treatment of CD patients in China, with first line treatment superior to second line treatment and faster than second line treatment.Keywords: ustekinumab, Crohn’s disease, first line, second line

Cost-benefit is an important consideration for ( eradication in Japan, where 1.5 million patients were reported to receive first-line eradication annually. This study aimed to identify the optimal cost-saving triple therapy regimen for eradication in Japan. This retrospective observational study used data from a large-scale, nationwide health insurance claims database (2015‒2018). Using success rates of first-line eradication, mean total costs of first-line and second-line eradications per patient were compared between regimens including a potassium-competitive acid blocker (P-CAB) or a proton pump inhibitor (PPI), and between two clarithromycin (CAM) doses (400 and 800 mg/day). Subgroup analyses by smoking habit or body mass index (BMI) were performed. Among propensity score (age, gender, CAM dose, disease name)-matched patients (P-CAB regimen, n=22,002; PPI regimen, n=22,002), total costs were lower with the P-CAB than the PPI regimen (Japanese yen [JPY] 12,952 vs 13,146) owing to significantly higher first-line eradication rates with the P-CAB regimen (93.6% vs 79.7%; <0.001). For both regimens, even among current smokers or patients with BMI ≥25 kg/m , eradication rates did not differ by CAM dose, and total costs were approximately JPY1000 lower with CAM 400 mg/day than with CAM 800 mg/day. High success rate of first-line eradication contributes to saving in total eradication costs by reducing costs of subsequent therapy, irrespective of patients' smoking status or BMI class. The combination of more potent acid-inhibitory medicine and low-dose CAM may be the optimal regimen in terms of efficacy and cost-benefit in Japan.

Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non‐small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment‐naïve tumor tissues. Survival benefits and resistance mechanisms of first‐line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression‐free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41–0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti‐vascular therapy (HR: 0.55, 95% CI: 0.39–0.77). Furthermore, EGFRL858Q/M patients showed enhanced first‐line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10–0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first‐line EGFR TKIs than those with the classical EGFRL858R. This study reveals that NSCLC patients with uncommon EGFR L858R mutations experience improved outcomes with EGFR TKIs compared to those with the classical EGFR L858R mutation, evidenced by longer PFS, fewer TP53 mutations, and higher chromosome stability. Furthermore, patients with EGFR L858Q/M showed enhanced first‐line PFS, potentially benefiting more from afatinib.

BackgroundThe therapeutic landscape of advanced hepatocellular carcinoma (HCC) has expanded beyond sorafenib, with multiple combination regimens now demonstrating improved outcomes. However, the absence of direct head-to-head comparisons complicates treatment selection in clinical practice.MethodsWe performed a Bayesian network meta-analysis of phase III randomized controlled trials to compare the efficacy and safety of first-line treatments for patients with advanced HCC. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events were assessed. Treatment rankings were estimated using surface under the cumulative ranking curve values.ResultsSixteen trials comprising 8, 753 patients were included. Hepatic arterial infusion chemotherapy (HAIC)-based regimens, particularly sorafenib plus HAIC and HAIC_(F)O, achieved the highest rankings for both PFS and OS. Several immunotherapy-based combinations also demonstrated significant survival benefits across multiple clinical subgroups without a corresponding increase in severe adverse events. Subgroup analyses suggested consistent benefits of selected regimens across age, sex, macrovascular invasion, extrahepatic spread, and ECOG performance status.ConclusionsHAIC-based strategies and selected immunotherapy combinations appear to provide superior survival outcomes as first-line treatment for advanced HCC. Given limitations related to comparator selection and evolving evidence, future head-to-head randomized trials and updated network analyses are warranted to refine optimal treatment strategies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251124082.

Wound management is a significant and growing issue worldwide. Knowledge of dressing products and clinical expertise in dressing selection are two major components in holistic wound management to ensure evidence-based wound care. With expanding global market of dressing products, there is need to update clinician knowledge of dressing properties in wound care. Optimal wound management depends on accurate patient assessment, wound diagnosis, clinicians' knowledge of the wound healing process and properties of wound dressings. We conducted a comprehensive review of the physical properties of wound dressing products, including the advantages and disadvantages, indications and contraindications and effectiveness of first-line interactive/bioactive dressing groups commonly used in clinical practice. These include semipermeable films, foams, hydroactives, alginates, hydrofibers, hydrocolloids, and hydrogels. In making decisions regarding dressing product selection, clinicians need to ensure a holistic assessment of patient and wound etiology, and understand dressing properties when making clinical decisions using wound management guidelines to ensure optimal patient outcomes. This review has highlighted there is lack of high quality evidence and the need for future well designed trials.

[This corrects the article DOI: 10.3389/fimmu.2026.1738352.].

The addition of atezolizumab (anti–PD-L1 antibody) to a platinum-based chemotherapy regimen improved progression-free survival among patients who had not previously received chemotherapy for metastatic NSCLC, regardless of PD-L1 expression and EGFR or ALK genomic alteration status.