bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of serum prolidase level in children with Familial Mediterranean Fever
Authors: Eyada Iman Khaled , Abdelfattah Walaa , Naguib Ahmed Mohamed , Shady Hend Mohamed Abu 
Published: July 2024

Abstract
Background
FMF (Familial Mediterranean Fever) is the most prevalent autoinflammatory disease. It arises due to mutations in the pyrin-encoding MEFV gene. Prolidase, an enzyme culpable of splitting the bonds of proline-containing dipeptides, is essential for matrix remodeling, collagen turnover, and cell proliferation. It has a crucial role in inflammation.

Aim
To compare serum levels of prolidase between FMF children during the attack-free periods and healthy children and to correlate it with different FMF disease criteria and inflammatory marker, also to investigate if it can serve as a marker for subclinical inflammation.

Results
Forty-one children diagnosed with FMF and 41 sex and age-matched apparently healthy children as a control group were included in this study, serum prolidase was measured by ELISA. The mean ± SD serum level of prolidase among FMF patients was 0.6 ± 0.2 mU/ml × 104, while among the control group, it was 1.3 ± 1.4 mU/ml × 104, a statistically significant difference existed between both groups, p value = 0.001. The level of serum prolidase was not correlated with FMF severity score, inflammatory markers, and other FMF disease criteria.

Conclusion
Serum prolidase level was lower among FMF patients during the attack-free period than in the healthy control group, it was not correlated with disease severity and was not predictive of the presence of subclinical inflammation. Further studies are needed to highlight the role of serum prolidase in FMF children.
Value-based preoperative assessment in a large academic hospital
Authors: Cecconi Maurizio , Goretti Giulia , Pradella Andrea , Meroni Patrizia , Pisarra Martina , Torzilli Guido , Montorsi Marco , Spinelli Antonino , Zerbi Alessandro , Castoro Carlo , Casale Paolo , Civilini Efrem , Quagliuolo Vittorio , Klinger Marco , Spriano Giuseppe , Vitobello Domenico , Maradei Leonardo , Reimers Bernhard , Piccioni Federico , Martucci Maria Rosaria , Stomeo Niccolò , Vanni Elena , Babbini Marco , Monzani Roberta , Capogreco Maria Rosaria , Lagioia Michele , Greco Massimiliano 
Published: July 2024

Abstract
Background
Value-based healthcare (VBHC) is an approach that focuses on delivering the highest possible value for patients while driving cost efficiency in health services. It emphasizes improving patient outcomes and experiences while optimizing the use of resources, shifting the healthcare system’s focus from the volume of services to the value delivered. Our study assessed the effectiveness of implementing a VBHC-principled, tailored preoperative evaluation in enhancing patient care and outcomes, as well as reducing healthcare costs.

Methods
We employed a quality improvement, before-and-after approach to assessing the effects of implementing VBHC strategies on the restructuring of the preoperative evaluation clinics at Humanitas Research Hospital. The intervention introduced a VBHC-tailored risk matrix during the postintervention phase (year 2021), and the results were compared with those of the preintervention phase (2019). The primary study outcome was the difference in the number of preoperative tests and visits at baseline and after the VBHC approach. Secondary outcomes were patient outcomes and costs.

Results
A total of 9722 patients were included: 5242 during 2019 (baseline) and 4,480 during 2021 (VBHC approach). The median age of the population was 63 (IQR 51–72), 23% of patients were classified as ASA 3 and 4, and 26.8% (2,955 cases) were day surgery cases. We found a considerable decrease in the number of preoperative tests ordered for each patient [6.2 (2.5) vs 5.3 (2.6) tests, p < 0.001]. The number of preoperative chest X-ray, electrocardiogram, and cardiac exams decreased significantly with VBHC. The length of the preoperative evaluation was significantly shorter with VBHC [373 (136) vs 290 (157) min, p < 0.001]. Cost analysis demonstrated a significant reduction in costs, while there was no difference in clinical outcomes.

Conclusions
We demonstrated the feasibility, safety, and cost-effectiveness of a tailored approach for preoperative evaluation. The implementation of VBHC enhanced value, as evidenced by decreased patient time in preoperative evaluation and by a reduction in unnecessary preoperative tests.
Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction cancer (GC/GEJC): A prospective, multi-center, phase II study.
Authors: Jiao Zuoyi , Zhou Huinian , Yu Zyuaun , Long Bo , Huang Zeping , Zhao Da , Wei Dengwen , Zhao Xiaonin , Jiang Zebin , Yang Xiaojun 
Published: July 2024

e16108 Background: FLOT remains the preferred neoadjuvant treatment (NAT) for locally advanced GC/GEJC, with evidence suggesting enhanced efficacy when plus PD-1 inhibitors. Cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, also exhibited survival benefits when combined with chemotherapy as first-line treatment for GC/GEJC. This study aimed to assess the efficacy and safety of Cadonilimab and FLOT as NAT in locally advanced GC/GEJC. Methods: Pathologically confirmed treatment-naïve patients (pts), aged 18-75, with radiologically evaluable primary GC/GEJC at stage cT3/4, ECOG PS 0-1, were enrolled. The study used simon-2 stage design with a total sample size of 38 pts and would be considered effective if more than 4 pts achieved pCR. Pts received surgery after completing NAT with Cadonilimab (10mg/kg, iv, Q3W) and FLOT (50mg/m² docetaxel, 85mg/m² oxaliplatin, 2600mg/m² 5-FU, and 200mg/m² leucovorin, iv). The primary endpoints were pCR and MPR rate. Secondary endpoints included ORR, DCR, R0 resection rate and safety (CTCAE 5.0). Results: In this phase II trial, initially enrolled 29 pts in stage I, with an additional 9 pts in stage II. Of the 34-evaluable pts, 30 pts underwent surgery. The median age was 57 years (range, 38-74), with 88.2% male and 64.7% diagnosed as stage cT4. According to RECIST1.1 criteria, 5 pts (14.7%) achieved CR, and 21pts (61.8%) achieved PR, with an ORR of 76.5% and DCR of 100.0%. According to Becker criteria for Tumor Regression Grade: 6 pts (20.0%) achieved TRG1a, 9 pts (30.0%) reached TRG1b, with a pCR rate of 20.0% and MPR rate of 50.0%. Pts with diffused and poorly differentiated tumors had higher rates of pCR and MPR (36.4%, 81.8%) than the overall population. A notable tumor downstaging was observed: 86.7% in T stage, 70.0% in N stage, and 70.0 in overall TNM stage. During the NAT phase, all 34 pts experienced TRAEs. Mild to moderate TRAEs (grade 1-2) were observed in 73.5% (25 patients), while 26.5% (9 patients) experienced grade 3 TRAEs. There were no reports of grade 4-5 or severe TRAEs. The most common TRAEs were nausea (100.0%), alopecia (97.1%), vomiting (85.3%), fatigue (85.3%), electrolyte disturbance (79.4%) and rash (73.5%). In post-surgery, all 30 pts achieved R0 resection. Surgical complications were relatively minor, predominantly fever (46.7%), ascites (30.0%) and pneumonia (23.3%). The survival benefit will be reported after the follow-up completed. Conclusions: Neoadjuvant Cadonilimab plus FLOT chemotherapy exhibit encouraging anti-tumor effectiveness and manageable toxicities, particularly in pts with diffused Lauren`s classification and poorly differentiation. This immunochemotherapy regimen might provide a promising alternative NAT option for locally advanced GC/GEJC. Clinical trial information: ChiCTR2200066893.
Patients with metastatic cholangiocarcinoma in Italy and their healthcare resource consumptions and related costs.
Authors: Esposito Immacolata , Ronconi Giulia , Dondi Letizia , Calabria Silvia , Piccinni Carlo , Dondi Leonardo , Dell'anno Irene , Addesi Alice , Martini Nello 
Published: July 2024

e16139 Background: Patients with cholangiocarcinoma (CCA) are often diagnosed at late-stage disease. Few or any therapeutic options are possible for older patients with metastases (mCCA) and comorbidities. This analysis aimed to identify and characterize newly mCCA diagnosed patients in Italy in terms of clinical features, healthcare resource consumptions and related costs charged to the Italian National Health Service (SSN). Methods: From the Fondazione ReS (Ricerca e Salute) database (~5 million inhabitants/year), among adults with primary/secondary in-hospital diagnosis of CCA in 2018 and analysable look-back period until 2013, patients newly diagnosed with lymph nodes/distant metastases (index date) were selected. They were characterized by age, sex, and comorbidities (cardiometabolic, respiratory and cerebrovascular disorders, depression, chronic kidney disease and inflammatory bowel diseases). Rate of antineoplastic treatment dispensations and hepatic metastasectomy, overall and progression-free survivals - through Kaplan-Meier curves - among patients treated (vs untreated), and healthcare costs charged to the SSN were assessed during 2 years following index date. Results: In 2018, 176 newly mCCA diagnosed patients (incidence: 4.4x100,000 adult inhabitants; 31% of CCA patients) were identified. Males were 52.3%. Mean age was 72±10 years, and 65% of patients had ≥2 comorbidities. During 1 year following index date, 45.5% of newly mCCA diagnosed patients underwent antineoplastic treatment and/or surgery (mean age was 69±9 years), of whom, 61% were males, 67% had ≥2 comorbidities. During 2 years following index date: 34 patients were lost from 1st to 2nd year; 77% of treated patients died (vs 93.8% untreated; p < 0.01); 87.5% of treated patients relapsed, on average after 6.3 months following index date. On average, during 1st and 2nd follow-up year, respectively: each mCCA patient weighed on the SSN € 12,699 and € 8,298; hospitalizations accounted 87% and 78% of the respective total expenditure. From 1st to 2nd follow-up year, respectively, the expenditure for hospitalizations and pharmaceuticals decreased from € 11,017 to € 6,498 and from € 700 to € 590, while costs for local outpatient services increased from € 982 to € 1,210. Conclusions: This study suggests that newly mCCA diagnosed patients strongly impact on the SSN, and that antineoplastic treatments and/or surgery, if applicable, can reduce mortality with substantial survival benefit.
Update results of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A single-arm, open-label phase II clinical trial.
Authors: Guo Wen-Zhi , Li Lu-Hao , Qiao Shishi , Li Ren-Feng , Zhang Weijie , He Wei , Su Chang , Pan Jie , Jin Shui-Ling , Zong Hong 
Published: July 2024

e16144 Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 498), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced BTC (ICC, ECC, GBC) were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and TQB2450 (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m2, iv, d1, q3w) and cisplatin (60mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The predefined sample size was 20. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker explore. Results: From April 2023 to Oct 2023, a total of 20 patients were enrolled. At the data cut-off date (Jan, 2024), the best overall response indicated that there were 12 PR (60.0%), 6 SD (30.0%) and 2 PD (10.0%). Therefore, the preliminary ORR was 60.0% (95%CI: 36.1%-80.9%), DCR was 90.0% (95%CI: 68.3%-98.8%). At the data cut-off date, the preliminary prognostic result exhibited that the median PFS of the 20 pts was 8.31 months (95%CI: NA~NA). Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 20 patients with the incidence > 30% were leukopenia (80%), peripheral sensory neuropathy (45%) and fever (35%). Common grade ≥3 treatment-emergent adverse events were leukopenia (30%), fever (5%), decreased platelet count (5%), malaise (5%), nausea (5%), stomachache (5%), oral mucositis (5%), vomit (5%), rash (5%) and hypotension (5%). Conclusions: Preliminary results suggested that anlotinib plus TQB2450 combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients consecutively. Clinical trial information: NCT05812430 .
Cadonilimab in combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial.
Authors: Ma Ji , Wang Tao , Chen Yidi , Yang Yi , Qiu Yiwen , Shen Shu , Yi Cheng , Wang Wentao 
Published: July 2024

e16158 Background: PD-1 or PD-L1 inhibitors plus chemotherapy as the first-line treatment has been proven to be effective in improving the prognosis of advanced biliary tract cancer (BTC) patients. However, there is still considerable demand for further improvement of BTC patients’ prognosis. This trial aims to evaluate the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) plus gemcitabine and cisplatin for patients with advanced BTC in first -line treatment. Methods: In this phase II, single-arm trial, we will enroll 65 patients with previously untreated, unresectable, locally advanced or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, days 1, every three weeks) plus gemcitabine (1000 mg/m2, days 1, 8, Q3W), and cisplatin (25 mg/m2, days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, days 1, Q3W) until disease progression or unacceptable toxicity. Treatment response was evaluated with image-based assessment according to response evaluation criteria insolid tumors (RECIST) version 1.1. by two experienced experts and further explored multiple methods, such as 3D visualisation and Spectral computed tomography Scan. The primary endpoint was the objective response rate (ORR); the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included associations between response, molecular characteristics, and the immune microenvironment. Results: Between June 30, and January 31, 2024, a total of 30 patients have undergone at least one imaging evaluation. 66.7% of these patients were diagnosed with ICC, 23.3% with GBC, and 10% with ECC. The mean age was 58.4 years, and 60% of the patients were male. 24 (80%) patients had metastasis. Among them, 1 (3.3%) patient acheived complete response (CR), 15 (50%) patients had partial response (PR) and 8 (26.7%) patients presented with stable disease (SD). The ORR was 53.3% and the DCR was 80%. The most common treatment-related adverse events (TRAEs) of any grade were rash (80%) and anaemia (76.7%). Grade 3 TRAEs were observed in 66.7% of the patients. The most frequent grade 3 TRAEs were anaemia (33.3%), and leukocytopenia (33.3%). No grade 4 or 5 events were observed. All patients were microsatellite stable (MSS), and the median TMB was 2.88 (0-109.44) Muts/Mb. Conclusions: Cadonilimab plus gemcitabine and cisplatin shown a promising efficacy and acceptable safety profile as first-line treatment for advanced BTC patients. Clinical trial information: NCT05978609 .
Efficacy and safety of regorafenib and/or immune checkpoint inhibitors as a second-line therapy for advanced hepatocellular carcinoma: A real-world study from a single center.
Authors: Liu Songtao , Huang Xueying , Chen Jingjing , Wei Qiaoxin , Liu Mei 
Published: July 2024

e16165 Background: This study aimed to assess the efficacy and safety of regorafenib and/or immune checkpoint inhibitors (ICIs) as a second-line treatment in patients with pretreated hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received regorafenib treatment in our hospital from January 2020 to November 2023 were reviewed. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary end points. Results: Forty-five patients were included with a median age of 61 (31-83) years. Thirty-two patients (71.1%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Twenty-three patients (51.1%) had extrahepatic metastasis. ICIs were applied to 30 patients (66.7%) at the use of regorafenib. Local treatments were applied to 17 patients (37.8%). The median OS was 14.5 (11.3, 26.4) months in all patients. Regorafenib plus ICIs had a longer survival than regorafenib alone (20.5 [11.6, NA] vs 11.3 [3.0, 13.9] months, P = 0.019). Local treatment had no obvious effect. The median PFS was 6.8 (4.5, 11.7) months in all patients. The median PFS was 9.7 (4.6, 14.5) months in regorafenib plus ICIs that was longer than regorafenib alone with 3.0 (2.0, 8.0) months. Local treatment only showed a trend of prolongation (11.8 [2.5, 22.6] vs 4.7 [3.5, 9.7] months, P = 0.059). The 1-year OS and PFS were 43.2% and 20.0%, respectively. ORR and DCR was 29.0% and 71.0% according to mRECIST criteria, respectively. The most common any-grade treatment-related adverse events (TRAEs) were rash/itching (41.3%), hand-foot syndrome (19.6%), and anorexia (13.0%). Grade≥3 TRAEs occurred in 8.9% (4/45) of the patients and hypertension (4.4%) had the highest proportion. Conclusions: Regorafenib plus ICIs therapy is an effective promising regimen regardless of first-line treatments in advanced HCC. Combined with local treatment only showed a trend of PFS, further prospective research is needed.
Efficacy and safety of regorafenib combined with PD-1 inhibitors in patients with advanced hepatocellular beyond atezolizumab plus bevacizumab: A retrospective analysis of real-world evidence.
Authors: Zhang Xinfeng , Cheng Jiamin , Chen Bowen , Zhang Tianlan , Li Yinyin , Zhang Linzhi , Dong Jinghui , Lu Yinying 
Published: July 2024

e16172 Background: In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapy scheme is debatable and the efficacy of regorafenib combined with PD-1 inhibitors is still unclear. Methods: In this retrospective study, advanced HCC patients who received regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab were consecutively enrolled from February 2022 to January 2024. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: A total of 11 eligible patients were enrolled, with 8 in Child-Pugh A and 3 in Child-Pugh B7. All patients had hepatitis B infection by with tumor embolus. All patients were classified as Barcelona Clinic Liver Cancer stage C. The AFP level is above 400ng/ml in all patients. At data cut-off at February 2024, the median OS was 16.9 months and the median PFS was 3.7 months. The 3-month and 6-month PFS rates were 70% and 35% , respectively. The 12-month OS rate was 71.4%. Grade≥3 TRAEs occurred in 9.1% (1/11) of the patients. Conclusions: Though application of regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab present safe and effective in our cohort, these data need to be confirmed in prospective comparative studies. [Table: see text]
The activity and safety of icaritin for patients with unresectable HCC: A real world, retrospective study.
Authors: Shao Guoliang , Jiang Wentao , Zheng Xin , Xiang Huiling , Wang Song , Zhou Xu , Lin Nan , Yu Zheng-Ping , Dong Ke , Cao Mingrong , Xie Qinfen , Zeng Hui , Zhang Zhewei , Luo Jun 
Published: July 2024

e16181 Background: Primary liver cancer is a major health burden globally, ranking sixth in incidence and third in mortality among all cancers[1]. Over the past 5 years, immune checkpoint inhibitors (ICIs) and multi-targeted tyrosine-kinase inhibitors have emerged as new treatment options for advanced hepatocellular carcinoma[2–4]. Nevertheless, only a small subset of patients with hepatocellular carcinoma derive a response to ICI monotherapy. Icaritin, a target tumor micro-environment(TME) modulating compound, which interacts with MyD88/IkB kinase-a (IKK)[5], inhibiting the TNF-a-induced IKK and nuclear factor-κB (NF-kB) signaling pathways and blocking PD-L1 expression in HBV-related HCC[6-9] and has been approved in China for the treatment of first-line advanced HCC. Icaritin phase III study previously reported at 2021 ASCO, we therefore investigated the efficacy of icaritin in patients with unresectable stage IIA-IIIB (CNLC stage) HCC in a real-world setting. Methods: This multi-center, retrospective study, conducted between May 2022 and Nov 2023. We retrospectively collected medical records of patients (pts) with unresectable IIA-IIIB (CNLC stage) HCC who received icaritin monotherapy (mono-group) or icaritin combined with PD-1/L1 and/or anti-VEGF therapy (combination group) as first line therapy. The primary endpoints were progression free survival (PFS); Secondary endpoints included overall survival (OS) rate, objective response rate (ORR) by RECIST v1.1, and safety. Results: Patients characteristics: 49 pts were eligible for inclusion with median age of 60.7 years old (range 18.0-89.0), 91.8% were ECOG PS 0-1, 86.5% had HBV infection, 79.6% were stage III and 48.9% were AFP>400 ng/ml. 33 pts administrated with combination therapy, other 16 pts’ regimen was icaritin monotherapy. Efficacy: As of the data cutoff for the preliminary analysis of progression free survival (Nov 30, 2023), the median follow-up was 11.17 months (95%CI 6.74–12.12). The ORR for the combination group was 6.06%, and 12.50% for the mono-group, the mPFS was 8.94(95%CI 6.90~9.76) and 5.52 (2.92~NE) for each group. The mOS was not reached for both group, the 6 and 12-months OS rates were 91.00% and 73.67% respectively. Safety: For the safety information, most of TRAEs were grade 1 or 2. No serious AEs were observed. Conclusions: This real-world retrospective study revealed that icaritin monotherapy and icaritin-based combination therapy are promising therapeutic options for unresectable HCC in China. Clinical trial information: ChiCTR2300074565.