bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment modalities for advanced solid pseudopapillary tumor of the pancreas.
Authors: Yue Mengli , Mao Yize , Yang Qiuxia , Wang Fang , Tang Honggui , Yu Xiaofang , Li Shengping , Wang Fenghua
Published: July 2024

e16327

Background: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. However, a minority of SPT patients present aggressive behavior and develop recurrent or metastatic diseases. The treatment strategies of advanced SPTs remain unclear. Our study aimed to explore the treatment modalities of aggressive SPTs and the role of endocrine therapy. Methods: The data on clinicopathologic characteristics and treatment of advanced SPT patients from Sun Yat-Sen University Cancer Center and Shen Zhen People's Hospital were collected. The treatment modalities were explored by co-analyzing our local cohort and published literatures. Single sample gene set enrichment analysis (ssGSEA) was used to explore the functional enrichment pathway (GSE43795). Fresh surgical specimens from 10 SPT patients were collected for endocrine drugs sensitive test in vitro by performing tumor histoculture end-point staining computer image analysis (TECIA). Results: A total of 77 advanced SPT patients including 14 cases in our local cohort and 63 cases from published literatures were enrolled. 60 patients received local treatment including cytoreductive surgery, interventional therapy or radiation therapy. 55 patients who had undergone cytoreductive surgery have better outcome compared with others (P = 0.046, HR = 4.12). 31 patients received systemic chemotherapy and 6 patients received targeted therapy. There were 2 patients achieved partial response after chemotherapy. In our local cohort, 5 patients received endocrine therapy with tamoxifen plus megestrol. One patient achieved partial response with duration of response (DOR) of 89 months. 4 patients showed stable disease. ssGSEA for GSE43795 showed that Wnt signaling pathway and its inhibitory pathway-progesterone receptor signaling pathway were simultaneously enriched in SPTs. The results of endocrine drug sensitive test in vitro by TECIA showed response rate of 50% (5/10) in megestrol group, 40% (4/10) in tamoxifen group, and 30% (3/10) in testosterone propionate group. Conclusions: Advanced SPTs did not appear chemosensitive. Cytoreductive surgery may improve survival. Simultaneously enriching Wnt and progesterone receptor signaling pathway may partially explain the low aggressive ability of SPT and their unbalance may lead to the aggressive behavior of SPT. Endocrine therapy with tamoxifen plus megestrol, by enhancing the progesterone signaling pathway, seems to be a promising regimen for advanced SPTs, which is worth to be noted and further studied.
Efficacy and safety of sitagliptin, in combination with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Zhou Tianxing , Wang Xiuchao , Yang Chao , Yu Jun , Hao Jihui
Published: July 2024

e16329

Background: Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to identify new targets and compounds to overcome chemotherapeutic resistance. Methods: The high-throughput virtual drug screening, molecular docking analysis and organoid biobank-based drug screening were performed to identify the candidates to efficiently overcome chemotherapy resistance. In vitro and in vivo PDOs, PDXs and KPC GEMM models were used to evaluate the effects of the compounds. Spatial single cell RNA-sequence, spatial metabolomics and proteomics were employed to elucidate the mechanism. Additionally, an ongoing open-label, randomized, single-arm, single-center phase 2 investigator-initiated clinical trial (NCT05947825) is investigating the efficacy and safety of the candidate in sensitizing gemcitabine plus nab-paclitaxel (GnP) in previously untreated advanced PDAC patients. Objective tumor responses were assessed according to RECIST1.1 criteria and any adverse events were graded using CTCAE 5.0. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and treatment-emergent adverse events (TEAEs). Results: High-throughput drug screening of chemotherapy-resistant PDOs identified Sitagliptin that could significantly induce the degradation of RRM1/RRM2 in a ubiquitin proteasome-dependent manner and further result in unrestrained pyrimidine biosynthesis and alleviation of replication stress. In vitro and in vivo assays confirmed that Sitagliptin could synergistically enhance the ability of GnP regimen to suppress PDAC progression. In the phase 2 study (NCT05947825), previously untreated advanced PDAC received Sitagliptin, 100mg/qd and gemcitabine (G, 1000mg/m2 )plus nab-paclitaxel (nP, 125 mg/m2 )on Days 1 and 8 in a 21-day cycle. Till February 1, 2024, 12 patients with ECOG 0 to 2 have been enrolled in the study. The primary endpoint has not been reached. Among the 8 evaluable patients, 3 showed partial responses and 5 had stable diseases. The objective response rate (ORR) and disease control rate (DCR) were 37.5% and 100% respectively. There were no instances of treatment-related death in this study. The most common treatment-emergent adverse events (TEAEs) were decreased white blood cells and fatigue. One patient experience skin rash. Conclusions: Sitagliptin could effectively improve efficacy of GnP regimen by suppressing RRM1/RRM2-mediated pyrimidine metabolism. Sitagliptin plus GnP regimen is a feasible regimen with a manageable safety profile. Sitagliptin in combination with GnP regimen shows encouraging antitumor activity in PDAC, meriting continued development. Clinical trial information: NCT05947825 .
Preliminary results from a multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).
Authors: Wen Feng , Tan Ping , Lin Tianhai , Zhang Peng , Shen Yali
Published: July 2024

e16595

Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting. The preliminary results would be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). 51 patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive MIBC will be included. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Treatment efficacy will be performed by imaging and transurethral resection of tumors after the neoadjuvant treatment. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are disease control rate (DCR), overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Results: Until now, 18 patients were included successfully, with 3 female patients and 15 male patients. And the median age was 64.47 years old. Of them, 7 patients were HER2(2+), and 11 patients were HER2(3+). The clinical stages were T2-4aN0-3M1a. Sixteen patients had the primary efficacy evaluation by now. After the neoadjuvant treatment, 7 patients were T0, 4 patients Tis, 2 patients partial response (PR), 2 patients stable disease (SD) and 1 patient suffered from progress of local disease. Hence the cCR rate was 68.75%, and the DCR was 90.91%. Fourteen patients chose radiotherapy as bladder-sparing therapy and no evidence of tumor in 6 patients who received treatment efficacy after radiotherapy. Two patients received radical cystectomy and pT3N0M0 was achieved for both. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 myositis, grade 1 elevated transaminase and grade 1 hyperthyroidism which led to treatment interruption of tislelizumab. And 10 patients experienced RC48-ADC related toxicities, including grade 1 elevated transaminase, grade 1 erythra and grade 1 paresthesia. No treatment related dose reduction happened. Conclusions: The novel neoadjuvant combination of RC48-ADC and tislelizumab showed promising down stage efficacy in patients with HER2 positive locally advanced MIBC and the toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiECRCT20210564.
Improved detection of homologous recombination deficiency using WES sequencing: Insights into a Chinese pan-cancer cohort.
Authors: Chen Yaru , Suo Peisu , Zhong Jiasheng , Cao Huiya , Ye Haoyang , Chen Shifu , Zhou Yanqing
Published: July 2024

e17503

Background: Homologous recombination (HR) deficiency has emerged as a novel biomarker for the clinical use of PARP inhibitors in advanced ovarian cancer, and may also be of value in guiding the clinical use of PARP inhibitors and platinum-based drugs in breast cancer, prostate cancer, and other tumors. This significant finding assists in precision medication and prognosis judgments for patients. Methods: This research incorporated a Chinese pan-cancer cohort comprising 1033 patients diagnosed across thirteen cancer types. All matched tumor tissues and peripheral blood samples were processed for the whole exome sequencing. The HRD scoring was conducted with ScarHRD R package with defined parameters for the heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) status. HR deficiency were defined as an HRD-score ≥50 or BRCA1/2 deficient, while HR proficiency were defined as an HRD-score <50 and BRCA1/2 intact. Results: Ovarian cancer demonstrates the highest HRD prevalence at 51.85%, surpassing the BRCA1/2 mutation rate of 20.37%. Breast cancer follows with an HRD rate of 45.45%, yet no BRCA1/2 mutations are detected. Other cancers like pancreatic, gastric, and sarcomas also present notable HRD rates (29.41%, 36.84%, and 29.79%, respectively) without corresponding BRCA1/2 mutations. In contrast, cancers such as urological, lung, intestinal, and neurological tumors exhibit a mismatch between HRD rates and BRCA1/2 mutation presence, few patients with notable BRCA1/2 mutations did not have consisted HR-deficient rate, and vice versa. Conclusions: Analysis HRD-score can help to screen a larger population of PARP inhibitor beneficiaries and provide hope to more patients. In the future we will do more dimensional data analysis statistics on this cohort. [Table: see text]
Clinical efficacy and safety of cadonilimab immunotherapy in patients with advanced cervical cancer: A retrospective study.
Authors: Han Xiuchen , Tan Huaming , Fang Minjie , Wang Minjie , Zhou Yayan , Sheng Xiugui
Published: July 2024

e17519

Background: For patients with recurrent or metastatic cervical cancer, especially those with negative PD-L1 expression, there is a lack of effective treatment and often indicate poor prognosis. A multicenter retrospective study was conducted to evaluate the safety and antitumor activity of cadonilimab in recurrent or metastatic cervical cancer patients. Methods: Patients with metastatic or recurrent cervical cancer, who underwent treatment of cadonilimab at Shenzhen People’s Hospital and Huazhong University of Science and Technology Union Shenzhen Hospital. All patients received immunotherapy of cadonilimab at a dose of 10mg/kg of body weight with/without the combination of chemotherapy/bevacizumab/ radiotherapy. Cadonilimab were repeated every 3 weeks until disease progression or intolerable toxicity. Antitumor activity and safety were assessed in all patients. Results: Since July 2022 to November 2023. A total of 18 patients (Figo stage IB1-IIIC) with recurrent/metastatic cervical cancer, 3 patients with newly diagnosed advanced cervical cancer (Figo stage IVB stage) were included. With a median follow-up of 7.0 months (IQR 1.9–15.4), the number of treatment cycles for cadonilimab ranged from 3 to 17 cycles, with a median of 7 cycles. 6 patients with PD-L1-positive expression, 5 patients with negative expression, and 10 patients were unknown. 8 patients combined of chemotherapy, 7 patients received cadonilimab monotherapy, 4 patients combined of chemotherapy and bevacizumab, 1 patient combined of bevacizumab, 1 patients combined of chemotherapy, bevacizumab and radiotherapy . 2 patients with newly diagnosed advanced disease and 2 patients with recurrent cervical cancer achieved complete response (CR), 11 patients with achieved partial response(PR) and 1 patients were in stable disease(SD). The objective response rate (ORR) was 71.4% (15 of 21 patients). The ORR of patients with the PD-L1-negative expression was 80% (4 of 5 patients).Grade 3–4 treatment-related adverse events occurred in 7 (33.3%) of 21 patients, the most frequent grade 3-4 adverse events were decreased white blood cell count (3 [14.3%]), decreased platelet count (2 [9.5%]) and anemia (2 [9.5%]). Immune-related AEs (irAEs) were all G1-2, and occurred in 2 (9.5%) patients. None of the patients discontinued treatment because of intolerable toxicity. Conclusions: In this study, cadonilimab containing therapies showed promising results in responses and survival outcomes among patients with metastatic or recurrent cervical cancer and have a favorable safety profile. [Table: see text]
Reflections on the changes in ascites and serum VEGF1 levels before and after intraperitoneal infusion of bevacizumab.
Authors: Du Zhenhua , Xia Yu , Li Xiuqin
Published: July 2024

e17539

Background: This study analyzes the levels of VEGF1 in ascites and serum before and after intraperitoneal infusion of bevacizumab, aiming to explore the optimal administration route for treating recurrent ovarian cancer accompanied by ascites. Methods: Sixty-seven patients with advanced recurrent ovarian cancer and significant ascites were treated with intraperitoneal infusion of bevacizumab combined with chemotherapy. Under ultrasound guidance, a peritoneal drainage tube was placed, and the volume of ascites was measured before the infusion. The effects of the treatment were assessed by measuring the ascites volume during the 2nd to 3rd treatment (final ascites drainage) and by analyzing and comparing the levels of Vascular Endothelial Growth Factor 1 (VEGF1) in both ascites and serum. Results: The average volumes of ascites before and after treatment were 4229.97 ml and 5.42 ml, respectively (P<0.0001), with an overall response rate (ORR) of 89.6% (60/67). Before and after treatment, the levels of VEGF1 in ascites were 283.86 pg/mL and 18.76 pg/mL, respectively (P<0.0001). Before and after treatment, serum levels of VEGF1 were 80.67 pg/mL and 61.25 pg/mL, respectively (P<0.0001). Before treatment, the level of VEGF1 in ascites at 283.86 pg/mL was significantly higher than in serum, which was 80.67 pg/mL (P<0.0001). The reduction in VEGF1 levels following intraperitoneal infusion was over tenfold greater in serum compared to ascites. When the cutoff value for VEGF1 in ascites was set at 37.12 pg/mL, the sensitivity was 80.28%, and the specificity was 91.55%. Conclusions: The combined treatment of intraperitoneal infusion of bevacizumab with chemotherapy is an effective strategy for controlling ascites in recurrent ovarian cancer. Keywords: Bevacizumab, Intraperitoneal Infusion, Recurrent Ovarian Cancer, Ascites, Vascular Endothelial Growth Factor 1 (VEGF1).
Overall survival in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer (PSROC) treated with olaparib maintenance: Real-world data of the C-PATROL study.
Authors: Marmé Frederik , Hilpert Felix , Welslau Manfred , Grabowski Jacek P. , Schneeweiss Andreas , Hartkopf Andreas D. , Bauerschlag Dirk , Fasching Peter A. , Brandi Christiane , Rehbein John-Kilian , Glowik Regina , Sehouli Jalid
Published: July 2024

e17542

Background: Maintenance monotherapy with PARP-inhibitor (PARPi), olaparib has previously shown good effectiveness and tolerability in total population of patients with PSROC who were in response to platinum-based chemotherapy (PBC) in the C-PATROL study. Here we present the overall survival (OS) data in different subgroups. Methods: The prospective German non-interventional study C-PATROL (NCT02503436) captured routine clinical data of olaparib maintenance according to label in patients with BRCA-mutated PSROC treated with PBC. The primary endpoint was PFS, relevant secondary endpoints included OS and safety. Data were analyzed by descriptive statistics. Results: Between 10/2015 and 10/2019, 277 patients were enrolled. The ITT set (study selection criteria fulfilled) comprised 267 patients (median age: 60 yrs; ECOG ≤1: 93%; ≥2 relapses: 32%; ≥3 prior PBC: 29%). Median follow-up was 23.5 months (range 0.0–80.5) and median olaparib treatment duration was 13.6 months (0.1–80.9). 10% of patients received olaparib for ≥ 5 years and 8% of patients received further PARPi also as subsequent treatment. Median OS was 35.4 months (95% CI 29.2–49.9). The longest median OS was observed in patients with a complete debulking after the surgery at current relapse, a complete response (CR) to the current PBC and a BRCA2 mutation. Adverse events (AEs) were consistent with the known tolerability profile of olaparib (safety set: n=274; any AE: 95%, AE of CTCAE grade ≥ 3: 40%, olaparib discontinuation due to AE: 11%; most common AE any CTCAE: nausea (46%), fatigue (39%), anaemia (31%), and vomiting (17%); most common AE CTCAE grade ≥ 3: anaemia (14%)). Conclusions: Olaparib is effective and safe in the real-world setting. In olaparib-treated patients with BRCA-mutated PSROC longer OS was observed mainly with respect to resection status after debulking surgery at current relapse, to tumor burden at the therapy start and BRCA mutation type. Our data underline the role of cytoreduction and platinum response in the context of PARPi maintenance therapy. Clinical trial information: NCT02503436 . [Table: see text]
Clinical features and prognostic analysis of 247 patients with ovarian clear cell carcinoma (OCCC) and an exploration of the treatment of recurrent OCCC: A single-center study in China.
Authors: Wu You , Lyu XueYan , Wang Kunyu , Ao Miao , Luo Haixia , Zhang He , Zhang Yuanyuan , Li Bin , Song Yan
Published: July 2024

e17548

Background: Ovarian clear cell carcinoma (OCCC) is relatively resistant to chemotherapy and has a worse prognosis than other ovary cancer. In this study, we reviewed the case files of OCCC in a single center to find its clinical characteristics and explore the treatment of recurrent cases, and the efficacy of immunotherapy. Methods: From August 2007 to August 2023 247 patients with OCCC were retrospectively involved. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors. The relapse OCCC were divided into four groups based on the different treatment who underwent chemotherapy or chemotherapy combined with surgery, bevacizumab, immune checkpoint inhibitors treatment. Kaplan–Meier curves were utilized to compare OS and DFS/PFS between the groups. Results: (1) 247 patients with OCCC were included, CA125 abnormality (> 35 U/ml) 65.2%, ascites cytology positive 10.1%, and the overall satisfactory reduction of tumor was 92.7%, CR and PR were 93.1 and 6.9%, respectively. 16.2% patients received more than 6 cycles of postoperative chemotherapy.(2)Univariate Cox regression analysis identified ascites (HR=4.012, 95% CI: 1.846 - 8.720, P<0.001), initial treatment effect (HR=2.714, 95% CI: 1.132 - 6.506, P=0.025), and chemotherapy cycles (HR=2.564, 95% CI: 1.402 - 4.689, P=0.002) were identified as independent prognostic factors for OS.(3)The patients who received chemotherapy cycles exceeding 6 cycles had worse prognosis(HR=3.01, 95%CI: 1.70-5.33, P<0.001), the result is the first proposal in our study.(4) Kaplan-Meier survival analysis showed that the OS of the chemotherapy combined with surgery relapse OCCC group was significantly better than the other three groups (HR=0.2732, 95%CI: 10.133-0.559, P=0.001). Subgroup analysis showed that relapse patients with satisfactory tumor reduction had more significant survival benefits(HR=3.86, 95%CI: 0.79-18.93, P=0.096).(5)The PFS of the chemotherapy combined with surgery group was also better than the other three groups (median PFS 25 months vs 8.5 months in chemotherapy vs12 months in chemotherapy combined immunotherapy vs 12 months in chemotherapy combined with bevacizumab). (6)4 patients who tested positive for PD-L1 received immune maintenance therapy after chemotherapy for 6-24months. There has been no recurrence since follow-up. Conclusions: Ascites, initial treatment effect and chemotherapy cycles were identified as independent prognostic factors for OCCC OS, chemotherapy combined with surgery for recurrent OCCC was significantly improving patient prognosis. For patients who achieve CR after initial treatment, if PD-L1 expression is positive, maintenance immunotherapy can be considered, but further studies with large samples are needed.
Real-world treatment patterns and outcomes of patients with advanced melanoma treated with nivolumab plus relatimab.
Authors: Thakker Sach , Belzberg Micah , Stahl Chelsea , Jang Sekwon , Al-Mondhiry Jafar
Published: July 2024

e21501

Background: Programmed death-1 (PD-1) receptor inhibitors significantly increase survival rates for advanced melanoma, yet first-line PD-1 inhibitor therapy shows limited overall response rates (32.6%) and progression-free survival (4.6 months). Relatimab (RELA) was recently approved for the treatment of metastatic and unresectable stage III to IV melanoma in combination with nivolumab (NIVO). RELATIVITY-047 showed an ORR of 43% as a first-line treatment while RELATIVITY 020 showed an ORR of 9-12% in patients progressed on anti-PD-1 therapy. Although clinical trials have demonstrated NIVO-RELA provides benefit for patients with advanced melanoma, little is known about real-world treatment patterns and outcomes. Methods: We performed a retrospective review of all patients with stage III and IV melanoma treated with NIVO-RELA as first-(1L) or second-line or beyond (2L+) therapy at Inova Schar Cancer Institute between September 2021 to September 2023. Primary endpoints were overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) which were evaluated using the RECIST v1.1 criteria. The Kaplan–Meier method was used to generate overall survival (OS) and progression free survival (PFS) median values. Results: Eighty-eight patients were followed for an average of 6.5 months following NIVO-RELA initiation. For 1L treated patients, ORR was 58% (21% PR, 37% CR). Median PFS was 11 months (95% CI 3.1-11). For 2L+ treated patients, ORR was 33% (14% PR, 19% CR). Median PFS was 9.8 months (95% CI 4.7-17.2). Subgroup analyses observed significantly different ORR between patients previously treated with versus without anti-CTLA4 therapy (29% v 44%; p = 0.017), patients treated with NIVO-RELA more than vs within 6 months from their last other therapy (50% v 27%; p = 0.004), and among patients with stage III vs stage IV disease (67% v 30%; p = 0.031) (Table 1). Conclusions: These real-world results support the use of NIVO + RELA in patients with advanced melanoma and emphasize the impressive efficacy of the drug combination in the IL and 2L+ settings compared to RELATIVITY-020 and 047. PFS and OS for 1L and 2L+ therapy with NIVO + RELA in this study aligned with or superposed results from previous trials. Further analyses with increased sample sizes and longer follow-up is warranted. [Table: see text]
The CROWN study: Cardiac outcomes with near-complete estrogen deprivation.
Authors: Bansal Rani , Douglas Emily H. , Ansley Katherine C. , Park Carolyn J. , Richardson Karl M. , Dent Susan Faye , Anders Carey K. , Westbrook Kelly E. , Hackney Mary Helen Helen , Vachhani Hetal Ravikumar , Barrows Elizabeth , Hatcher Sarah , D'Agostino Ralph , Jordan Jennifer , Thomas Alexandra
Published: July 2024

TPS12146

Background: Treatment for premenopausal women with high/intermediate risk hormone receptor (HR)-positive breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near-complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV morbidity. Given the overall CV injury associated with BC treatment and the future life-years of these women, the CV impact of NCED warrants further study. The CROWN study uses sophisticated imaging assessments of cardiac dysfunction and biomarker and demographic correlates to understand the evolution of CV injury with the goal of developing tools to assess and mitigate CV risk. Methods: This is an NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Duke University, Wake Forest University and Virginia Commonwealth University) that includes premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-2. HR-positive BC patients are receiving an AI and OFS. Women with HR-negative BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table). These assessments include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. Correlation of CMR imaging with CCTA detail of coronary plaque changes is planned. The relevance of pre-existing risk factors on study outcomes, including an emphasis on race and dynamic change in modifiable and treatment related risk factors will also be assessed. We plan to enroll 90 women,65 in the NCED group and 25 in the HR-negative group, allowing for a 10% drop out rate. The first primary statistical analyses will include testing hypotheses between group (NCED vs HR-negative) and within group (longitudinal changes within the NCED group). Secondary analyses involve developing predictive equations to determine if patient demographics, clinical parameters and serum biomarkers are associated with CV changes over time. We have currently enrolled 34 women (31 NCED and 3 HR-negative). 2 out of 3 patients entering the 2nd year of the study have returned for their year 1 imaging. Retention will be a key component of this study as analysis of the primary and secondary endpoints are dependent on completion of imaging. Clinical trial information: NCT05309655 . [Table: see text]
Urolithiasis Causes Osteoporosis in Asians: Genetic Evidence from Mendelian Randomization and Pathway Analysis
Authors: Zhou Zijie , Xu Haoying , Fu Jiehui , Wei Penghui , Mei Jian
Published: July 2024

Background

It is an indisputable fact that patients with urolithiasis are prone to osteoporosis (OP), but the specific mechanism of their association is unclear. Previous studies have focused on the mediation of environmental factors such as diet; however, the potential of urolithiasis itself to induce OP remains uncertain.

Methods

In this study, we used data from the Japan BioBank (6638 urolithiasis and 7788 OP cases) to investigate the direct causal relationship and mechanism between urolithiasis and OP, applying Mendelian randomization, genetic correlation analysis, colocalization, and pathway analysis. We selected 10 genetic variants as instrumental variables for urolithiasis.

Results

The results showed a positive association between genetically predicted urolithiasis and OP, with significant direct effects persisting after adjusting for OP-associated factors in 4 models. Reverse analysis revealed no significant causal effect of genetically predicted OP on urolithiasis. While genetic correlation analysis and colocalization did not find conclusive evidence, mediation analysis identified estimated glomerular rate as a significant contributor. Co-risk factor analysis unveiled cardiovascular elements as common risks for both conditions. Bioanalysis implicates that cytokine, metabolic, and calcium signaling pathways may bridge urolithiasis and OP, with BCAS3, DGKH, TBX2, and TBX2-AS1 identified as potential causal genes.

Conclusion

In conclusion, the study establishes a direct causal link between urolithiasis and OP, independent of environmental factors. Regardless of lifestyle, urolithiasis patients should remain vigilant about the risk of OP and consider regular OP screening. The biological mechanism of urolithiasis combined with OP and related drugs still needs to be further explored.
Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease
Authors: Korakas Emmanouil , Kountouri Aikaterini , Pavlidis George , Oikonomou Evangelos , Vrentzos Emmanouil , Michalopoulou Eleni , Tsigkou Vasiliki , Katogiannis Konstantinos , Pliouta Loukia , Balampanis Konstantinos , Pililis Sotirios , Malandris Konstantinos , Tsapas Apostolos , Siasos Gerasimos , Ikonomidis Ignatios , Lambadiari Vaia
Published: July 2024

Context

The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known.

Objective

To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Methods

Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study.

Results

Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (−6% vs −4%, P = .048 and −11% vs −9%, P = .039), augmentation index (AIx) (−59% vs −52%, P = .041 and −70% vs −57%, P = .022), and pulse wave velocity (PWV) (−6% vs −3.5%, P = .019 and −12% vs −10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores.

Conclusion

Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.
Geographic Variation in Osteoporosis Treatment in Postmenopausal Women: A 15-Year Longitudinal Analysis
Authors: Jones Alicia R , Enticott Joanne E , Ebeling Peter R , Mishra Gita D , Teede Helena J , Vincent Amanda J
Published: July 2024

Context

Osteoporosis affects more than half of older women, but many are not treated. Whether treatment differs between rural and urban areas is unknown.

Objective

To examine differences in osteoporosis treatment among postmenopausal women living in urban and rural areas of Australia.

Methods

Women participating in the Australian Longitudinal Study on Women's Health, a prospective longitudinal cohort study, born between 1946-1951, and with osteoporosis or fractures, were included. Surveys from 2004 to 2019 were linked to the Pharmaceutical Benefits Scheme (government-subsidized medications) to assess osteoporosis treatment and adherence, comparing geographical areas.

Results

Of the 4259 women included (mean age, 55.6 years), 1703 lived in major cities, 1629 inner regional, 794 outer regional, and 133 remote areas. Over the 15-year follow-up, 1401 (32.9%) women received treatment, including 47.4% of women with osteoporosis and 29.9% with fractures. Women in outer regional and remote areas were less likely to use antiosteoporosis treatment than those in major cities on univariable analysis (outer regional odds ratio, 0.83; 95% CI, 0.72-0.95; remote, 0.65; 0.49-0.86), but this did not remain significant on multivariable analysis. Median duration of use was 10 to 36 months, adherence varied by treatment type (34%-100%) but was not related to incident fractures, and of the women who stopped denosumab, 85% did not receive another consolidating treatment.

Conclusion(s)

One-third of women with osteoporosis/fractures received treatment, and adherence was low. There was no difference in treatment use between urban and rural areas after adjusting for risk factors, although the specific treatment used, and adherence, differed.
Case Report of Hyponatremic Seizures in a Term Neonate Attributed to Excessive Maternal Coconut Water Ingestion During Labor
Authors: Soriano Laura P. , Rollins Mark D. , Barreto Chang Odmara L.
Published: July 2024

We report the case of a term neonate who was somnolent at birth with ventilatory distress and experienced 2 seizures shortly after delivery. Laboratory tests revealed the neonate had a serum sodium of 113 mmol/L. The seizures stopped after treatment with midazolam, and the sodium was corrected slowly with 3% hypertonic saline without further sequelae. The severe neonatal hyponatremia and seizures were attributed to maternal consumption of excessive amounts of coconut water during labor. This case demonstrates the importance of careful consideration of both fluid volume and fluid electrolyte composition during labor to prevent adverse maternal and neonatal outcomes.
Development of a hepatic cryoinjury model to study liver regeneration
Authors: Sande-Melon Marcos , Bergemann David , Fernández-Lajarín Miriam , González-Rosa Juan Manuel , Cox Andrew G.
Published: July 2024

The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. After this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma within an individual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.
Model of the impact of intangible resources on the competitiveness of listed companies from the WIGtech index in Poland
Authors: Perło Dorota , Arszułowicz Norbert
Published: July 2024

Motivation: The complexity of the phenomenon of competitiveness among contemporary enterprises implies the legitimacy of searching for sources of competitive advantages beyond traditional success factors. The concepts of enterprise competitiveness have evolved from classical economics to the present day and theories with a practical purpose such as: the theory of five forces by M.E. Porter and the theory of key competences by G. Hamel and C.K. Prahalad. Nowadays research on the phenomenon of the competitiveness of enterprises seeks answers to the following questions: what is the role of intangible resources in being competitive on the market and what types of intangible resources are the most important from the point of view of the research?Aim: The aim of the article is to examine the strength and direction of the impact of intangible resources on the competitiveness of listed companies. The article presents a theoretical model of the impact of intangible resources on the competitiveness of listed companies. The case study used for the empirical verification of the constructed model will be joint-stock companies from the Warsaw Stock Exchange selected according to the criteria defined in the article. Statistical data of the tested objects from 2021 will be implemented in the model in order to analyze its stability.Results: To achieve the aim of the article, the PLS-SEM method of modeling structural equations was used, which allows for the study of relationships between directly unobservable variables. The model consists of two parts: a structural (internal) model and a measurement (external) model. These models are also used in the parameter estimation process — they are interrelated. Two unobservable (hidden) variables were adopted in the constructed model: intangible resources (IR) and competitiveness of companies (CC). Hidden variables were defined based on a potential set of indicators (observable variables). The specification of the PLS-SEM model will make it possible to determine the strength and direction of the impact of intangible resources on the competitiveness of listed companies, based on the theory of key competences. Identification of the most important variables among intangible resources shaping the competitiveness of enterprises will contribute to the determination of theoretical conclusions and practical recommendations for listed companies in Poland.
Enhancing Awareness and Management of Carpal Tunnel Syndrome Among Medical Professionals and Athletes
Authors: Makuch Rafał , Chrościcka Alicja , Gała Kamil , Czajka Andrzej , Lenard Paweł , Kucharski Adam , Michalska Sara , Pilarski Konrad , Dewicka Martyna , Wawrzyniak Alicja Maria
Published: July 2024

Introduction and objective: The objective of this research is to enhance the awareness of carpal tunnel among medical professionals and individuals engaged in sports. The acquired knowledge will enable medical professionals to more effectively identify, treat, and prevent issues related to carpal tunnel. Additionally, individuals engaged in sports will be able to prevent the occurrence of carpal tunnel syndrome in themselves or their pupils, thereby allowing them to engage in long-term and safe physical activity.
Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed.
Abbreviated description of the state of knowledge: Carpal tunnel syndrome is a disease belonging to the group of compression neuropathies. The symptoms of carpal tunnel syndrome typically manifest as an uncomfortable sensation in the thumb, index finger, and half of the ring finger. Such symptoms may include numbness and tingling. In some cases, weakness of the hand muscles may occur, and in rarer instances, atrophy of the hand muscles. The condition of carpal tunnel syndrome is primarily the result of repetitive movements of the fingers and wrist. Such activities include  typing, using a mouse, riding a bicycle, or playing a musical instrument.
Summary: Carpal tunnel syndrome is a prevalent condition among the general population. This condition may affect individuals who engage in regular physical activity, resulting in diminished efficiency and a notable reduction in the quality of life. The objective of this study is to examine the risk factors, symptoms, and diagnostic methods associated with carpal tunnel syndrome. In the context of sports, we will examine the mechanisms of disease development in athletes and focus on prevention. This encompasses the rehabilitation of individuals at risk of developing the disease and patient education, which will facilitate the minimisation of the appearance or recurrence of disease symptoms.
Therapeutic Applications and Challenges of a Widely Used Antifolate Drug
Authors: Makuch Rafał , Chrościcka Alicja , Gała Kamil , Czajka Andrzej , Lenard Paweł , Kucharski Adam , Michalska Sara , Pilarski Konrad , Dewicka Martyna , Wawrzyniak Alicja Maria
Published: July 2024

Introduction and purpose: Methotrexate (MTX) is an antifolate metabolite that interferes with the synthesis and repair of DNA and with cell replication. It has anti-inflammatory and immunomodulatory properties and was first used in 1951 for the treatment of RA and psoriasis. Methotrexate (4-amino-10-methylfolic acid, MTX) is a popular disease-modifying drug for the treatment of rheumatoid arthritis, psoriasis and leukaemia. MTX is an antagonist of folic acid, primarily through inhibition of the proliferative effect. MTX and its metabolites are associated with many serious adverse effects, including gastrointestinal and hepatic toxicity, myelosuppression, stomatitis, etc. Taking methotrexate may contribute to a reduction in the quality of life for patients. Additionally, long-term use of methotrexate requires regular monitoring, which can be burdensome and stressful for patients. In this context, different approaches have been used to improve the therapeutic properties of MTX and to reduce its adverse effects. The long history of the drug has made it possible to assess its efficacy and to collect data on adverse events, including potentially life-threatening adverse events. This article aims to provide a literature-based overview of current knowledge about methotrexate in clinical practice.
Materials and Methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed.
Conclusion: The result is a picture of methotrexate as a drug that is used for many conditions, but is associated with many side effects that can be a significant problem for patients and healthcare professionals.
Treatment of NAFLD: Diet, Physical Activity, and Potential Pharmacological Options
Authors: Śliz Justyna , Popławska Natalia Aleksandra , Skorupska Marta , Czeczotka Magdalena Joanna , Woźniak Krzysztof , Martka Martyna Magdalena
Published: July 2024

Introduction and purpose
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and according to current data, it affects 38% of the global population. NAFLD includes non-alcoholic fatty liver and the progressive form called non-alcoholic steatohepatitis, which is characterized by damage, inflammation of hepatocytes, and fibrosis. NASH can lead to cirrhosis and hepatocellular carcinoma. Moreover, it increases the risk of diabetes mellitus type 2, lipid disorders, and death due to cardiovascular causes. Currently, no cure is aimed at reducing the severity of NALFD and liver fibrosis. The aim of this study was to provide a total review of the current state of knowledge regarding NAFLD treatment and to identify potential areas for further evaluation.
Materials and method
The PubMed and Google Scholar databases were thoroughly searched to select appropriate sources for this article.
A brief description of the state of knowledge
Diet, weight management, and physical activity constitute fundamental elements of every treatment regimen for NAFLD. Regarding pharmacological treatment, European guidelines recommend the use of vitamin E or pioglitazone in certain patients. Recently, the topic of NAFLD treatment has been a popular subject among scientists who are striving to discover new therapeutic options. A lot of recent research has exhibited promising outcomes for GLP-1 agonists, metformin, SGLT2 inhibitors, FXR, and PPAR ligands.
Summary
The findings of the conducted studies so far are encouraging and offer promise for novel pharmacological interventions in the treatment of NAFLD. Nonetheless, before implementation, further research in this area will be imperative to comprehensively evaluate the efficacy and safety profiles of these pharmaceuticals.
Innovative Internet of Things-based Integrated Liquid Waste Monitoring for Sustainable Batik Industry
Authors: Qodri Muhammad Fatih , Pratama Bagus Gilang , Yuliani Oni , Permana Irvan Ardhi
Published: July 2024

Background: Batik, a UNESCO-recognized art form, experiences rising production demands. However, traditional waste disposal methods pollute waterways and degrade soil. This study addresses this concern.
Contribution: We implemented an Internet of Things (IoT)-based liquid waste monitoring system in CV Smart Batik Indonesia to promote a green economy and sustainable practices. The system monitors critical waste parameters (temperature, pH, TDS, DO, turbidity) in real-time.
Method: We integrated sensors to collect waste data, which is then transmitted through an internet network for monitoring.
Results: The system offers automated monitoring with notifications via a website or mobile application while ensuring data confidentiality through Wireguard protection.

Conclusion: This community service activity demonstrates the effectiveness of IoT-based monitoring systems in promoting sustainable batik production by ensuring compliance with environmental standards and reducing human workload in waste monitoring
Experiment Evaluation on the Porosity of Plasma Coating from Ceramic Al2O3 – TiO2 Using the Metallography
Authors: Vu Duong , Hung Ha Minh
Published: July 2024

Background: The objective of this paper is an experimental investigation of the metallographic porosity of plasma coating using standard materials from the ceramic system Al2O3-TiO2 on the substrate of steel SS400 at laboratory scale Lab at the Research Institute of Mechanical Engineering.
Contribution: The main contribution of the research is the evaluation of the porosity of the coating under the influence of the main technological parameters since the porosity plays a significant role in the performance of the working surface using the built-in Image Pro-Analyzer software in the Axiovert 25 MAT microscope.
Method: The spraying material is Al2O3-TiO2 powder. The input parameters are: spraying distance (Lp; current of plasma stream (Ip); powder feed flow (Gp and spraying rate (Vp).
Results: The findings show that the average porosity of the Al2O3-TiO2 plasma coating is inversely decreasing in the increasing direction of the distance: spray in the range Lp = 100–200 mm, increase proportional to the increase of the current plasma flow rate in the range Ip = 400–600 A, provided that the powder feed flow Gp = 1.7 kg/h and the spraying rate Vp = 50 mm/min.

Conclusion: The degree of influence of the three main technological parameters (Lp, Ip, and Gp) in the survey limit domain may be due to the selected Lp spray distance within the relatively wide recommended range of the plasma spraying equipment supplier. It is recommended to conduct the experimental planning of the L27 type to localize the optimum area.