bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zolbetuximab + CAPOX versus CAPOX in first-line treatment of claudin18.2+/HER2– advanced/metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW phase 3 study.
Authors: Shah Manish A. , Ajani Jaffer A. , Al-Batran Salah-Eddin , Bang Yung-Jue , Catenacci Daniel V.T. , Enzinger Peter C. , Ilson David H. , Kim Sunnie S. , Lordick Florian , Shitara Kohei , Van Cutsem Eric , Arozullah Ahsan , Raizer Jeffrey J. , Park Jung Wook , Xu Rui-hua 
Published: January 2022

TPS365 Background: Despite standard treatment options (eg, CAPOX, capecitabine + oxaliplatin), 5-year survival with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ) is poor and limited biomarkers exist to inform treatment selection. Claudin 18.2 (CLDN18.2), a targetable biomarker, is a tight junction protein that is normally confined to gastric mucosa of healthy tissue and is often retained in G/GEJ. Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Phase 2 (FAST; Sahin, Ann Oncol. 2021) results showed prolonged survival with zolbetuximab + EOX (epirubicin, oxaliplatin, capecitabine) vs EOX in CLDN18.2+ advanced G/GEJ. Preliminary phase 2 (NCT03505320, ILUSTRO Cohort 2; Klempner, J Clin Oncol. 2021) results showed promising antitumor activity with combination zolbetuximab + mFOLFOX6 (5-fluorouracil, folinic acid, oxaliplatin) in CLDN18.2+ advanced G/GEJ. Methods: GLOW (NCT03653507) is enrolling ̃500 adults from global sites. Patients are required to have radiologically evaluable (RECIST v1.1) CLDN18.2+/HER2– locally advanced unresectable or metastatic G/GEJ. Prior chemotherapy for advanced/metastatic G/GEJ is not permitted. Patients will be randomized 1:1 to zolbetuximab + CAPOX or placebo + CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at 800 mg/m2 IV on Cycle 1 Day 1 (loading dose), then at 600 mg/m2 IV every 3 weeks; 8 cycles of CAPOX will be administered. Central testing of tumor tissue will determine CLDN18.2 status; tumors will be considered CLDN18.2+ if ≥75% of tumor cells show moderate to strong membranous immunohistochemical staining. Primary endpoint: progression-free survival per independent review. Secondary endpoints: overall survival; objective response rate; duration of response; safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of September 22, 2021, 135 sites were open for screening and enrollment. Clinical trial information: NCT03653507.
LEAP-014: An open-label, randomized, phase 3 study of first-line lenvatinib plus pembrolizumab plus chemotherapy in esophageal squamous cell carcinoma.
Authors: Sun Jong-Mu , Enzinger Peter C. , Adenis Antoine , Shah Manish A. , Kato Ken , Bennouna Jaafar , Doi Toshihiko , Hawk Natalyn Nicole , Yu Li , Shah Sukrut , Bhagia Pooja , Shen Lin 
Published: January 2022

TPS367 Background: Recent data from the KEYNOTE-590 study demonstrated the superiority of pembrolizumab plus chemotherapy compared with chemotherapy as first-line treatment for unresectable locally advanced recurrent or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, or advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal junction. Prior data also suggest promising antitumor activity of lenvatinib plus pembrolizumab in advanced solid tumors. LEAP-014 (NCT04949256) is a randomized, 2-part, open-label, phase 3 study that will evaluate the efficacy and safety of first-line lenvatinib plus pembrolizumab plus chemotherapy versus pembrolizumab plus chemotherapy in patients with metastatic esophageal squamous cell carcinoma (ESCC). Methods: Key eligibility criteria include metastatic ESCC, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and Eastern Cooperative Oncology Group performance status ≤1. In part 1 (safety run-in), ̃6 patients will be treated for induction with intravenous (IV) pembrolizumab 400 mg every 6 weeks (Q6W) for 2 cycles plus oral lenvatinib 8 mg daily (QD) plus IV 5-fluorouracil (FU; 4000 mg/m2 on days 1-5) plus IV cisplatin (80 mg/m2) (FP) for 4 cycles and treated for consolidation with pembrolizumab 400 mg Q6W for ≤16 doses plus lenvatinib 20 mg QD; patients will be closely monitored for 21 days after the first dose of study intervention for dose-limiting toxicities. Approximately 850 patients will be randomly assigned 1:1 to induction with pembrolizumab plus lenvatinib plus chemotherapy (FP or mFOLFOX6 [Q2W for 6 cycles {IV oxaliplatin 85 mg/m2 plus bolus IV 5-FU 400 mg/m2 plus continuous IV 5-FU 2400 mg/m2 plus IV leucovorin 400 mg/m2 or IV levoleucovorin 200 mg/m2}]) followed by consolidation with pembrolizumab plus lenvatinib (arm 1) or pembrolizumab plus chemotherapy (FP or mFOLFOX6; arm 2). Randomization will be stratified by PD-L1 combined positive score (CPS; ≥10 vs < 10), region (East Asia vs North America and Western Europe vs rest of world), and chemotherapy backbone (FP vs mFOLFOX6). Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. Tumor imaging assessment will be performed Q6W for ≤1 year and Q9W thereafter. In part 1, the primary end point is safety and tolerability. In part 2, the dual primary end points are overall survival and progression-free survival (per RECIST v1.1 assessed by blinded independent central review [BICR]); secondary end points include objective response rate and duration of response (per RECIST v1.1 assessed by BICR) and safety and tolerability. Clinical trial information: NCT04949256.
TALENTACE: A phase III, open-label, randomized study of on-demand transarterial chemoembolization combined with atezolizumab + bevacizumab or on-demand transarterial chemoembolization alone in patients with untreated hepatocellular carcinoma.
Authors: Kudo Masatoshi , Guo Yabing , Hua Yongqiang , Zhao Ming , Xing Wenge , Zhang Yonghong , Liu Ruibao , Ren Zhenggang , Gu Shanzhi , Lin Zhengyu , Lv Weifu , Wang Yumeng , Dong Jiahong 
Published: January 2022

TPS487 Background: In 2020, there were ̃905,000 new cases and ̃830,000 deaths from liver cancer globally, and a respective 410,038 and 391,152 in China (5-year overall survival [OS]: 14.1%).1,2,3 Hepatocellular carcinoma (HCC) accounts for 75%–85% of liver cancers.1 Transarterial chemoembolization (TACE) is the preferred treatment for patients with intermediate-stage unresectable HCC (uHCC); however, there are issues with the need for repeated dosing and the heterogenous target population (median OS: 13–43 mo). Treatment with TACE + systemic therapy may improve this. Although several trials reported negative results for TACE + sorafenib (sor) vs TACE alone in patients with uHCC, the TACTICS trial showed improved untreatable (unTACEable) progression-free survival (PFS) (25.2 vs 13.5 mo; P= 0.006).4 While promising, the unmet need for combination therapies remains. The recent IMbrave150 trial showed significantly improved OS with atezolizumab (atezo) + bevacizumab (bev) vs sor (19.2 vs 13.4 mo; P= 0.0009) in patients with uHCC5, making it an attractive option for combination with TACE. Methods: TALENTACE (NCT047126430) is a phase III, open-label, randomized study to evaluate the efficacy and safety of TACE + atezo + bev or TACE alone in patients with uHCC. Key inclusion criteria are ≥18 years old, HCC diagnosis, no prior systemic treatment, no prior locoregional treatment of target lesions, eligible for TACE treatment, tumor max diameter + tumor number ≥6, and not a candidate for curative therapy. Patients with tumors that have macrovascular invasion (MVI) or extrahepatic spread (EHS) are excluded. Patients will be randomized (1:1) to receive TACE + atezo + bev or TACE alone. TACE will be performed by clinical demand; atezo (1200 mg) and bev (15 mg/kg) will be administered by intravenous infusion on Day 1 of each 21-day cycle. Co-primary endpoints are independent review committee-determined TACE-PFS (randomization to unTACEable progression, TACE failure/refractoriness, or death) and OS. Secondary endpoints include investigator-determined TACE-PFS; time to unTACEable progression, progression, MVI, EHS, and MVI/EHS; objective response rate, duration of response, patient reported outcomes, and incidence of adverse events. References: Sung, H., et al. CA Cancer J Clin. 2021;71(3):209–249. World Health Organisation: Globocan 2020 – China Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf [accessed 1 June 2021] Allemani, C., et al. Lancet. 2018, 391(10125): 1023–1075. Kudo, M., et al. Gut. 2020;69(8):1492–1501. Finn, RS., et al. J Clin Oncol. 2021;39(no. 3_suppl):267–267. Clinical trial information: NCT04712643.
Phase 1b expansion study of CX-5461 in patients with solid tumors and BRCA2 and/or PALB2 mutation.
Authors: Knox Jennifer J. , Oza Amit M. , Provencher Diane M. , Soong John , McCormick Daniel , Chen Jimmy , Chen Jenny , Chang Ariel 
Published: January 2022

TPS622 Background: BRCA and PALB2 proteins play important roles in the maintenance of genomic stability as they are essential for error-free repair of double-stranded DNA breaks, while deficiency of these proteins promotes error-prone DNA repair, chromosomal instability and carcinogenesis. Inherited mutations in BRCA genes predispose to various early onset cancers. Poly(ADP-ribose) polymerase inhibitors (PARPi) inducing synthetic lethality in tumors with homologous recombination (HR)-mediated DNA repair deficiencies have been approved for treatment in patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma. Unfortunately, resistance to PARPi associated with multiple mechanisms can be observed over time, suggesting a prominent unmet need for the development of new treatment options. CX-5461, a G-quadruplex stabilizer, employs an alternative mechanism in destabilizing the DNA replication fork to promote DNA damage resulting in cancer cell lethality in HR-deficient (HRD) tumors, thus represent a promising therapeutic strategy for patients with defects in HR-repair. Methods: A prior phase I dose escalation study has been completed for CX-5461 (CCTG IND.231, NCT02719977) but additional safety data are required to define the chronic tolerable dose for phase 2 trials. Therefore, a phase Ib expansion trial was designed for two doses preselected from our previous phase I trial to determine the final recommended phase II dose (RP2D) by evaluating safety, tolerability and objective response rate in a more selected population. This trial will enroll patients in two cohorts; the main cohort recruiting patients with pancreatic, breast, ovarian or prostate cancer with germline BRCA2 and/or PALB2 mutation, and an exploratory cohort recruiting ovarian cancer patients with BRCA1 and/or other HRD-associated mutations. Major eligibility criteria include documented evidence of pathogenic or likely pathogenic germline mutation in BRCA2 and/or PALB2 for main cohort patients, documented evidence of pathogenic or likely pathogenic germline mutation or a clinically actionable somatic mutation in BRCA1 and/or other HRD-associated mutation for exploratory cohort. Patients with non-adenocarcinoma histology of pancreatic cancer, known photosensitivity disorders of the skin, or patients with ophthalmological conditions will not be enrolled. An initial 16 eligible patients for the main cohort and 10 eligible patients for the exploratory cohort will be enrolled in parallel to receive CX-5461 at 250mg/m2, delivered via IV infusion on Day 1 and Day 8 of a 28-day cycle. Upon completion of the initial arms with no safety concerns, another two arms will open to enroll an additional 16 patients for the main cohort and 10 patients for the exploratory cohort to receive CX-5461 at 325mg/m2 of the same dosing schedule. Clinical trial information: NCT04890613.
A phase 2, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of select human epidermal growth factor receptor 2 (HER2)-expressing solid tumors (DESTINY-PanTumor02).
Authors: Meric-Bernstam Funda , Anoka Chiedozie , Dobrowolska Anna , Chaudhry Anubhavini , Rowbottom Jacqui , Gustavson Mark , Puvvada Soham D. 
Published: January 2022

TPS623 Background: Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in both breast and gastric cancer. However, HER2-targeting therapies are not approved beyond these malignancies despite a high prevalence of HER2 expression across cancers of epithelial origin. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor payload. In a cohort of pretreated patients with multiple HER2-expressing tumors, T-DXd demonstrated promising antitumor activity, with an investigator-assessed confirmed objective response rate of 40.9% (9 of 22 patients) and median progression-free survival of 11.1 months (95% CI, 5.4-20.5 months; Tsurutani J, et al. Cancer Discov. 2020;10:688-701). Here we describe the phase 2 DESTINY-PanTumor02 trial evaluating T-DXd in patients with select HER2-expressing solid tumors. Methods: DESTINY-PanTumor02 (NCT04482309) is an open-label, multicenter, multicohort, phase 2 study evaluating T-DXd for the treatment of patients with select HER2-expressing locally advanced, unresectable, or metastatic tumors. The study will consist of 7 cohorts of patients (n≈40 each) with urothelial bladder, biliary tract, cervical, endometrial, ovarian, pancreatic, or rare tumors (tumors excluding those in the other cohorts and breast, gastric, colorectal, and non-small cell lung cancer). Patients are required to have disease progression following ≥1 prior systemic treatment for advanced or metastatic disease or have no satisfactory alternative treatment options. Prior HER2-targeting therapy is allowed. The primary endpoint is investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include duration of response, disease control rate, progression-free survival (all per investigator assessment according to RECIST 1.1), overall survival, safety, pharmacokinetics, and immunogenicity. Previously presented at the ESMO Congress 2021, FPN: 1869 TiP, Meric-Bernstam et al. Reused with permission. Clinical trial information: NCT04482309.
Strain-dependent doping behavior of WSe2 monolayer: A first-principle calculation
Authors: Chowdhury S. , Venkateswaran P. , Somvanshi D. 
Published: January 2022

Abstract
Control and enhancement of doping concentration in two-dimensional (2D) semiconductors is a critical issue. Here, we investigate the strain-dependent behavior of dopant formation energy (E

form
) for transition-metal–doped WSe2 monolayer using density functional theory (DFT) calculations. We found that E

form
tends to reduce under tensile and compressive strain for rhenium (Re) and vanadium (V) dopants, where the change in volume

due to substitution is negligible. However, E

form
is energetically more favorable under tensile strain for niobium (Nb) and tantalum (Ta) dopants, where

is significantly larger. This suggests strain engineering can be used to enhance the doping concentration in 2D semiconductors.
Comparison of efficacy of systemic antibiotics alone and combination of systemic antibiotics with gentamicin cream in diabetic foot infections
Authors: Memon Munawer Latif , Ikram Muhammad , Azhar Muhammad , Balouch Varda 
Published: January 2022

Objective: To compare efficacy of systemic antibiotics alone and combination of systemic antibiotics with gentamicin cream in diabetic foot infections.
Methods: Prospective Observational Study was conducted at Department of Surgery, Pakistan Ordinance Factories (POF) Hospital, Wah Cantt for duration of two years (January 2018-December 2019). A sample size of 140 diabetic foot infection patients (70 patients in each group) was calculated using WHO calculator. DFI patients were selected through non probability (consecutive) sampling technique. All patients signed consent forms before participation into study. Patients were randomly divided into two group (computer generated random number table); Group-A patients were given systemic antibiotics alone while Group-B was given combination of gentamicin cream and systemic antibiotics. SPSS version 24 was utilized for analysis purpose. Chi-square test was applied in our study. Results with p-value ≤0.05 found significant.
Results: Total 140 patients were included in study. There were 87(62.1%) male and 53(37.9%) females in our data. Mean age of patients was 46 years±11.3SD. Group-B (combination of gentamicin and systemic antibiotics) showed significant reduction in inflammation (p=0.03), culture negativity(p=0.001), increase clinical cure (p=0.02) and pathological eradication (p=0.03) as compared to Group-A (systemic antibiotics alone). Gender, age and duration of diabetes mellitus had insignificant association with outcomes (p>0.05).
Conclusion: Diabetic foot infections are significant contributors of morbidity in our country. Combination of gentamicin cream with systemic antibiotics is highly effective in inflammation reduction, increasing clinical cure rate and pathological eradication as compared to systemic antibiotics alone in diabetic foot infections. Early identification of risk factors, proper patients care and multidisciplinary approach for diabetic foot infections prevention is required.
doi: https://doi.org/10.12669/pjms.38.3.3277
How to cite this:Memon ML, Ikram M, Azhar M, Balouch V. Comparison of efficacy of systemic antibiotics alone and combination of systemic antibiotics with gentamicin cream in diabetic foot infections. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.3277
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cardiac cycle time-corrected electromechanical activation time greater than 15% is an independent risk factor for major adverse cardiovascular events in chronic heart failure outpatients
Authors: Zhang Jing , Liu Wenxian 
Published: January 2022

Objectives: This study aimed to investigate the predictive value of cardiac cycle time-corrected electromechanical activation time (EMATc) for major adverse cardiovascular events (MACEs) in outpatients with chronic heart failure (CHF) in comparison with other clinic indexes.
Methods: This prospective observational study at Beijing Anzhen Hospital from January 01, 2015 to January 01 2018 enrolled 120 CHF patients who were admitted for acute onset of CHF and followed up after discharge for 616.5 days (range: 202.75–875.25 days). Based on the different endpoints, cardiogenic death, all-cause death, and HF-related readmission, patients were assigned to the following groups: cardiogenic death and non-cardiogenic death groups, all-cause death and survival groups, and HF readmission and non-readmission groups. EMATc and other clinic indexes were measured and compared between these groups. Cox regression analysis was used to identify independent risk factors for MACEs.
Results: The hazard ratio for EMATc>15% for cardiogenic death was 3.493 (P=0.046), suggesting that an EMATc>15% was an independent risk factor for cardiogenic death in CHF patients. The hazard ratios for B-type natriuretic peptide (BNP) >400 ng/L for all-cause death and CHF readmission were 3.810 (P=0.008) and 2.764 (P=0.031), respectively. Thus, BNP >400 ng/L was an independent risk factor for all-cause death and readmission for CHF. EF<40% was not found to be a significant risk factor for MACEs.
Conclusions: BNP level can predict the risk for poor prognosis in CHF patients. EMATc>15% is an independent risk factor for cardiogenic death and should be considered as a supplement to serum BNP level and other clinical indexes for predicting cardiogenic death in CHF outpatients.
doi: https://doi.org/10.12669/pjms.38.3.4500
How to cite this:Zhang J, Liu W. Cardiac cycle time-corrected electromechanical activation time greater than 15% is an independent risk factor for major adverse cardiovascular events in chronic heart failure outpatients. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4500
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Racial and socioeconomic inequalities in the financial stress of medical school
Authors: McMichael Brennan , Lee IV Anderson , Fallon Brian , Matusko Niki , Sandhu Gurjit 
Published: January 2022

Background: The authors analyzed the distribution of medical student debt and identified demographic features that placed students at high risk for increased debt and financial stress. Methods: From April to May 2019, a cross-sectional, anonymous, web-based survey was administered to first-year (M1) to fourth-year (M4) medical students at the University of Michigan to assess financial literacy, debt burden, financial stress, and demographic factors. A total of 216 of 680 (32%) students completed the survey. Respondents voluntarily answered 15 multiple-choice questions on personal finance and 30 questions on their demographics, current financial situation, and debt burden. To quantify debt burden, students estimated anticipated education-related debt in one of four categories: no debt, $1–99,999; $100,000–$199,999; and $200,000 or more. A chi-square test was used to identify associations between categorical variables and logistic regression was used to identify risk factors for debt and worry. Results: Fifty-four respondents (25%) reported $0 in education related debt, while 44 (16%) had $200,000 or more. Race (p=0.006), first-generation college student status (p=0.004), first-generation medical student status (p<0.001), household income (p<0.001), and parental education (p=0.008) were associated with higher levels of debt. Students who were underrepresented in medicine (URiM) had higher odds of higher debt compared to Arab and Asian students (p=0.02). URiM students (p=0.02), first-generation college students (p=0.009), and parental education (p=0.01) were associated with increased financial stress. Additionally, female students had higher odds of increased financial stress (OR=1.85, p=0.045) on logistic regression. Conclusions: URiM and socioeconomically disadvantaged students feel the burden of the high cost of medical school disproportionately more, suggesting that our current systems are not adequately supporting these students. Reducing this burden may serve to further promote diversity in medicine.