bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness, Knowledge, and Current Practice of Breast Cancer Among Surgeons in Jordan
Authors: Al-Balas Mahmoud , Al-Balas Hamzeh , Al-Amer Zain , Ashour Laith , Obiedat Mufleh
Published: June 2024

PURPOSE

Breast cancer (BC) is the most prevalent cancer in Jordan. De-escalation in treatment reflects a paradigm shift in BC treatment. More tailored strategies and the adoption of a multidisciplinary approach are essential to apply recent changes in management. In the era of breast surgery fellowship, adopting well-structured training is essential to apply recent therapeutic guidelines and meet patients' expectations.

METHODS

A cross-sectional study using a customized, self-reported questionnaire was used. Data collection occurred anonymously using a link via WhatsApp in the period between February 2023 and April 2023.

RESULTS

A total of 89 surgeons were involved in this study, and only 14 (15.7%) completed a subspecialty in breast surgery. About 58.4% considered the age of 40 years as the starting point for screening, and 84.3% reported that mammogram screening is associated with improved BC survival. Only 10.1% and 28.1% acknowledged the applicability of both tomosynthesis and breast magnetic resonance imaging in screening, respectively. A significant difference in the mean knowledge score about BC is observed between general surgeon and those with subspecialty. Varying levels of awareness concerning different risk factors and their correlation with the likelihood of BC occurrence observed. Although 56.2% of participants could offer breast conserving surgery and consider it oncological safe, only 48.3% defined it correctly. Of the participants, 61.8% and 76.4% stated that sentinel lymph node biopsy can be safely applied in clinically negative or suspicious axillary nodes, respectively, with <50% of surgeon performing it in their practice.

CONCLUSION

More efforts are required to enhance the knowledge and practice of surgeons in the field of breast surgery. Adopting national guidelines can facilitate the acceptance and improvement of current practices among surgeons in Jordan.
Long-term outcomes of ablation versus surgery in patients with colorectal lung oligometastasis: A retrospective cohort study.
Authors: Zhang Tian-Qi , Cao Yu-Zhe , Zheng Xin , Fan Wei-Jun , Wu Pei-Hong , Huang Jin-Hua
Published: June 2024

3581

Background: Lung is the common metastatic site of colorectal carcinoma. Treatment of colorectal lung oligometastasis (CLOM) by surgical and ablative procedures has been proved to prolong survival and palliate symptoms. We aimed to analyze the long-term outcomes of patients with CLOM treated with surgery or ablation. Methods: From January 2012 to October 2018, patients diagnosed with CLOM that underwent surgery or ablation at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Results: The study included 96 patients with 134 lesions, including 25 females (26.0%) and 71 males (74.0%). All the patients had received the primary colorectal lesion resection before treatment of metastasis. There were 41 patients with 75 lesions receiving ablation and 55 patients with 59 lesions receiving surgery. The median follow-up time was 58.3 months (IQR: 38.6-73.7). The median overall survivals (mOS), 3- and 5-year survival rates between the two groups showed no significant difference (Ablation vs. Surgery, mOS: 73.3 months vs 70.4 months, P=0.64; 3-year survival rate: 82.6% vs. 79.8%; 5-year survival rate: 59.9% vs. 58.7%. The median progression-free survivals (mPFS) were 12.1 months in the ablation group and 11.5 months in the surgery group (P=0.48), respectively. Local rates of recurrence per lesion were 26.7% and 22.0% (P=0.68). And the pulmonary mPFS were 14.5 months vs. 14.1 months (P=0.95). Conclusions: Our retrospective cohort data showed that there was no significant difference between surgery and ablation in long-term survival benefit to CLOM patients. [Table: see text]
Long-term survival comparison of adjuvant FLOT versus XELOX chemotherapy for locally advanced gastric cancer in a large real-world cohort.
Authors: Jiao Zuoyi , Gan Shiying , Long Bo , Zhou Huinian , Yu Zyuaun , Mao Jie
Published: June 2024

4080

Background: Recent Attraction-5 study has shown that logically advanced gastric cancer (LAGC) patients can't benefit from postoperative immunochemotherapy. The preferred adjuvant regimen for LAGC remains two-drug based chemotherapy as XELOX protocol, though three-drug based adjuvant FLOT regimen has not been well studied yet. This studyaimsto explore 10-year survival advantages of adjuvant FLOT versus XELOX regimen for LAGC. Methods: We retrospectively collected and analyzed data from 248 LAGC patients mainly composed of pathological T (pT) 3-4 stage, who received at least 4 cycles of FLOT or XELOX adjuvant chemotherapy at Lanzhou University Second Hospital from 2013 to 2018. To eliminate interference of confounding factors, we conducted a propensity score matching (PSM). The median follow-up time for all patients was 90.90 months. Results: After PSM, the median overall survival (OS) was 44.80 months in FLOT group and 34.87 months in XELOX group, with 5-year OS rate of 41.4% versus 25.3% and 10-year OS rate of 31.9% versus 11.8%. Subgroup analysis showed that patients with ECOG performance status 0 or pT3-4 stage attained significant survival benefits from adjuvant FLOT regimen. Grade 3-4 treatment-related adverse events occurred in 57.9% patients of FLOT group and 33.6% patients of XELOX group, while most of them were manageable. Conclusions: This study demonstrates that adjuvant FLOT regimen exhibits significantly long-term survival advantages for LAGC patients with good performance status and late disease stage compared with XELOX regimen, facilitating adjuvant FLOT regimen as a prospectively alternative option for LAGC.
Cabozantinib plus atezolizumab in patients with advanced and progressive neuroendocrine neoplasms (NENs): A prospective multi-cohort basket phase II trial (CABATEN / GETNE-T1914).
Authors: Hernando Jorge , Molina-Cerrillo Javier , Grande Enrique , Benavent Viñuales Marta , Garcia-Carbonero Rocio , Teule Alex , Custodio Ana , Jimenez-Fonseca Paula , Hierro Cinta , López López Carlos , Sevilla Isabel , Llanos Marta , Carmona-Bayonas Alberto , Alonso Vicente , Gallego Javier , Gallego Jiménez Inmaculada , Orta Alberto , Franco Fernando , García-Álvarez Alejandro , Capdevila Jaume
Published: June 2024

4128

Background: Early results with immune-checkpoint inhibitors (ICI) in NENs when used as single agents achieve limited response rates. Angiogenesis plays a key role in development and progression of NENs and synergism has been observed when antiangiogenics are combined with ICI in other tumors, whereas. We aimed to assess the efficacy and safety of cabozantinib (Cabo) plus atezolizumab (Atezo) in advanced and progressive NENs. Methods: CABATEN was a single-arm basket study using Atezo 1200 mg every 3 weeks plus Cabo 40 mg/day until progression or unacceptable toxicity in 6 NENs independent cohorts. We here focus in: well-differentiated lung neuroendocrine tumors (LungNET), pheochromocytoma paraganglioma (PPGL), well-differentiated gastroenteropancreatic (GEPNET) and grade 3 extrapulmonary neuroendocrine carcinomas (G3 EP-NEN). Primary endpoint was Overall Response Rate (ORR) by RECIST 1.1. The study had a Simon-II design. Here we present a subgroup analysis of efficacy for NENs (n=55), and for Cabo reduction using a relative dose intensity (RDI)<81% threshold and 3-month interval by Landmark analysis. Baseline characteristics were analyzed in subgroups with prolonged disease stability (PFS>12m or >15m) Results: Median (95%CI) age was 60 (56.0, 63.0) years and 62% were male. Cabo and Atezo treatment were administered for a median of 8.7m (95%CI: 6.2-11.9) and 9.0m (95%CI: 6.8-13.5) and interrupted due to AE’s in 80.0% and 40.0% of pts respectively. Cabo was reduced to 20 mg/day in 58,2% of patients. The 12-m PFS was 50% (95%CI: 29.6-84.4) RDI<81% vs 55.6% (95%CI: 39.7-77.9) RDI≥81% (p=0.9), 12-m OS was 86.7% (CI 95%: 71.1-100) RDI<81% vs 84.7% (CI 95%: 72.0-99.7) RDI≥81% (p=0.6), Cox. LungNET, PPGL, GEPNET and G3 EP-NEN presented a median PFS (m, 95% CI) of 8.4 [7.7-NR], 8.4 [5.7-NR], 13 [11.2-NR] and 2.7 [2.6-NR] respectively. PFS>12m subgroup had a trend towards better ECOG. PFS>15m GEP-NET presented a non-significant trend towards a lower Ki67 index and less previous treatment (no chemotherapy). ORR were 15.4% (95%CI:1.9-45.5) in PPGL and 16.7% (95%CI:4.7-37.4) in GEP-NET. LungNETs and G3 EP-NEN had no responses. Duration of response (DoR) were 12.2m (5.5-19.0) and 15.8m (10.6 - 20.2) in PPGL and GEP-NET cohorts, respectively. Conclusions: Cabo and Atezo showed limited activity but achieved prolonged disease control in a small group of patients with PPGL and GEPNET but not in LungNET and G3 EP-NEN, regardless of RDI of Cabo. Clinical trial information: 2019-002279-32.
Treatment landscape, outcome and quality of life in patients with pancreatic cancer: IKF642/PARAGON study.
Authors: Goetze Thorsten , Liersch Ruediger , Scheuer Lars , Göhler Thomas , Kaiser Ulrich , Denzlinger Claudio , Pink Daniel , Wierecky Jan , Klagges Jorge , Pauligk Claudia , Zäpf Bianca , Hofheinz Ralf-Dieter , Al-Batran Salah-Eddin
Published: June 2024

4155

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year relative survival rate of only 13% for all stages combined (1). All treatment options available to date are options that can prolong survival and/or alleviate symptoms, but rarely cure. Therefore, it seems important to obtain more real-world data covering the entire clinical life cycle of PDAC patients, including quality of life (QoL) for all therapies used. Methods: Since November 2019 until October 2021 the multicenter, prospective, PARAGON study (NCT04119362) included patients (pts) diagnosed with PDAC planned for or recently started with neoadjuvant, adjuvant or 1st line therapy. Pts were followed during the entire course of their disease and all treatment lines for efficacy and QoL. Follow up ended June 2023. 46 German study sites participated at the study. Analysis included data on demography, comorbidities, treatments, and efficacy as well QoL (EORTC QLQ-C30). Results: PARAGON enrolled 468 PDAC pts, comprising 52% male, median age of 69 years [31- 90] with ECOG 0 to 1 in 76% at baseline. Six percent of all pts started in a neoadjuvant setting (FFX, 50%; NP-G, 38%), 32% in the adjuvant setting (FFX, 52%; gemcitabine, 28%; NP-G, 4%), and 76% in the first-line setting (NP-G, 44%; FFX, 36%; gemcitabine, 13%). 37% of all pts received 2nd line therapy with NP-G (39,5%), NalIRI-5FU (12%) and gemcitabine (6%). 14% of all pts started a 3rd line therapy and 4% a 4th line therapy. The median overall survival (mOS) in the adjuvant-therapy setting was 30 months, median progression free survival (mPFS) 16 months. mOS in the 1st line therapy was 10.0 months, mPFS 5.6 months. mOS in 2nd line was 7.7 months, mPFS 3.0 months. Differences can be described, among others, for mOS in 1st line FFX with 12.7 months, in NP-G with 10.7 months and in the Gemcitabine subgroup with 8.3 months. QoL data is available for all pts at baseline and throughout the further course of therapy. Results according to treatment line will be presented in detail at the meeting. Conclusions: PARAGON is the largest study on QoL and treatment landscape in PDAC so far. Data allow broad insight in real-world efficacy and QoL in the different treatment lines, regimens, and subgroups of pts. 1. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. Clinical trial information: NCT04119362 .
Comparative effectiveness of NALIRIFOX vs. FOLFIRINOX in pancreatic cancer.
Authors: Jiao Xiayu , Barzi Afsaneh
Published: June 2024

4160

Background: Metastatic pancreatic cancer is associated with limited survival, poor quality of life, and limited treatment options. FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP) are associated with survival gain compared to gemcitabine and NALIRIFOX is associated with survival improvement compared to GNP. NALIRIFOX and FOLFIRINOX are not directly compared to each other. We conducted an analysis of oncologic benefits and costs of NALIRIFOX vs. FOLFIRINOX. Methods: A cost-effectiveness model was developed using partitioned survival analysis with three health states: progression-free, progression, and death. Data on overall survival and progression-free survival were derived from PRODIGE and NAPOLI-3 published data to reconstruct the states in the model. The time horizon of the model was set to 36 months. Costs included treatment costs and adverse event management as well as supportive care cost. We used Veteran Affair’s data for unit cost of each agent. To calculate the cost of treatment we assumed the average body surface area to be 1.79. Five adverse events (AEs) were included in the cost analysis: neutropenia, febrile neutropenia, anemia, diarrhea, and thrombocytopenia. We used the utility of 0.80 during PFS and 0.73 during progression for assessment of Quality Adjusted Life Year (QALY). The benefits and costs of treatment was calculated and used to estimate the incremental cost-effectiveness ratio (ICER) of NALIRIFOX compared with FOLFIRINOX. Results: The calculated PFS for FOLFIRINOX was 6.8 months and for NALIRIFOX was 8.9 months. Compared to FOLFIRINOX, NALIRIFOX was associated with an improvement in life year gain (11.97 months vs. 10.95 months). The monthly acquisition cost for NALIRIFOX was $13,610 and for FOLFIRINOX $5,501. Based on the probabilities of selected AEs, the monthly cost of AE management for NALIRIFOX was $5,589 and for FOLFIRINOX was $ 15,511. QALY for NALIRIFOX was 10.23 and for FOLFIRINOX was 9.59 months. The incremental cost effectiveness ratio for NALIRIFOX vs. FOLFIRINOX was $1,368,937. Conclusions: In this modeling analysis, NALIRIFOX is associated with improvement in PFS and QALY. The analysis highlights the importance of AE management for improving quality of life and cost in the recipients of FOLFIRINOX. The economic value for use of NALIRIFOX is very high and outside of any conventional boundary of acceptable value threshold for treatment.
KRAS mutations allelic frequency dynamics using plasma extracellular vesicles: Association with survival outcomes in localized pancreatic adenocarcinoma.
Authors: Chopra Asmita , He Hongzhang , Milosevic Jadranka , Tirukkovalur Nikhil , El Asmar Rudy , Nassour Ibrahim , Nunns Geoffrey , Chen Mingxi , Chen Jiaqi , Jiang Siyu , Singhi Aatur D. , Saeed Anwaar , Zhang Janie Yue , Lee Kenneth K. , Zureikat Amer H. , Jiang Si-Yang , Paniccia Alessandro
Published: June 2024

4167

Background: Pancreatic ductal adenocarcinoma (PDAC) lacks an effective and consistent biomarker to emulate treatment response and predict survival. Extracellular vesicles (EV) carrying tumor-specific mutations are disease-specific biomarkers that hold promise to address this unmet need. Methods: Informed by tumor profiling, plasma from 44 PDAC patients with confirmed KRAS mutations, treated with neoadjuvant therapy (NAT) and definitive surgery between 2019 and 2021, was analyzed. Samples were collected at diagnosis, day of surgery, and 1-month post-surgery. A lipid nanoprobe technique was used for EV isolation and droplet digital PCR was used for detection of tumor-specific KRAS mutations. Patients were categorized based on the temporal change in KRAS mutation allelic frequencies (MAF) into ND (no detection at any time point), ID (increasing MAF detection), or DD (decreasing MAF detection). Optimal CA19-9 response was defined as >50% reduction from baseline and normalization (<37 U/mL) before surgery. Survival associations were evaluated using Kaplan-Meier analysis and log-rank tests. The median follow-up was 36.1 months. Results: Among the cohort (mean age 66.5±8.2 years, 36% females), 29 (65.9%) patients had ND, 7 (15.9%) had ID and 8 (18.2%) had DD of KRAS MAF. No significant differences were noted in demographic or clinical variables (p > 0.05). Stages III, II, and I PDAC had detectable mutant KRAS in 50%, 30%, and 21% cases, respectively. The ND group exhibited significantly longer restricted mean disease-free survival (rmDFS) [31.2 months (95% CI: 24.1–38.3)] compared to DD [27.8 months (95% CI: 12.4–43.1)] and ID [9.8 months (95% CI: 0.1–19.7)] (p=0.010). The ND group also showed a superior rmOS [40.3 months (95% CI: 34.2–46.4)] outperforming DD [35.7 months (95% CI: 22.1–49.2)] and ID [17.7 months (95% CI: 6.4–28.9] (p = 0.012). Eleven patients (25%) exhibited optimal CA19-9 response. Patients in ND cohort with optimal CA19-9 response (n=6; 20%) had the longest DFS and OS (median DFS and OS not reached), outperforming all other subgroups (p<0.001). Conversely, patients in ID group had the lowest rmDFS (5.1 months 95%CI 2.4-7.8), irrespective of CA19-9 response (p<0.001). Conclusions: Detection and temporal increase of EV-KRAS MAF are significant indicators of reduced DFS and OS in PDAC patients. These findings highlight the potential of dynamic EV-KRAS profiling as a prognostic biomarker and underscore the need for expansive validation studies.
Predicting real-world overall survival for post-operative pancreatic ductal adenocarcinoma: An ASCO CancerLinQ Discovery analysis.
Authors: Ahmed Kaleem Sohail , Issaka Sheriff M , Marcinak Clayton Thomas , Zafar Syed Nabeel
Published: June 2024

4169

Background: Pancreatic ductal adenocarcinoma (PDAC) is the second leading cause of cancer-related deaths in the US. There is a need to improve risk-stratification of patients to facilitate treatment decisions. Novel datasets such as the American Society of Clinical Oncology (ASCO)’s CancerLinQ Discovery (CLQD) combined with machine learning (ML) methods provide an opportunity to generate new insights from “real-world data” (RWD) to study patient outcomes. The objective of this study was to develop an ML model using RWD to predict 1-year survival (1YS) for patients undergoing pancreatectomy for PDAC. Methods: Using the CLQD database, we identified patients diagnosed with PDAC who had undergone surgical resection between July 1998 and May 2021. Patients with complete data on procedure and tumor characteristics were included. Patients lost to follow-up within 12 months of surgery were excluded. We trained a multivariable Logistic Regression (LR) for baseline comparison. Gradient Boosting Classifier (GBC) and Random Forest (RF) models were then trained on demographic and clinico-pathologic data, with and without pre-operative laboratory (lab) data. GBC-1 and RF-1 were trained only on demographic and clinico-pathologic data (n=1440). GBC-2 and RF-2 were trained on a subset of patients who had non-missing lab data (n=669). We performed a one-way ANOVA to compare the area-under-the-curve (AUC) scores for each GBC and RF model to the corresponding LR. Results: Of the 1440 patients analyzed, 44.7% were male, 53.6% were White, and the mean age was 69.7 ± 10.9 years. Majority had a T3-stage tumor (53.7%) and 70.3% received either neoadjuvant, adjuvant, delayed and/or recurrent chemotherapy. Unadjusted median OS was 16.5 months [95% CI: 15.1-17.6], and 1YS was 60.8% [95% CI: 58.2-63.3]. GBC and RF models were able to outperform the baseline LRs (Table 1). RF-2 and LR-2 performed the best (AUC: 0.83 each) with lab data, followed by RF-1 (AUC: 0.81) without lab data. Factors that were most predictive of survival were: receipt of chemotherapy, tumor size, pre-operative BMI, age, and pre-operative neutrophil count, serum cholesterol, and serum CA-19-9 levels. Conclusions: In this study, we show that ML models using clinicopathologic, demographic, and laboratory data provide more accurate prediction of 1 year survival than prior strategies. Such models can be used to identify patients at high risk for poor outcomes following pancreatectomy and alternative treatments may be offered. [Table: see text]
Molecular insights into oxaliplatin-induced peripheral neuropathy in colorectal cancer: Unraveling a potential signature.
Authors: Modekurty Suneeta , Iglesia Michael , Pedersen Katrina Sophia , Salvador Carolina , Haroutounian Simon , Lim Kian-Huat , Trikalinos Nikolaos , Suresh Rama , Aranha Olivia , Grierson Patrick , Tan Benjamin R. , Khushman Moh'd M.
Published: June 2024

e15506

Background: Oxaliplatin (OXA) is a platinum chemotherapy utilized for treating patients with colorectal cancer (CRC). OXA-induced peripheral neuropathy (OXAIPN) stands as the primary non-hematological dose-limiting toxicity. Despite its clinical significance, there exists no reliable molecular predictive biomarker of OXAIPN in current clinical practice. In this study, we delved into the molecular signature associated with OXAIPN in CRC. Methods: OXAIPN-related genes were curated through an extensive literature review. Utilizing publicly available bulk transcriptomic data from the Illumina HiSeq 2500 platform, encompassing tumor and adjacent normal tissues from 18 individuals with CRC, we identified differentially expressed genes (DEGs). Furthermore, single-cell RNA sequencing (scRNA-seq) data from 10X genomics, including normal and tumor tissues from 3 CRC patients, underwent analysis using Seurat and sctype R packages to unveil DEGs associated with cancer cells. Functional and pathway enrichment analysis was performed using the Genecodis4 web-based tool. To validate the inhibition of a curated list of neuropathy-associated genes, RNA-seq data from CRC cell lines (HCT116 and DLD1) treated with Oxaliplatin were processed, and DEGs were determined. Results: A total of 1367 OXAIPN-related genes were identified. Bulk transcriptomic data analysis revealed 715 DEGs, while scRNA-seq analysis uncovered 2,854 DEGs. Noteworthy, upregulated genes from scRNA-seq analysis, including LGALS4, SPINK4, TFF3, REG4, and REG1A, were associated with tumor proliferation through epithelial-mesenchymal transitions, oxidative stress, dysregulated immune system, and inflammation. In CRC cell lines (HCT116 and DLD1), the administration of oxaliplatin resulted in the downregulation of proteins involved in axon excitability (NGF, SOD1, ROBO1, CNTNAP2, and KCNMB1), normal sensory neuron function (SOX10, APOE, SST, S1PR1, and KCND3), voltage-gated sodium (SCNN1B, SCNN1G, SCNN1A, SCN1B, and SCN2B), calcium (CACNA2D2, CACNA1A, CACNA1C, CACNA1E, and CACNA1F), and potassium channels (KCND3, KCNMB1, KCNMA1, KCNJ2, and KCNN4). Conclusions: A molecular signature associated with OXAIPN was identified in patients with CRC and validated in CRC cell lines (HCT116 and DLD1). Further studies to reproduce and evaluate its potential in predicting OXAIPN in CRC patients in the clinic are warranted.
The association of protein-energy malnutrition and in-hospital clinical outcomes among patients with colorectal cancer hospitalized for gastrointestinal bleeding: A nationwide analysis.
Authors: Elom Hilary , Verinumbe Tarfa , Obomanu Elvis , Jones Colton , Mayo Ryan
Published: June 2024

e15531

Background: Patients with colorectal cancer (CRC) commonly present with gastrointestinal (GI) bleeding and are at risk of developing protein-energy malnutrition (PEM) either due to effects of therapeutic interventions (chemotherapy, immunotherapy, radiation) or primary disease on appetite and caloric intake. There are several existing studies on CRC and gastrointestinal hemorrhage, however the impact of concurrent PEM on in-hospital outcomes for patients with CRC admitted for GI bleeding is unclear. Our study aims to assess the association of PEM and clinical outcomes among patients with CRC hospitalized for GI bleeding. Methods: We analyzed data from the 2020 National Inpatient Survey on patients with CRC who were admitted with GI bleeding. To determine our study sample, we used International Classification of Diseases, 10th Revision (ICD10) codes for CRC (C18.X, C19 and C20), and GI bleeding (K92.2 and K62.5). The primary exposure was a comorbid diagnosis of PEM (defined based on the ICD 10 codes E40 – E46). The clinical outcomes assessed in this study were all-cause mortality, sepsis, septic shock and length of stay in the hospital. A multivariate logistic regression was used to assess the association of comorbid PEM with all-cause mortality and sepsis. A cox proportional hazard regression was used to investigate the association between the PEM and time to discharge. Covariates adjusted for in our final analyses included age, sex, insurance status and number of comorbidities present on the patients record at discharge. Results: Of the 2223 patients with CRC who were admitted for GI bleeding, 55% were male, 64% were White and mean age was 63 years (SD 14.2). A quarter (23%) had comorbid PEM, 14.6% had sepsis and 5.4% had septic shock. About 6.5% died during hospitalization and the mean length of hospital stay was 7.8 days. Comorbid PEM was significantly associated with a two-fold increase in the risk of all-cause in-hospital mortality (aOR 2.05; 95% CI: 1.41 – 3.98), sepsis (aOR 2.33; 95% CI: 1.78 – 3.05) and septic shock (aOR 2.0; 95% CI:1.35 – 3.09). Additionally, compared to patients without PEM, those with concomitant PEM had a lower discharge rate (HR 0.71, 95%CI: 0.64-0.78). Conclusions: Our study demonstrated that comorbid PEM in patients with CRC hospitalized for GI bleeding is associated with increased risk of all-cause in-hospital mortality, sepsis, septic shock and prolonged length of stay. The findings from this study highlight the need for nutritional considerations when managing patients with CRC and GI bleeding to prevent adverse health outcomes and potentially improve survival among these patients.
Prognostic implications of distal resection margin length in rectal cancer proctectomy: A retrospective analysis.
Authors: Li Ming , Wang Xiaodong , Niu Pengfei , Yang Yong , Chen Jiajia , Xu Jingxuan , Cheng Yu , Wang Yanzhao , Zhang Chang
Published: June 2024

e15605

Background: Proctectomy remains pivotal in rectal cancer treatment for 70% of patients, even post-neoadjuvant therapy. The determination of an appropriate distal resection margin (DRM) in proctectomy for rectal cancer is critical for achieving both curative resection and organ preservation. However, the prognostic impact of DRM length, especially measured before the shrinkage caused by fixation in pathology, remains unclear. Methods: This retrospective study include 224 stage II-III rectal cancer patients who underwent proctectomy between 2015 and 2020. Patient demographics, tumor characteristics, and follow-up data (median: 44.4 months) were collected. The lengths of mesorectal and rectal DRM were both measured on fresh specimens before pathological processing. A specific metric, (rectal DRM - mesorectum DRM)/rectal DRM > 10%, identified patients with shorter mesorectal DRMs, denoted as the "MS group". Results: Out of 224 patients, 68 (30.4%) had a rectal DRM ≤1 cm, and 156 (69.6%) > 1 cm. There were no significant differences between the groups in terms of gender, use of neoadjuvant therapy, or high-risk factors like extramural venous and perineural invasion. The local recurrence (LR), disease-specific survival (DSS) and overall survival (OS) rates did not differ significantly between groups, with P = 0.66, 0.082, 0.054, respectively. Cox univariate analysis identified pT, pN, gender, and CEA level as significant factors for OS and DSS, while DRM group was not (p = 0.06). A 5-year OS predictive model (AUC = 0.864) indicated DRM's insignificant impact on OS, validated against SEER and TCGA databases. Further analysis in 182 Dixon surgery cases revealed no significant OS or DSS differences between patients with mesorectal DRM < 1cm and those with > 1cm. Notably, 23.6% (43/182) belonged to the MS group with shorter mesorectal DRM, showing significantly inferior OS (P = 0.026) and DSS (P = 0.000265) compared to the ML group. Conclusions: In this study, while a 1 cm DRM in mesorectal and rectal regions is validated as safe for rectal cancer proctectomy, our findings indicate this is not an absolute measure of oncological safety. Patients with a mesorectal DRM shorter than the rectal DRM had inferior outcomes, suggesting the need for a more nuanced approach. Thus, a comprehensive DRM evaluation, beyond a fixed length threshold, is essential to improve surgical outcomes and patient prognosis.
MIRACLE1: Phase II study of radiotherapy followed by CapeOx and tirelizumab as first-line treatment in MSS rectal cancer with synchronous resectable liver/lung metastases.
Authors: Shan Zezhi , Zhou Menglong , Ye Zilan , He Weijing , Yang Yufei , Luo Dakui , Xia Fan , Shen Lijun , Chen Yikuan , Zhou Changming , Li Qingguo , Zhang Zhen , Li Xinxiang
Published: June 2024

TPS3631

Background: Rectal cancer (RC) with synchronous resectable liver/lung metastases is commonly treated with surgery combined with systemic chemotherapy or local therapies. Prognosis remains poor. Microsatellite stable (MSS) are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and Radiotherapy have been reported to potentially promote immunotherapy response. MIRACLE1 will investigate the safety and efficacy of Short-course radiotherapy (SCRT) combined with CapeOx and tirelizumab in MSS metastatic RC. Methods: We designed a single-arm, multicenter, phase II trial in MSS RC. MSS status is determined by normal immunohistochemical nuclear expression of all the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. Additional inclusion criteria include RC with a distance of ≤ 10 cm from the anus by MRI evaluation and single or multiple measurable metastases in the liver and/or lungs (RECIST version 1.1) evaluated as resectable after MDT discussion. Exclusion criteria include patients with distant metastasis to parts other than the liver and lungs, including the brain, bone, ovary, peritoneum, and multiple retroperitoneal lymph node metastases.Patients are treated with radiotherapy including 25 Gy/5 fractions short-course hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions. Afterward, six cycles of chemoimmunotherapy consisting of CapeOX and tislelizumab will be administered. Tislelizumab is administered intravenously (200 mg) along with each cycle of chemotherapy. Efficacy evaluations are conducted after the third and sixth cycles of chemoimmunotherapy and include radiological and serological evaluations. According to the efficacy evaluation results, a watch-and-wait nonoperative approach or surgical resection is performed. After surgery, postoperative treatment is to be determined by the investigators. Tislelizumab is to be maintained until one year after surgery. The primary endpoint of this study is the 1-year no-evidence of disease (NED) rate. The secondary endpoints include objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute toxicity related to immunotherapy. 52 patients will be enrolled to ensure 47 evaluable. The design has 80% power to detected improvement in NED rate from 60 to 77% with significance level of 0.05. The first patient was recruited on 27th March 2023. To date, 15 patients have been enrolled. Full accrual is anticipated by late 2024. Correlative studies include genomic characterization of baseline tumors, assessment of immune infiltration of tumor microenvironment and serial circulating cell-free DNA and immune biomarkers. Clinical trial information: NCT05359393 .
STELLAR-303: A randomized phase 3 study of zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated metastatic colorectal cancer.
Authors: Saeed Anwaar , Tabernero Josep , Wang Guan , Ma Xia , Smith Robina , Hecht J. Randolph
Published: June 2024

TPS3634

Background: Metastatic colorectal cancer (mCRC) has seen increased rates in overall survival (OS) as novel targeted agents have become available. Unfortunately, the median OS is still less than 2 years, and the 5-year survival rate is only about 16%. This underscores an unmet need in this population that necessitates finding therapeutic options to enhance treatment outcomes. As monotherapy, immune checkpoint inhibitors (ICIs) have shown limited efficacy in non–microsatellite instability-high (non–MSI-H) mCRC, which represents a majority of mCRC cases. However, addition of tyrosine kinase inhibitors (TKIs) to ICIs has demonstrated encouraging efficacy in mCRC, particularly in patients without liver metastases (LM). Clinical data suggest synergy whereby TKIs may increase sensitivity to ICIs by promoting an immune-permissive tumor microenvironment. Zanzalintinib is a novel TKI targeting VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER), which are involved in tumor angiogenesis, metastasis, and immunosuppression. In a phase 1 study, zanzalintinib in combination with atezolizumab (an anti–PD-L1 ICI) showed antitumor activity and a manageable safety profile across multiple tumor types, including mCRC. The present study, STELLAR-303, was designed to evaluate the efficacy and safety of zanzalintinib + atezolizumab in patients with non–MSI-H mCRC. Methods: STELLAR-303 (NCT05425940) is a global, randomized, open-label, phase 3 study. Patients must be aged ≥18 years and have non–MSI-H/non-mismatch repair deficient disease, with documented RAS status by tissue-based analysis, measurable disease per RECIST v1.1, and ECOG performance status of 0–1. Patients must have had intolerance to, or radiographic progression during/after, standard-of-care treatments for mCRC. Patients previously treated with regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are excluded. Patients with or without active LM at baseline are eligible; those with definitively treated LM (including surgical resection, microwave/radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) are considered to have non-active LM if treated ≥6 months before enrollment with no evidence of radiologic progression on subsequent imaging. Patients are randomized 1:1 to receive either zanzalintinib + atezolizumab, or regorafenib alone. Planned enrollment is 874 patients, and the number of patients with/without LM will be capped to ensure relevance to the real-world mCRC population. The primary endpoint is OS in patients without LM, while OS in all randomized patients is the key secondary endpoint. A hierarchical testing strategy will be employed for primary and key secondary endpoints. Safety will also be assessed. STELLAR-303 enrollment is ongoing in the US, Europe, and Asia-Pacific region. Clinical trial information: NCT05425940 .
Metastatic Non–Small Cell Lung Cancer Mimicking Metaplastic Breast Cancer: A Case Report
Authors: Pai Tanmayi S. , McKinley Blake , Seby Robert , Lewis Jason T. , Komforti Miglena K. , Accurso Joseph , Sonavane Sushilkumar , Baumgarten Deborah A. , Advani Pooja P. , Lou Yanyan , Rao Rohit
Published: June 2024

NGS used to diagnose and treat NSCLC patient with initial concern for metaplastic breast cancer
Zora Neale Hurston, Participatory Listenership, and Boasian Anthropology
Authors: Jung Junha
Published: June 2024

Zora Neale Hurston’s Their Eyes Were Watching God (1937) is known as a “speakerly” text. This essay argues that the novel is also a “listenerly” text—that, as in her work in general, in Their Eyes Hurston celebrates close listening as much as speaking—and that this valuing of listening is informed by the practices of the Black folk she encountered doing research for her anthropological project. In Their Eyes the protagonist Janie performs the kind of critical listenership Hurston observed in the southern Black rural communiuties, and, in contrast to Black communities centered on the male voice, she envisions a different kind of Black community, the organizing principle of which is less individual speaking and more mutual, careful, and sympathetic listening to each other. Widening its focus, finally the essay considers how, with its free indirect discourse, the novel gestures toward establishing a collaboration among the author, the folk characters, and the reader to help bring that “listenerly” Black community into being.
Ordinary Culture in “The Dead”
Authors: Stasi Paul
Published: June 2024

Ordinary Culture in ‘The Dead’” reads James Joyce’s short story through the lens of Raymond Williams’s essay “Culture Is Ordinary.” Each work represents the gap between education and social solidarity in narratives about the return of an educated protagonist to his place of origin. Williams’s essay is a powerful demolition of the kind of cultural hierarchies in which Joyce’s protagonist, Gabriel Conroy, is invested. Nevertheless, Joyce’s story offers a similar critique of Gabriel’s elitism through its presentation of a “hyper-educated” Dubliner who fits uneasily in a cultural world that he has fled but that has also produced him. Both thinkers offer similar accounts of how English colonialism affects the consciousness of the colonized, producing the sort of elitist disdain we see in Gabriel as well as the ideal of an “authentic” Irish culture typically mobilized to critique him.
Diabetic gastroparesis: how to recognise and manage it
Authors: Morris David
Published: June 2024

David Morris looks at the impact of diabetes on gastric emptying, and how nurses can treat it
Traveller's diarrhoea: latest updates and the dangers of leaving it untreated
Authors: Pandya Preeti
Published: June 2024

Dr Preeti Pandya explains how nurses can advise travellers on this common complaint
How to reverse type 2 diabetes
Authors: Winter George
Published: June 2024

George Winter looks at how new research is being used to send the metabolic disorder into remission
The Pedagogical Knowledge of Technology Education Teachers
Authors: González-Ferro Vilma , Alfaro-Ponce Hidis , Torres-Rivero José Felipe , Martínez-Díaz Linda , Cárdenas-Barrios Luis
Published: June 2024

The research on the pedagogical knowledge of teachers in technological education arises from the need to address the problem of pedagogical practices, which are traditional. The classes are at the graduate level, focusing on lecturing the student while the student remains with a passive attitude. It is believed that making explicit that teachers' pedagogical knowledge will allow reflection and awareness, thereby transforming pedagogical practices. Therefore, the objective is to understand the teachers’ constructions on pedagogical knowledge in technology programs in Plant Operations and Industrial Instrumentation of the Faculty of Engineering in order to reconstruct it theoretically, as well as identify its characteristics and trace action routes for teacher training. In this way, it allows education to be accessible to low-income and resource-poor populations, whose purpose is to strengthen the productivity and competitiveness of the economy through the training of human talent according to the needs of the working sector in a unique context. This research uses grounded theory as a methodological tool for data processing. In this sense, data collection procedures such as in-depth interviews were conducted with 16 teachers and seven of them were related to the industry. Whereas, 9 were linked to the teaching(educational) sector including elementary, high school and college level. The results showed differentiated, and socially constructed pedagogical knowledge that responds to teachers’ nature in a particular context. These results contribute to consolidate a broad vision about the pedagogical knowledge’s characteristics that the teacher builds.
Sir Thomas Browne’s Faith, Hope, and Love in Religio Medici , Hydriotaphia , and “A Letter to a Friend”
Authors: Kim Jeong Oh
Published: June 2024

Abstract: In this essay, I suggest Sir Thomas Browne as a new religious and medical author of influence. Based on a radical perspective of the anatomy of the human soul, he emphasizes the importance of a rational faith to fulfill the demand of reason and to create a Reformative social milieu in defense of cultural Christianity. In a situation where there is a geographic turn in religious studies and a religious turn in literary studies, I redefine Sir Thomas Browne’s geography of religion as an environment where God’s love, including the human practice of charity, unfolds for Christian tolerance and reconciliation.
Sacrifice and Atonement in Toni Morrison’s Beloved and William Faulkner’s Light in August
Authors: Busch Austin
Published: June 2024

Abstract: Reading Beloved and Light in August in dialogue with New Testament intertexts and theological traditions of Christian atonement reveals the redemptive logic underlying Sethe’s infanticide and the exorcistic expulsion of Beloved, and the sacrificial logic underlying Joe Christmas’s lynching. Triangulating these and related scenes of racialized violence against models of sacrifice drawn from Girard, Freud, and other theorists discloses the novels’ critique of certain Christian theological interpretations of Jesus’s death that imply the self-perpetuating futility of surrogate sacrifice. This article considers the ideological purposes those assessments play in the historical-cultural contexts the novels imagine and in which they written.
School-Based Health Services and Chronic Absenteeism: Evidence from Hawai’i Public High Schools
Authors: Murphy Mark , Neely Jennifer
Published: June 2024

Abstract: Chronic absenteeism is a widespread and troubling phenomenon affecting high school students nationwide. Existing research identifies an inverse link between student health and chronic absenteeism. Illness is a top cause of student absence, suggesting that school-based health services may play an important role in mitigating chronic absenteeism. Since 2014, a school-based health program which provides school nurses has been introduced in certain public high schools in Hawai’i. Using a merged panel of school-level directory, enrollment, chronic absenteeism, graduation rate, and program participation data from the 2010–11 to 2018–19 academic years, we estimate how the program impacted high school chronic absenteeism. Using a synthetic control method approach, we find that school-based health programs reduced overall chronic absenteeism two years and three years following program adoption. Sensitivity analyses (i.e., including leave one out exercises and alternative combinations of predictor variables) highlight the robustness of these findings. These results demonstrate the potential for school-based health services to reduce chronic absenteeism among high school students.
Analysis of Human Y Chromosome Haplogroup E-M81 Sublineages in Portuguese Samples
Authors: Bouabdallah Selsabil , Alves Diana , Manco Licínio
Published: June 2024

The human Y-chromosome haplogroup E-M81 is predominant in northwestern Africa and almost absent
elsewhere, except for the Iberian Peninsula. In the present study, we investigated the internal branches
of E-M81 (E1b1b1b1a) in 29 unrelated men from mainland Portugal. All individuals sampled carried the
derived allele for the marker M183 (hg E1b1b1b1a1), and all but two had the derived allele for the marker
SM001. Eleven individuals carried the derived allele for the marker Z5009 (hg E1b1b1b1a1c), and 16
were assigned to the paragroup E-SM001*(xZ5009, PF6794, CTS12227, M165, M5043). Median-joining
networks based on seven Y-chromosome short tandem repeats (DYS19, DYS389I, DYS389II, DYS390,
DYS391, DYS392, and DYS393) showed 14 different haplotypes, revealing a clear star-like structure, with
the common central haplotype distributed by the three different subclades identified (M183*, SM001*,
and Z5009) encompassing the typical Maghrebin core haplotype in northern African populations.
The relatively high frequency of the E-M81 lineage in mainland Portugal supports a North African Y-chromosomal contribution that may have occurred during the Islamic period in the country
Monetary Policy Transmission in an Emerging Economy: The Key Role of Credibility Regimes
Authors: Lopes Luckas Sabioni , Rotatori Corrêa Wilson Luiz
Published: June 2024

ABSTRACT: This paper investigates the effects of the Brazilian Central Bank (BCB) credibility on the outcomes of its monetary policy. In this sense, we seek to characterize periods in which the central bank can be categorized as strong (high credibility) or weak (low credibility) through a VAR methodology with an endogenously estimated threshold parameter. The econometric model includes the credibility variable, which defines the regimes, along with the output gap, inflation, 12 months ahead inflation expectations, the policy interest rate, and a long-term interest rate. Our dataset spans from 2003 to 2022, with monthly data. The estimations suggest a significant threshold parameter at 1%, with a value of 1.75 percentage points. Thus, we highlight that the BCB operates in a low credibility regime when inflation expectations exceed the tolerance bands around the inflation target. In fact, this occurred in 19% of the considered sample, equivalent to 46 months. Despite the relatively low frequency of periods in which the Brazilian Central Bank operated in a low credibility context, such a regime should be diligently avoided, as our evidence demonstrates that this regime is associated with a substantial reduction in the effectiveness of monetary policy in the country. We show, for example, that with low credibility, the BCB practically loses the ability to affect productive activity and the dynamics of prices (inflation and inflation expectations). When examining the possible causes of the reduction in the effectiveness of monetary policy conditional on the credibility regimes, we show that this variable can affect the existing trade-off between output and inflation in the economy. In other words, our results suggest that credibility regimes can influence the observed inclinations in the country's Phillips curve. Specifically, we point out that in a low credibility regime, inflation shocks generate recessionary effects on output, and inflation becomes more responsive to increases in inflation expectations, thereby reducing the degree of price rigidity. In conclusion, monetary policy in Brazil has effects that systematically depend on the credibility regime in operation. Therefore, maintaining a high credibility regime should remain a priority for the BCB, as it facilitates the achievement of favorable outcomes, including meeting inflation targets.
Multi-band microbolometer in CMOS technology
Authors: Liao Yiming , Wang Ke , Zhou Wenbin , Yan Feng , Ji Xiaoli
Published: June 2024

Multi-spectral imaging enhances the information diversity of the object with complex, expensive, and low integrated components. Here, we demonstrated an antenna-coupled microbolometric detector in complementary metal-oxide-semiconductor (CMOS) technology, utilizing SiO2 absorption and L-shaped fractal antenna to achieve multi-band detection from infrared (IR) to terahertz (THz). Experimental results demonstrate that the detector can achieve high sensitivity detection in both THz and IR bands, with the maximum detectivity of 5 (108 cm·Hz1/2/W @305 GHz and 7 (108 cm·Hz1/2/W @8.55 µm, respectively. The presented multi-spectral detector is easily implementable in integrated circuit process, conducive to high-density, low-cost, and high-performance array imaging.