bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative data sharing: The International Acute Myeloid Leukemia Consortium (INTERACT).
Authors: Tomizawa Daisuke , Wyatt Kirk D. , Kolb E. Anders , Reinhardt Dirk , Tasian Sarah K , Rubnitz Jeffrey E , Zwaan C Michel , Hindi Enal , Alonzo Todd Allen , Tanaka Shiro , Furner Brian , Birz Suzi , Petit Arnaud , Watkins Michael , Gerbing Robert B , Tanoshima Reo , Pounds Stanley B. , Achen Bhavya , Volchenboum Samuel Louis , Cooper Todd Michael
Published: August 2024

169

Background: Outcomes for children and adolescents/young adults (AYAs) with acute myeloid leukemia (AML) remain suboptimal and are decidedly poor for patients with subtypes defined by high-risk features, including canonical genetic alterations and relapsed/refractory presentation. Due to their rarity, these subtypes are difficult to study within the existing clinical trials paradigm. Data sharing efforts aim to increase our understanding of rare cancer subtypes by pooling data from multiple sources. The INTERnational Acute myeloid leukemia ConsorTium (INTERACT) was established to pool and share data on pediatric and AYA patients with AML. Methods: In 2019, a data dictionary was created through an iterative, consensus-driven process that analyzed pre-existing clinical trials case report forms as the initial basis. By developing this standardized representation for data on patients with AML, data could be harmonized and integrated. A memorandum of understanding was signed in 2021, formally establishing INTERACT. An executive committee was convened to establish scientific priorities, facilitate ongoing data dictionary work, usher agreements with data contributors and review data requests submitted by investigators. In January 2024, the initial set of AML data was released on the Pediatric Cancer Data Commons (PCDC) data portal. Results: As of April 2024, the data dictionary includes 157 standardized data elements that were used to harmonize clinical data on 3,413 patients who participated in seven clinical trials conducted by four pediatric oncology cooperative groups across the United States, Europe, and Asia. Elements in the data dictionary include demographics, initial disease characteristics, genetic alterations, and survival status. Aggregate data can be freely explored using the publicly-available PCDC data portal (portal.pedscommons.org) and investigators seeking line-level access to data may submit a project request to the INTERACT executive committee for consideration. Conclusions: International collaborative data-sharing efforts will advance our understanding of pediatric and AYA AML by reducing barriers that constrain our study of AML to smaller cohorts of data. We hope that an early outcome of data sharing will be to increase our understanding of optimal treatments for patients with relapsed/refractory disease. Future goals of INTERACT include identifying data from additional studies to include, establishing relationships with new data contributors, and establishing working groups to advance the consortium’s scientific and clinical trials goals.
Unveiling the impact: Exploring malnutrition rates in patients with cancer and its association with anticancer treatments.
Authors: Pradeep Roshini , Deora Kunal , Danca Emily , Young Tarra , Mott Kelly , Chezik Ashley , Rocca Neychelle , Kudelka Andrzej Piotr
Published: August 2024

189

Background: Malnutrition is a common cause of morbidity and mortality in patients with cancer. Malnutrition is seen in 40 to 80% of patients with cancer. Recent literature has shown loss of lean body mass in cancer population can be an independent factor for poorer outcomes. Anorexia, the loss of appetite has been either secondary to the disease itself or as a side effect of treatment. The mechanism of anorexia development is due to physiologic alteration in metabolism during carcinogenesis. Hence, it becomes important to screen for malnutrition in all patients with diagnosis of cancer. Methods: This single-center cohort study, conducted between January 15, 2024, and February 9, 2024, involved 106 patients receiving outpatient oncology care. Patients aged 18 to 90 years who consented to participate were administered the Mini Nutritional Assessment (MNA) questionnaire at the oncology registration desk. Exclusion criteria included patients with a dietician and those with pure nonmalignant hematological diagnoses. Data analysis comprised identifying patients at risk of malnutrition (8-11 points) or malnourished (0-7 points) using the MNA scale, followed by retrospective chart review. Primary outcomes focused on identifying prevalent cancer types among malnourished or at-risk patients, while secondary outcomes included comparing malnutrition proportions among different treatment groups and assessing gastrointestinal tract metastases and common causes of malnutrition. Results: The data encompassed 106 patients, among whom 29 (27.3%) were identified as at risk of malnutrition, while 9 (8.4%) were malnourished. Notably, a majority of at-risk or malnourished patients (60.5%) were classified as overweight or obese. The most prevalent cancers among these patients were breast cancer (26.3%), genitourinary cancer (23.6%), and gastrointestinal cancer (18.4%). Chemotherapy use was noted in 16 (42.1%) patients, immune checkpoint inhibitor treatment in 12 (31.5%), and a combination of both in 7 (18.4%). Gastrointestinal metastasis was observed in 5 (13.1%) patients. Among those at risk of malnutrition, the primary contributing factors identified were tumor impact and location (63.1%), diarrhea (18.4%), and fatigue (18.4%). Conclusions: The study underscores the significant prevalence of malnutrition risk among cancer patients, emphasizing the importance of systematic screening during outpatient oncology follow-ups.
Real-world outcomes with lurbinectedin in second-line and beyond for small cell lung cancer in Korea.
Authors: Shim Joosung Gabriel , Lim Sun Min , Cho Byoung Chul , Hong Min Hee , Lee Jii Bum
Published: August 2024

211

Background: Small-cell lung cancer (SCLC) accounts for approximately 10~15% of all lung cancers and is characterized by a strong tendency for early metastasis, and a poor prognosis. Most patients are diagnosed with extensive disease, with only one-third presenting with earlier-stage disease amenable to potentially curative multimodality therapy. Before the advent of lurbinectedin in 2020, only few options existed for treating patients with SCLC that had progressed after first-line therapy. The sole available second-line option for metastatic SCLC was topotecan, which is associated with hematological toxicities and only modest efficacy. Although lurbinectedin has been added to the arsenal against metastatic SCLC, real-world data on its efficacy has been scarce due to its recent implementation. In this study, we investigated the demographics and clinical outcomes of metastatic SCLC patients treated with lurbinectedin in Korea. Methods: Patients with metastatic SCLC who had failed first-line therapy were identified (n=51) at Yonsei Cancer Center, Seoul, Republic of Korea, and received lurbinectedin at a starting dose of 3.2mg/kg. Efficacy data, including investigator-assessed tumor response, progression data, survival, and demographic information, were recorded. Results: A total of 51 patients were treated with lurbinectedin at a single center in Korea. Thirty-four patients were eligible for assessment. The median age of diagnosis was 68. The overall objective response rate and disease control rate were 20% and 47%, respectively. For patients treated with lurbinectedin in the second-line therapy, the ORR and DCR were 12% and 15% respectively, while the ORR was 18% and DCR was 29% for patients in beyond third-line of therapy. The median progression-free survival was 1.8 months (95% CI 0.38 to 2.08), and the median overall survival was 2.8 months (95% CI 0.55 to 2.70). A patient group with a history of smoking showed prolonged overall survival and disease control rate. The most common adverse effects related to lurbinectedin were anemia (55%), leukopenia (53%), nausea (35%), loss of appetite (25%), general weakness (19%), neutropenia (12%), dizziness (6%), alopecia (6%), phlebitis (3%), thrombocytopenia (3%), pneumonia (3%). Conclusions: The real-world data of lurbinectedin in SCLC patients suggests that it is still a viable option in this disease area with dismal prognosis. [Table: see text]
Infusion-related reactions from immune checkpoint inhibitors: A proportional and network meta-analysis.
Authors: Fujiwara Yu , Tsuchiya Kazuya , Koseki Mako , Estaris Jonathan , Elias Evelyn , Chesta Fnu , Takaoka Kensuke , Nishimura Yoshito , Gopalakrishnan Dharmesh , Puzanov Igor
Published: August 2024

38

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with solid tumors. Infusion-related reactions (IRRs) to ICIs have been reported in up to 20%, but the incidence varies among ICIs. Therefore, we aimed to report and compare the incidence of IRRs to each ICI therapy. Methods: We searched PubMed/MEDLINE, Embase, and Web of Science to identify phase 3 randomized controlled trials (RCTs) evaluating ICIs (CTLA-4, PD-1, PD-L1, and LAG-3 inhibitors) in solid tumors. We performed a random-effects model network meta-analysis to compare the odds ratio (OR) of IRRs by using RCTs comparing dual ICIs, ICI monotherapy, and placebo/observation. For a proportional meta-analysis, treatment arms evaluating ICI monotherapy, or dual ICIs, were selected to pool the incidence of IRRs. Results: A total of 25,250 patients from 47 phase 3 RCTs were included in the analysis. A network meta-analysis of treatment-related IRRs included 10 RCTs and showed that avelumab (OR 70.2, 95% confidence interval [CI]: 4.32-1140) and atezolizumab (40.72, 2.47-671.4) had a significantly higher risk of treatment-related IRRs compared with placebo/observation. Network ranking revealed that avelumab, atezolizumab, and relatlimab plus nivolumab were the top three therapies with risk of treatment-related IRRs. Proportional meta-analyses revealed that the pooled incidence of treatment-related IRRs was 5.39% for PD-1 plus CTLA-4 inhibitors, 8.25% for PD-L1 (avelumab: 13.1%, non-avelumab: 1.93%), 1.97% for CTLA-4, and 1.95% for PD-1 inhibitors. Results of immune-related IRRs were relatively consistent with those of treatment-related IRRs (Table). Conclusions: Avelumab has the highest risk of IRRs followed by atezolizumab and dual ICIs. This comparative study provides insight into the incidence of IRRs with ICI regimens. These results are useful in assessing which systemic therapies are responsible for IRRs, particularly when ICIs are combined with other agents. [Table: see text]
Surufatinib plus toripalimab in advanced soft tissue sarcoma (STS): Results from a multicenter, single-arm, basket study.
Authors: Cheng Ying , Zhang Xing , Lu Ming , Shi Si , Ye Feng , Chen Zhendong , Ji Dongmei , Song Lijie , Yin Fei , Shi Haiyan , Zhou Jinghong , Tan Panfeng , Fan Songhua , Xu Qian , Shi Michael , Su Weiguo
Published: August 2024

42

Background: Soft tissue sarcomas (STS) are highly malignant despite their low incidence and prone to recurrence, with limited therapeutic options after failure of first-line treatment. Several antiangiogenic monotherapies have shown some efficacy but limited benefit. The open-label, multi-cohort, single-arm, basket study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-programmed death 1 [PD-1] antibody) for Chinese patients (pts) with advanced solid tumors. Here, we reported the results from the STS cohort. Methods: Pts with STS who had progressed on ≤ 2 lines of systemic chemotherapy, or were intolerant to standard treatment, or for whom there was currently no effective therapy were eligible. They received 21-day cycles of surufatinib 250 mg orally, once daily, plus toripalimab 240 mg intravenously, once every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of data cutoff (Feb 28, 2023), a total of 20 pts (incl. 4 treatment-naïve pts) were enrolled and received the combination treatment (mean duration: 5.81 months [m]). Median (range) age was 50 (23-74) years, 10 pts were male, 17 pts were TNM stage IV. The pathological types include leiomyosarcoma (n=4, incl. 1 naïve patient), synovial sarcoma (n=4), alveolar soft part sarcoma (n=3, incl. 2 naïve pts), undifferentiated pleomorphic sarcoma (n=3), liposarcoma (n=2, incl. 1 naïve patient) and fibrosarcoma (n=1), malignant fibrous histiocytoma (n=1) and others (n=2). Seven (35%) pts had PD-L1 combined positive score of ≥1. The median follow-up duration was 27.14 m. Confirmed ORR and disease control rate (DCR) for 19 efficacy-evaluable pts was 10.5% and 68.4%, respectively; median duration of response was 7.05m. The median progression-free survival (mPFS) and median overall survival (mOS) was 2.69 m and 16.23 m for all dosed pts. For 16 previously treated pts, ORR and DCR was 6.3% and 62.5% respectively; median duration of response (DoR) was 7.13 m; mPFS was 2.65 m; mOS was 14.32 m. 18 (90%) pts experienced at least one treatment-related adverse event (TRAE), and 7 (35%) of them reported grade ≥3 TRAEs. The incidence of immune-related adverse events (irAEs) was 70%, only 2 pts had grade ≥3 irAEs, which were immune-related pancreatitis and immune-related diabetes. 2 pts were permanently discontinued due to TRAEs, which were grade 2 renal impairment and grade 3 hyperglycemia. No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with advanced STS. Clinical trial information: NCT04169672 .
A phase I/II study of nanoliposomal irinotecan and carboplatin in patients with advanced or metastatic, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma characterized by tissue and liquid next-generation sequencing.
Authors: Chiang Nai-Jung , Li Chien-Feng , Bai Li-Yuan , Huang Chien-Jui , Yen Chih Chieh , Hsiao Chin-Fu , Wu Li-Ching , Chen Ming Huang
Published: August 2024

52

Background: For locally advanced or metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), standard chemotherapy typically incorporates etoposide or irinotecan plus platinum agents. Herein, we initiate a phase I/II trial to apply Nal-IRI in combination with carboplatin as the 1st line treatment in patients with GEP-NECs to define the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D). Methods: In the phase I part, traditional 3+3 design was applied. Enrolled patients would receive escalating dose of 60 (level -1), 80 (starting dose, level 0) or 100 (level 1) mg/m2 salt-form nal-IRI plus carboplatin AUC=4 with maximum total dose of 600 mg on D1, every 21 days as a cycle. DLTs were evaluated during the first one cycle of treatment with tumor assessment every 6 weeks. Prophylaxis G-CSF was not allowed in the first cycle Paired testing of tissue (TBx) and liquid biopsy (LBx) was done by Illumina TSO500 platform before treatment. The second LBx would be repeated for confirmed partial responders when progression. Results: Totally 6 GEP-NEC patients with primary sites of colon in three, and each one in esophagus, ampulla of Vater and pancreas were enrolled to level 0. One patient had DLT of grade 4 neutropenia lasting for 3 days even under salvage G-CSF. Treatment-related adverse events showed grade 3/4 neutropenia (33.4%), grade 2 anemia (16.7%), grade 3 fatigue (16.7%), and grade 2 skin rash (16.7%). Four patients achieved confirmed partial response and 2 patients got stable disease, with the objective response rate of 66.7% (95% confidence interval: 22%-96%). After the data and safety monitoring board meeting, level 0 was decided as RP2D but not escalation to level 1 because of acceptable toxicity profiles and promising efficacies. Comprehensive genomic profiling showed that driver mutations were identified in three cases including two harboring BRAFV600E mutation and one with KRASG12D mutation. The other three cases lacking driver mutation showed frequent copy number alteration including 1 with MDM2 amplification (copy number 27) and a wild-type TP53. Homologous recombination deficiency (HRD), as determined by GIS score, was identified in a colon GEP-NEC who remained to be HRD-positive at progression but a higher TMB (from 4.7 to 10.2 Muts/Mb) and a higher BRAFV600E mutation allele frequency (from 24.1% to 43.6%) in tumor tissue, compared to the baseline profiling. Conclusions: Based on current data, the RP2D is 80 mg/m2 of nal-IRI (salt-form) and carboplatin of AUC=4, every 3 weeks. The extension phase II study in GEP-NEC is ongoing. Clinical trial information: NCT05385861 .
Navigating the future of pancreatic cancer treatment: Systematic review insights from immunotherapy clinical trials.
Authors: Sarfraz Zouina , Anwar Junaid
Published: August 2024

68

Background: Pancreatic cancer remains a formidable challenge, being the seventh leading cause of cancer-related deaths globally. Despite advances in medical science, survival rates have not significantly improved, primarily due to late diagnosis and the limited efficacy of conventional treatments. This study investigates the potential of immunotherapy, offering a new horizon for treatment strategies. Methods: A systematic review was conducted, encompassing Phase I-III clinical trials that utilized immunotherapy in treating pancreatic cancer. Databases such as PubMed/Medline, CINAHL, Scopus, and ClinicalTrials.Gov were searched following PRISMA guidelines. A total of 29 completed trials and 106 ongoing studies were analyzed, focusing on survival rates, response to treatment, and adverse events. Results: Analysis of 29 completed clinical trials revealed that immunotherapy could extend the median OS in selected cohorts, with a notable trial showing an increase in OS from 6 to 13.6 months in patients receiving PD-1 blockers. Phase I trials demonstrated a cumulative OS of 13.6 months and a PFS of 5.1 months across various interventions. Ongoing studies, numbering 106, are exploring a wide range of immunotherapeutic agents, aiming to improve these outcomes further. Adverse events were consistent with expectations for immunotherapy, indicating a manageable safety profile. The most promising interventions appear to be combination therapies that include checkpoint inhibitors, showing an increase in the 5-year survival rate of up to 30% for patients undergoing adjunctive treatment post-surgery. Conclusions: Immunotherapy presents a potential paradigm shift in the treatment of pancreatic cancer. However, more robust clinical trials are necessary to fully understand its efficacy and safety. Future research should focus on identifying biomarkers for patient selection and exploring combination therapies to enhance treatment responses. The disparity in access to these therapies, especially in low- and middle-income countries, underscores the need for global efforts to make advanced treatments more accessible.
Circulating tumor DNA analysis in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy followed by surgery.
Authors: Xie Mian
Published: August 2024

69

Background: The aim of this prospectively study is to investigate circulating tumor DNA (ctDNA) as a prognostic marker for survival in locally advanced esophageal squamous cell cancer (ESCC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery. Methods: Serial plasma samples were collected from 68 ESCC patients treated with neoadjuvant chemoradiotherapy before surgery. ctDNA was detected before treatment, after neoadjuvant chemoradiotherapy and after surgery by personalized, next-generation sequencing assay. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for recurrence-free survival (RFS) and overall survival (OS). Results: ctDNA was detectable in 89.7%, 17.2%, and 6.9% of pretreatment, post-neoadjuvant chemoradiotherapy and post-surgery plasma samples, respectively. The conversion of ctDNA status from positive at baseline to negative at 4-6 weeks after neoadjuvant chemoradiotherapy was significantly associated with pathological complete response (pCR) ( P = 0.02). Significant worse RFS was related to detectable ctDNA after neoadjuvant chemoradiotherapy ( P = 0.008) or after surgery ( P = 0.001). Detectable ctDNA at baseline ( P = 0.01) and after surgery ( P = 0.008) were associated with worse OS. In multivariate analysis, detectable postoperative ctDNA was significantly associated with RFS ( P = 0.012) and OS ( P = 0.025) after adjusting for other clinicopathological risk factors. Conclusions: ctDNA status is a strong prognostic factor of recurrence in locally advanced ESCC patients. Consequently, ctDNA could potentially improve pre- and post-treatment risk assessment and facilitate individual therapy for ESCC patients.
Association of vitamin D deficiency with liver cirrhosis and hepatocellular carcinoma risk: A retrospective cohort study from the TriNetX US collaborative networks.
Authors: Tseng Yuan-Tsung , Wang Chun-Hsiang
Published: August 2024

77

Background: Emerging evidence highlights the critical role of vitamin D in liver health, especially concerning the risk of liver cirrhosis and hepatocellular carcinoma (HCC). This investigation aims to explore the association between vitamin D deficiency and the prevalence of these liver diseases, contrasting outcomes between individuals with deficient and normal vitamin D levels. Methods: This cohort study utilized the US Collaborative Network within the TrinetX database, encompassing 63 medical institutions. It enrolled participants aged 20 years and older from 2011 to 2023. Vitamin D status was determined through serum 25-hydroxyvitamin D levels, categorizing deficiency as 20-30 ng/mL and normal levels as 30-80 ng/mL. Employing 1:1 propensity score matching, the study controlled for 32 characteristics, such as demographic information, health conditions, and medication use, to ensure equitable group comparisons. Additionally, a 1-year washout period was established. The primary aim was to assess the incidence of liver cirrhosis and HCC over a decade. Results: Analyzing data from over 1.86 million participants, the study ensured a balanced comparison across all variables. Participants had an average age of 50.6 years, with 66% identifying as white and 9% as black. Notably, vitamin D deficiency was significantly associated with an increased risk of liver cirrhosis (HR 1.16 [CI 1.11-1.21]) and HCC (HR 1.25 [CI 1.15-1.36]). Kaplan-Meier cumulative risk analysis further confirmed these elevated risks for both liver conditions in individuals with vitamin D deficiency compared to those with sufficient levels. Conclusions: This study confirms a significant association between vitamin D deficiency and a higher risk of liver cirrhosis and HCC, underscoring the importance of vitamin D in maintaining liver health. The findings support the potential of vitamin D level management as a preventive strategy against liver diseases. The implications of this research necessitate further exploration into the efficacy of vitamin D supplementation for liver disease prevention.
Comparative analysis of cirrhosis and hepatocellular carcinoma outcomes in Asian populations with non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatohepatitis liver disease (MASLD): A five-year retrospective study.
Authors: Tseng Yuan-Tsung , Wang Chun-Hsiang
Published: August 2024

78

Background: Metabolic Dysfunction-Associated Steatohepatitis Liver Disease (MASLD) represents the most up-to-date definition of Non-Alcoholic Fatty Liver Disease (NAFLD) for Asian populations, acknowledging that manifestations may differ across racial/ethnic groups. Due to metabolic and anthropometric differences, adapted criteria for MASLD have been proposed for Asian adults. This analysis aims to compare clinical outcomes between Asian patients diagnosed with MASLD and those with NAFLD. Methods: In this retrospective analysis, 48,189 Asian adults suspected of having MASLD were identified from the TriNetX global research network between January 1, 2010 and December 31, 2023. An equal number of patients (48,189) diagnosed with NAFLD were matched on a 1:1 basis with MASLD patients through propensity score matching. MASLD criteria were adapted to be Asia-specific, requiring a Body Mass Index (BMI) of ≥23 along with the presence of four aspects of metabolic dysfunction. Over a 5-year follow-up period, primary outcomes of cirrhosis and hepatocellular carcinoma (HCC) incidences were determined using Kaplan-Meier methods. Cumulative incidence curves depicted the rates of these events over time. Hazard ratios (HR) for the outcomes were calculated using Cox regression models to estimate the risk associated with MASLD. Results: Over 5 years, the cumulative incidence of cirrhosis (3.0% vs 3.0%, p=0.800) and HCC (1.3% vs 1.4%, p=0.695) were numerically lower in MASLD compared to NAFLD patients, respectively. Adjusted HRs for MASLD were: cirrhosis 1.00 (0.87-1.14) and HCC 0.86 (0.68-1.10). Conclusions: This study compared the clinical outcomes of MASLD and NAFLD in Asian populations and found no significant differences in identifying the risk of cirrhosis and hepatocellular carcinoma between the two diagnostic criteria. However, introducing the new term and diagnostic criteria of MASLD helps reduce the stigmatization associated with NAFLD, emphasizing the central role of metabolic dysfunction in disease occurrence. Although this study did not find significant differences between MASLD and NAFLD in predicting cirrhosis and hepatocellular carcinoma, the concept of Asian-specific diagnostic criteria remains important, highlighting that disease manifestations and risk factors may vary across different races and populations, necessitating personalized prevention and treatment strategies for specific populations. Future research should further explore the similarities and differences between MASLD and NAFLD in different Asian subgroups to optimize diagnostic criteria, improve the accuracy of risk prediction, and develop targeted interventions.
Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.
Authors: Oba Atsushi , Taguchi Tomoyuki , Fujikawa Naoto , Okami Suguru , Tsuji Takashi , Michel Alexander , Kado Yuki , Goshima Satoshi
Published: August 2024

88

Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. Clinical trial information: NCT06106568 . [Table: see text]
The correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer treated with first-line chemotherapy.
Authors: Pretta Andrea , Cau Flaviana , Ziranu Pina , Spanu Dario , Donisi Clelia , Moledda Giusy , Cadoni Andrea , Cimbro Erika , Murgia Sara , Mariani Stefano , Lai Eleonora , Puzzoni Marco , Pusceddu Valeria , Faa Gavino , Scartozzi Mario
Published: August 2024

95

Background: L1CAM is a cell adhesion molecule and stem cell marker belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). L1CAM may be aberrantly expressed in several types of human tumors. The aim of the present study was to evaluate the correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer. Methods: We retrospectively collected data from 51 mCRC pts treated between 2017 and 2022 at the Medical Oncology Unit of the University Hospital of Cagliari. Tumor samples were retrospectively tested for L1CAM immunohistochemical (IHC) expression with the aim of evaluating the correlation with clinical outcome in terms of overall survival (OS) and progression-free survival (PFS). The primary endpoint was the mOS while secondary endpoint was mPFS. The aim of the present analysis was to evaluate the role of L1CAM expression in tumor cells in predicting the clinical outcome of CRC patients treated with standard chemotherapy. Statistical analysis was performed with the MedCalc Statistical Sofware Version 14.10.2. Results: Median age was 70 (±13), 58.8% were males and 41.2% were females. 29.4% of pts had carcinoma of the right colon, 39.2% left colon and 31.4% rectum. Negative or weak L1CAM score 0 was observed in 39.2% patients; 43.1% pts showed a score 1+; 11.8% showed score 2+, and 5.9% showed score 3+. Positivity for L1CAM correlated with a worse prognosis. The median OS for pts not expressing L1CAM was 74.0 months versus 32.0 for patients expressing the biomarker ( p = 0.0021). The mPFS for patients not expressing L1CAM was 21.0 months, vs 6.0 for patients expressing the biomarker ( p = 0.0066). The same negative correlation on outcomes was shown based on the degree of L1CAM expression. A different L1CAM score corresponded to a different OS and PFS. Pts with score 0 showed a mOS of 74 months vs 37 and 18 months for scores 1+ and 2+/3+, respectively ( p < 0.0001). Similar results were obtained with the mPFS: patients with score 0 showed a median of 21 months vs 8 and 2 months for scores 1+ and 2+/3+, respectively ( p = 0.0138). Conclusions: L1CAM expression in cancer cells correlates with a worse prognosis in mCRC patients. Immunohistochemical evaluation of this biomarker could allow the identification of a subgroup of patients capable of benefiting from a targeted therapy.
Ultrasound-Guided Microwave Ablation of Thyroid Schwannoma
Authors: Han Xue , Zhang Yuzhi , Li Yu , Li Ruiping , Liu Chao , Xu Shuhang
Published: August 2024

Thyroid schwannoma, a rare neoplasm of the thyroid gland, originates from Schwann cells that form the myelin sheath. A 47-year-old woman presented with a progressively enlarging thyroid nodule, which was monitored by repeated ultrasonography over the previous 2 years. Following a diagnosis of thyroid schwannoma by core needle biopsy and immunohistochemical staining, the patient underwent ultrasound-guided microwave ablation (MWA). Subsequent thyroid ultrasounds indicated a gradual decrease in the tumor's volume, achieving a 12-month volume reduction ratio of 79.20%. No complications were observed. Ultrasound-guided MWA may serve as an effective alternative to conventional surgery for managing thyroid schwannomas.
Detection and Evaluation of Procalcitonin Variants As Diagnostic Tools in Systemic Inflammation
Authors: Kintrup Sebastian , Brabenec Laura , Zurek-Leffers Finnja-Marie , Hellenthal Katharina E. M. , Cyran Laura , Meybohm Patrick , Gerke Volker , Wagner Nana-Maria
Published: August 2024

BACKGROUND:

Procalcitonin is an indicator of systemic inflammation associated with major surgery or sepsis. Procalcitonin exists in a full-length and truncated variant as a result of dipeptidylpeptidase-4 (DPP4)-cleavage. We recently identified differential biological activity of both variants. Here, we present an immunoassay-based method for the separate detection of procalcitonin variants and correlation to clinical data in patients with severe systemic inflammation.

METHODS:

Rabbits were immunized with peptides of N-terminal sequences of both human procalcitonin variants and polyclonal antibodies purified from rabbit plasma. Antibodies were used for the detection of procalcitonin variants in an indirect sandwich enzyme-linked immunosorbent assay (ELISA) using a commercially available monoclonal anti-procalcitonin antibody as capture. Serum was collected from 19 septic patients exhibiting hyperprocalcitonemia as part of a cross-sectional study; clinical data were analyzed and correlated with procalcitonin variant measurements. DPP4 activity was determined by a DPP4 activity assay.

RESULTS:

Purified antibodies allowed for the separate detection of both procalcitonin variants in all patients. Levels of truncated procalcitonin (truncPCT) correlated with DPP4-activity (Pearson’s R = 0.85, P < .001) and negatively correlated with patients’ Sequential Organ Failure Score (SOFA) scores (Pearson’s R = –0.56, P = .013). In contrast, the correlation between full-length procalcitonin (fullPCT) and SOFA scores was positive (Pearson’s R = 0.56, P = .013). Separation of the patient collective into groups with higher amounts of fullPCT versus truncPCT revealed higher SOFA scores in patients with fullPCT > truncPCT (mean ± standard error of the mean; 11. 3 ± 0.8 vs 6. 1 ± 1.5, P = .003). Patients with fullPCT > truncPCT showed a tendency towards higher doses of vasopressor (0. 2 ± 0.1 vs 0. 1 ± 0.03 µg/kg/min norepinephrine within the first 24 hours after sepsis diagnosis, P = .062) and exhibited higher creatinine (2. 0 ± 0.2 vs 1. 4 ± 0.3mg/dL, P = .019) and leukocyte levels (31. 0 ± 5.4 vs 12. 8 ± 1.9cells/µL, P = .012). In addition, patients with fullPCT > truncPCT were more often subjected to treatment with hydrocortisone (49.0 vs 0%, P = .018).

CONCLUSIONS:

Polyclonal antibodies generated using procalcitonin N-terminal variant peptides as immunogens are suitable for procalcitonin variant assessment. The separate detection of procalcitonin variants may offer additional diagnostic value and can be correlated with organ dysfunction and clinical outcomes in patients with systemic inflammation.
Step-by-Step Description of Percutaneous Full-Endoscopic C2 Ganglionectomy: An Anatomic Feasibility Study in Human Cadavers
Authors: Li Chen , Jiang Ye , Yuan Lutao , Luo Cong , Liu Tengfei , Tang Yifan , Yu Yong
Published: August 2024

BACKGROUND AND OBJECTIVES:

The percutaneous full-endoscopic C2 ganglionectomy (PEC2G), an innovative procedure developed for the surgical treatment of intractable occipital neuralgia, was firstly reported by us in 2021. However, a universally accepted and well-articulated protocol modality remains elusive. The primary objective of this anatomic investigation was to meticulously elucidate the standard procedural steps of PEC2G and assess the anatomic features supporting the safe implementation of PEC2G.

METHODS:

Eighteen fresh adult cadavers were incorporated into this study. From this sample, 3 cadavers were subjected to bilateral PEC2G. Each procedure was documented and assessed, leading to the formulation of standard procedure criteria for PEC2G. Subsequently, 10 sets of anatomic parameters pertinent to this procedure were identified, quantified, and analyzed in 15 cadavers after complete bilateral endoscopic exposure of the C2 ganglion. An assessment of the technical feasibility and potential constraints associated with PEC2G was conducted, providing invaluable insights into the procedure's anatomic considerations.

RESULTS:

All 3 cadavers successfully underwent the PEC2G without any observed complications, such as dura tears or vertebral artery injuries. The C2 inferior articular process emerged as the optimal bony target for puncture, with the C2 pedicle serving as the standard guiding landmark en route to the C2 ganglion. In the 15 cadavers subjected to the planned procedure, 10 sets of anatomic parameters were quantified, establishing a foundational understanding of the anatomy in the context of PEC2G procedure. The results demonstrated that the characteristic of anatomic data pertinent to surgical site supported the safe implementation of PEC2G.

CONCLUSION:

This study contributes the standard surgical steps and crucial anatomic parameters relevant to PEC2G. The characteristic of anatomic data bolsters the safety credentials of this technique, which offers a reliable approach to achieve C2 ganglionectomy. These insights undeniably establish a robust foundation for the ongoing refinement and broader adoption of PEC2G.
Role of a novel uropod-like cell membrane protrusion in the pathogenesis of the parasite Trichomonas vaginalis
Authors: Blasco Pedreros Manuela , Salas Nehuen , dos Santos Melo Tuanne , Miranda-Magalhães Abigail , Almeida-Lima Thainá , Pereira-Neves Antonio , de Miguel Natalia
Published: August 2024

Trichomonas vaginalis causes trichomoniasis, the most common non-viral sexually transmitted disease worldwide. As an extracellular parasite, adhesion to host cells is essential for the development of infection. During attachment, the parasite changes its tear ovoid shape to a flat ameboid form, expanding the contact surface and migrating through tissues. Here, we have identified a novel structure formed at the posterior pole of adherent parasite strains, resembling the previously described uropod, which appears to play a pivotal role as an anchor during the attachment process. Moreover, our research demonstrates that the overexpression of the tetraspanin T. vaginalis TSP5 protein (TvTSP5), which is localized on the cell surface of the parasite, notably enhances the formation of this posterior anchor structure in adherent strains. Finally, we demonstrate that parasites that overexpress TvTSP5 possess an increased ability to adhere to host cells, enhanced aggregation and reduced migration on agar plates. Overall, these findings unveil novel proteins and structures involved in the intricate mechanisms of T. vaginalis interactions with host cells.
Nutrient characteristics and proline accumulation in relation to Picea abies status on drained peat soils
Authors: Cekstere Gunta , Osvalde Anita , Snepsts Guntars , Laivins Maris
Published: August 2024

Monocultures of Norway spruce widely used for afforestation of drained peat soils often have low productivity and decline in vitality. The research aim was to elucidate: (1) imbalances in the nutrient status of soil and plants in relation to Norway spruce crown status and annual increment on drained peat soil in the sub-boreal zone; (2) the suitability of using proline accumulation as a biomarker for Norway spruce vitality and stress in nutrient imbalance conditions. The study was conducted at five forest (Oxalidosa turf. mel.) sites in Latvia, each containing trees with different crown condition status. Chemical analyses of soil and spruce needles, assessment of tree crown vitality and annual increment measurements were done. Our results revealed serious disturbances in the supply of nutrients, which is an important factor in the decline of Norway spruce in monoculture stands on drained peat soils. Deficiency of K, Fe, Cu, B, N and P was found in the current year needles for all trees, but in damaged trees (≥61% defoliation, ≥61% discoloration) Zn deficiency was also found. For 2-year-old needles, deficiency of K, P, S, Zn, and Cu was found in all trees, additionally, deficiency of Fe was found in healthy and medium damaged trees (26–60% defoliation, 21–60% discoloration), and N deficiency was found for medium damaged and damaged trees. Thus, K, Cu, B, Fe concentrations had significant negative correlations with crown status parameters – defoliation, discoloration, and density. K and B deficiency could play the most significant causal role in decreased stem increment. The results revealed that the stress amino-acid proline is a reliable biomarker, having a significant relationship with spruce crown condition parameters, annual increment and nutrient status in needles – low levels of K, Fe, S, Cu, B, N. The increase in proline content in spruce needles was pronounced in moderately damaged trees, indicating the potential for the use of proline accumulation as early stress indicator for spruce. Therefore, further studies on the identification of early stress and factors affecting nutrient uptake and accumulation in needles are particularly valuable for evaluation of stand management options before significant decline of spruce stands.
The genome sequence of the lesser black-backed gull, Larus fuscus Linnaeus, 1758
Authors: Lopez Colom Rosa , O’Brien Michelle F. ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female Larus fuscus (the lesser black-backed gull; Chordata; Aves; Charadriiformes; Laridae). The genome sequence spans 1,324.30 megabases. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.75 kilobases in length.
The genome sequence of the red ripple bryozoan, Watersipora subatra (Ortmann, 1890)
Authors: Bishop John , Wood Christine A. ,   Marine Biological Association Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual Watersipora subatra (the red ripple bryozoan; Bryozoa; Gymnolaemata; Cheilostomatida; Watersiporidae). The genome sequence spans 783.70 megabases. Most of the assembly is scaffolded into 11 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 14.14 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,835 protein-coding genes.
Organizacja i funkcjonowanie nadzoru nad „pionem propagandowym” w centralnych strukturach PZPR w latach 1948–1956
Authors: Wojsław Jacek
Published: August 2024

W badaniach podjęto próbę przybliżenia funkcjonowania nadzoru nad tzw. pionem propagandowym w centralnych strukturach PZPR w latach 1948–1956. Przeprowadzona analiza pozwoliła na sformułowanie opinii, że największy wpływ na politykę propagandową i działalność mass mediów wywierały wydziały KC PZPR, którym została przypisana bezpośrednia kontrola nad funkcjonowaniem prasy i radia, a jednym z najważniejszych instrumentów nadzorczych stała się prowadzona przez ścisłe kierownictwo PZPR polityka kadrowa.
Role of vagus nerve stimulation in epilepsy
Authors: Kmak Bożena
Published: August 2024

ABSTRACT
Introduction and purpose:
Epilepsy affects 1% globally, with 2.6 to 6 million cases in Europe. 30-40% of the 50 million epilepsy patients globally don't respond to drugs. For those ineligible for surgery, Vagus Nerve Stimulation (VNS) therapy offers an alternative for drug-resistant epilepsy and major depression.
A brief description of the state of knowledge:
Vagus Nerve Stimulation (VNS) is a modern therapy using implanted or non-invasive devices to regulate nerve activity with controlled electrical impulses. Vagus Nerve Stimulation (VNS) is effective for focal seizures, including simple partial seizures and auras. It also shows promise in reducing seizures in generalized tonic-clonic seizures and benefits patients with epileptic encephalopathies like Lennox-Gastaut syndrome. VNS effectively decreases both the frequency and duration of seizures in individuals contending with intractable epilepsy. The use of vagus nerve stimulation is generally a safe and well-tolerated form of treatment. VNS therapy improves psychomotor functions in patients with severe drug-resistant epilepsy, showing positive effects on cognitive aspects. The precise mechanism through which VNS affects the body is not fully understood, but it has demonstrated effectiveness, especially in cases of drug-resistant epilepsy.
Conclusions:
Extensive research backs Vagus Nerve Stimulation (VNS) as an effective palliative for intractable epilepsy, reducing seizures. Yet, identifying specific patients who would benefit most from VNS treatment lacks clear criteria. Neuromodulation remains crucial for healthcare professionals handling drug-resistant epilepsy.
Neurodivergence among healthcare professionals and implications for midwifery: A literature review
Authors: Taylor Amy , Miller Suzanne , Davies Lorna
Published: August 2024

Background: Societal awareness of neurodivergence is increasing and diagnostic pathways are becoming more accurate; more people are therefore pursuing assessments, often later in life. Health professionals, including midwives, may also be traversing this journey of self-discovery. Overseas estimates suggest that neurominorities may account for as much as 20% of the general population; this is a significant minority group. The healthcare professions require empathy and social skills, and neurodivergent (ND) people may be seen as unsuitable due to deficits in diagnostic, cognitive and communication skills. Research bias in favour of white males, alongside pervasive stereotypes, has contributed to the underdiagnosis of ND women and gender-diverse people. As a predominately female workforce, including ND colleagues will inevitably become more relevant to the midwifery workforce in the future. Aim: This integrative literature review asks: what is known about the workplace experiences of ND healthcare professionals? The intention is to reflect on the possible ramifications for midwives in Aotearoa New Zealand, and to establish a rationale for future research. Method: Google Scholar, PubMed, CINAHL and ProQuest databases were searched using combinations of key terms. Following the Critical Appraisals Skills Programme (CASP) evaluation, only ethics-approved, peer-reviewed papers in English were included. Findings: Nine studies investigating the workplace experiences of ND healthcare professionals were evaluated. The findings coalesced around two main concepts: (1) The internal experience, with sub-topics Diagnosis and disclosure, Strengths associated with neurodivergence, Sensory processing and Executive functioning; and (2) Navigating a neurotypical world, with sub-topics Social dynamics, Self-management strategies and Workplace accommodations. Conclusion: Ableist barriers to equitable employment experiences were pervasive throughout healthcare workplace settings. All nine studies highlighted workplace challenges for ND healthcare professionals, relating to social, sensory and executive function differences. The absence of literature specific to the unique contextual experiences of ND midwives in Aotearoa New Zealand signifies the scope for future research.