bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.
Authors: Chen Xi , ji Lei , Qian Xiaoyan , Xiao Min , Li Qing , Li Qiao , Wang Jiayu , Fan Ying , Luo Yang , Ma Fei , Xu Binghe , Zhang Pin
Published: May 2024

583

Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P<0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 > 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P<0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.
Neoadjuvant chemotherapy as an indication to preserve nipple areolar complex in advanced breast cancer.
Authors: Alsafi Sarah , Kim Hee Jeong , Yoo Tae-Kyung , KIM Jisun , Lee Sae Byul , Chung Il Yong , Ko Beom Seok , Lee Jong Won , Sohn Byung Ho
Published: May 2024

e12655

Background: Nipple areolar skin sparing mastectomy (NASSM) has similar oncologic and surgical safety compared to skin sparing mastectomy (SSM) and conventional mastectomy. It provides a superior cosmetic outcome, patient satisfaction and quality of life. With the increasing rate of pathological response rate with neoadjuvant chemotherapy (NAT), nipple preservation can be achieved. The aim of our study is to evaluate whether NASSM is an appropriate surgical procedure for patients in whom there is radiological evidence of extension or involvement of nipple areolar complex (NAC) prior to NAT. Methods: Patients with advanced breast cancer received neoadjuvant chemotherapy and NASSM or SSM between June 2006 and December 2021 at Asan Medical Center were retrospectively reviewed. We excluded patients with metastatic breast cancer on presentation, bilateral cancer and inflammatory breast cancer. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine clinicopathological and radiological factors to determine NAC preservation. Our primary objective to assess tumor cells persistence in the NAC after radiological complete response or resolution of extension to NAC. Results: Total of 1,105 patients included. 71.7% of patients underwent NASSM and 17.2% SSM as a final operation. 144 patients (13%) had a change in the pre- NAT type of surgery decision. 83(7.5%) patients had nipple involvement on final pathology. Out of 312 patients who underwent SSM, only 76 patients had nipple involvement on final pathology When comparing patients who had nipple involvement to those who didn’t on final pathology, clinical T & N stage, histologic & nuclear grade, breast cancer subtype, presence of multifocality/multicentric disease on MRI pre or post NAT, distance of mass to NAC and mass size pre and post NAT, the presence of non mass extension to NAC post NAT, NAC thickening on any image pre and post NAT and presentation symptoms of nipple retraction and skin changes were statistically significant. A multivariate regression analysis was performed to compare all the above factors and showed that breast cancer subtype, tumor nipple distance on MRI pre NAT, nipple areolar thickening on MRI pre NAT, clinical response and nipple retraction on MMG post NAT were statistically significant and indicators of nipple involvement on final pathology. Only 8 patients developed NAC recurrence in the NASSM group. Conclusions: NASSM is a safe procedure in patients who had tumor extension to NAC prior to NAT and showed improvement post NAT as evident on MRI. Further prospective studies are needed to establish and criteria to preserve NAC in this subgroup of patients.
“What you're hearing from all of us is simplify the language”: A focus group study on biomarker testing in oncology.
Authors: Smith Anna Jo Bodurtha , Ang Ian Lee , Acharya Rashmi , Moore Tracy , DeFeo Sarah , O'Brien Caroline , Ko Emily Meichun
Published: May 2024

e13540

Background: In oncology, somatic biomarker testing is increasingly driving treatment decision-making. Exploration of patients’ understanding of, and perspectives on, biomarker testing has been limited, yet these are needed to improve health education and communication about biomarkers. Our objectives were to explore the perspectives of patients with gynecologic cancers on biomarker and genetic testing and to identify factors that influenced their decision-making on testing. Methods: Patients with gynecologic cancer enrolled in the University of Pennsylvania’s Biobank were invited to participate. Of the 82 patients contacted, 7 participated in 3 focus groups in fall 2023. Participants reviewed educational materials (pamphlet, slide set) about biomarker testing based on the Cancer Precision Medicine Commons’ patient education materials, explored understanding and perspectives around biomarker testing, and then discussed barriers and facilitators to testing. Thematic analyses by two researchers were performed using verbatim transcripts. Results: All patients strongly agreed that both genetic and biomarker testing were important after a gynecologic cancer diagnosis and impacted their treatment options. However, patients did not understand what a biomarker was and expressed confusion over terms and testing methods, labeling unknown terms as “jargon.” 85% of participants had received germline genetic testing, and 85% received biomarker testing, with the remaining participants uncertain about testing status. Participants utilized a variety of resources such as the Internet, peer forums, articles on the patient portal, discussions with clinicians, and scientific papers to understand their cancer diagnosis and the role of genetic and biomarker testing. They mentioned fear (i.e., seeing low survival rates for ovarian cancer online as a “death sentence”) and financial circumstances as key barriers to accessing genetic or biomarker testing. Patients desired simple tailored written materials that were relevant from diagnosis to across the disease course. Conclusions: Patients understand the importance of biomarker testing in oncology but reported difficulties understanding existing resources. Current online resources had jargon and induced fear in some participants. Work to develop patient-centered resources on biomarker testing is needed.
Promptable foundation model for automatic whole body RECIST measurement.
Authors: Hérent Paul , Philippe Hélène , Ferreres Elodie , Machado Leo , Dancette Corentin , Khlaut Julien , Manceron Pierre , Tordjman Daniel
Published: May 2024

e13643

Background: RECIST 1.1 is the gold standard for tumor evaluation in clinical trials and patient care. However, it faces challenges due to the subjective selection and measurement of lesions, notably because of inter-observer variability in the 20-30% range (1), which can potentially result in inaccuracies in therapeutic response classification (2). The main objective of this study is to assess the added value of a radiological foundation model to assist the radiologist to measure RECIST across different lesion topographies, using visual prompting. Methods: We use a promptable segmentation algorithm, based on a visual foundation model, pre-trained on various CT-scans and then trained on a subset of the Medical Segmentation Decathlon (MSD) dataset, covering 538 patients with pancreas, liver, colon and lung lesions. It outputs a 3D segmentation mask of the lesion, using a visual prompt, i.e. a 3D bounding box (BBox) as input. We then measure the capacity of the model to measure RECIST on the MSD validation set and on the KiTS validation set (99 samples), which features a new lesion type (kidney). To simulate inter-reader variability of up to 23%, we provide as inputs BBoxes centered on the lesions but with a varying error (15% variability: +10 pixels, 23% variability: +15 pixels). Results: The model is able to correct variability in BBox input: with all BBox error ranges, it beats the input variability (15% and 23% thresholds in each column) across many organ types, except in the pancreas when using large error BBoxes. Moreover, the model is able to generalize to new lesion types not seen during training, on an external dataset (KiTS - Kidney). Conclusions: Unlike existing supervised machine learning models dedicated to lesion detections in specific organs, our approach is organ and lesion agnostic and offers a more reliable, precise tumor assessment. This is a first step before allowing the longitudinal evaluation of tumors while safeguarding the clinical intuition necessary for selecting the right target lesions. Moreover, we believe that these methods will be crucial in advancing beyond RECIST 1.1, facilitating the identification of new prognostic biomarkers and proxies for tumor burden derived from previously underexplored radiomics features, ultimately refining the efficacy of clinical trial assessments and elevating the standard of patient care. 1. Yoon, S et al. 2015. 2. Kuhl et al. 2018. [Table: see text]
Impact of eligibility criteria discordance on clinical trial accrual in diffuse large B-cell lymphoma (DLBCL).
Authors: Anderson Clare E , Wang Mei , Wuliji Natalie , Patel Anand Ashwin , Lin Chenyu
Published: May 2024

e13707

Background: Excessively stringent clinical trial eligibility criteria may hinder trial accrual, differentially exclude racial-ethnic minority groups, and limit generalizability. This study reviewed the association between trial accrual and concordance of eligibility criteria with known drug safety data in DLBCL clinical trials. Methods: Eligibility criteria and accrual of completed phase II/III clinical trials for DLBCL that opened in the US between 2010-2020 were abstracted from ClinicalTrials.gov. Trials missing posted results or studying cellular therapy / transplant were excluded. Concordance with known safety data was assessed by comparing study eligibility criteria for QTc, renal, hepatic, and cardiac function to FDA labels and phase I safety signals of study drugs. Excessively strict discordant criteria (ExSDC) were defined as eligibility criteria without supporting safety signals. Logistic regression +/- dispersion was used for analysis. Results: 58 trials met criteria for inclusion, accruing 6,232 participants. 88% of studies involved a non-FDA-approved agent, 74% were multicenter, 55% were industry sponsored, 66% only accrued in the US, and 86% were phase II. Eligibility criteria were highly variable (Table). Discordance of renal, hepatic, cardiac function, and QTc criteria from known safety data occurred in 31%, 26%, 41%, and 29% of studies, respectively. Race and ethnicity data were not reported in 22% and 45% of studies, respectively. Trials after 2015 were more likely to report race (p=0.04) and ethnicity (p=0.01). In a multivariable model adjusted for international study sites, greater number of ExSDC was associated with a lower proportion of black patients in the trial (OR 0.45, CI 0.29-0.71, p=0.001). ExSDC in cardiac function were most associated with reduced accrual of this minority group (OR 0.17, CI 0.05-0.58, p=0.007). 11 studies (19%) had early termination for lack of accrual (ETLA). In multivariable analysis, greater number of ExSDC was independently associated with ETLA (OR 3.53, CI 1.45-8.64, p=0.006), while multicenter status protected against ETLA (OR 0.05, CI 0.01-0.31, p=0.002). Industry sponsor and concordance of cardiac criteria protected against ETLA in univariable analysis only. Other eligibility criteria were not associated. Conclusions: Eligibility criteria in DLBCL trials varied widely and were often discordant with known safety data. Higher number of ExSDC was associated with lower accrual of black patients and higher risk of ETLA. Optimizing concordance of eligibility criteria with safety data may improve trial accrual and diversity. [Table: see text]
Trends of demographic and clinical traits of young patients with breast cancer from the National Cancer Database: Disproportionate effect on underrepresented underserved populations.
Authors: Mark Cynthia , Pujara Vivek , Boyle Marissa K. , Yuan Yuan , Bitar Jin Sun
Published: May 2024

e13715

Background: Over the past decade, there has been increasing incidence of young patients diagnosed with cancer. Despite these developments, there is still uncertainty surrounding the factors and patterns contributing to the rising incidence in young age. This study aims to explore the demographic and clinical characteristics of young breast cancer (YBC) patients. Methods: We obtained characteristics and survival data from 206,156 of young patients (≤ 40 years of age) diagnosed with breast cancer between 2005 and 2019 in the National Cancer Database (NCDB). The demographic and clinical data were subdivided the patients into two comparison groups based on year of diagnosis with 10 years interval (2005-2009, Old vs. 2015-2019, New group). The z-score test was employed to measure the changes in the 2 groups. Cox proportional hazards model was used to explore the variables influencing overall survival (OS). Results: Overall, the absolute number of YBC patients have been increasing every year. The comparison between Old (55397 pt) and New groups (67930 pt) showed increase in Hispanic (4,575 (8.3%) vs 6,720 (9.9%), p <0.0001), Black (8,695 (15.7%) vs 11,156 (16.4%), p=0.0005), Asian (2,592 (4.7%) vs 4,512 (6.6%), p<0.0001), and other minority populations. Non-Hispanic White showed no change (p=0.1902). Additionally, there was a reduction in the proportion of patients with private insurance (43,940 (79.3%) vs 51,104 (75.2%), p<0.0001) and an increase in patients with Medicaid (5,893 (10.6%) vs 10,694 (15.7%), p<0.0001). Interestingly, there was a significant increase in hormone positive disease (35,142 (63.4%) vs 49,409 (72.7%), p<0.0001), while no change in hormone negative disease. In New group, the influence of race is evident in the observed variations in OS (Table). Finally, patients with Medicaid or without insurance exhibited a diminished OS compared to those with private insurance, and a lower median income was associated with a negative impact on OS. Conclusions: For YBC patients, the proportion of underrepresented and underserved population is increasing. There is an increasing rate of hormone positive disease. This can cause substantial personal and societal implications, such as family planning and early menopause. Therefore, awareness of these at-risk populations is important for early identification of breast cancer and mitigation of poorer outcomes. [Table: see text]
Ethnicity and health insurance disparities in rectal carcinoma.
Authors: Sankhe Rachel , Cholankeril Michelle , Salinas Flavio Eduardo , Smith Keia
Published: May 2024

e13732

Background: Ethnicity and insurance coverage affect healthcare delivery in rectal carcinoma (RC). RC pts (pts) with Medicaid or no insurance are more likely to present with distant stage RC compared to Medicare/private insurance pts, and have a worse prognosis even when stage is accounted for. To combat such issues, federal law requires that non-profit hospitals, which make up 58% of all community hospitals, to provide charity care, or financial assistance, to those eligible. As insurance status, ethnicity and race have been found to independently affect colon cancer care, we expect similar results for RC in our limited but diverse cohort. Methods: Trinitas Medical Center RWJBH is an urban, community hospital that predominantly treats a minority population and provides financial assistance to eligible underinsured pts. Due to this assistance, or Charity Care, we can provide access to cancer care for many who would not ordinarily have such means. With institutional IRB approval, we completed a retrospective chart review of 59 pts diagnosed with Stage I-IV RC from 2017-2023. We assessed ethnicity, insurance carriers and treatment choices. Results: We reviewed 59 pts with the following ethnic distribution: 22 Hispanic (H), 21 White (W), 11 Black (B) and 5 Asian (A) pts. The median age at diagnosis with RC was 57 in H, 64 in B, 71 in W and 71 in A pts. B pts were found to be diagnosed with more advanced disease: 36% at Stage III and 45% at Stage IV, with none diagnosed at Stage I or II. H pts had comparatively fewer distant stage diagnoses (23% at Stage III, 18% at Stage IV). Neoadjuvant chemotherapy and radiation therapy to 20 of 59 pts treated at our center, 15 of whom subsequently received surgery. Four of five of these declined surgical intervention post neoadjuvant therapy. H pts had the following primary insurance carriers: 36% Medicaid, 36% Medicare, 27% Charity care. 62% of W pts had Medicare and 14% Medicaid. 27% had B pts had Medicare, 27% Medicaid and 9% had Charity care. 50% of the 59 pts had Charity care, with most pts in this group being H. Conclusions: Research suggests that immigrants utilize healthcare facilities less than U.S. citizens and programs like Charity care may be underutilized. In our RC cohort, 38 of 59 (64%) pts were racial minorities, of these 50% received Charity care. Most did not receive screening prior to a diagnosis of rectal cancer and many applied for Charity Care only after their diagnosis. Despite offering significant financial assistance to our pts, we suggest education to immigrants regarding insurance coverage, broader screening efforts and the ability to offer improved subspecialty care to RC pts. In particular, we look to target B and H who present at younger ages and are not Medicare eligible. We believe this will lead to earlier staging of RC, which should lead to improved survival for minority pts.
Disparities in patients with HER2-positive breast cancer receiving optimal treatment: Analysis of the real-world ASCO CancerLinQ dataset.
Authors: Kantor Olga , Jones Alyssa N , Mayer Erica L. , Chavez-MacGregor Mariana , King Tari A. , Mittendorf Elizabeth A.
Published: May 2024

e13739

Background: Racial/ethnic disparities in locoregional second breast cancer events (SBCE) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) are not well defined. We examined rates of SBCE and overall survival (OS) by race and ethnicity in the ASCO CancerLinQ Discovery (CLQD) real-world dataset in HER+ BC pts receiving optimal and not-optimal treatment. Methods: CLQD was used to identify pts undergoing surgery for stage I-III HER2+ BC from 2005-2022. Race/ethnicity were self-reported. Optimal treatment was defined as HER2-directed therapy for stage II-III HER2+ BC starting in 2008, adjuvant endocrine therapy for hormone-receptor positive (HR+) HER2+ BC, radiation after lumpectomy, and regional nodal irradiation for N2-N3 disease. The primary endpoint was SBCE defined as a second event in the ipsilateral or contralateral breast or axilla, with OS as a secondary endpoint. Kaplan-Meier analysis was used to estimate SBCE-free survival and OS. Results: Of 8,795 stage I-III HER2+ BC pts, 5,487 (62.4%) were Non-Hispanic White (NHW), 1,083 (12.3%) Non-Hispanic Black (NHB), 418 (4.7%) Hispanic, 323 (3.7%) Asian or Pacific Islander (API), and 1,484 (16.9%) other/unknown. Overall, 39.2% had HR-HER2+ and 60.7% had HR+HER2- BC. NHW pts were the most likely to present with stage I disease (40.2% vs 31.9%, 29.0%, and 30.3% of NHB, Hispanic, and API pts, respectively, p<0.01) and less likely to be age <50 at diagnosis (26.1% vs 32.3%, 41.0%, and 36.6% in NHB, Hispanic, and API, p<0.01). Overall, 54.2% of HER2+ BC pts received optimal treatment: 54.1%, 60.2%, 60.5%, and 58.8% of NHW, NHB, Hispanic, and API pts (p<0.01). Neoadjuvant HER2-therapy was given in 42.4%, 46.3%, 53.8%, and 51.2% of NHW, NHB, Hispanic, and API pts (p<0.01) and endocrine therapy in 64.7%, 56.8%, 59.3%, and 54.7%, respectively (p<0.01). 5-yr SBCE-free survival and OS are shown (Table). SBCE-free survival was not statistically different by race and ethnicity in optimally or non-optimally treated pts. Optimal treatment increased OS by 4.1% and 0.9% in NHW and NHB pts with HR-HER2+ BC and 2.4% and 8.9% in NHW and NHB pts with HR+HER2+ BC. Conclusions: Differences in OS, but not SBCE, were seen by race/ethnicity in HER2+ BC. OS differences were not completely mitigated by receipt of optimal treatment. [Table: see text]
Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.
Authors: Ibraheem Abiola Falilat , Gadi VK , Hoskins Kent , Chaudhry Amina
Published: May 2024

TPS616

Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive >85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) > 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if >25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]
LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
Authors: Ramirez Pedro T. , Robledo Kristy P. , Frumovitz Michael , Pareja Rene , Ribeiro Reitan , Lopez Aldo , Yan Xiaojian , Isla David , Moretti Renato , Bernardini Marcus Q. , Gebski Val , Asher Rebecca , Behan Vanessa , Coleman Robert L. , Obermair Andreas
Published: May 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of –11.1; 95% CI, –15.8 to –6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.
Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology
Authors: Vince Carolina Sgarioni Camargo , Brassesco Maria Sol , Mançano Bruna Minniti , Gregianin Lauro Jose , Carbone Edna Kakitani , do Amaral e Castro Adham , Dwan Viviane Sayuri Yamachira , Menezes da Silva Roberta Zeppini , Mariano Cassia Silvestre , da Mata Juliana França , Silva Marcelo Oliveira , Caran Eliana Maria Monteiro , Macedo Carla Donato , Alves da Costa Gildene , Esteves Tereza Cristina , Silva Luciana Nunes , Ferman Sima Esther , Martins Flavia Delgado , Cristófani Lilian Maria , Odone-Filho Vicente , Silva Marcelo Milone , Reis Rui Manuel , Pianovski Mara Albonei Dudeque , Campregher Paulo Vidal , Kunii Mayara Satsuki , de Sá Rodrigues Karla Emilia , Carvalho Filho Neviçolino Pereira , Valera Elvis Terci ,   The Brazilian Committee of Precision Medicine in Pediatric Oncology (BC-PMPO)—the Brazilian Society of Pediatric Oncology (SOBOPE)
Published: May 2024

PURPOSE

Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)–fused tumors, emphasizing access, responses, side effects, and outcomes.

PATIENTS AND METHODS

Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness.

RESULTS

Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause.

CONCLUSION

This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.
Post-extraction Possibility: Genre and Landscape in George Eliot's The Mill on the Floss
Authors: Rose Kristin
Published: May 2024

Set in an era of increasing global extraction, George Eliot's The Mill on the Floss (1860) explores the coproductive relationship between humanity and nature in Victorian fiction. Victorian texts frequently depicted mines and quarries as dystopic sites of environmental exhaustion and human suffering. However, The Mill on the Floss centers an exhausted quarry, called “the Red Deeps,” to imagine utopic alternatives to environmental and human ruin. In Eliot's experimental bildungsroman, Maggie Tulliver's coming of age is doubled with and embedded in the Red Deeps’ vibrantly regenerating landscape. Though Eliot's novel famously ends with a tragic flood, Maggie and Phillip Wakem's mid-novel meetings in the Red Deeps entwine feminist and environmental possibility into a narrative arc that looks beyond the spatiotemporal limits of its immediate ending. The result is a mutually open-ended sense of futurity for post-extraction sites and their inhabitants. At the dawn of the Anthropocene, Eliot's redevelopmental bildungsroman counters the capitalist fantasy of endless, extractive progress.
Murat Kaş. İrade ve Özgürlük Eylem ve Değer: Mukaddimât-ı Erbaa Tartışmaları Kavram-Problem-Argüman-Yaklaşım Haritası. Ankara: Sonçağ Akademi Yayınları, 2023. 195 sayfa. ISBN: 9786256569010
Authors: Bilgin Tiryaki Kübra
Published: May 2024

BOOK REVIEW
Murat Kaş. İrade ve Özgürlük Eylem ve Değer: Mukaddimât-ı Erbaa Tartışmaları Kavram-Problem-Argüman-Yaklaşım Haritası. Ankara: Sonçağ Akademi Yayınları, 2023. 195 sayfa. ISBN: 9786256569010
Public value
Authors: Τσαγδή Γεωργία
Published: May 2024

Η θεωρία της δημόσιας αξίας, που θεωρείται ως μία από τις πιο καθοριστικές θεωρίες, έχει τύχει αδιάλειπτης προσοχής από τους ακαδημαϊκούς επί τέσσερις δεκαετίες. Ωστόσο, παρά την επιστημονική συζήτηση, η πρακτική εφαρμογή και η εμπειρική κατανόηση της δημόσιας αξίας παραμένει γεμάτη προκλήσεις. Η παρούσα διατριβή διερευνά την έννοια της δημόσιας αξίας στο πλαίσιο της σχέσης υπουργείο- (εποπτευόμενος) φορέας, δίνοντας έμφαση στο ρόλο που διαδραματίζουν η εμπιστοσύνη, η ηγεσία, οι εμπορευματοποιητικές, συνεργατικές και διοικητικές καινοτομίες στη δημιουργία της. H επιρροή αυτών των παραγόντων στη δημιουργία δημόσιας αξίας εξετάζεται κριτικά μέσω της εμπειρικής ανάλυσης, αντιμετωπίζοντας σημαντικά κενά που υπαρχουν στη σημερινή έρευνα. Χρησιμοποιώντας δομημένα ερωτηματολόγια σε ένα δείγμα 7 υπουργείων, 150 εποπτευόμενων οργανισμών και 300 πολιτών, η παρούσα μελέτη αποκαλύπτει τη θετική επίδραση της ηγεσίας εξιδανικευμένης επιρροής και της συνεργατικής διακυβέρνησης στη δημιουργία δημόσιας αξίας, σε αντιπαράθεση με τις αρνητικές επιπτώσεις που έχουν πρακτικές προσανατολισμένες στην αγορά. Το εύρημα αυτό αμφισβητεί κριτικά την αποτελεσματικότητα του δόγματος τoυ Νέου Δημόσιου Μάνατζμεντ, υποδηλώνοντας ότι η μεταφορά στρατηγικών του ιδιωτικού τομέα στο δημόσιο τομέα συχνά υπονομεύει τη δημόσια αξία που παράγεται. Η τρέχουσα διατριβή διερευνά επίσης, τo αυξανόμενο φαινόμενο της δημιουργίας ημιαυτόνομων οργανισμών που εποπτεύονται από τα "καθ' ύλην" υπουργεία (agencification), εξετάζοντας τις επιπτώσεις του στη δημιουργία δημόσιας αξίας, υπό το πρίσμα της θεωρίας της κηδεμονίας. Η προοπτική αυτή προσφέρει μια νέα οπτική για τη δυναμική (σχέση) εμπιστοσύνης μεταξύ υπουργείων και οργανισμών τους, τονίζοντας πώς η εμπιστοσύνη των υπουργείων ενισχύει τον θετικό αντίκτυπο της ηγεσίας των φορέων αυτών στη δημόσια αξία που παράγεται. Η συμβολή της έρευνας μας έγκειται στην ανάπτυξη ενός ευέλικτου δομικού πλαισίου που μπορεί να εφαρμοστεί σε διάφορες περιπτώσεις. Η ανάλυσή μας επίσης υπερκεράζει τις συμβατικές έρευνες ικανοποίησης πελατών και συμπεριλαμβάνει τις απόψεις άτομων που δεν λαμβάνουν υπηρεσίες. Αυτή η διευρυμένη προσέγγιση ενσωματώνει τη θεμελιώδη αρχή της θεωρίας της δημόσιας αξίας, η οποία δίνει έμφαση στην εξυπηρέτηση των συλλογικών αναγκών των πολιτών έναντι της απλής ικανοποίησης των ατομικών επιθυμιών των πελατών ή των χρηστών υπηρεσιών. Η παρούσα διατριβή παρέχει ουσιαστικές προτάσεις προς τους υπεύθυνους χάραξης πολιτικής, τους δημόσιους μάνατζερς και τους ακαδημαϊκούς ερευνητές, οδηγώντας την θεωρία της δημόσιας αξίας σε μια πιο συνεργατική προσέγγιση.
COVID-19 in the Arab countries: Three-year study
Authors: Alwahaibi Nasar , Al Maskari Muna , Al-Jaaidi Samiya , Al Dhahli Buthaina , Al Issaei Halima , Al Bahlani Shadia
Published: May 2024

Background

Twenty-two Arab countries share a common language, history, and culture. Nevertheless, governmental policies, healthcare systems, and resources differ from one Arab country to another. We have been following Coronavirus (COVID-19) from the beginning in each Arab country. In the present study, we aimed to assess the prevalence of COVID-19 in the Arab world and to compare these findings with other significantly affected countries.

Methods

Websites of the World Health Organization, World COVID-vaccinations tracker, Worldometer, and Ministries of Health were used to extract COVID-19 data in all Arab countries between the period January 2020 to December 2022.

Results

All Arab countries had 14,218,042 total confirmed COVID-19 cases, 13,384,924 total recovered cases and 173,544 total related deaths. The trend demonstrated that the third quarter of 2021 recorded the highest death toll and the first quarter of 2022 recorded the highest number of confirmed and recovered cases. Compared to the top 15 affected countries, the Arab world ranked last as it had the lowest overall incidence per million population (PMP) of 31,609. The data on total deaths PMP showed that India had the lowest number of deaths with only 377 cases followed by the Arab world with 386 cases.

Conclusions

Although the number of confirmed, death, and recovered cases of COVID-19 have greatly reduced in the last quarter of 2022 in most Arab countries, many Arab countries still need to re-campaign about COVID-19 vaccines and raise awareness programs about boosters. COVID-19 has had a relatively smaller impact on Arab countries than on other countries that have been significantly affected.
Underground hydrogen storage: The techno-economic perspective
Authors: Gianni Eleni , Tyrologou Pavlos , Couto Nazaré , Carneiro Júlio Ferreira , Scholtzová Eva , Koukouzas Nikolaos
Published: May 2024

The changes in the energy sector after the Paris agreement and the establishment of the Green Deal, pressed the governments to embrace new measures to reduce greenhouse gas emissions. Among them, is the replacement of fossil fuels by renewable energy sources or carbon-neutral alternative means, such as green hydrogen. As the European Commission approved green hydrogen as a clean fuel, the interest in investments and dedicated action plans related to its production and storage has significantly increased. Hydrogen storage is feasible in aboveground infrastructures as well as in underground constructions. Proper geological environments for underground hydrogen storage are porous media and rock cavities. Porous media are classified into depleted hydrocarbon reservoirs and aquifers, while rock cavities are subdivided into hard rock caverns, salt caverns, and abandoned mines. Depending on the storage option, various technological requirements are mandatory, influencing the required capital cost. Although the selection of the optimum storage technology is site depending, the techno-economical appraisal of the available underground storage options featured the porous media as the most economically attractive option. Depleted hydrocarbon reservoirs were of high interest as site characterisation and cavern mining are omitted due to pre-existing infrastructure, followed by aquifers, where hydrogen storage requires a much simpler construction. Research on data analytics and machine learning tools will open avenues for consolidated knowledge of geological storage technologies.
Deficiency of thiamine and Wernicke-Korsakoff syndrome – review of pathophysiology, clinical presentation , diagnostics and treatment
Authors: Zdunek Roksana , Strus Karolina , Madera Magdalena , Dąbrowska Natalia , Mazur Sylwia , Mazur Agata , Bizan Aleksy , Nagórska Emilia , Marcinkowski Krzysztof , Kublińska Aleksandra
Published: May 2024

Introduction and aim of the study: Thiamine is a water-soluble vitamine, which bioactive form is necessary for energy metabolism in all cells. Deficiency of thiamine may be caused by malnutrition, alcoholism and certain diseases and it leads to an acute neuropsychiatric disorder called Wernicke encephalopathy. Untreated patients can develop a residual syndrome called Korsakoff syndrome. The aim of our study is to present current knowledge of history, pathophysiology, causes, symptoms and treatment of vitamine B1 depletion and Wernicke-Korsakoff’s syndrome.
Material and methods: Our review is based on the analysis of materials collected in „Pubmed”, „Google Scholar” and other scientific articles using keywords: „thiamine”, „thiamine deficiency”, „Wernicke encephalopathy”, „Korsakoff syndrome”.
Conclusions: Despite numerous studies, Wernicke encephalopathy is still difficult to diagnose. Attention should be paid to the possibility of vitamin B1 deficiency in people who are at risk of it like alcoholics, malnourished or psychiatric patients. Wernicke encephalopathy is an acute neuropsychiatric disorder so the treatment should be started as soon as possible to reduce the risk of developing Korsakoff syndrome.
Garlic (Allium sativum L.): A review of varied health benefits
Authors: Popławska Natalia Aleksandra , Śliz Justyna , Skorupska Marta , Czeczotka Magdalena Joanna , Woźniak Krzysztof
Published: May 2024

Introduction:  
Garlic (Allium sativum L.), has been cultivated in various countries and is valued for its medicinal and culinary properties. It contains bioactive compounds such as phenolic compounds, organic sulfides, polysaccharides, and saponins, with allicin being a particularly studied compound. These compounds have been shown to possess antioxidant, antimicrobial, antiviral, anticancer, anti-inflammatory, anti-hyperlipidemic and antihypertensive effects. Garlic has been used for over 5000 years as a curative plant and has potential applications in food science, medicine, and nutraceuticals. 
Aim of the Study:  
The aim of the study is to provide a comprehensive review of the overall impact of Allium sativum L. on human health and in order to draw attention to the benefits of regular consumption. 
Materials and methods: 
A comprehensive review of scientific and medical literature was conducted utilizing PubMed and Google Scholar databases. Searching terms were: garlic, Allium sativum L., garlic anti-inflammatory, garlic anticancer, garlic health effects.  
Conclusion:  
Allium sativum L. is associated with a comprehensive range of beneficial effects on the human body. These include anti-inflammatory and antioxidant properties, positive influence on lipid profile, cardiovascular system, and the anticancer activity among others by stimulation of tumor apoptosis. As a result, garlic and its bioactive compounds hold promise as functional foods or nutraceuticals for the prevention and treatment of various diseases.
The Zitelli bilobed flap for soft tissue coverage after mucoid cyst resection: a retrospective cohort study
Authors: Oh Sangho , Chung Jaein , Son Daegu
Published: May 2024

Purpose: Digital mucoid cysts are frequently found at the distal interphalangeal (DIP) joint in patients with degenerative osteoarthritis. In complicated cases, surgical treatment with mucoid cyst resection is considered, and soft tissue is covered with one of various local flap techniques. Among these, bilobed flaps are reliable and aesthetically favorable, with primary healing of the donor site. In this study, we investigated a case series of bilobed flaps for digital mucoid cysts.Methods: We retrospectively reviewed our electronic medical records and found 26 digital mucoid cysts treated with bilobed flaps at our facility between July 2022 and February 2024. We extracted data from the records of these patients on sex; age; time to surgery; clinical findings including nail ridging, the presence of osteophytes, cyst size and location, and additional procedures (arthrodesis); and follow-up data including the occurrence of complications, such as delayed wound healing, infection, stiffness, and recurrence.Results: Among the 26 patients in our sample, 19 were female and seven were male. The average age was 62.2 years, and the average time to surgery was 10.8 months. Preoperatively, the average cyst measured 6.9×8.3 mm. Nail ridging was found in 19 patients (73.1%) and osteophytes in 22 patients (84.6%). The most commonly affected digit was the middle finger, which accounted for 10 cases (38.5%). All the flaps totally survived, without major complications.Conclusion: Based on our series, a bilobed flap for soft tissue coverage after mucoid cyst excision can achieve high-quality surgical results.
Instituciones del derecho procesal administrativo en la obra de Carlos Betancur Jaramillo
Authors: Calle López Jorge Humberto
Published: May 2024

En este artículo nos proponemos, a partir de su obra escrita, sus libros y sus sentencias, evidenciar cómo a partir del ejercicio de pensar bien, compartir generosamente el fruto de su esfuerzo y lograr comunicar con las palabras precisas, ni una menos, ni una más, se puede obtener el sentido de justicia que cada caso requiere para ser resuelto.
Segundo centenario del Consejo de Estado, “doble dualidad” y un solo rol: el control
Authors: Sánchez Luque Guillermo
Published: May 2024

Este artículo está basado en una charla dictada en 2017 en la École nationale d'administration (ENA) de París, en el marco del seminario realizado con ocasión de la celebración del bicentenario de la creación del Consejo de Estado de Colombia (France/Colombie: un dialogue entre systèmes juridiques). Agradezco muy especialmente a mis colegas Gabriel de Vega Pinzón, Santiago Zuleta, Juan Felipe Baene, Perla Molina, Margarita Forero, Diego Rueda, Andrea López, Carlos Colmenares y Paola Páez por su invaluable colaboración en la búsqueda y consulta de algunas de las fuentes bibliográficas que apoyan este documento, lo mismo que a Carolina Moyano y a Ingrid Viasús por sus observaciones a este texto.
Patients with a rheumatological diagnosis in a psychiatrist's office - neuropsychiatric lupus
Authors: Szarpak Julita , Tomasik Justyna , Stanicki Paweł , Kasprzak Karol , Morylowska-Topolska Justyna
Published: May 2024

Introduction: Systemic lupus erythematosus is an autoimmune disease affecting up to 210 per 100,000 people in Europe, more often among women. The inflammatory process in lupus causes changes in various organs. However, somatic changes are not the only effects of lupus. The neuropsychiatric manifestations of this disease have been given a separate name – neuropsychiatric lupus.
Material and methods: A review of the literature available on the PubMed platform in the period of 1987-2023 was performed using the key words: neuropsychiatric systemic lupus erythematosus, mental disorders, mood disorders, sleep disorders, systemic lupus erythematosus. Original studies, review works, meta-analyses and Internet sources were analyzed.
Results: Psychotic disorders in lupus occur with a frequency of up to 3%. Risk factors include young age, male gender and glucocorticoids treatment. Mood disorders occur in several to several dozen percent of lupus patients, including depression affecting up to ⅓ of patients. Belimumab, psychotherapy and improving the quality of sleep, the disturbance of which is observed in most patients with lupus, have potential in treatment. Anxiety disorders are seen primarily in the teenage age group, where social phobia predominates – the fear of rejection due to the disease – and they worsen and are exacerbated by rheumatic disease. Cognitive dysfunctions occur in up to 80% of lupus patients. They are probably related to enzymes of metabolic pathways, dyslipidemia and thyroid dysfunction.
Conclusions: Mental disorders develop more often in patients with lupus than in the general population and they predispose to autoimmune diseases. Comprehensive diagnosis and psychiatric care of patients with lupus are necessary.

Keywords: systemic lupus erythematosus, sleep disorders, mood disorders, neuropsychiatric systemic lupus erythematosus, mental disorders
Measure to improve: a pilot study of Birthrate Plus in the Netherlands
Authors: Cronie Doug John , Rosman Ageeth , de Vries Raymond
Published: May 2024

Background/Aims

Evidence-based standards are an important means for ensuring safe and effective care for birthing women. The provision of one-to-one care for women in labour is one such standard, which should be the norm in Dutch maternity care. However, no audit measures of this standard are available. This study examined the use of Birthrate Plus, a validated instrument for the measurement of patient acuity. This tool has the added benefit of allowing measurement of birth characteristics in relation to staffing numbers, providing a basis for auditing the standard of one-to-one care for women in labour in hospitals in the Netherlands.

Methods

This pilot study used the Birthrate Plus tool to retrospectively examine birth characteristics and staffing levels in a 4-month period, in five hospitals in the Netherlands.

Results

The review of 11 582 patient cases found that most births in the sample were classified as occurring in the higher acuity levels of Birthrate+ tool. Examination of staffing levels showed that when comparing actual staffing levels with recommended levels, hospitals had a shortfall of between 47% and 64%.

Conclusions

The Birthrate Plus tool could be useful in auditing staffing levels in Dutch maternity care. Analysis of the data provided by hospitals in the sample showed that none were able to meet the Dutch standard of providing consistent one-one-one care.