bluuebunny/crossref_metadata_2025_split huggingface dataset:
HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
Authors: Li Pu-Chun , Zhu Yi-Fan , Pan Jia-Ni , Zhu Qiao-Yan , Liao Yu-Yang , Ding Xiao-Wen , Zheng Lin-Feng , Cao Wen-Ming 
Published: April 2024

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation’s effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers ( p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64–1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61–1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.
Effect of a Legal Clinic Program Within an Urban Primary Health Care Center on Social Determinants of Health: A Program Evaluation
Authors: Agarwal Gina , Pirrie Melissa , Edwards Dan , Delleman Bethany , Crowe Sharon , Tye Hugh , Mallin Jayne 
Published: April 2024

Background: Individuals living in poverty often visit primary healthcare clinics for health problems stemming from unmet legal needs. We examined the impact of a medical-legal partnership on improving the social determinants of health (SDoH), health-related quality of life, and perceived health status of attendees of a Legal Clinic Program (LCP). Methods: This was a pre-post program evaluation of a weekly LCP established within an urban primary healthcare clinic to provide free legal consultation. Patients aged 18 years or older were either approached or referred to complete a screening tool to identify potential legal needs. Those identified with potential legal needs were offered an appointment with LCP lawyers who provided legal counsel, referrals, and services. For those who attended the LCP, changes in SDoH and health indicators were collected via a self-reported survey 6 months after they attended the LCP and compared to their baseline scores using paired t-tests, McNemar’s test for paired proportions, and the Wilcoxon Signed Rank Test for related samples. Results: During the 6-month evaluation period, 31 participants attended the LCP and completed both the baseline and 6-month surveys; 67.8% were female, 64.5% were white, 90.3% were not working full-time, and 61.3% had a household income of $700 to 1800 per month. At follow-up, 25.8% were receiving at least 1 new benefit and there was a statistically significant reduction in food insecurity (35.5% vs 9.7%, P < .05). Also, perceived health status using the visual analog scale (ranges from 0 to 100) significantly improved from 42.5 points (SD = 25.3) at baseline to 56.6 points (SD = 19.6) after 6 months ( P < .05). Conclusions: The LCP has the potential to improve the health and wellbeing of patients in primary healthcare clinics by addressing unmet legal needs and SDoH.
Utility of Adult-Based Discoid Lateral Meniscus Diagnostic Criteria in a Pediatric Population
Authors: Beck Jennifer J. , Wahle Charlotte F. , Wood Anna , Bennett Abbie , Jackson Nicholas 
Published: April 2024

Background: Commonly cited discoid lateral meniscus (DLM) imaging definitions are based on adult magnetic resonance imaging (MRI) measurements. This pathology commonly presents in pediatric populations; however, whether accepted adult measurements reliably apply to children and adolescents is unknown. Purpose/Hypothesis: This purposes of the study were to determine (1) the utility of applying adult-accepted MRI definitions of DLM to pediatric patients, (2) whether sex differences affect the applicability of the criteria, and (3) whether MRI magnet strength and/or tear presence affect MRI measurements for diagnosing DLM in pediatric patients. It was hypothesized that MRI criteria for DLM would be similar in adults and pediatric patients. Study Design: Case series; Level of evidence, 4. Methods: A total of 100 consecutive MRIs from pediatric patients with DLM were evaluated, with 91 scans included. Two study authors independently reviewed the MRIs, evaluating meniscal height and width on sagittal and coronal images, “bow tie signs” on sagittal images, tibial sagittal and coronal width, and tear presence. For analysis, MRI magnet strength was dichotomized into high (>1.5 T) and low (<1.5 T) groups. Results: The mean age of the patients at MRI evaluation was 12.3 ± 3.4 years; 51% of the patients were male, and 56% of the scans were of left knees. Included patients with DLM showed a mean of 3.68 bow tie signs, a sagittal total anterior to posterior meniscal width/tibial width ratio of 73%, a coronal meniscal width/tibial width ratio of 30%, and a coronal, transverse width of the lateral meniscus at the midportion of the meniscal body of 20.6 ± 7.7 mm. The MRI tesla strength of the images included in this study ranged from 0.3 to 3. It was determined that high- versus low-resolution MRI scans did not affect the inter- or intraobserver reliability of the MRI measurments ( P > .05). However, several measurements showed improved intraclass correlation coefficients with increased tesla strength. Conclusion: This study confirms that pediatric patients with DLM, diagnosed by board-certified pediatric sports medicine orthopaedic surgeons, have measurements on MRI consistent with adult DLM diagnostic criteria. This finding held true regardless of sex or MRI tesla strength. Pediatric patients with DLM had >3 bow tie signs, >70% sagittal tibial plateau coverage, >14 mm coronal width, and >20% coronal tibial plateau coverage on MRI.
Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study
Authors: Buus Sine Mette Øgendahl , Behrndtz Anne Brink , Schmitz Marie Louise , Hedegaard Jakob Nebeling , Cordsen Pia , Johnsen Søren Paaske , Phan Thanh , Andersen Grethe , Simonsen Claus Ziegler 
Published: April 2024

Introduction: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. Patients and methods: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. Results: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%–18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5–17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7–19.4). Discussion and conclusion: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.
Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies
Authors: McCabe John J , Walsh Cathal , Gorey Sarah , Harris Katie , Hervella Pablo , Iglesias-Rey Ramon , Jern Christina , Li Linxin , Miyamoto Nobukazu , Montaner Joan , Pedersen Annie , Purroy Francisco , Rothwell Peter M , Sudlow Catherine , Ueno Yuji , Vicente-Pascual Mikel , Whiteley William , Woodward Mark , Kelly Peter J 
Published: April 2024

Introduction: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear. Materials and Methods: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event. Results: Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17–1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06–1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03–1.39), but not after adjustment (RR 1.11, 95% CI 0.94–1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16–1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82–1.18) ( Pinteraction = 0.01). Similar associations were observed for recurrent stroke. Discussion and Conclusion: Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.
Longitudinal Assessment of Emergency Responders’ Attitudes Toward People Who Overdose and Naloxone Following an Overdose Education Training
Authors: Phillips Sarah , Budesa Zach , Smith Ryan , Wood Claire , Winograd Rachel 
Published: April 2024

Background: In addition to teaching overdose recognition and response, overdose education and naloxone distribution (OEND) trainings for emergency responders aim to improve trainee attitudes toward people who use drugs and toward naloxone. This study examines the training effectiveness long term, as well as the extent to which improvements are dependent on profession type or recent experience administering naloxone. Methods: A total of 774 emergency responders, consisting of law enforcement officers (LEOs) (n = 624, 81%) and emergency medical service (EMS) personnel (n = 150, 19%), attended OEND trainings and completed surveys immediately prior to (“pre”) and following (“post”) the training, as well as 6 months later (“follow-up”). Survey items assessed attitudes toward people who have overdosed, naloxone-related risk compensation (ie, “enabling”) beliefs, and whether participants had administered naloxone since attending the training. Multiple regression and estimated marginal means were used to evaluate changes in scores. Results: Emergency responders showed improved attitudes (pre = 2.60, follow-up = 2.45, P < .001) and risk compensation beliefs (pre = 2.97, follow-up = 2.67, P < .001) 6 months following the training. Follow-up scores differed by profession, with LEOs endorsing worse attitudes (difference = 0.55, P = .013) and more risk compensation beliefs (difference = 0.67, P = .014) than EMS. In addition, having recently administered naloxone predicted more negative attitudes (EMS: difference = 0.55, P = .01; LEO: difference = 0.54, P = .004) and risk compensation beliefs (EMS = 0.73, P = .006; LEO = 0.69, P = .002) at follow-up. Conclusion: Six months after an OEND training, emergency responders’ attitudes toward people who overdose, and their risk compensation beliefs remained improved. However, LEOs had more negative follow-up attitudes and beliefs compared to EMS. Emergency responders who had administered naloxone had worse attitudes and beliefs at follow-up than those who had not. Of note, our sample evidenced sizable attrition between pre and follow-up assessments, leaving room for selection bias. Future studies should investigate how to mitigate negative effects of administering naloxone on attitudes toward those who overdose, and belief that naloxone is “enabling.”
What clinicians should know about surrogate end points in hematologic malignancies
Authors: Bommier Côme , Maurer Matthew John , Lambert Jerome 
Published: April 2024

Abstract
Use of surrogates as primary end points is commonplace in hematology/oncology clinical trials. As opposed to prognostic markers, surrogates are end points that can be measured early and yet can still capture the full effect of treatment, because it would be captured by the true outcome (eg, overall survival). We discuss the level of evidence of the most commonly used end points in hematology and share recommendations on how to apply and evaluate surrogate end points in research and clinical practice. Based on the statistical literature, this clinician-friendly review intends to build a bridge between clinicians and surrogacy specialists.
Dual role of signaling pathways in myeloma requires cell type–specific targeting of ligand-receptor interactions
Authors: Hernandez-Lopez Pablo , Vijaykumar Tushara , Anand Praveen , Auclair Daniel , Frede Julia , Knoechel Birgit , Lohr Jens G. 
Published: April 2024

Abstract
Although most patients with multiple myeloma respond to treatment initially, therapy resistance develops almost invariably, and only a subset of patients show durable responses to immunomodulatory therapies. Although the immune microenvironment has been extensively studied in patients with myeloma, its composition is currently not used as prognostic markers in clinical routine. We hypothesized that the outcome of immune signaling pathway engagement can be highly variable, depending on which 2 cellular populations participate in this interaction. This would have important prognostic and therapeutic implications, suggesting that it is crucial for immune pathways to be targeted in a specific cellular context. To test this hypothesis, we investigated a cohort of 25 patients with newly diagnosed multiple myeloma. We examined the complex regulatory networks within the immune compartment and their impact on disease progression. Analysis of immune cell composition and expression profiles revealed significant differences in the B-cell compartment associated with treatment response. Transcriptional states in patients with short time to progression demonstrated an enrichment of pathways promoting B-cell differentiation and inflammatory responses, which may indicate immune dysfunction. Importantly, the analysis of molecular interactions within the immune microenvironment highlights the dual role of signaling pathways, which can either be associated with good or poor prognosis depending on the cell types involved. Our findings therefore argue that therapeutic strategies targeting ligand-receptor interactions should take into consideration the composition of the microenvironment and the specific cell types involved in molecular interactions.
Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival
Authors: Shimony Shai , Keating Julia , Fay Christopher J. , Luskin Marlise R. , Neuberg Donna S. , LeBoeuf Nicole R. , Lane Andrew A. 
Published: April 2024

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) can involve skin, bone marrow (BM), central nervous system (CNS), and non-CNS extramedullary sites. Preclinical models demonstrated clonal advantage of TET2-mutated plasmacytoid dendritic cells exposed to UV radiation. However, whether sun exposure, disease characteristics, and patient survival are clinically related is unclear. We classified organ involvement in 66 patients at diagnosis as skin only (n = 19), systemic plus skin (n = 33), or systemic only (n = 14). BM involvement was absent, microscopic (&lt;5%), or overt (≥5%). UV exposure was based on clinical and demographic data. Patients with skin only BPDCN were more frequently aged ≥75 years (47% vs 19%; P = .032) and had lower rates of complex karyotype (0 vs 32%, P = .022) and mutated NRAS (0 vs 29%, P = .044). Conversely, those without skin involvement had lower UV exposure (23% vs 59%, P = .03) and fewer TET2 mutations (33% vs 72%, P = .051). The median overall survival (OS) was 23.5, 20.4, and 17.5 months for skin only, systemic plus skin, and systemic only, respectively. Patients with no BM involvement had better OS vs overt involvement (median OS, 27.3 vs 15.0 months; P = .033) and comparable with microscopic involvement (27.3 vs 23.5 months; P = .6). Overt BM involvement remained significant for OS when adjusted for baseline characteristics and treatment received. In summary, BPDCN clinical characteristics are associated with disease genetics and survival, which together may impact prognosis and indicate informative disease subtypes for future research.
Unmet need in pulmonary hypertension-associated interstitial lung disease (PH-ILD): a clinician survey of real-world management of PH-ILD in Europe
Authors: Montani David , Cifrián José M. , Rojo Raquel P. , Nunes Hilario , Meloni Federica , Ghio Stefano , Cannon John , Günther Andreas , Gálvez García Héctor , Delgado Míriam Fernández , Jeanneret Gabriela Silvina Bacchini , Howard Luke 
Published: April 2024

BackgroundWith no approved therapies for pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD) in Europe, we surveyed clinician perceptions on PH-ILD management and unmet need to understand current real-world practices.MethodsAn online clinician survey on PH-ILD management was conducted in France, Germany, Italy, Spain and the UK.Results55 clinicians (78% pulmonologists), each managing a median 20 PH-ILD patients (interquartile range (IQR) 10–50), participated. Upon PH suspicion, clinicians referred a median 50% (IQR 20–73%) of patients for echocardiography alone and 35% (IQR 20–78%) for echocardiography, followed by right heart catheterisation. Upon diagnosis, a median 20% (IQR 9–30%), 40% (IQR 20–50%) and 35% (IQR 20–55%) of patients fell under the pulmonary arterial pressure ranges of 21–24 mmHg, 25–34 mmHg and >35 mmHg, respectively. 50% of patients received off-label treatment for their PH and, of those, off-label phosphodiesterase-5 inhibitor (PDE-5i), endothelin receptor antagonist (ERA) and prostacyclin analogues were prescribed first-line by 78%, 9% and 7% of clinicians, respectively. Upon PDE-5i non-response, 35% of clinicians proceed with an ERA, 35% with no further therapy. 55% of clinicians used dual-therapy. Yearly median inpatient admissions and emergency visits were 2.0 (IQR 1.3–2.9) and 1.5 (IQR 1.0–2.0), respectively (n=31 responses). Most clinicians (69%) highlighted lack of efficacy or evidence for current therapies as a key gap in PH-ILD management.ConclusionsThis study gives insight into real-world European PH-ILD diagnosis and management. With significant use of off-label treatment, there is a large unmet need due to lack of approved therapies. Despite updated guidelines, more evidence is needed to standardise PH-ILD management.
Diagnostic accuracy, feasibility and acceptability of stool-based testing for childhood tuberculosis
Authors: Yenew Bazezew , de Haas Petra , Babo Yohannes , Diriba Getu , Sherefdin Bihil , Bedru Ahmed , Tegegn Ben , Gudina Tilaye , Getahun Tadesse , Abdella Saro , Jerene Degu , Klinkenberg Eveline , Tiemersma Edine ,   the ASTTIE study group
Published: April 2024

BackgroundChildhood tuberculosis (TB) diagnosis remains challenging, partly because children cannot provide sputum. This study evaluated the diagnostic accuracy of the Simple One-Step (SOS) stool method with Xpert MTB/RIF Ultra (Xpert-Ultra) for childhood TB compared to culture and Xpert-Ultra on a respiratory sample (RS) and clinical diagnosis. It also assessed the feasibility and acceptability of stool testing according to laboratory staff, and caregivers’ sample preference.MethodsWe enrolled children (≤10 years) with presumptive pulmonary tuberculosis in Ethiopia. RS was tested using Xpert-Ultra and culture; stool samples were tested using the SOS stool method with Xpert-Ultra. Laboratory staff and caregivers’ opinions were assessed using standardised questionnaires.ResultsOf the 898 children enrolled, 792, 832 and 794 were included for assessing the diagnostic accuracy of SOS stool with Xpert-Ultra against culture, RS Xpert-Ultra and clinical diagnosis, respectively, yielding sensitivity estimates for SOS stool with Xpert-Ultra of 69.1% (95% confidence interval (CI) 56.0–79.7%), 76.8% (95% CI 64.2–85.9%) and 59.0% (95% CI 47.9–69.2%), respectively. The specificity was ≥98.8% for all comparisons. The rate of non-determinate test results was 2.8% after one repeat test. According to laboratory staff, stool collection was feasible and acceptable and the SOS stool method was easy to perform. Most caregivers (75%) preferred stool for TB diagnosis over RS.ConclusionThis study shows that SOS stool Xpert-Ultra testing offers a good alternative to RS testing for TB in children who cannot spontaneously produce a sputum sample and would otherwise need to undergo invasive procedures to obtain RS for diagnosis.