bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Role of Ultrasound in Prostate Cancer trial – phase 1: Early experience of micro-ultrasound in the United Kingdom
Authors: Parker Pamela , Twiddy Maureen , Rigby Alan , Whybrow Paul , Simms Matthew 
Published: February 2024

Purpose: The purpose of this study was to evaluate if the use of micro-ultrasound can detect clinically significant prostate pathology when compared to histology obtained during a transperineal prostate biopsy. Methods: Patients suspected of having prostate cancer, who had a pre-biopsy magnetic resonance imaging and could tolerate a transrectal examination, were prospectively recruited. All patients had a micro-ultrasound scan prior to their biopsy. The findings of magnetic resonance imaging, micro-ultrasound and histology were risk stratified in accordance with local pathways. Comparison of assigned risk scores was made using histology as the reference standard. Results: Data from 101 patients were evaluated. Histology showed that clinically significant prostate cancer was detected in 48.5% ( n = 49/101) of patients. Moderate inter-rater agreement was found in both magnetic resonance imaging and micro-ultrasound with К of 0.31 in both modalities. High-risk findings were identified in 81% ( n = 82/101) patients at magnetic resonance imaging and in 66% ( n = 67/101) patients at micro-ultrasound. Sensitivity and specificity of magnetic resonance imaging were found to be 87% and 34.6% and for micro-ultrasound 73.3% and 53.8%, respectively. Conclusion: A limitation of this study was that the biopsy was not performed with micro-ultrasound which may have resulted in unidentified cancers and lowered the apparent accuracy of the technique. However, we conclude that while micro-ultrasound was diagnostic, magnetic resonance imaging demonstrated higher sensitivity in our local population and remains the pre-biopsy imaging modality of choice. However, the higher specificity of micro-ultrasound identified does indicate that it may be of value when magnetic resonance imaging is contraindicated. The role of micro-ultrasound, within an active surveillance pathway for prostate cancer, warrants further investigation.
The diagnostic journey of pulmonary arterial hypertension patients: results from a multinational real-world survey
Authors: Small Mark , Perchenet Loïc , Bennett Alex , Linder Jörg 
Published: February 2024

Background: Pulmonary arterial hypertension (PAH) is a life-threatening, progressive disease often diagnosed late in its course. Objectives: To present patient-reported data that were captured within a large, multinational, point-in-time survey of PAH-treating physicians and their patients to better understand the diagnostic journey. Design: Cross-sectional survey conducted in five European countries (EU5), Japan and the USA. Methods: PAH-treating pulmonologists, cardiologists, rheumatologists or internists (USA only) completed a patient record form (PRF) for the next four consecutive adult PAH patients they saw; these patients filled in a patient self-completion (PSC) form on an anonymous, voluntary basis. Our report focuses on patient data; data are from PSC forms unless stated otherwise. Results: Physician-reported PRFs and self-completed PSC forms were obtained for 1152 and 572 patients, respectively. Patients’ mean (SD) age was 59.1 (14.0) years, 55.6% were female, and 57.3% had idiopathic PAH. Patient-reported data showed an average delay of 17.0 months between symptom onset and PAH diagnosis. This is longer than physicians estimated (13.8 months): this disparity may be partly due to the time taken by patients to consult a physician about their symptoms [9.6 months overall, longest in the USA (15.3 months)]. Most patients (71.6%) initially consulted primary care physicians about their symptoms and 76.4% of patients were referred to a specialist. Misdiagnoses occurred in 40.9% of patients [most frequent in the USA (51.3%), least common in Japan (27.6%)] and they saw an average of 2.9 physicians overall (3.5 in EU5 versus 2.0 in Japan/USA) before being diagnosed. Diagnosis was most often made by cardiologists (50.4%) or pulmonologists (49.3%). Conclusion: Our data suggest that diagnostic delay in PAH results from patient- and physician-related factors, which differ across regions and include lack of awareness of PAH on both sides. Development of better screening strategies may help address this barrier to timely PAH diagnosis.
Evaluation of a Novel Equity-Focused Curriculum for Early-Stage Medical Students
Authors: Roper Karen L. , South Anna-Maria , Palmer Skyler , Johnson Julia , Sims Lillian , Hustedde Carol , Mangino Anthony A. 
Published: February 2024

OBJECTIVES Medical school curricula have increasingly incorporated topics and content related to health equity and affiliated social determinants of health. However, there is limited literature to guide how programs might measure the success of these initiatives. Previous studies assessed medical student attitudes and perceived knowledge, preparedness, and skills. Based on self-reported measures of these attributes, we compared within-group and between-group differences at the onset of a novel equity-focused curriculum implementation. METHODS A multi-component approach to “thread” lectures, panel discussions, and other content dedicated to health equity concepts was assessed using adapted versions of two validated survey instruments of the measured constructs. Baseline data were collected prior to coursework and at follow-up early in students’ second year assessed change attributable to the equity-focused curriculum thread, with additional comparison to a cohort of second-year students who had no exposure to the curriculum. Data were collected at the beginning of academic years 2021–2022 and 2022–2023. RESULTS The multivariate analysis of variance indicated significant change over time (p < 0.001) with the analyses of variance identifying students’ perceived current skills and topic knowledge increasing over time. No significant differences were found between two separate groups of M2 students. CONCLUSIONS Students’ perceived skills at working with diverse patient populations and knowledge of topics focused on health equity increased across the study, despite a much smaller response rate for the same student cohort at follow-up. Students’ perception that they are prepared to care for patients of diverse backgrounds was unaffected. Attitudinal assessment revealed a ceiling effect at baseline, which should be explored further with longitudinal assessment. For the ongoing effort to evaluate the success of equity-focused curricula and programs, this study contributes evidence of change on some but not all outcomes, and can help guide other programs in determining which outcomes best reflect areas of programmatic need and impact.
Drug classes affecting intracranial aneurysm risk: Genetic correlation and Mendelian randomization
Authors: Ruigrok Ynte M , Veldink Jan H , Bakker Mark K 
Published: February 2024

Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach. Patients and methods: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA ( N = 2140 cases), ASAH ( N = 5140) or the combined group, and liability to drug usage from 23 drug classes ( N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks. Results: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09–2.39, p = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07–2.65, p = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA. Conclusions: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.
Tumor mutational load is prognostic for progression to therapy among high-count monoclonal B-cell lymphocytosis
Authors: Kleinstern Geffen , Boddicker Nicholas J. , O’Brien Daniel R. , Allmer Cristine , Rabe Kari G. , Norman Aaron D. , Griffin Rosalie , Yan Huihuang , Ma Tao , Call Timothy G. , Bruins Laura , Brown Sochilt , Bonolo de Campos Cecilia , Hanson Curtis A. , Leis Jose F. , Ding Wei , Vachon Celine M. , Kay Neil E. , Oakes Christopher C. , Parker Alexander S. , Brander Danielle M. , Weinberg J. Brice , Furman Richard R. , Shanafelt Tait D. , Cerhan James R. , Parikh Sameer A. , Braggio Esteban , Slager Susan L. 
Published: February 2024

Abstract
High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.
Differences of ventilatory muscle recruitment and work of breathing in COPD and interstitial lung disease during exercise: a comprehensive evaluation
Authors: Ferreira Jeferson George , Iamonti Vinícius Carlos , Caleffi Pereira Mayra , Pletsch-Assunção Renata , Macchione Marcelo Ceneviva , Santana Pauliane Vieira , Cardenas Letícia Zumpano , Caruso Pedro , de Carvalho Carlos R.R. , de Albuquerque André L.P. 
Published: February 2024

IntroductionCOPD and interstitial lung disease (ILD) are significant chronic respiratory disorders, impacting quality of life. Respiratory muscle roles and differences remain not entirely clear. The objective of the present study was to evaluate the degree of recruitment of the respiratory muscles and the work of breathing in COPD and ILD during exercise.MethodsWe compared the sensory–mechanical relationships in COPD, ILD and healthy controls (n=20 each). They performed pulmonary function, noninvasive and invasive respiratory muscle strength, surface electromyography and work-of-breathing assessments.ResultsCOPD and ILD did not show lower static muscle strength compared to controls, but did show poor performance in the exercise test with increased transdiaphragmatic pressure (Pdi). In ILD, there was a higher increase in oesophageal pressure and a lower gastric pressure (Pga) on inspiration; in COPD, there was a significant increase inPgaon inspiration. In ILD, there is greater recruitment of accessory inspiratory muscles, whereas in COPD, there is marked use of both inspiratory and expiratory muscles. The neuromechanical inefficiency (increased neural respiratory drive without the corresponding tidal volume) was found in both diseases. In COPD, there is a considerable increase in elastic work to overcome intrinsic positive end-expiratory pressure (PEEPi) and expiratory work of breathing, whereas in ILD, non-PEEPielastic work of breathing is the highest part of the total work of breathing.ConclusionsEarly and increased activity of the respiratory muscles and work-of-breathing components significantly contribute to dyspnoea, exercise intolerance and neuromechanical inefficiency of ventilation in COPD and ILD. The mechanisms ofPdigeneration were different between diseases.
Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia
Authors: Steenhorst Jarno J. , Helbing Willem A. , van Genuchten Wouter J. , Bowen Daniel J. , van den Bosch Annemien , van der Velde Nikki , Kamphuis Lieke S. , Merkus Daphne , Reiss Irwin K.M. , Hirsch Alexander 
Published: February 2024

BackgroundWorldwide, 1–2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD.Methods40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26–28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27–29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38–40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise.ResultsResting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mLversus61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18%versus106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13%versus25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects withversuswithout BPD (−10±8%versus−3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely.ConclusionsIn preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.
Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2
Authors: Bauer Martin , Jorda Anselm , al-Jalali Valentin , Wölfl-Duchek Michael , Bergmann Felix , Nussbaumer-Pröll Alina , Steindl Ariane , Gugenberger Romana , Bischof Sarah , Wimmer Doris , Idzko Marco , Zeitlinger Markus 
Published: February 2024

BackgroundAPN01 is a soluble recombinant human angiotensin-converting enzyme 2 (rhACE2), a key player in the renin–aldosterone–angiotensin system (RAAS). In clinical studies, APN01 was administered intravenously only, so far. The aim of this study (ClinicalTrials.gov:NCT05065645) was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled APN01.MethodsThis was a phase I, double-blind, placebo-controlled, dose-escalation study. Inhalation was conductedviaa nebuliser over 15 min in three single ascending dose (SAD) cohorts (n=24) and two multiple ascending dose (MAD) cohorts (n=16: every 12 h for 7 days). Doses in the SAD cohort were 1.25, 2.5 and 5 mg·mL−1; doses in the MAD cohort were 2.5 and 5 mg·mL−1. Safety (including adverse events (AEs), laboratory findings and lung function results), PK and PD data were assessed.ResultsIn the SAD and MAD cohorts, treatment-related AEs were slightly more frequent in the active treatment group than in the placebo group. AEs were mild to moderate, with no dose-limiting toxicities. No clinically relevant changes in lung function and laboratory results were observed. The mean maximum observed plasma concentration (Cmax) values after single and multiple doses of 5 mg·mL−1APN01 were 1.88 and 6.61 ng·mL−1, respectively. Among the PD variables, significance was found for ACE2 and angiotensin 1–5.ConclusionsThe application of aerosolised APN01 is safe and well tolerated after single and multiple doses. By achieving a high local concentration in the lungs and low systemic bioavailability, inhaled rhACE2 may present a therapeutic option in ACE2-related diseases.
Single-centre prospective evaluation of the first 5 years of cystic fibrosis newborn screening in Germany
Authors: Gesenhues Florian , Michel Katarzyna , Greve Tobias , Röschinger Wulf , Gothe Florian , Nübling Jenna , Feilcke Maria , Kröner Carolin , Pawlita Ingo , Sattler Franziska , Seidl Elias , Griese Matthias , Kappler Matthias 
Published: February 2024

BackgroundIn 2016, nationwide cystic fibrosis newborn screening (CFNS) was newly implemented in Germany, using an immunoreactive trypsin/pancreatitis-associated protein/DNA screening algorithm that differs from most other nationwide screening programmes.MethodsWe analysed real-life feasibility of the confirmation process with respect to our pre-specified procedural objectives. These included overall accuracy through false-negative and false-positive results, effectiveness of the Bavarian tracking system, and accuracy of Macroduct and Nanoduct sweat conductivity compared with quantitative chloride determination. All consecutive CFNS-positive newborns assigned to our CF centre and born between 1 September 2016 and 31 August 2021 (n=162) were included.ResultsThe German CFNS was feasible at our CF centre as all procedural objectives were met. The positive predictive value (PPV) of positive CFNS was low (0.23) and two initially negatively screened children were later diagnosed with CF. The tracking system was highly efficient with a 100% tracking rate. The Macroduct and Nanoduct systems had comparable success rates (93.2%versus95.9%). Importantly, conductivityviaMacroduct was more accurate thanviaNanoduct (zero and four false-positive newborns, respectively).ConclusionsCF confirmation diagnostics of neonates in a certified regional CF centre was well managed in daily routine. The PPV of the German CFNS needs to be improved,e.g.by extending the DNA analysis within the screening algorithm and by increasing the number of variants tested. The Bavarian tracking system can serve as a successful model for other tracking systems. We preferred the Macroduct system because of its more accurate sweat conductivity readings.
The treatable traits of asthma in pregnancy: a clinical audit
Authors: Duszyk Katarzyna , McDonald Vanessa Marie , Thomas Dennis , Steel Kelly , Gibson Peter Gerard 
Published: February 2024

RationalePoor asthma control in pregnancy is associated with adverse perinatal outcomes. Treatable traits improve patient outcomes but the pattern and prevalence of treatable traits in pregnant women with asthma is unknown. Whether treatable traits in pregnant women with asthma can be identifiedviaa virtual care consult is also unknown. The objective of the present study was to assess the prevalence of treatable traits in pregnant women with asthma using a virtual model of care.MethodsPregnant women with asthma (n=196) underwent an assessment by an asthma nurse educator and a respiratory physicianviatelehealth. In this clinical audit, 16 treatable traits were assessed including two traits in the pulmonary domain, five traits in the behavioural/risk factors domain and nine traits in the extrapulmonary domain.ResultsPregnant women with asthma had a mean±sdof 7.5±2.0 treatable traits per person including 1.0±0.7 treatable traits per person in the pulmonary domain, 3.5±1.56 in the extrapulmonary domain and 2±0.9 in the risk factor/behavioural domain. Treatable traits in the behavioural/risk factor domain were most prevalent and these included limited asthma knowledge (96%), inadequate inhaler technique (84%) and no written asthma action plan (80%). On average 3.8±1.24 interventions per person were delivered for a mean±sdof 7.5±2.0 treatable traits per person.ConclusionVirtual antenatal asthma care is a feasible approach for assessing treatable traits in pregnant women with mild asthma.Pregnant women with asthma exhibit multiple management issues. Virtual models of care might increase asthma in pregnancy service uptake and acceptability.