bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyper-Personalization for Customer Engagement with Artificial Intelligence
Authors: Davenport Thomas H.
Published: August 2024

Personalization based on customer attributes and behavior is a familiar concept among marketers, and artificial intelligence is making it increasingly effective. AI-based hyper-personalization employs both sophisticated methods and far more data than previous methods and is far more precise as a result. Thomas H. Davenport discusses the role of AI in personalization as well as the growing backlash against personalization fueled by data privacy concerns.
The Leader’s Strategic Mindset: A Key Factor for AI Success
Authors: Rydén Pernille , Ringberg Torsten , El Sawy Omar A.
Published: August 2024

Businesses are increasingly using artificial intelligence (AI) to transform their processes and create new ways of engaging with customers. But leaders who project old assumptions about customer engagement onto the breathless use of AI risk creating a dangerous disconnect that will deprive their companies and their customers of value. Pernille Rydén, Torsten Ringberg, and Omar A. El Sawy present a strategic mindset framework to help leaders avoid this pitfall.
Machines that Dream: How AI-Human Collaborations in Art Deepen Audience Engagement
Authors: Anadol Refik , Kivrak Pelin
Published: August 2024

Human engagement in the realm of digital art will take many forms, both in the physical world and in the metaverse. Refik Anadol and Pelin Kivrak explore how Refik Anadol Studio experiments and collaborates with AI to create art that evokes multiple senses, using immersive experiences to engage with audiences.
Commonwealth Bank: Amplifying Customer Centricity with AI
Authors: Randazzo Steven , Paik Jin H. , Grushka-Cockayne Yael
Published: August 2024

Steven Randazzo, Jin H. Paik, and Yael Grushka-Cockayne describe how Commonwealth Bank used data and AI to maintain a competitive edge by bridging gaps between retail, call center, and digital services. By making data more available and standardized, the bank improved customization and enhanced its interactions with customers.
Congenital May-Thurner Syndrome With Thrombosis of Left Common Iliac Vein: A Rare Case Report
Authors: Farina Renato , Foti Pietro Valerio , Tona Emanuela , Timpanaro Concetta , Motta Claudia , D’Urso Mattia , Basile Antonio
Published: August 2024

“May-Thurner syndrome” (MTS) or “Cockett’s syndrome” is a vascular disease in which the left common iliac vein is compressed against the spine by the right common iliac artery, very rarely by the left or by both common iliac arteries. The congenital form is even more rare and is due to an anomaly of embryological development. This case describes compression and thrombosis of the left common iliac vein. A 12-year-old girl reported for observation with fever and arthralgia in the left lower limb. Sonography and computed tomography revealed thrombosis of the left common iliac vein caused by a congenital reduction of the iliac-vertebral space. Due to the rarity and non-specificity of the symptoms related to MTS, patients can suffer from repeated thrombosis and potentially pulmonary embolism.
Spatial transcriptomics reveals profound subclonal heterogeneity and T-cell dysfunction in extramedullary myeloma
Authors: John Mara , Helal Moutaz , Duell Johannes , Mattavelli Greta , Stanojkovska Emilia , Afrin Nazia , Leipold Alexander M. , Steinhardt Maximilian J. , Zhou Xiang , Žihala David , Anilkumar Sithara Anjana , Mersi Julia , Waldschmidt Johannes M. , Riedhammer Christine , Kadel Sofie-Katrin , Truger Marietta , Werner Rudolf A. , Haferlach Claudia , Einsele Hermann , Kretzschmar Kai , Jelínek Tomáš , Rosenwald Andreas , Kortüm K. Martin , Riedel Angela , Rasche Leo
Published: August 2024

Extramedullary disease (EMD) is a high-risk feature of multiple myeloma (MM) and remains a poor prognostic factor, even in the era of novel immunotherapies. Here, we applied spatial transcriptomics (RNA tomography for spatially resolved transcriptomics [tomo-seq] [n = 2] and 10x Visium [n = 12]) and single-cell RNA sequencing (n = 3) to a set of 14 EMD biopsies to dissect the 3-dimensional architecture of tumor cells and their microenvironment. Overall, infiltrating immune and stromal cells showed both intrapatient and interpatient variations, with no uniform distribution over the lesion. We observed substantial heterogeneity at the copy number level within plasma cells, including the emergence of new subclones in circumscribed areas of the tumor, which is consistent with genomic instability. We further identified the spatial expression differences between GPRC5D and TNFRSF17, 2 important antigens for bispecific antibody therapy. EMD masses were infiltrated by various immune cells, including T cells. Notably, exhausted TIM3+/PD-1+ T cells diffusely colocalized with MM cells, whereas functional and activated CD8+ T cells showed a focal infiltration pattern along with M1 macrophages in tumor-free regions. This segregation of fit and exhausted T cells was resolved in the case of response to T-cell–engaging bispecific antibodies. MM and microenvironment cells were embedded in a complex network that influenced immune activation and angiogenesis, and oxidative phosphorylation represented the major metabolic program within EMD lesions. In summary, spatial transcriptomics has revealed a multicellular ecosystem in EMD with checkpoint inhibition and dual targeting as potential new therapeutic avenues.
Longitudinal detection of prion infection in preclinical sheep blood samples compared using 3 assays
Authors: Thomas Charlotte M. , Salamat M. Khalid F. , Almela Florian , Cooper Jillian K. , Ladhani Kaetan , Arnold Mark E. , Bougard Daisy , Andréoletti Olivier , Houston E. Fiona
Published: August 2024

Variant Creutzfeldt-Jakob disease (vCJD) is a devastating disease caused by transmission of bovine spongiform encephalopathy to humans. Although vCJD cases are now rare, evidence from appendix surveys suggests that a small proportion of the United Kingdom population may be infected without showing signs of disease. These “silent” carriers could present a risk of iatrogenic vCJD transmission through medical procedures or blood/organ donation, and currently there are no validated tests to identify infected asymptomatic individuals using easily accessible samples. To address this issue, we evaluated the performance of 3 blood-based assays in a blinded study, using longitudinal sample series from a well-established large animal model of vCJD. The assays rely on amplification of misfolded prion protein (PrPSc; a marker of prion infection) and include real-time quaking-induced conversion (RT-QuIC), and 2 versions of protein misfolding cyclic amplification (PMCA). Although diagnostic sensitivity was higher for both PMCA assays (100%) than RT-QuIC (61%), all 3 assays detected prion infection in blood samples collected 26 months before the onset of clinical signs and gave no false-positive results. Parallel estimation of blood prion infectivity titers in a sensitive transgenic mouse line showed positive correlation of infectivity with PrPSc detection by the assays, suggesting that they are suitable for detection of asymptomatic vCJD infection in the human population. This study represents, to our knowledge, the largest comparison to date of preclinical prion detection in blood samples from a relevant animal model. The outcomes will guide efforts to improve early detection of prion disease and reduce infection risks in humans.
Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D
Authors: Chou Stella T. , Mewha Julia , Friedman David F. , Lazariu Victoria , Makrm Shaimaa , Ochoa Gorka , Vege Sunitha , Westhoff Connie M.
Published: August 2024

Anti-D can occur in D-positive patients who inherit RHD genetic variants encoding partial D antigen expression, but unexpected anti-D is also found in the plasma of patients with sickle cell disease who have conventional RHD gene(s) and are transfused with units from Black donors. These anti-D are likely stimulated by variant Rh expressed on donor cells; however, patients with anti-D, regardless of cause, are transfused for a lifetime with D-negative (Rh-negative) blood. This results in significant increased use of Rh-negative units, especially for those requiring chronic transfusion, which can strain Rh-negative blood inventories. We tested whether D-positive patients who made anti-D and had conventional RhD by RHD genotyping could safely be returned to D-positive transfusions without anti-D reappearance or compromised red blood cell survival using RHD genotype-matched units from Black donors. Five patients receiving chronic red cell exchange received an increasing number of D-positive units per procedure with a total of 72 D-positive RHD genotyped units transfused, with no anti-D restimulation. Unexpected anti-C and anti-E were identified during the study associated with donors with variant RHCE alleles. RH genotyping of D-positive units for transfusion may improve use and allocation of valuable Black donor units and reduce demand for Rh-negative blood. This trial was registered at www.clinicaltrials.gov as NCT04156906.
Evolving consolidation patterns and outcomes for a large cohort of patients with primary CNS lymphoma
Authors: Tringale Kathryn R. , Scordo Michael , Yahalom Joachim , White Charlie , Zhang Zhigang , Schefflein Javin , Cederquist Gustav , Schaff Lauren R. , DeAngelis Lisa , Imber Brandon S. , Grommes Christian
Published: August 2024

Consolidation for primary central nervous system lymphoma (PCNSL) after induction chemoimmunotherapy include whole-brain radiotherapy (WBRT; ≤24 Gy reduced-dose [RD], >24 Gy standard-dose) and cytarabine, nonmyeloablative chemotherapy (NMC), or autologous hematopoietic cell transplantation (AHCT). Comparative outcomes are lacking. Outcomes from 1983-2020 were stratified by decade and Memorial Sloan Kettering Cancer Center recursive partitioning analysis (RPA) class. Clinicodemographic associations were analyzed by multinomial logistic regression. Progression-free survival (PFS) and overall survival (OS) were analyzed by proportional hazards. Of 559 patients, 385 (69%) were consolidated. Median follow-up and OS were 7.4 and 5.7 years, respectively. WBRT use declined (61% (1990s) vs 12% (2010s)), whereas AHCT (4% (1990s) vs 32% (2010s)) and NMC (27% (1990s) vs 52% (2010s)) rose. Compared with RPA 1, RPA 2 was more likely to receive NMC. Those with partial response to induction were less likely to receive AHCT (odds ratio, 0.36; P = .02). Among 351 with complete response to consolidation, only receipt of rituximab, methotrexate, procarbazine, and vincristine induction was associated with improved PFS (hazard ratio, 0.5; P = .006). Among RPA 1, median PFS and OS were not reached for AHCT or RD-WBRT, vs 2.5 and 13.0 years, respectively, after NMC. Among RPA class 3, median PFS and OS after RD-WBRT were 4.6 and 10 years, vs 1.7 and 4.4 years after NMC. No significant adjusted survival differences were seen across consolidation strategies. NMC is increasingly used in lieu of RD-WBRT despite a trend toward less favorable PFS. RD-WBRT can be considered in patients ineligible for AHCT.
Priorities and barriers for research related to primary ciliary dyskinesia
Authors: Goutaki Myrofora , Lam Yin Ting , Rubbo Bruna , Chalmers James D. , Kouis Panayiotis , Marsh Gemma , Papon Jean-François , Raidt Johanna , Robinson Phil , Behan Laura , Lucas Jane S.
Published: August 2024

Background

Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease-specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research.

Methods

To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with PCD specialists selected using purposive sampling. We transcribed, coded and analysed interview data using thematic analysis. Based on interview themes that we identified, we developed an anonymous survey and circulated it widely through the BEAT-PCD network.

Results

We interviewed 28 participants from 15 countries across different disciplines and expertise levels. The main themes identified as priorities for PCD research were improving diagnosis; understanding prevalence and disease course; phenotypic variability; disease monitoring; treatment strategies; clinical trial end-points; and poorly researched areas. In total, 136 participants (49% paediatric pulmonologists) from 36 countries completed the survey. Most commonly reported barriers for research were low awareness about PCD and difficulties securing funding – in more than one-third of cases, participants reported undertaking predominantly unfunded research. Research questions ranked highest included priorities related to further improving diagnosis, treating PCD, managing upper and lower airway problems, and studying clinical variability and disease prognosis.

Conclusion

We need to overcome barriers of limited funding and low awareness and promote collaborations between centres, disciplines, experts and patients to address identified PCD priorities effectively. Our results contribute to the ongoing efforts of guiding the use of existing limited research resources and setting up a roadmap for future research activities.
Chronic Cough Patient Perspective: questionnaire validation and symptom impact
Authors: Braido Fulvio , Candeliere Maria Giulia , Bondi Benedetta , Arnaboldi Enrico , Bruno Matteo , Colombo Nicole , de Tommaso Cesare , Fassio Omar , Ferraris Melissa , Martinelli Sofia , Melissari Laura , Napoli Ludovica , Terracciano Federica , Folli Chiara , Baiardini Ilaria
Published: August 2024

Background

Chronic cough (CC) is underevaluated and underreported. The introduction of a tool that is easy to complete, score and interpret and with the psychometric properties requested for use in individual patients could improve clinical practice.

Objective

This cross-sectional study aimed to validate the Chronic Cough Patient Perspective (CCPP) for assessing CC in daily practice.

Methods

A provisional CCPP was created by iteratively reducing the Chronic Cough Impact Questionnaire (CCIQ). Its psychometric properties were tested in CC patients at baseline (visit 1) and after 1 month (visit 2).

Results

The reduction process yielded an 8-item provisional version, subsequently validated in 150 patients (36.33% males, mean age 50±16.9 years). Exploratory factor analysis revealed a one-dimensional structure, with one item being deleted as it did not align with the extracted dimension. The 7-item version of the CCPP showed a strong correlation with the CCIQ (r=0.902 at visit 1, r=0.932 at visit 2) and internal consistency (Cronbach's alpha values: 0.85 at visit 1, 0.93 at visit 2); discriminant and convergent validity were satisfactory. The reliability, assessed in 21 patients with no change in CC (Global Rating Scale=0), was high (concordance correlation coefficient=0.815; interclass coefficient=0.823). A score ≤5 indicates optimal health-related quality of life (HRQoL) attainment, with a minimum important difference of 3. The mean CCPP score was 20.5±6.24 at enrolment, and only 37.33% of the participants achieved an optimal HRQoL at visit 2.

Conclusion

The CCPP exhibited good psychometric properties suitable for clinical use, providing a valid, reliable and standardised assessment of CC's impact on HRQoL.
Surfactant-derived protein type B: a new biomarker linked to respiratory failure and lung damage in mild to moderate SARS-CoV-2 pneumonia
Authors: Mapelli Massimo , Salvioni Elisabetta , Mattavelli Irene , Banfi Cristina , Ghilardi Stefania , Greco Arianna , Biondi Maria Luisa , Rovai Sara , Mancini Elisabetta , Harari Sergio , Agostoni Piergiuseppe
Published: August 2024

Background

The COVID-19 pandemic has led to significant concern due to its impact on human health, particularly through pneumonia-induced lung damage. Surfactant proteins A and D (SP-A and SP-D) are implicated in COVID-19 lung damage, but the role of surfactant protein B (SP-B) remains unclear.

Methods

We conducted a single-centre, prospective observational study involving 73 hospitalised COVID-19 pneumonia patients. SP-B levels were measured within 48 h of admission, alongside SP-A and SP-D in a subset. Clinical data were collected, and follow-up visits were conducted after 6 months.

Results

At hospitalisation, circulating immature SP-B levels measured in 73 patients (median 26.31 arbitrary units (AU) (interquartile range 14.27–41.31)) correlated significantly with lung involvement (r=0.447, p<0.001) and oxygen support requirement (p=0.005). SP-B levels did not predict mechanical ventilation or intensive care unit admission. SP-B decreased significantly (p<0.001) from 25.53 AU (14.36–41.46) at the acute hospitalisation to 12.73 AU (9.12–20.23) at the 6-month follow-up, whereas SP-A and SP-D did not change significantly. Immature SP-B (but not SP-A and SP-D) was confirmed to be significantly associated with the need for oxygen support (n=26, 58%) during the hospitalisation (p<0.05).

Conclusion

Immature SP-B emerges as a potential biomarker for COVID-19 pneumonia severity and prognosis. Its dynamic changes suggest utility in monitoring disease progression and long-term outcomes, despite limitations in predicting hard end-points. Larger studies are needed to validate these findings and understand the underlying mechanisms of surfactant protein dysregulation in COVID-19 pathogenesis.
Utility of adding oesophageal to endobronchial endosonography when staging lung cancer: a randomised trial
Authors: Oki Masahide , Saka Hideo , Seki Yukio , Kogure Yoshihito , Niwa Hideyuki , Yamada Arisa , Torii Atsushi , Kitagawa Chiyoe , Ando Masahiko
Published: August 2024

Introduction

Both combined endobronchial ultrasonography (EBUS) and transoesophageal bronchoscopic ultrasonography (EUS-B) and EBUS alone have been recommended for preoperative mediastinal staging of nonsmall cell lung cancer (NSCLC). However, no randomised study comparing these two methods has been published. The purpose of the present study was to compare the sensitivity of EBUS and that of combined EBUS and EUS-B (EBUS/EUS-B) in terms of detecting N2/N3 disease during staging of NSCLC.

Methods

Patients with known or suspected, potentially operable NSCLC were recruited and randomised to undergo EBUS or EBUS/EUS-B under conscious sedation. The primary end-point was a comparison of the sensitivity of EBUS alone and EBUS/EUS-B.

Results

A total of 240 patients were enrolled and randomised, among whom 219 (105 EBUS group; 114 EBUS/EUS-B group) were included in the analysis. The sensitivities of EBUS and EBUS/EUS-B in terms of detecting N2/N3 disease were 75.0% and 79.3% respectively (p=0.698). In the EBUS/EUS-B group, only EUS-B yielded diagnostic results in two patients; the sensitivity thus increased from 72.4% to 79.3% on addition of EUS-B to EBUS.

Conclusions

The difference in the sensitivities of EBUS alone and EBUS/EUS-B in terms of diagnosing N2/N3 disease was not statistically significant. Although the increase in sensitivity with the addition of EUS-B is modest, it is maximised when EUS-B is used to sample lymph nodes not accessible by EBUS alone.
The Canadian Bronchiectasis and Nontuberculous Mycobacteria Registry: a study protocol
Authors: Thornton Christina S. , Boechler Nicole , Desai Vidhi , Somayaji Ranjani , Purighalla Swathi , Brode Sarah , Marras Theodore K. , Cooper Ryan , Smith Maeve , Jarand Julie
Published: August 2024

Background

Bronchiectasis is a complex, chronic disease with geographic and ethnic diversity. While the most substantial cohort studies have been conducted in Europe and the USA, Canada also faces considerable challenges. The comprehensive Canadian Bronchiectasis and Nontuberculous Mycobacterial (NTM) Registry aims to 1) outline the clinical characteristics and natural history of bronchiectasis in Canada, 2) identify risk factors contributing to disease progression within Canadians, 3) integrate comprehensive clinical information to better understand the phenotypes of bronchiectasis and 4) support the development of large-scale, randomised controlled trials in Canada.

Methods

The Canadian Bronchiectasis and NTM Registry is an ongoing prospective, longitudinal, multi-centre, observational cohort study. It aims to enrol at least 2000 participants to collect data such as medical history, aetiological assessments, lung function tests, microbiological profiles, radiographic evaluations, comorbidities and quality of life (QoL) metrics. Participants will undergo annual follow-ups to gather longitudinal information regarding outcomes, treatments and changes in QoL. The inclusion criteria are a diagnosis of bronchiectasis by clinical history and computed tomography and/or pulmonary NTM infection as defined by American Thoracic Society/Infectious Diseases Society of America guidelines. The study's protocol received ethical approval from the lead site, the University of Calgary, with future additional approval from local ethics committees at all participating centres.

Discussion

The outcomes of the registry will be instrumental in uncovering the clinical traits and natural history of bronchiectasis. This longitudinal study will be used for analysis to form evidence-based clinical practices and serve as a resource in Canada to inform future studies in NTM and bronchiectasis.
Control of hypercapnia and mortality in home mechanical ventilation: the population-based DISCOVERY study
Authors: Palm Andreas , Ekström Magnus , Emilsson Össur , Ersson Karin , Ljunggren Mirjam , Sundh Josefin , Grote Ludger
Published: August 2024

Background

Studies on the survival of patients with home mechanical ventilation (HMV) are sparse. We aimed to analyse the impact of controlled hypercapnia on survival over 27 years among patients with HMV in Sweden.

Study design and methods

Population-based cohort study of adult patients starting HMV in the Swedish Registry for Respiratory Failure (Swedevox) during 1996–2022 cross-linked with the National Cause of Death registry. Mortality risk factors were analysed using crude and multivariable Cox regression models, including adjustments for anthropometrics, comorbidities, the underlying diagnosis causing chronic hypercapnic respiratory failure (CRF) and the control of hypercapnia (PaCO2≤6.0 kPa) at follow-up.

Results

We included 10 190 patients (50.1% women, age 62.9±14.5 years). Control of hypercapnia at follow-up after 1.3±0.9 years was associated with lower mortality, hazard ratio (HR) 0.74 (95% CI 0.68–0.80) and the association was strongest in those with pulmonary disease, restrictive thoracal disease (RTD), obesity hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS). Predictors for increased mortality included age, Charlson Comorbidity Index, supplemental oxygen therapy and acute start of HMV therapy. Median survival varied between 0.8 years (95% CI 0.8–0.9 (n=1401)) for ALS and 7.6 years (95% CI 6.9–8.6 (n=1061)) for neuromuscular disease. Three-year survival decreased from 76% (95% CI 71–80) between 1996 and 1998 to 52% (95% CI 50–55) between 2017 and 2019. When adjusting for underlying diagnosis and age, the association between start year and decreased survival disappeared, HR 1.00 (95% CI 0.99–1.01).

Conclusion

ControllingPaCO2is a key treatment goal for survival in HMV therapy. Survival differed markedly between diagnosis and age groups, and survival rates have declined as the patient group has aged.
Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial
Authors: Chalmers James D. , Loebinger Michael R. , Teper Ariel , McShane Pamela J. , Fernandez Carlos , Fucile Sebastian , Haworth Charles S. , Lauterio Melanie , van der Laan Roald , Shih Vivian H. , Metersky Mark L.
Published: August 2024

Introduction

Bronchiectasis is a chronic inflammatory airway disease. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces pulmonary inflammation by preventing the activation of neutrophil serine proteases. In the phase II WILLOW trial, brensocatib prolonged time to first exacerbation in patients with bronchiectasis. In thispost hocanalysis we compare clinical outcomes in patients from WILLOW according to baseline disease characteristics.

Methods

Adults with bronchiectasis treated with brensocatib (10 or 25 mg) or placebo once daily were analysed by baseline Bronchiectasis Severity Index (BSI) score (≤4 (mild), 5–8 (moderate), or ≥9 (severe)), exacerbation history (2 or ≥3 in the previous year), blood eosinophil count (<300 cells per µL or ≥300 cells per µL), long-term macrolide use (≥6 months; no or yes) andPseudomonas aeruginosaculture at screening (negative or positive). End-points were time to first exacerbation, annualised exacerbation rate, change in lung function from baseline, and safety. All patients who received brensocatib were pooled and compared with placebo.

Results

Treatment with brensocatibversusplacebo was associated with a longer time to first exacerbation (hazard ratio (95% confidence interval), BSI: ≤4, 0.28 (0.08–0.96); 5–8, 0.75 (0.35–1.60); ≥9, 0.61 (0.35–1.04); prior exacerbations: 2, 0.56 (0.34–0.90); ≥3, 0.71 (0.32–1.59); blood eosinophils per µL: <300, 0.66 (0.42–1.06); ≥300, 0.49 (0.20–1.20); long-term macrolide use: no, 0.60 (0.38–0.94); yes, 0.60 (0.25–1.45);P. aeruginosaculture: negative, 0.54 (0.32–0.92); positive, 0.68 (0.37–1.27)). Safety results were similar across subgroups.

Discussion

Patients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbationversusplacebo across all key baseline disease characteristics.
Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis
Authors: Araújo Márcia , Beltrão Marília , Sokhatska Oksana , Melo Natália , Caetano Mota Patrícia , Bastos Helder Novais , Terras André , Coelho David , Delgado Luís , Morais António
Published: August 2024

Introduction

Progressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs. This study aimed to investigate the role of serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.

Methods

Newly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline and disease progression was monitored. PPF was defined according to the recent European Respiratory Society, American Thoracic Society, Japanese Respiratory Society and the Latin American Thoracic Society Clinical Practice Guidelines.

Results

79 patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (adjusted OR 1.263, 95% CI 1.029–1.551; p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL−1for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.

Conclusions

In patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.
Effectiveness of early Anakinra on cardiac function in children with multisystem inflammatory syndrome of COVID-19: a systematic review
Authors: Shabil Muhammed , Khatib Mahalaqua Nazli , Banda Godfrey T , Zahiruddin Quazi Syed , Ballal Suhas , Bansal Pooja , Srivastava Manish , Arora Isha , Kumar M Ravi , Sinha Aashna , Pant Kumud , Al-Jishi Jumana M. , Albayat Hawra , Al Fares Mona A. , Garout Mohammed , Alrasheed Hayam A , Al-Subaie Maha F. , Rabaan Ali A.
Published: August 2024

Background

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C.

Methods

A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale.

Results

Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra’s role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements.

Conclusion

Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra’s effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols.
Facilitators and barriers to implementing successful exclusion among children with shiga toxin-producing Escherichia coli: a qualitative analysis of public health case management records
Authors: Vusirikala Amoolya , Yanshi  , Robin Charlotte , Rowell Sam , Dabke Girija , Fox Georgina , Bell Jade , Manuel Rohini , Jenkins Claire , Love Nicola K , McCarthy Noel , Sumilo Dana , Balasegaram Sooria
Published: August 2024

Background

Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health concern as they can cause serious illness and outbreaks. In England, STEC incidence is highest among children and guidance recommends that children under six diagnosed with STEC are excluded from childcare until two consecutive stool cultures are negative. We aimed to describe the barriers and facilitators to implementing exclusion and the impact of exclusion policies on young children and their families.

Methods

Individual level data was obtained from a wider study focusing on shedding duration among STEC cases aged < 6 years between March 2018 – March 2022. Data was extracted from England’s public health case management system. The case management system includes notes on telephone conversations, email correspondence and meeting minutes relating to the case. Collected data consisted of free text in three forms: (1) quotes from parents, either direct or indirect, (2) direct quotes from the case record by health protection practitioners or environmental health officers, and (3) summaries by the data collector after reviewing the entire case record. We analysed free text comments linked to 136 cases using thematic analysis with a framework approach.

Results

The median age of included cases was 3 years (IQR 1.5-5), with males accounting for 49%. Nine key themes were identified. Five themes focused on barriers to managing exclusion, including (i) financial losses, (ii) challenges with communication, engagement and collaboration, (iii) issues with sampling, processing, and results, (iv) adverse impact on children and their families and (v) conflicting exclusion advice. Four themes related to facilitators to exclusion, including (i) good communication with parents and childcare settings, (ii) support with childcare, (iii) improvements to sampling, testing, and reporting of results, and (iv) provision of supervised control measures.

Conclusions

Qualitative analysis of public health case records can provide evidence-based insights around complex health protection issues to inform public health guidelines. Our analysis highlights the importance of considering wider social and economic consequences of exclusion when developing policies and practices for the management of STEC in children.
Oral health knowledge, attitudes, and practices of people living with mental illness: a mixed-methods systematic review
Authors: Johnson Alisha Maree , Kenny Amanda , Ramjan Lucie , Raeburn Toby , George Ajesh
Published: August 2024

People living with mental illness experience poorer oral health outcomes compared to the general population, yet little is known about their oral health knowledge, attitudes, and practices. The aim of this mixed-methods systematic review was to synthesise evidence regarding oral health knowledge, attitudes, and practices of people living with mental illness to inform preventative strategies and interventions. Database searches were conducted in PubMed, MEDLINE, PsycINFO, CINAHL, ProQuest, and Scopus with no limitations placed on the year of study. All studies available in the English language, that explored the oral health knowledge, attitudes, and/or practices of people with a mental illness were included. Articles were excluded if they primarily pertained to intellectual disability, behavioural and psychological symptoms of dementia, drug and alcohol or substance use, or eating disorders. A thematic synthesis was undertaken of 36 studies (26 high-moderate quality), resulting in 3 themes and 9 sub-themes. Study participants ranged from n = 7 to n = 1095 and aged between 15–83 years with most having a diagnosis of schizophrenia, schizoaffective, or bipolar affective disorder. People diagnosed with a mental illness were found to have limited oral health knowledge, particularly regarding the effects of psychotropic medication. Various barriers to oral health care were identified, including high dental costs, the negative impact of mental illness, dental fears, lack of priority, and poor communication with dental and health care providers. Study participants often displayed a reduced frequency of tooth brushing and dental visits. The findings highlight the potential for mental health care providers, oral health and dental professionals, mental health consumers, and carers to work together more closely to improve oral health outcomes for people with mental illness. The systematic review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO), (registration ID CRD42022352122).
Pediatric head injury guideline use in Sweden: a cross-sectional survey on determinants for successful implementation of a clinical practice guideline
Authors: Wickbom Fredrik , Berghog William , Bernhardsson Susanne , Persson Linda , Kunkel Stefan , Undén Johan
Published: August 2024

Background

The Scandinavian Neurotrauma Committee guideline (SNC-16) was developed and published in 2016, to aid clinicians in management of pediatric head injuries in Scandinavian emergency departments (ED). The objective of this study was to explore determinants for use of the SNC-16 guideline by Swedish ED physicians.

Methods

This is a nationwide, cross-sectional, web-based survey in Sweden. Using modified snowball sampling, physicians managing children in the ED were invited via e-mail to complete the validated Clinician Guideline Determinants Questionnaire between February and May, 2023. Baseline data, data on enablers and barriers for use of the SNC-16 guideline, and preferred routes for implementation and access of guidelines in general were collected and analyzed descriptively and exploratory with Chi-square and Fisher's tests.

Results

Of 595 invitations, 198 emergency physicians completed the survey (effective response rate 33.3%). There was a high reported use of the SNC-16 guideline (149/195; 76.4%) and a strong belief in its benefits for the patients (188/197; 95.4% agreement). Respondents generally agreed with the guideline's content (187/197; 94.9%) and found it easy to use and navigate (188/197; 95.4%). Some respondents (53/197; 26.9%) perceived a lack of organizational support needed to use the guideline. Implementation tools may be improved as only 58.9% (116/197) agreed that the guideline includes such. Only 37.6% (74/197) of the respondents agreed that the guideline clearly describes the underlying evidence supporting the recommendation. Most respondents prefer to consult colleagues (178/198; 89.9%) and guidelines (149/198; 75.3%) to gain knowledge to guide clinical decision making. Four types of enablers for guideline use emerged from free-text answers: ease of use and implementation, alignment with local guidelines and practice, advantages for stakeholders, and practicality and accessibility. Barriers for guideline use were manifested as: organizational challenges, medical concerns, and practical concerns.

Conclusions

The findings suggest high self-reported use of the SNC-16 guideline among Swedish ED physicians. In updated versions of the guideline, focus on improving implementation tools and descriptions of the underlying evidence may further facilitate adoption and adherence. Measures to improve organizational support for guideline use and involvement of patient representatives should also be considered.
Plexin C1 influences immune response to intracellular LPS and survival in murine sepsis
Authors: Bernard Alice , Eggstein Claudia , Tang Linyan , Keller Marius , Körner Andreas , Mirakaj Valbona , Rosenberger Peter
Published: August 2024

Background

Intracellular sensing of lipopolysaccharide (LPS) is essential for the immune response against gram-negative bacteria and results in activation of caspase-11 and pyroptotic cell death with fatal consequences in sepsis. We found the neuronal guidance receptor plexin C1 (PLXNC1) influences the intracellular response to LPS.

Methods

We employed a murine model of sepsis via cecal ligation and binding (CLP), using PLXNC1-/- mice and littermate controls, and additionally transfected murine bone-marrow-derived macrophages (BMDMs) from both genotypes with LPS to achieve activation of the noncanonical inflammasome ex vivo. Additionally, we transfected the PLXNC1 ligand SL4c-d in vivo and ex vivo to examine its effect on intracellular LPS response.

Results

We found the neuronal guidance receptor PLXNC1 dampens the intracellular response to LPS by interacting with adenylate cyclase 4 (ADCY4) and protein kinase A activity, which in turn diminishes caspase-11 expression. The absence of PLXNC1 results in excessive inflammation marked by increased cytokine release, increased secondary organ injury and reduced sepsis survival in a murine sepsis model induced by CLP. Notably, administration of SL4c-d—peptide ligand of PLXNC1—reduces the inflammatory response during CLP-induced sepsis and improves survival.

Conclusions

These results elucidate a previously unknown mechanism for PLXNC1 suppressing excessive noncanonical inflammasome activity and offer a new potential target for treatment of sepsis with its detrimental effects.
ECG changes following balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension: a retrospective study
Authors: Guo Tao , Zeng Xiao-mei , Huang Hou-quan , Wu Xiao-feng , Guo Wen-liang , Chen Hai-ming , Zhong Qiao-nan , Yang Xin , Ye Hui-ling , Hong Cheng
Published: August 2024

Purpose

This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results.

Results

BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range − 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score.

Conclusions

BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.
Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy
Authors: Chan Wei Yen , Lee Jenny H. , Stewart Ashleigh , Diefenbach Russell J. , Gonzalez Maria , Menzies Alexander M. , Blank Christian , Scolyer Richard A. , Long Georgina V. , Rizos Helen
Published: August 2024

Background

Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

Methods

Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.

Results

Pre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.

Conclusion

Post-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.
Hyperoxaemia in acute trauma is common and associated with a longer hospital stay: a multicentre retrospective cohort study
Authors: Iten Manuela , Pietsch Urs , Knapp Juergen , Jakob Dominik Andreas , Krummrey Gert , Maschmann Christian , Steinmetz Jacob , Arleth Tobias , Mueller Martin , Hautz Wolf
Published: August 2024

Background

Trauma poses a significant global health challenge. Despite advancements in the management of severely injured patients, (poly)trauma continues to be a primary contributor to morbidity and mortality worldwide. In the context of trauma resuscitation, supplemental oxygen is commonly administered generously as suggested by guidelines. Yet, it remains uncertain whether the trauma population might derive advantages from a more conservative approach to supplemental oxygen.

Methods

In this retrospective cohort study from two Swiss trauma centers, severely injured adult (> 16 years) trauma patients with an Injury Severity Score (ISS) ≥ 16 were divided into four groups according to the first blood gas analysis taken: hypoxaemia (PaO2 < 10.7 kPa/80 mmHg), normoxaemia (PaO2 10.7–16.0 kPa/80–120 mmHg), which served as reference, moderate hyperoxaemia (PaO2 > 16.0–40 kPa/120–300 mmHg) and severe hyperoxaemia (PaO2 > 40 kPa/300 mmHg). The primary outcome was 28-day mortality. Length of hospital stay (LOS) and length of intensive care unit stay (LOS-ICU) were analyzed as secondary outcomes.

Results

Of 1,189 trauma patients, 41.3% had hyperoxaemia (18.8% with severe hyperoxaemia) and 19.3% had hypoxaemia. No difference was found for 28-day mortality (hypoxaemia: 15.7%, normoxaemia: 14.1%, hyperoxaemia: 13.8%, severe hyperoxaemia: 16.0%, p = 0.846). Patients with severe hyperoxaemia had a significant prolonged LOS (median 12.5 [IQR 7–18.5] days vs. 10 [7–17], p = 0.040) and extended LOS-ICU (3.8 [1.8–9] vs. 2 [1–5] days, p = 0.149) compared to normoxaemic patients. In multivariable analysis, oxygen group was not associated with the primary outcome 28-day mortality or LOS-ICU. Severe hyperoxaemia patients had a tendency towards longer hospital stay (adjusted coefficient 2.23 days [95% CI: − 0.32; 4.79], p = 0.087).

Conclusion

Hyperoxaemia was not associated with an increased 28-day mortality when compared to normoxaemia. However, both moderate and severe hyperoxaemia is frequently observed in trauma patients, and the presence of severe hyperoxaemia showed a tendency with extended hospital stay compared to normoxaemia patients. Robust randomized controlled trials are imperative to thoroughly evaluate the potential correlation between hyperoxaemia and outcomes in trauma patients .

Trial Registration Retrospectively registered.
Gulf war illness: a tale of two genomes
Authors: Golomb Beatrice A. , Kelley Richard I. , Han Jun Hee , Miller Bruce , Bui Leeann
Published: August 2024

Introduction

Gulf War illness (GWI) is an environmentally-triggered chronic multisymptom illness typified by protean symptoms, in which mitochondrial impairment is evident. It has been likened to accelerated aging. Nuclear genetics of detoxification have been linked to GWI.

Objective

To see whether mitochondrial (mt) haplogroup U – a heritable profile of mitochondrial DNA that has been tied to aging-related conditions – significantly predicts greater GWI severity; and to assess whether GWI severity is influenced by mitochondrial as well as nuclear genetics. 54 consenting Gulf War veterans gave information on GWI severity, of whom 52 had nuclear DNA assessment; and 45 had both nuclear and mitochondrial DNA assessments. Regression with robust standard errors assessed prediction of GWI severity as a function of nuclear genetics (butyrylcholinesterase variants), mitochondrial genetics (haplogroup U, previously tied to aging-related conditions); or both.

Results

BChE “adverse” variants significantly predicted GWI severity (β(SE) = 23.4(11.4), p = 0.046), as did mt haplogroup U (β(SE) = 36.4(13.6), p = 0.010). In a model including both, BChE was no longer significant, but mt haplogroup U retained significance (β(SE) = 36.7(13.0), p = 0.007). This is the first study to show that mitochondrial genetics are tied to GWI severity in Gulf-deployed veterans. Other data affirm a tie to nuclear genetics, making GWI indeed a “tale of two genomes.”