bluuebunny/crossref_metadata_2025 huggingface dataset:
The National Institutes of Health COVID-19 Neuro Databank/Biobank: Creation and Evolution
Authors: Meropol Sharon B. , Norris Cecile J. , Frontera Jennifer A. , Adeagbo Adenike , Troxel Andrea B. ,   the COVID-19 Neuro Databank/Biobank Consortium
Published: July 2024

Introduction: Diverse neurological conditions are reported associated with the SARS-CoV-2 virus; neurological symptoms are the most common conditions to persist after the resolution of acute infection, affecting 20% of patients 6 months after acute illness. The COVID-19 Neuro Databank (NeuroCOVID) was created to overcome the limitations of siloed small local cohorts to collect detailed, curated, and harmonized de-identified data from a large diverse cohort of adults with new or worsened neurological conditions associated with COVID-19 illness, as a scientific resource. Methods: A Steering Committee including US and international experts meets quarterly to provide guidance. Initial study sites were recruited to include a wide US geographic distribution; academic and non-academic sites; urban and non-urban locations; and patients of different ages, disease severity, and comorbidities seen by a variety of clinical specialists. The NeuroCOVID REDCap database was developed, incorporating input from professional guidelines, existing common data elements, and subject matter experts. A cohort of eligible adults is identified at each site; inclusion criteria are: a new or worsened neurological condition associated with a COVID-19 infection confirmed by testing. De-identified data are abstracted from patients’ medical records, using standardized common data elements and five case report forms. The database was carefully enhanced in response to feedback from site investigators and evolving scientific interest in post-acute conditions and their timing. Additional US and international sites were added, focusing on diversity and populations not already described in published literature. By early 2024, NeuroCOVID included over 2,700 patient records, including data from 16 US and 5 international sites. Data are being shared with the scientific community in compliance with NIH requirements. The program has been invited to share case report forms with the National Library of Medicine as an ongoing resource for the scientific community. Conclusion: The NeuroCOVID database is a unique and valuable source of comprehensive de-identified data on a wide variety of neurological conditions associated with COVID-19 illness, including a diverse patient population. Initiated early in the pandemic, data collection has been responsive to evolving scientific interests. NeuroCOVID will continue to contribute to scientific efforts to characterize and treat this challenging illness and its consequences.
Stasis and Inflammation in Varicose Vein Development: An Interleukin-Mediated Process from Intima to Media
Authors: Ku Min Jung , Maeng Young Hee , Chang Jee Won , Song Jung-Kook , Kim Young Ree
Published: July 2024

Introduction: This study investigated the combination of venous stasis and inflammation in varicose vein development. Methods: The study included patients with primary varicose veins operated using high ligation and stripping of greater saphenous vein. All of them showed reflux at sapheno-femoral junction on preoperative Doppler ultrasound. Mesenteric veins from early or advanced gastric cancer specimens were used as control group. Inflammatory mediators expressed in the venous wall were measured via immunohistochemistry and compared between the two groups. Results: Thirty-five (59.3%) men and 24 women with a mean age of 52.8 years (range, 23–77 years) were included and 29 (49.2%) patients had edema or skin changes according to Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification and reporting standards for chronic venous disorders. The expression of interleukin 6 (IL-6) and transforming growth factor β1 (TGF-β1) in intima and those of IL-6 in media of greater saphenous veins increased, with statistically significant differences between the two groups (p < 0.001). IL-6 in media and TGF-β1 levels in intima were independent predictors of varicose veins (adjusted odds ratios 74.62 and 66.69, respectively). Conclusion: Elevated venous pressure represented by reflux on Doppler ultrasound and increased expression of inflammatory cytokines including IL-6 in media and TGF-β1 in intima are associated with the development of varicose veins.
Value of Biochemical Amniotic Fluid Analysis and Fetal Magnetic Resonance Imaging in the Prenatal Diagnosis of Congenital Microgastria
Authors: Lepee Aurelie , Massardier Jerome , Atallah Anthony , Massoud Mona , Pettazzoni Magali , Huissoud Cyril , Dubois Remi , Guibaud Laurent , Cabet Sara
Published: July 2024

Introduction: Congenital microgastria (CM) is a rare condition due to early interruption of stomach development between the 4th and 8th week of gestation, leading to a small midline tubular stomach. Prenatal diagnosis of CM is a challenge with important implications. This study explores the value of biochemical amniotic fluid (AF) analysis and fetal magnetic resonance imaging (MRI) for the prenatal diagnosis of CM in case of nonvisible stomach on fetal ultrasound. Case Presentation: Four cases of CM were retrospectively investigated in terms of fetal ultrasound, MRI findings, and biochemical AF analyses. The patients were referred to the Prenatal Diagnosis Unit of the Hôpital Femme Mère Enfant (Lyon, France) at a mean age of 21 weeks of gestation for absent or small fetal stomach on ultrasound with a suspected diagnosis of esophageal atresia (EA). Ultrasound examination confirmed that the stomach was absent in two of the four fetuses and small in the other two. This feature was associated with a congenital heart defect in two cases and a terminal transverse limb defect in one case. Standard genetic workup (array-CGH) results were normal. Biochemical AF analysis, including the EA index, was not suggestive of EA. Fetal MRI showed a small midline tubular stomach, associated with a dilated esophagus, highly suggestive of CM. Conclusion: If the fetal stomach is absent on ultrasound, CM should be considered if the AF volume is normal, especially during the third trimester, and if the EA index is not suggestive of gastrointestinal obstruction. In these cases, the diagnosis can be confirmed by fetal MRI, through observation of a small midline tubular stomach associated with a dilated esophagus.
Polymyalgia rheumatica: Klinische Analyse von Geschlecht und vorbestehendem Diabetes mellitus
Authors: Adler Sabine
Published: July 2024

Objective: This study clarifies the involvement of gender and pre-existing diabetes mellitus (DM) in the clinical characteristics of polymyalgia rheumatica (PMR). Methods: The clinical records of patients diagnosed with PMR in our department between January 2011 and June 2021, especially in terms of gender and DM were retrospectively analysed. Results: We identified 89 patients with the median age of 75. 37 cases were men and 52 cases were women. Pre-existing DM was found in 21 patients (23.6%). Male PMR patients exhibited a higher complication rate of pre-existing DM and C-reactive protein (CRP) levels at diagnosis (p = .04 and p < .01, respectively) than female patients, and men were more common in the patient group with pre-existing DM (p = .04). The CRP levels of male PMR patients without pre-existing DM were higher than female PMR patients without pre-existing DM.
Percutaneous Ultrasound-Guided Medication Injection: A Potential Technique for Subglottic Stenosis
Authors: Deng Mingming , Tong Run , Lin Jieru , Bian Yiding , Zhou Guowu , Herth Felix J.F. , Hou Gang
Published: July 2024

Introduction: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and anti-inflammatory properties. Submucosal injection of glucocorticoids, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks. Case Presentation: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost. Conclusion: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.
Differences between Chronically Hepatitis B Virus-Infected Pregnant Women with and without Intrafamilial Infection: From Viral Gene Sequences to Clinical Manifestations
Authors: Gao Fan , Li Xia , Wang Xiaona , Liu Hankui , Zhang Wentao , Zhang Yidan , Jia Yanju , Zhao Ziyan , Bai Guiqin
Published: July 2024

Introduction: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. Methods: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. Results: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (β = −0.43, 95% confidence interval [CI]: −0.76 to −0.12, p = 0.009), HBeAg (β = −195.15, 95% CI: −366.35 to −23.96, p = 0.027), and hemoglobin changes (β = −8.09, 95% CI: −15.54 to −0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (β = 73.9, 95% CI: 38.92–108.95, p < 0.001) and albumin (β = 2.73, 95% CI: 0.23–5.23, p = 0.033). Conclusion: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.
Elective Direct Current Cardioversion of Atrial Fibrillation: Silent Brain Infarction and Health-Related Quality of Life
Authors: Andel Peter M. , Aamodt Anne Hege , Gleditsch Jostein , Melin Erik , Rootwelt-Revheim Mona Elisabeth , Steine Kjetil , Atar Dan
Published: July 2024

Introduction: Atrial fibrillation (AF) increases the risk for stroke, dementia, and impaired health-related quality of life (HRQL). Elective direct current cardioversion (ECV) is often used to restore sinus rhythm but is associated with thromboembolism. While larger strokes usually produce symptoms, subclinical ones may go unrecognized and may cause cognitive and functional decline over time. In the current study, we sought to evaluate the effects of ECV on silent brain infarctions and HRQL in patients with AF. Methods: Patients with AF (n = 46) underwent brain magnetic resonance imaging (MRI) and HRQL assessment using the EuroQL-5D5L questionnaire before and after ECV. Implantable loop recorders (ILRs) were used to observe the rate of early AF recurrences within the first 30 days. All patients were treated with anticoagulants according to guidelines. The primary endpoint was silent brain infarction assessed by brain MRI within the first 2 weeks after ECV. Secondary endpoints were the change in HRQL and its association with AF recurrence at follow-up and by ILR recordings. Results: New silent brain infarction after ECV was detected in 1 patient. At follow-up visit after 19.1 days AF recurrence was detected by 12-lead ECG in 13 patients (28.3%), whereas 27 patients (58.7%) had AF recurrence recorded by ILR within the first 30 days after ECV. European Heart Rhythm Association (EHRA) symptom score and the EuroQL-5d5L score were improved after ECV. Conclusion: Silent brain infarctions may occur after ECV despite anticoagulation treatment. Early AF recurrence is frequent. ECV positively affects HRQL mainly in those patients with sustained sinus rhythm at follow-up.
Pulmonary Langerhans Cell Histiocytosis: Diagnosis in Bronchoalveolar Lavage Liquid-Based Cytology Samples
Authors: Gupta Anjali , Gupta Parikshaa , Gupta Nalini , Dhooria Sahajal , Vaidya Pankaj C. , Prabhakar Nidhi , Bal Amanjit , Mathew Joseph L.
Published: July 2024

Introduction: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations. Case Presentation: We present 2 cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxidase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH. Conclusion: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.
Extended Computed Tomography Angiography for the Successful Diagnosis of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA: Study Protocol for a Randomized Controlled Trial
Authors: Sposato Luciano A. , Ayan Diana , Ahmed Mobeen , Fridman Sebastian , Mandzia Jennifer L. , Lodol Facundo F. , Elrayes Maged , Pandey Sachin , Bagur Rodrigo
Published: July 2024

Introduction: Cardiac imaging is one of the main components of the etiological investigation of ischemic strokes. However, basic and advanced cardiac imaging remain underused in most stroke centers globally. Computed tomography angiography (CTA) of the supra-aortic and intracranial arteries is the most frequent imaging modality applied during the evaluation of patients with acute ischemic stroke to identify the presence of a large vessel occlusion. Recent evidence from retrospective observational studies has shown a high detection of cardiac thrombi, ranging from 6.6 to 17.4%, by extending a CTA a few cm below the carina to capture cardiac images. However, this approach has never been prospectively compared against usual care in a randomized controlled trial. The Extended Computed Tomography Angiography for the Successful Screening of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA (DAYLIGHT) prospective, randomized, controlled trial evaluates whether an extended CTA (eCTA) + standard-of-care stroke workup results in higher detection rates of cardiac and aortic source of embolism compared to standard-of-care CTA (sCTA) + standard-of-care stroke workup. Methods: DAYLIGHT is a single-center, prospective, randomized, open-blinded endpoint trial, aiming to recruit 830 patients with suspected acute ischemic stroke or transient ischemic attack (TIA) being assessed under acute code stroke at the emergency department or at a dedicated urgent stroke prevention clinic. Patients are randomized 1:1 to eCTA versus sCTA. The eCTA expands image acquisition caudally, 6 cm below the carina. All patients receive standard-of-care cardiac imaging and diagnostic stroke workup. The primary efficacy endpoint is the diagnosis of a cardioaortic thrombus after at least 30 days of follow-up. The primary safety endpoint is door-to-CTA completion time. The diagnosis of a qualifying ischemic stroke or TIA is independently adjudicated by a stroke neurologist, blinded to the study arm allocation. Patients without an adjudicated ischemic stroke or TIA are excluded from the analysis. The primary outcome events are adjudicated by a board-certified radiologist with subspecialty training in cardiothoracic radiology and a cardiologist with formal training in cardiac imaging. The primary analysis is performed according to the modified intention-to-diagnose principle and without adjustment by logistic regression models. Results are presented with odds ratios and 95% confidence intervals. Conclusion: The DAYLIGHT trial will provide evidence on whether extending a CTA to include the heart results in an increased detection of cardioaortic thrombi compared to standard-of-care stroke workup.
Primal World Belief Research, for Skeptics
Authors: Clifton Jeremy D.W. , Love Noah S. , Kerry Nicholas
Published: July 2024

Sometimes skeptics are tempted to dismiss world beliefs as meaningful phenomena. Such dismissal, we argue, is a mistake. How beliefs about many broad topics impact behavior is well-established. Psychologically rich world beliefs have also peppered the cultural milieu for centuries. Multiple, decades-old literatures have already established psychometrically the existence of world beliefs, proposed effects, and developed sufficient theory to define the beliefs and explain effects (e.g., Belief in a Just World literature). However, a shared, operationalized list of belief dimensions was lacking. Does one craft such a list a priori, with a specific outcome in mind – the typical approach – or seek to discover pre-existing dimensionality empirically, with no outcome privileged – similar to how Big Five traits were identified? The former being tried (Janoff-Bulman, 1989), Clifton and colleagues (2019) chose the latter, sparking an emerging, interdisciplinary effort. Yet the origins of these beliefs remain unknown and developmental psychologists are, now, sorely needed.
Association between Smoking Habit Changes and the Risk of Myocardial Infarction in Ischemic Stroke Patients: A Nationwide Cohort Study
Authors: Cheon Dae Young , Han Kyung-Do , Ye Dong A , Lee Yeon Jung , Lee Jeen Hwa , Choi Jae Hyuk , Lee Sook Jin , Han Seongwoo , Park Myung Soo , Lee Minwoo
Published: July 2024

Background: Smoking is a well-known risk factor for cardiovascular diseases, including myocardial infarction (MI) and ischemic stroke (IS). While the relationship between smoking and the risk of cardiovascular diseases is established, the impact of changing smoking habits post-IS on the risk of subsequent MI remains unclear. This study aims to elucidate the effects of alterations in smoking behavior following an IS diagnosis on the likelihood of experiencing an MI. Methods: Utilizing data from the Korean National Health Insurance Services Database, this nationwide population-based cohort study included 199,051 participants diagnosed with IS between January 2010 and December 2016. Smoking status was categorized based on changes in smoking habits before and after IS diagnosis. The association between changes in smoking behavior and the risk of subsequent MI was analyzed using multivariable Cox proportional hazard regression models. Results: During a median follow-up of 4.17 person-years, a total of 5,734 (2.88%) patients were diagnosed with MI after IS. Smoking quitters (2.93%) or former smokers (2.47%) have a similar or lower rate of MI than the average, even if they have smoked cigarettes, while sustained smokers (3.46%) or new smokers (3.81%) have much higher rates of MI. Among sustained and new smokers, the risk of incident MI was significantly higher than never smokers (new smoker adjusted HR [aHR]: 1.496, 95% CI: 1.262–1.774; sustained smoker aHR: 1.494, 95% CI: 1.361–1.641). Also, among the study participants, approximately two-thirds continued smoking after their IS diagnosis. Conclusion: Changing smoking habits after an IS diagnosis significantly influences the risk of subsequent MI. Specifically, continuing or starting to smoke after an IS diagnosis is associated with a higher risk of MI. These results underscore the importance of targeted smoking cessation interventions for stroke patients to reduce the risk of subsequent MI.
COPD, Bronchiektasen und neutrophile Inflammation: Den Einfluss von Atemwegsentzündungen, Infektionen und Rauchen bedenken
Authors: Gülsen Askin
Published: July 2024

Background: The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. Results: COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis-COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. Conclusion: COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.
Activation of the alpha 7 nicotinic acetylcholine receptor by GTS-21 mitigates contrast nephropathy in a rat model
Authors: Akcay Seckin , Ozdemir Kumral Zarife Nigar , Cilingir-Kaya Ozlem Tugce , Peker Eyüboglu Irem , Akkiprik Mustafa , Yegen Berrak C. , Koc Mehmet
Published: July 2024

Introduction: Contrast nephropathy (CN) is characterized by oxidative stress, vasoconstriction, tubular toxicity and hypoxia of the renal medulla. We aimed to test the therapeutic effects of an α7 nicotinic acetylcholine receptor (nAChR) agonist, GTS-21, in an experimental CN model.
Methods: Male Sprague‒Dawley rats (n=40) were divided into 4 groups: saline-treated control, GTS-21-treated control, contrast, and GTS-21-treated contrast groups. Starting on the 1st day, GTS-21 (4 mg/kg, intraperitoneally) or saline was administered twice a day for 3 days. CN was induced on the second day by intravenous injection of indomethacin (10 mg/kg), L-NAME (10 mg/kg), and a contrast agent with high osmolarity (6 ml/kg; Urografin 76%). At the 72nd hour, blood and kidney samples were obtained for the determination of biochemical, histological, and gene expression parameters.
Results: Compared to those in control rats, the elevated serum BUN level in the contrast group decreased with GTS-21 treatment, while H&E staining and TUNEL assays showed that contrast-induced renal injury was improved by GTS-21. Moreover, GTS-21 treatment in the CN also increased the antioxidant glutathione level. In the contrast group, a significant increase in IL-6 expression and a decrease in TGF-β expression were observed; however, GTS-21 treatment decreased IL-6 expression and increased TGF-β expression.
Conclusion: GTS-21 significantly alleviated renal injury parameters through antioxidant, anti-inflammatory, and antiapoptotic mechanisms in the CN model.
Noonan Syndrome Growth Charts and Genotypes: 15-Year Longitudinal Single-Centre Study
Authors: Cappa Marco , d’Aniello Francesco , Digilio Maria Cristina , Gagliardi Maria Giulia , Minotti Chiara , Leoncini Pier Paolo , Pietropoli Alberto , Nicolucci Antonio , Graziano Giusi , Ubertini Graziamaria
Published: July 2024

Introduction: Growth patterns in Noonan syndrome (NS) remain relatively unknown. The objective of this study was to provide growth reference curves for patients with NS and identify correlations between their growth, genotype, and clinical features. Methods: This was a 15-year-long, monocentric, observational, retrospective, non-interventional study. Children with NS followed up between 2005 and 2022 at “Bambino Gesù” Children’s Hospital, Italy, were included and excluded if they had received growth hormone treatment. Comparison of growth curves of participants with NS versus the general Italian population and further genotypic analyses were performed. Results: Overall, 190 eligible participants with NS were identified, with median (interquartile range) age of 14.01 (9.05–19.25) years (55.8% male). Cardiovascular anomalies were present in 85.3% of participants, most commonly pulmonary stenosis (52.6%) and atrial septal defects (36.8%); 48.1% of male participants had cryptorchidism. The most frequently detected mutations were in PTPN11 (66.3%) and SOS1 (13.9%). NS sex-specific centile curves for height, weight, body mass index, and height velocity were produced. For both sexes, the 50th percentile of height and weight for participants with NS overlapped with the 3rd percentile for the general Italian population. Both sexes with a PTPN11 mutation had a significantly lower height and weight than those with “other mutations” at 5 years old. No significant associations were observed between cardiac anomalies and PTPN11 mutation status. Conclusion: We present longitudinal data describing growth curves and trends, the natural history, and genotypes of the NS population, which provide a useful tool for clinicians in the management of NS.
Current Practices and Considerations in Lung Biopsy for Suspected Granulomatous-Lymphocytic Interstitial Lung Disease: A Clinician Survey
Authors: Bintalib Heba M. , Davidsen Jesper Rømhild , Van de Ven Annick A.J.M. , Goddard Sarah , Burns Siobhan O. , Warnatz Klaus , Hurst John R.
Published: July 2024

Introduction: This study explores clinicians’ diagnostic practices and perceptions in the context of granulomatous-lymphocytic interstitial lung disease (GLILD), a pulmonary manifestation of common variable immunodeficiency disorder. The aim was to gain valuable insights into key aspects, such as the utilization of radiological features for diagnostic purposes, indications for lung biopsy, preferred biopsy techniques, and the relative importance of different histopathological findings in confirming GLILD. Method: A survey targeting expert clinicians was conducted, focusing on their experiences, practices, and attitudes towards lung biopsy in suspected GLILD cases. Results: The survey revealed that the majority of respondents accepted high-resolution computed tomography as a sufficient alternative to biopsy for making a probable GLILD diagnosis in most patients. There was a consensus among most respondents that the presence of extrapulmonary granulomatous disease is adequate for making a diagnosis of GLILD where the chest imaging and clinical picture are consistent. When a biopsy was recommended, there was notable variation in the preferred initial biopsy technique, with 35% favouring transbronchial biopsy. Conclusion: Our findings underscore the complexity of diagnosing GLILD, indicating varied clinician opinions on the necessity and efficacy of lung biopsies. They highlight the need for further research and the development of consistent diagnostic criteria and management protocols, ultimately aiming to enhance the accuracy and safety of GLILD diagnosis and treatment strategies.
Radiation Principles, Protection, and Reporting for Interventional Pulmonology: A World Association of Bronchology and Interventional Pulmonology White Paper
Authors: Wijma Inge N. , Casal Roberto F. , Cheng George Z. , Einsiedel Paul F. , Fantin Alberto , Hall David J. , Herth Felix J.F. , Ng Calvin S.H. , Pritchett Michael A. , Shah Pallav L. , Steinfort Daniel P. , Trisolini Rocco , Verhoeven Roel L.J. , van der Heijden Erik H.F.M.
Published: July 2024

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.
Hospital Admission, Medical, and Surgical Procedures for Acute Diverticulitis Are More Appropriate when Using a Diagnostic and Therapeutic Assistance Pathway: An Experience from a Referral Center
Authors: Elisei Walter , Marini Pierluigi , Faggiani Roberto , Manfroni Stefano , Ricci Gabriele , Di Fuccia Noemi , Papa Valerio , Tursi Antonio
Published: July 2024

Introduction: Our aim was to assess the impact of the Diagnostic and Therapeutic Assistance Pathway (PDTA) developed for acute diverticulitis (AD) on the management of patients with AD and referring to the emergency room (ER) in a referral center. Methods: This retrospective study includes all patients diagnosed with AD and referring to the ER between January 1, 2021, and December 31, 2022 (after approval of PDTA), compared to the same period of 2015–2019. Length of stay in ER, medical and surgical management, and length in hospital stay (in days) were also measured according to the type of disease (uncomplicated vs. complicated). Results: ER admission due to AD during the period 2015–2019 was 240 ± 13 cases per year, while it was 290 cases in 2022 (p = 0.05). After adopting the PDTA, the rate of length of stay in ER >24 h for AD was significantly reduced (p = 0.01); the median rate of hospital admission for AD was significantly reduced (p < 0.05); the rate of medical treatment of uncomplicated disease was increased (p = 0.01), while the rate of surgical management was decreased (p = 0.05); the rate of medical treatment of complicated disease was increased (p = 0.01), while the rate of surgical management was decreased (p = 0.001); the hospital stay was significantly reduced in both uncomplicated (p = 0.05) and complicated (p = 0.05) AD. Conclusions: The development and the routine use of a PDTA dedicated to AD have significantly improved the management of these patients, reducing the ER stay, the surgical procedures, and the overall hospital stay.
Sex-Based Analysis of Treatment, Time Metrics, and Outcomes in Acute Ischemic Stroke Patients Treated in the Netherlands
Authors: Exalto Lieza Geertje , Ali Mariam , Stolze Lotte J. , Baharoglu M. Irem , Wermer Marieke J.H. , Kappelle L. Jaap ,   on behalf of the Consortium of the Dutch Acute Stroke Audit
Published: July 2024

Introduction: Sex disparities in stroke treatment have gained increasing interest, especially since women have worse post-stroke functional outcomes compared with men. Existing studies provide conflicting evidence, with some indicating women have longer delays and less often receive acute treatment, whereas others show no differences between men and women. We aimed to explore sex differences in acute treatment modalities and time metrics of patients with acute ischemic stroke (AIS) in a real-world setting. Second, we examined whether functional outcomes differed by sex and whether this was influenced by treatment timing. Methods: We analyzed data from the Dutch Acute Stroke Audit, a prospective consecutive registry of AIS patients from 72 hospitals in the Netherlands, between 2017 and 2020. We captured data on type of treatment administered (intravenous thrombolysis [IVT] and endovascular thrombectomy [EVT]), time metrics (onset-to-door time [OTDT], door-to-needle and door-to-groin times), and functional outcomes at 3 months (modified Rankin scale [mRS]). The association between sex and poor outcome (mRS 3–6) was assessed with Cox proportional hazard models stratified by type of treatment and adjusted for age, additionally for National Institutes of Health Stroke Scale (NIHSS) and OTDT. Results: Of the 58,632 patients, 26,941 (46%) were women. Compared with men, women were older (mean age 74.6 vs. 71.0, p < 0.001) and presented with slightly higher NIHSS scores (median 3 [IQR 2–7] vs. 3 [IQR 1–6], p < 0.001). Treatment modalities distribution (no treatment, IVT, EVT) was similar between women and men (64; 29; 10 vs. 63; 30; 9%, p = 0.16). Women had a slightly longer OTDT (median 145 vs. 139 min, p < 0.01). Women had increased odds of poor outcomes (OR 1.49 [95% CI: 1.43–1.56]). This was still statistically significant after adjusting for age and NIHSS score (OR 1.22 [95% CI: 1.16–1.28]). Neither treatment modality nor OTDT had an additional influence on this association. Conclusion: In this large real-world registry, we observed no differences in distribution of treatment modalities between sexes. We did find a minor pre-hospital delay in women and worse functional outcomes in women. The minor delay in OTDT does not fully explain the observed worse outcomes in women. Our results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Dutch centers.
The Association of Hematological Markers with Occurrence of Thrombotic and Bleeding Events following Left Atrial Appendage Occlusion
Authors: Aarnink Errol , Della Rocca Domenico , Cepas-Guillen Pedro , Benito-González Tomás , Polzin Amin , Branca Luca , Spoon Daniel , Adamo Marianna , Freixa Xavier , Natale Andrea , Boersma Lucas V.A.
Published: July 2024

Introduction: Patients undergoing left atrial appendage occlusion (LAAO) are at increased risk for bleeding or thromboembolic events. Concurrently, biomarkers are of growing importance in risk stratification for atrial fibrillation patients. We aimed to evaluate the association of hematological markers and clinical characteristics with the occurrence of thromboembolic and bleeding events following LAAO. Methods: Seven implanting centers retrospectively gathered data on hematological markers (i.e., platelet count [PC], mean platelet volume [MPV], and fibrinogen) prior to LAAO. Prespecified thromboembolic and major bleeding outcomes were collected and the association with pre-procedural hematological markers and clinical characteristics was evaluated using Cox regression analysis. Results: In total, 1,315 patients were included (74 ± 9 years, 36% female, CHA2DS2-VASc 4.3 ± 1.5, HAS-BLED 3.3 ± 1.1). Over a total follow-up duration of 2,682 patient years, 77 thromboembolic events and 107 major bleeding events occurred after LAAO. Baseline PC was the only biomarker showing a signal for a relation to thromboembolic events (HR 1.18, 95% CI: 1.00–1.39) per 50*109 increment, p = 0.056). Thrombotic event rates, including device-related thrombus, increased within higher PC quartiles. Thromboembolism was associated with age (HR 1.05, 95% CI: 1.00–1.10, per year increase) and prior thromboembolism (HR 2.08, 95% CI: 1.07–4.03), but with none of the biomarkers in multivariate analysis. No association of any of the hematological markers with major bleeding was observed. Major bleeding following LAAO was associated with prior major bleeding (HR 5.27, 95% CI: 2.71–10.22), renal disease (HR 1.93, 95% CI: 1.17–3.18), and discharge on dual antiplatelet therapy (DAPT) (HR 1.71, 95% CI: 1.05–2.77). Conclusion: Most thrombotic events occurred in the highest PC quartile, but no association of any of the hematological markers with thromboembolism or major bleeding was observed in our analysis. In multivariate analysis, older age and prior thromboembolism were associated with thromboembolism. Prior major bleeding, renal disease and discharge on DAPT were multivariate predictors of major bleeding after LAAO.
Fine-Needle Aspiration for Actionable Diagnosis of Mandibular Osteosarcoma Recurrence
Authors: Maffei Elisabetta , De Giulio Francesco , Rizzo Paola Chiara , Zeppa Pio , Caputo Alessandro
Published: July 2024

Introduction: Mandibular osteosarcoma (MOS) is a rare malignant bone tumour known for its rapid and aggressive behaviour, particularly in cases of relapse. Early and accurate diagnosis is crucial for effective treatment. Case Presentation: We report the case of a 48-year-old woman with recurrent MOS. Fine-needle aspiration cytology (FNAC) was utilized for diagnosis, facilitating prompt and appropriate treatment. The FNAC technique proved essential in confirming the diagnosis quickly, allowing for timely intervention. Conclusion: This case underscores the importance of FNAC in diagnosing MOS, especially in relapse situations where swift treatment is critical. FNAC can be a valuable tool in ensuring rapid and accurate diagnosis, leading to better patient outcomes.
SIRT1 Promotes Chemoradiotherapy Resistance in Esophageal Squamous Cell Carcinoma
Authors: Morishita Hiroki , Otsuka Ryota , Murakami Kentaro , Endo Satoshi , Toyozumi Takeshi , Matsumoto Yasunori , Shiraishi Tadashi , Iida Shinichiro , Makiyama Tenshi , Nishioka Yuri , Hu Jie , Maiyulan Abula , Matsubara Hisahiro
Published: July 2024

Introduction: Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remain unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC. Methods: This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively. Results: High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control. Conclusion: Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC.
Intra-Cochlear Electrode Position Impacts the Preservation of Residual Hearing in an Animal Model of Cochlear Implant Surgery
Authors: Meuser Max , Schwitzer Susanne , Thiele Mario , Boyle Patrick , Ernst Arne , Basta Dietmar
Published: July 2024

Introduction: Preservation of residual hearing after cochlear implantation remains challenging. There are several approaches to preserve residual hearing, but the configuration of the implant electrode array seems to play a major role. Lateral wall electrode arrays are seemingly more favorable in this context. To date, there are no experimental data available which correlate the spatial electrode position in the scala tympani with the extent of hearing preservation. Methods: Based on micro-computed tomography (µCT) imaging data, this study analyses the exact position of a pure silicone electrode array inserted into the cochlea of four guinea pigs. Array position data were correlated with the extent of hearing loss after implantation, measured using auditory brainstem measurements in the frequency range of the area occupied by the electrode array area as well as apical to the array. Results: The use of pure silicone arrays without electrodes resulted in artifact-free, high-resolution µCT images that allowed precise determination of the arrays’ positions within the scala tympani. The electrode arrays’ locations ranged from peri-modiolar to an anti-modiolar. These revealed a correlation of a lower postoperative hearing loss with a higher spatial proximity to the lateral wall. This correlation was found in the low-frequency range only. A significant correlation between the inter-individual differences in the diameter of the scala tympani and the postoperative hearing loss could not be observed. Conclusion: This study demonstrates the importance of the intra-cochlear electrode array’s position for the preservation of residual hearing. The advantage of such an electrode array’s position approximated to the lateral wall suggests, at least for this type of electrode array applied in the guinea pig, it would be advantageous in the preservation of residual hearing for the apical part of the cochlea, beyond the area occupied by the electrode array.
Acute Care, Secondary Prevention, and Outcomes after Ischaemic and Haemorrhagic Stroke in Men and Women: A Data-Linkage Study
Authors: Sterling Kadie-Ann , MacLeod Mary Joan , Barber Mark , Turner Melanie
Published: July 2024

Introduction: There is evidence that sex differences exist in stroke presentation, risk factors, severity, treatment, and outcomes. To further understand this, we explored how sex differences influence acute stroke management, secondary prevention prescribing, and mortality outcomes in a well-characterised cohort of first-ever stroke patients in Scotland. Methods: This is a retrospective, population-based, data-linkage study of stroke admissions to acute care hospitals in Scotland between January 1, 2011, and December 31, 2018. Data sources included the Scottish Stroke Care Audit (SSCA), the Prescribing Information System (PIS), the Scottish Morbidity Record 01 (SMR01), and the National Records of Scotland (NRS) death records. Multivariable logistic regression was used to explore the association between patient sex, acute stroke care, and secondary prevention prescribing, while Cox proportional hazards models were used to explore the association between patient sex and all-cause mortality up to 1 year after index event. Results: This study included 5,901 patients with a first-ever intracerebral haemorrhage (ICH) and 47,087 patients with a first-ever acute ischaemic stroke (AIS). After an ICH, women had significantly lower odds of receiving all components of the stroke care bundle (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69–0.87) and were less likely to be prescribed antihypertensives within 90 days after discharge to the usual place of residence (aOR, 0.78; 95% CI, 0.63–0.97). There was no sex difference in stroke care bundle achievement for those admitted with AIS; however, women had significantly lower odds of receiving antihypertensives, lipid-lowering drugs, or oral anticoagulants after discharge. The risk of all-cause mortality was lower in women at 1 year after both ICH (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.83–0.98) and AIS (aHR, 0.91; 95% CI, 0.87–0.95) after adjusting for potential confounders. Conclusion: The sex differences in stroke treatment and outcomes may be partly explained by the older age of women at the time of stroke, which influences stroke presentation, severity, and prognosis. However, following adjustment, women had a reduced risk of all-cause mortality after both ICH and AIS.
The Prognostic Test Accuracy of the Short and Standard Forms of the Montreal Cognitive Assessment
Authors: Abzhandadze Tamar , Berg Olga I. , Mavridis Anastasios , Lindvall Elias , Quinn Terry , Sunnerhagen Katharina S. , Lundström Erik
Published: July 2024

Introduction: Cognitive impairment is a critical concern in stroke care, and international guidelines recommend early cognitive screening. The aim of this study was to determine the prognostic accuracy of both the short and standard forms of the Montreal Cognitive Assessment (MoCA) in predicting long-term cognitive recovery following a stroke. Methods: For this study, we used data from the Efficacy of Fluoxetine – a Randomized Controlled Trial in Stroke (EFFECTS) study, which encompassed stroke patients from 35 Swedish centers over the period from 2014 to 2019. Cognitive assessments were initially conducted at 2–15 days post-stroke, with follow-up data gathered at 6 months. We used the MoCA for objective cognitive evaluation. For assessing subjective cognitive impairment, we used the memory and thinking domain of the Stroke Impact Scale. For psychometric evaluation of the short Swedish version of MoCA (s-MoCA-SWE), we used cross tables and binary logistic regression. Results: The study included 1,141 patients (62.2% men; median [interquartile range; IQR] age, 72.3 [13.2] years; median [IQR] stroke severity, 3.0 [3.0]). At baseline, the prevalence of cognitive impairment was 71.7% according to the s-MoCA-SWE (≤12) and 67.0% according to the MoCA (≤25). The s-MoCA-SWE demonstrated a sensitivity of 92.3% for correctly identifying patients with objective cognitive impairment and 81.5% for identifying those with subjective impairments at 6 months. Although the s-MoCA-SWE had higher sensitivity, the MoCA had a more balanced sensitivity and specificity in detecting both subjective and objective cognitive impairments. In both crude and multivariable models, the s-MoCA-SWE was more strongly associated than the MoCA with cognitive impairment at 6 months. Conclusions: Both the short and standard versions of the MoCA appear to be effective in identifying individuals likely to experience persistent cognitive issues following a stroke. Considering the limited time available in an acute stroke unit, the short-form version may be more practical. Nevertheless, further prospective studies are required to validate these findings.