bluuebunny/crossref_metadata_2025 huggingface dataset:
Orofacial Granulomatosis Associated with Crohn’s Disease: a Multicentre Case Series
Authors: Phillips Frank , Verstockt Bram , Sladek Malgorzata , de Boer Nanne , Katsanos Konstantinos , Karmiris Konstantinos , Albshesh Ahmad , Erikson Carl , Bergemalm Daniel , Molnar Tamas , Ellul Pierre
Published: September 2021

Background

Orofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn’s disease [CD]. We aimed to characterise this relationship and the management options in the biologic era.

Methods

This multicentre case series was supported by the European Crohn’s and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form.

Results

This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs.

Conclusions

OFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.
Validation of a novel risk score to predict mortality after surgery for acute type A dissection
Authors: Kofler Markus , Heck Roland , Seeber Fabian , Montagner Matteo , Gasser Simone , Stastny Lukas , Kurz Stephan D , Grimm Michael , Falk Volkmar , Kempfert Jörg , Dumfarth Julia
Published: September 2021

OBJECTIVES

The aim of this study was to externally validate a lab-based risk score (lactate, creatinine, aspartate aminotransferase, alanine aminotransferase or bilirubin) by Ghoreishi et al. to predict perioperative mortality in patients undergoing surgical repair for acute type A aortic dissection.

METHODS

The risk score to predict operative mortality was applied to a large and homogenous validation cohort that consisted of 632 patients undergoing surgery for acute type A aortic dissection in 2 centres. Multivariable regression analysis was performed to determine the impact on survival. Receiver operating characteristics with deduced area under the curve were used to assess the ability to predict perioperative mortality.

RESULTS

A total of 632 patients (54% male, mean age 62 ± 14 years) were assigned to 3 different risk groups according to the calculated mortality score [low risk <7 (31.2%), moderate risk 7–20 (36.1%) and high >20 (32.7%)]. Perioperative mortality was 8% in the low-risk group, 10% in the moderate-risk group and 24% in the high-risk group (P < 0.0001). Receiver operating characteristic analysis of this new score revealed an area under the curve of 0.69 with adequate calibration. In addition, multivariable analysis revealed an independet assocation with perioperative mortality (odds ratio 1.509; 95% confidence interval 1.042–2.185). While overall survival differed between the risk groups (P < 0.0001), the score does not serve as an independent predictor of long-term mortality when adjusted for relevant covariates.

CONCLUSIONS

The external validation process confirmed that a newly proposed risk score offers clinicians a helpful and reliable tool to improve the preoperative risk assessment of acute type A aortic dissection patients based on easily accessible and broadly available laboratory parameters.
Malocclusion severity and its associations with oral health-related quality of life in an adult population
Authors: Närhi Linnea , Tolvanen Mimmi , Pirttiniemi Pertti , Silvola Anna-Sofia
Published: September 2021

Aim

The aim of this study was to investigate malocclusion severity and its associations with oral health-related quality of life (OHRQoL) among middle-aged adults.

Materials and methods

The study material consisted of 1786 subjects from the Northern Finland Birth Cohort 1966 who attended dental and oral examination as part of the 46-year-old follow-up study. Malocclusion severity was assessed using the Dental Health Component (DHC) of the Index of Orthodontic Treatment Need (IOTN) and the Peer Assessment Rating index (PAR) from digital 3D dental models. Participants also answered a questionnaire including the Oral Health Impact Profile (OHIP-14) and a question on their satisfaction with occlusal function. Differences between malocclusion severity groups were evaluated for both genders separately. For adjusted models, multivariate Poisson regression models were conducted.

Results

In this study population, 31.3% had great or very great orthodontic treatment need according to DHC and the mean PAR total score was 22.05. The most severe malocclusions were associated with OHRQoL, especially the psychosocial and handicap dimensions, and satisfaction with occlusal function. There was a significant difference between genders, men having more severe malocclusion but women reporting more OHRQoL impacts.

Conclusion

One third of the study population were considered to have severe malocclusion. There was an association between malocclusion severity and OHRQoL in adult population, particularly in women.
Addressing sociolinguistic challenges in teaching spoken grammar
Authors: Ruivivar June
Published: September 2021

Over the last 25 years, scholars have proposed several recommendations for including spoken grammar in second language classrooms. However, recent studies point to potential challenges in this endeavour: learners may feel inauthentic when using what they see as ‘native-speaker’ forms, and interlocutors may see these forms as less acceptable when used by non-native speakers. This paper examines current recommendations for teaching spoken grammar in light of these issues and proposes a functional teaching approach that presents spoken grammar as a communicative resource rather than a formal characteristic of native-speaker usage. It then reports on a pilot study exploring the feasibility and students’ reception of such an approach. The paper concludes that it is possible to adapt spoken grammar pedagogy to be more socioculturally sensitive, and that teaching should aim towards a fuller understanding and appreciation of the affordances of spoken grammar.
Jakob Adlung’s ‘Anweisung zum Fantasiren’ (c.1725–7): edition, translation and introduction
Authors: Remeš Derek , Maul Michael
Published: September 2021

Jakob Adlung’s recently rediscovered manuscript treatise, ‘Anweisung zum Fantasiren’ (‘Instruction in improvisation’, c.1725–7), proves definitively that some 18th-century musicians understood improvisation modularly in terms of stock voice-leading patterns, or schemas. The manuscript is a compendium containing 28 typical voice-leading patterns that are to be memorized, varied and combined in myriad ways. Adlung’s treatise is thus of particular value, not only because of its numerous musical examples and extensive textual commentary, but because it reveals some of the musical and social expectations of the average central German church organist in the early 18th century. This article offers an introduction to the treatise in the context of Adlung’s biography, with an online appendix containing a critical edition of the treatise and an English translation.
Evolution and Reproducibility of Simulation Modeling in Epidemiology and Health Policy Over Half a Century
Authors: Jalali Mohammad S , DiGennaro Catherine , Guitar Abby , Lew Karen , Rahmandad Hazhir
Published: September 2021

Simulation models are increasingly being used to inform epidemiologic studies and health policy, yet there is great variation in their transparency and reproducibility. In this review, we provide an overview of applications of simulation models in health policy and epidemiology, analyze the use of best reporting practices, and assess the reproducibility of the models using predefined, categorical criteria. We identified and analyzed 1,613 applicable articles and found exponential growth in the number of studies over the past half century, with the highest growth in dynamic modeling approaches. The largest subset of studies focused on disease policy models (70%), within which pathological conditions, viral diseases, neoplasms, and cardiovascular diseases account for one-third of the articles. Model details were not reported in almost half of the studies. We also provide in-depth analysis of modeling best practices, reporting quality and reproducibility of models for a subset of 100 articles (50 highly cited and 50 randomly selected from the remaining articles). Only 7 of 26 in-depth evaluation criteria were satisfied by more than 80% of samples. We identify areas for increased application of simulation modeling and opportunities to enhance the rigor and documentation in the conduct and reporting of simulation modeling in epidemiology and health policy.
Maternal and neonatal complications in women with congenital heart disease: a nationwide analysis
Authors: Lammers Astrid Elisabeth , Diller Gerhard-Paul , Lober Rieke , Möllers Mareike , Schmidt Renate , Radke Robert M , De-Torres-Alba Fernando , Kaleschke Gerrit , Marschall Ursula , Bauer Ulrike M , Gerß Joachim , Enders Dominic , Baumgartner Helmut
Published: September 2021

Aims

The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD).

Methods and results

Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, ∼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001).

Conclusions

This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.
Clinical features and survival in Takayasu’s arteritis-associated pulmonary hypertension: a nationwide study
Authors: Jiang Xin , Zhu Yong-Jian , Zhou Yu-Ping , Peng Fu-Hua , Wang Lan , Ma Wei , Cao Yun-Shan , Pan Xin , Zhang Gang-Cheng , Zhang Feng , Fan Fen-Ling , Wu Bing-Xiang , Huang Wei , Yang Zhen-Wen , Hong Cheng , Li Meng-Tao , Wang Yi-Ning , Xu Xi-Qi , Wang Duo-Lao , Zhang Shu-Yang , Jing Zhi-Cheng
Published: September 2021

Aims

This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu’s arteritis-associated pulmonary hypertension (TA-PH).

Methods and results

We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu’s arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77–16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03–1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01–1.13), P = 0.015].

Conclusion

Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators’ personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.
Cardiovascular immunotoxicities associated with immune checkpoint inhibitors: a safety meta-analysis
Authors: Dolladille Charles , Akroun Julia , Morice Pierre-Marie , Dompmartin Anne , Ezine Emilien , Sassier Marion , Da-Silva Angélique , Plane Anne-Flore , Legallois Damien , L’Orphelin Jean-Mathieu , Alexandre Joachim
Published: September 2021

Aims 

The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown.

Methods and results

We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56–12.50, P < 0.01; I  2 = 0%, P = 0.93) and dyslipidemia (Peto OR: 3.68, 95% CI: 1.89–7.19, P < 0.01; I  2 = 0%, P = 0.66). The incidence of these CVAEs ranged from 3.2 (95% CI 2.0–5.1) to 19.3 (6.7–54.1) per 1000 patients, in studies with a median follow-up ranging from 3.2 to 32.8 months.

Conclusion

In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.
Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure
Authors: Cox Zachary L , Rao Veena S , Ivey-Miranda Juan B , Moreno-Villagomez Julieta , Mahoney Devin , Ponikowski Piotr , Biegus Jan , Turner Jeffrey M , Maulion Christopher , Bellumkonda Lavanya , Asher Jennifer L , Parise Helen , Wilson Perry F , Ellison David H , Wilcox Christopher S , Testani Jeffrey M
Published: September 2021

Aims

In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.

Methods and results

Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47).

Conclusion

On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
Impact of COVID-19 pandemic restrictions on ST-elevation myocardial infarction: a cardiac magnetic resonance imaging study
Authors: Lechner Ivan , Reindl Martin , Tiller Christina , Holzknecht Magdalena , Troger Felix , Fink Priscilla , Mayr Agnes , Klug Gert , Bauer Axel , Metzler Bernhard , Reinstadler Sebastian J
Published: September 2021

Aims

The severity of myocardial tissue damage following ST-elevation myocardial infarction (STEMI) strongly determines short- and long-term prognosis. This study explored the impact of the coronavirus disease 2019 (COVID-19) pandemic and associated public health restrictions on infarct severity.

Methods and results

STEMI patients treated with primary percutaneous coronary intervention (PCI) and included in the prospective Magnetic Resonance Imaging in Acute ST-Elevation Myocardial Infarction (MARINA-STEMI) cohort study from 2015- 2020 (n = 474) were categorized according to (i) timeframes with and without major public health restrictions in 2020, and (ii) timeframes of major public health restrictions during 2020 and during the corresponding timeframes between 2015-2019. Myocardial damage was evaluated by cardiac magnetic resonance imaging. During major public health restrictions in 2020 (n = 48), there was an increase in infarct size (22 [IQR 12-29] vs. 14 [IQR 6-23]%, P < 0.01), a higher frequency (77% vs. 52%, P < 0.01) and larger extent of microvascular obstruction (1.5 [IQR 0.1-11.4] vs. 0.2 [IQR 0.0-2.6]%, P < 0.01) and a higher rate of intramyocardial haemorrhage (56% vs. 34%, P = 0.02) as compared to the phases without major restrictions in 2020 (n = 101). These findings were confirmed in adjusted analysis and were consistent when comparing patients admitted in 2020 versus patients admitted in the “pre-pandemic” era (2015-2019). Patient characteristics were comparable between groups, except for a significantly longer total ischemia time (P < 0.01) and higher frequency of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow 0 during times of major restrictions (P = 0.03).

Conclusion

This study provides novel mechanistic insights demonstrating a significant increase in myocardial damage in STEMI patients admitted during the COVID-19 pandemic with a temporal relation to major public health restrictions.
Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects
Authors: Ansell Jack , Bakhru Sasha , Laulicht Bryan E , Tracey Gregory , Villano Stephen , Freedman Daniel
Published: September 2021

Aims 

Ciraparantag is a reversal agent for anticoagulants including direct oral anticoagulants. The aim was to evaluate the efficacy and safety of ciraparantag to reverse anticoagulation induced by apixaban or rivaroxaban in healthy elderly adults.

Methods and results 

Two randomized, placebo-controlled, dose-ranging trials conducted in healthy subjects aged 50–75 years. Subjects received apixaban (Study 1) 10 mg orally twice daily for 3.5 days or rivaroxaban (Study 2) 20 mg orally once daily for 3 days. At steady-state anticoagulation subjects were randomized 3:1 to a single intravenous dose of ciraparantag (Study 1: 30, 60, or 120 mg; Study 2: 30, 60, 120, or 180 mg) or placebo. Efficacy was based on correction of the whole blood clotting time (WBCT) at multiple timepoints over 24 h. Subjects and technicians performing WBCT testing were blinded to treatment. Complete reversal of WBCT within 1 h post-dose and sustained through 5 h (apixaban) or 6 h (rivaroxaban) was dose related and observed with apixaban in 67%, 100%, 100%, and 17% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, or placebo, respectively; and with rivaroxaban in 58%, 75%, 67%, 100%, and 13% of subjects receiving ciraparantag 30 mg, 60 mg, 120 mg, 180 mg, or placebo, respectively. Adverse events related to ciraparantag were mild, transient hot flashes or flushing.

Conclusions 

Ciraparantag provides a dose-related reversal of anticoagulation induced by steady-state dosing of apixaban or rivaroxaban. Sustained reversal was achieved with 60 mg ciraparantag for apixaban and 180 mg ciraparantag for rivaroxaban. All doses of ciraparantag were well tolerated.
Application of artificial intelligence to the electrocardiogram
Authors: Attia Zachi I , Harmon David M , Behr Elijah R , Friedman Paul A
Published: September 2021

Artificial intelligence (AI) has given the electrocardiogram (ECG) and clinicians reading them super-human diagnostic abilities. Trained without hard-coded rules by finding often subclinical patterns in huge datasets, AI transforms the ECG, a ubiquitous, non-invasive cardiac test that is integrated into practice workflows, into a screening tool and predictor of cardiac and non-cardiac diseases, often in asymptomatic individuals. This review describes the mathematical background behind supervised AI algorithms, and discusses selected AI ECG cardiac screening algorithms including those for the detection of left ventricular dysfunction, episodic atrial fibrillation from a tracing recorded during normal sinus rhythm, and other structural and valvular diseases. The ability to learn from big data sets, without the need to understand the biological mechanism, has created opportunities for detecting non-cardiac diseases as COVID-19 and introduced challenges with regards to data privacy. Like all medical tests, the AI ECG must be carefully vetted and validated in real-world clinical environments. Finally, with mobile form factors that allow acquisition of medical-grade ECGs from smartphones and wearables, the use of AI may enable massive scalability to democratize healthcare.
Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction
Authors: Sinha Aish , Rahman Haseeb , Webb Andrew , Shah Ajay M , Perera Divaka
Published: September 2021

Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD–HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD–HFpEF, as well as the clinical and research implications of the CMD–HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients.
Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms
Authors: Liu Xiu , Guo Jia-Wei , Lin Xiao-Chun , Tuo Yong-Hua , Peng Wan-Li , He Su-Yue , Li Zhao-Qiang , Ye Yan-Chen , Yu Jie , Zhang Fei-Ran , Ma Ming-Ming , Shang Jin-Yan , Lv Xiao-Fei , Zhou An-Dong , Ouyang Ying , Wang Cheng , Pang Rui-Ping , Sun Jian-Xin , Ou Jing-Song , Zhou Jia-Guo , Liang Si-Jia
Published: September 2021

Aims

Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin–ASK1 pathway, not the classical calcineurin–nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis.

Methods and results

Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages.

Conclusion

Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.
Patient delay prior to care-seeking in acute myocardial infarction during the outbreak of the coronavirus SARS-CoV2 pandemic
Authors: Lidin Matthias , Lyngå Patrik , Kinch-Westerdahl Annika , Nymark Carolin
Published: September 2021

Aims

To examine patient delay in seeking medical care when afflicted by an acute myocardial infarction during March–June 2020.

Methods and results

This was a cross-sectional study in a region in Sweden during the first wave of the COVID-19 pandemic examining patients selected from the national registry (SWEDEHEART). Eligible patients were those with acute myocardial infarction, and a total of 602 patients were invited. A self-administered psychometric evaluated questionnaire, ‘Patients' appraisal, emotions, and action tendencies preceding care-seeking in acute myocardial infarction’ (AMI), was sent to the patients, and questions regarding COVID-19 were added. A total of 326 patients answered the questionnaire. Of these, 19% hesitated to seek medical care because of the pandemic, which was related to a fear that the healthcare services were already overcrowded with patients with COVID-19, followed by a fear of becoming infected with COVID-19 in hospital. Characteristics of this cohort were significantly higher prevalences of women, immigrants, smokers, and patients with type 2 diabetes.

Conclusions

During the outbreak and first wave of the COVID-19 pandemic, women and immigrants delayed seeking medical care for AMI because of fears about overcrowded hospitals and about becoming infected themselves. Therefore, during the COVID-19 pandemic, it is especially important to convey information about how and when to seek medical care. A collaboration involving the healthcare professionals, patient organizations, and the media would be desirable.
Current clinical practice in patients with cardiac implantable electronic devices undergoing radiotherapy: a literature review
Authors: Azraai Meor , D’Souza Daniel , Lin Yuan-Hong , Nadurata Voltaire
Published: September 2021

Patients with cardiac implantable electronic devices (CIED) undergoing radiotherapy (RT) are more common due to the ageing of the population. With newer CIEDs’ implementing the complementary metal-oxide semiconductor (CMOS) technology which allows the miniaturization of CIED, it is also more susceptible to RT. Effects of RT on CIED ranges from device interference, device operational/memory errors of permanent damage. These malfunctions can cause life-threatening clinical effects. Cumulative dose is not the only component of RT that causes CIED malfunction, as neutron use and dose rate effect also affects CIEDs. The management of this patient cohort in clinical practice is inconsistent due to the lack of a consistent guideline from manufacturers and physician specialty societies. Our review will focus on the current clinical practice and the recently updated guidelines of managing patients with CIED undergoing RT. We aim to simplify the evidence and provide a simple and easy to use guide based on the recent guidelines.
The use of social media for professional purposes by healthcare professionals: the #intEHRAct survey
Authors: Guerra Federico , Linz Dominik , Garcia Rodrigue , Kommata Varvara , Kosiuk Jedrzej , Chun Julian , Boveda Serge , Duncker David
Published: September 2021

Social media (SoMe) represents a medium of communication in everyday life and has gained importance for professional use among clinicians. In the #intEHRAct survey, we aimed to describe the use of SoMe by the healthcare community in a professional setting. The EHRA e-Communication Committee and the Scientific Initiatives Committee prepared a questionnaire and distributed it via newsletters, Twitter, LinkedIn, and Facebook. The survey consisted of 19 questions made on an individual basis and collected anonymously. Two hundred and eighty-five responders from 35 countries (72.3% male, age 49 ± 11 years old) completed the survey. Most respondents (42.7%) declared to use SoMe as passive users while 38.3% and 19.0% declared to share content on a non-daily and daily basis, respectively. The respondents estimated they spent a median of 5 (Q1–Q3: 2–10) h per week on SoMe. The most widely used SoMe was LinkedIn (60.8%), but the use of each platform was heterogeneous between countries. Among the advantages of SoMe, respondents indicated the chance of being updated on recent publications (66.0%), networking (48.5%), and the availability of rare or interesting cases (47.9%) as the most useful. Regarding the disadvantages of SoMe, the respondents underlined the loss of personal contact (40.7%), the inability to get ‘hands-on’ training (38.7%), and the lack of control regarding quality of scientific evidence (37.1%). Social media is increasingly used for professional purposes for scientific updating, networking, and case-based learning. The results of this survey encourage scientific societies, journals, and authors to enhance the quality, reach and impact of scientific content provided through SoMe.
Combined endo- and epicardial pace-mapping to localize ventricular tachycardia isthmus in ischaemic and non-ischaemic cardiomyopathy
Authors: Hanaki Yuichi , Komatsu Yuki , Nogami Akihiko , Kowase Shinya , Kurosaki Kenji , Sekiguchi Yukio , Aonuma Kazutaka , Ieda Masaki
Published: September 2021

Aims

A high-density pace-mapping can depict an abrupt transition in paced QRS morphology from a poor to excellent match, unmasking the critical component of ventricular tachycardia (VT) isthmus from the entrance to exit. We sought to assess pace-mapping at multiple sites within the endo- and epicardial scars to identify the VT isthmus in patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM).

Methods and results

Colour-coded maps correlating to the percentage matches between 12-lead electrocardiograms during VT and pace-mapping [referred to as correlation score maps (CSMs)] were analysed. We studied 115 CSMs (80 endo- and 35 epicardial CSMs) in 37 patients (17 ICM, 20 NICM). The CSM with an abrupt change (AC) in pacemap score (AC-type) on the endocardium was more frequently observed in ICM than in NICM [11/39 (28%) vs. 1/41 (2%); P = 0.001]. Among 35 CSMs that were analysed by the combined endo- and epicardial mapping, 10 (29%) CSMs exhibited non-AC-type on the endocardium; however, AC-type was present on the opposite epicardium. Although 24 (69%) CSMs did not show AC-type on both the endocardium and epicardium, 16 of them had either an excellent (>90%) or poor (<0%) correlation score on either side, associated with isthmus exit or entrance, respectively. However, the remaining eight CSMs had neither excellent nor poor scores.

Conclusion

The CSM may provide electrophysiological information to localize the endo- and epicardial VT isthmus. The absence of AC-type CSM on the endocardium, which is frequently observed in NICM, appears to indicate the sub-epicardial or intramural course of the critical isthmus.
Social inequalities in obesity and overweight: secular changes in Poland between 1983 and 2020
Authors: Żegleń Magdalena , Kryst Łukasz , Kowal Małgorzata , Woronkowicz Agnieszka
Published: September 2021

Background

Human development is strongly influenced by environmental factors, including the socioeconomic status (SES) of the family. The aim of this study is to analyze the prevalence of excess body weight among Polish children and adolescents from families of varying SES examined in 1983 and 2020.

Methods

The study group included 3–15-year olds from two cross-sectional surveys (1983 and 2020) conducted in kindergartens and schools. The 1983 cohort consisted of 3394 individuals and the one from 2020—of 1253 children and adolescents. Body height and weight were measured and body mass index was calculated. Inclusion into underweight, normal weight and overweight/obese categories was based on Cole’s cutoff points. SES was established based on the place of the parents’ birth, parents’, education status and the number of children in the family, which were self-reported in a questionary by the parents of the examined individuals.

Results

The mean overall SES was higher in the 2020 cohort, in comparison to the one examined in 1983. This change was also reflected by the changing prevalence of excess body weight, which, in 1983 was the greatest in the high socioeconomic category. On the other hand, in 2020 overweight/obesity was the most prevalent among individuals from families of low SES.

Conclusions

The present results confirm the findings obtained in other countries, which suggest that changing the level of socioeconomic development modifies the changes regarding the prevalence of excess body weight. It is an important observation because a study of this type has not yet been conducted in the Polish population.
Social disadvantage and gambling severity: a population-based study with register-linkage
Authors: Latvala Tiina A , Lintonen Tomi P , Browne Matthew , Rockloff Matthew , Salonen Anne H
Published: September 2021

Background

Studies have found an association between problem gambling and poverty. However, there is relatively little research on social inequalities and problem gambling using population representative data.

Methods

A population-representative self-report web-based and postal survey with register-based linkage was conducted in the three geographical areas of Finland. Participants (n = 7186, aged 18 or older) were randomly selected from the population register. Sociodemographic factors and social welfare benefits were studied among gambling groups and their statistical difference were examined by χ2 test. Seven logistic regression models were calculated, where unemployment, social security benefits and low income were treated as dependent variables and where sex, age, family structure and education were controlled as covariates. The results were presented as odds ratios (OR) with 95% confidence intervals (CIs).

Results

Problem and at-risk gambling (ARG) was more common among people who were unemployed [PG: χ2=6.4 (1), P < 0.01, ARG: χ2=12.4 (1), P < 0.001] or had received social security benefits [PG: χ2=41.6 (1), P < 0.001, ARG: χ2=22.9 (1), P < 0.001]. The OR for problem gambling was high as 5.6 (CI: 3.22–9.61) among respondents who had received social assistance even when covariates were taking into count. Almost a third of those experiencing problem or at-risk gambling received at least one form of social security benefit.

Conclusions

The most important task of gambling policy should be reducing gambling-related harms and diminishing social inequality. However, even in government organized system where gambling profits are used for common good, profits come from the most socially disadvantaged people thereby exacerbating inequality.
Proportion of deaths in hospital in European countries: trends and associations from panel data (2005–2017)
Authors: Jiang Jingjing , May Peter
Published: September 2021

Background

End-of-life care attracts major policy interest. Place of death is an important metric of individual experience and health system performance. Most people prefer to die at home, but hospital is the most common place of death in high-income countries. Little is known about international trends in place of death over time.

Methods

We aimed to collate population-level data on place of death in Europe from 2005 to 2017, and to evaluate association with national characteristics and policy choices. We sought data on hospital as the place of death from the 32 European Economic Area countries. We identified national economic, societal, demographic and health system predictors from Eurostat, OECD and the WHO. We analyzed these cross-national panel data using linear regression with panel-corrected standard errors.

Results

Our analytic dataset included 30 countries accounting for over 95% of Europe’s population. Average national proportion of deaths occurring in hospital in the study period ranged from 26% to 68%, with a median of 52%. Trends vary markedly by region and wealth, with low and decreasing rate in the North–West, and high and increasing prevalence in the South and East. Controlling for demographic and economic factors, strong palliative care provision and generous government finance of long-term care were associated with fewer hospital deaths.

Conclusions

We found modifiable policy choices associated with hospital mortality, as well as wider structural economic and societal factors. Policymakers can act to reduce the proportion of dying in hospital.
Family history recording in UK general practice: the lIFeLONG study
Authors: Dineen Molly , Sidaway-Lee Kate , Pereira Gray Denis , Evans Philip H
Published: September 2021

Background

In order to integrate genomic medicine into routine patient care and stratify personal risk, it is increasingly important to record family history (FH) information in general/family practice records. This is true for classic genetic disease as well as multifactorial conditions. Research suggests that FH recording is currently inadequate.

Objectives

To provide an up-to-date analysis of the frequency, quality, and accuracy of FH recording in UK general/family practice.

Methods

An exploratory study, based at St Leonard’s Practice, Exeter—a suburban UK general/family practice. Selected adult patients registered for over 1 year were contacted by post and asked to complete a written FH questionnaire. The reported information was compared with the patients’ electronic medical record (EMR). Each EMR was assessed for its frequency (how often information was recorded), quality (the level of detail included), and accuracy (how closely the information matched the patient report) of FH recording.

Results

Two hundred and forty-one patients were approached, 65 (27.0%) responded and 62 (25.7%) were eligible to participate. Forty-three (69.4%) EMRs contained FH information. The most commonly recorded conditions were bowel cancer, breast cancer, diabetes, and heart disease. The mean quality score was 3.64 (out of 5). There was little negative recording. 83.2% of patient-reported FH information was inaccurately recorded or missing from the EMRs.

Conclusion

FH information in general/family practice records should be better prepared for the genomic era. Whilst some conditions are well recorded, there is a need for more frequent, higher quality recording with greater accuracy, especially for multifactorial conditions.
Succession and potential role of bacterial communities duringPleurotus ostreatusproduction
Authors: Bánfi Renáta , Pohner Zsuzsanna , Szabó Attila , Herczeg Gábor , Kovács Gábor M , Nagy Adrienn , Márialigeti Károly , Vajna Balázs
Published: September 2021

There is an increasing interest in studying bacterial-fungal interactions (BFIs), also the interactions of Pleurotus ostreatus, a model white-rot fungus and important cultivated mushroom. In Europe, P. ostreatus is produced on a wheat straw-based substrate with a characteristic bacterial community, where P. ostreatus is exposed to the microbiome during substrate colonisation. This study investigated how the bacterial community structure was affected by the introduction of P. ostreatus into the mature substrate. Based on the results obtained, the effect of the presence and absence of this microbiome on P. ostreatus production in an experimental cultivation setup was determined. 16S rRNA gene-based terminal restriction fragment length polymorphism (T-RFLP) and amplicon sequencing revealed a definite succession of the microbiome during substrate colonisation and fruiting body production: a sharp decrease in relative abundance of Thermus spp. and Actinobacteria, and the increasing dominance of Bacillales and Halomonas spp. The introduced experimental cultivation setup proved the protective role of the microbial community against competing fungi without affecting P. ostreatus growth. We could also demonstrate that this effect could be attributed to both living microbes and their secreted metabolites. These findings highlight the importance of bacterial-fungal interactions during mushroom production.
Methanotroph community structure and processes in an inland river affected by natural gas macro-seeps
Authors: Burrows Ryan M , van de Kamp Jodie , Bodrossy Levente , Venarsky Michael , Coates-Marnane Jack , Rees Gavin , Jumppanen Paavo , Kennard Mark J
Published: September 2021

Methane availability in freshwaters is usually associated with spatial-temporal variation in methanogenesis. Unusually, however, natural gas macro-seeps occur along the Condamine River in eastern Australia which elevate ambient water-column methane concentrations more than 3,000 times. We quantified the spatial-temporal variation in methane oxidation rates and the total microbial and methanotroph community composition (through the amplification and sequencing of 16S rRNA and particulate methane monooxygenase (pmoA) genes), and the factors mediating this variation, in reaches with and without macro-seeps. Sediment methane oxidation rates were, on average, 29 times greater, and the abundance of methanotrophs significantly higher, in the vicinity of methane macro-seeps compared to non-seep sites. Methylocystis was the most abundant methanotroph group at all sites, but type Ib methanotrophs showed the steepest increase in abundance at seep sites. pmoA gene analysis identified these as clade 501, while 16S rRNA gene analysis identified these as the closely related genus Methylocaldum. Sediment methane oxidation rates and the relative abundance and composition of benthic microbial communities were primarily influenced by methane availability which was in turn related to variation in river discharge. Methane-derived carbon may be an important energy source for the aquatic food webs in reaches affected by natural gas macro-seeps.
Certain Listeria monocytogenes plasmids contribute to increased UVC ultraviolet light stress
Authors: Anast Justin M , Schmitz-Esser Stephan
Published: September 2021

Listeria monocytogenes is the causative agent of the highly fatal foodborne disease listeriosis and can persist in food production environments. Recent research highlights the involvement of L. monocytogenes plasmids in different stress response mechanisms, which contribute to its survival in food production facilities. Ultraviolet (UV) light in the UVC spectrum (200–280 nm) is used in food production to control microbial contamination. Although plasmid-encoded UV resistance mechanisms have been described in other bacteria, no research indicates that L. monocytogenes plasmids contribute to the UV stress response. The plasmids of L. monocytogenes strains 6179, 4KSM and R479a are genetically distinct and were utilized to study the roles of plasmids in the UV response. Wild-type and plasmid-cured variant cells were grown to logarithmic or late-stationary phase, plated on agar plates and exposed to UVC for 60 or 90 s, and colony-forming units (CFUs) were determined. CFUs of 6179 and 4KSM, bearing pLM6179 and p4KSM, respectively, were significantly (P-value < 0.05) higher than those of the plasmid-cured strains in both logarithmic and stationary phases. No difference in survival was observed for the R479a strain. Our data show for the first time that certain L. monocytogenes plasmids contribute to the survival of UVC light stress.