bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially avoidable hospitalizations for diabetes in Switzerland
Authors: Maung K , Gouveia A L E X , Mauron C H A R L È , Marques-Vidal P E D R O 
Published: June 2024

Abstract

Background
Timely and appropriate outpatient care can prevent potentially avoidable hospitalizations (PAH) for diabetes. We analysed the trends, determinants, and consequences of PAH for diabetes in Switzerland over two decades.

Methods
Hospital discharge data for years 1998 to 2018 were used. PAH were defined according to the Organization for Economic Cooperation and Development criteria.

Results
Overall, 90,853 admissions were considered as PAH, of which 25,376 (27.8%), 9,789 (10.8%) and 55,688 (61.4%) represented uncontrolled diabetes, short-term and long-term complications, respectively. The number of PAH increased from 2,600 in 1998 to 5,730 in 2018, mostly due to long-term complications. Compared to PAH for long-term complications, admissions for uncontrolled diabetes and short-term complications were more frequently women, in the younger age categories, more frequently non-Swiss, without health insurance, were more frequently admitted in an emergency setting, at the patient’s initiative or via emergency services (ambulance, police), and had a lower comorbidity index. PAH for uncontrolled diabetes and short-term diabetic complications were more frequent in the non-German speaking regions. Patients with PAH for short-term diabetic complications were more frequently admitted to the intensive care unit, and their length of stay was shorter. In 2018, PAH for diabetes represented 56,255 days, corresponding to 155 hospital beds occupied yearly, and an estimated cost of 76 million CHF.

Conclusion
In Switzerland, the number PAH for diabetes increased during the period 1998-2018. PAH types differ according to geographic region and to the patient’s characteristics, and a sizable fraction is related to uncontrolled diabetes or likely preventable short-term complications.
Efficacy of oral hypolipidemic therapies in a real world population
Authors: Garcia A , Martins A , Oliveira C , Abrantes A , Raposo M , Gregorio C , Alves Da Silva P , Cunha N , Aguiar Ricardo I , Abreu A , Pinto F 
Published: June 2024

Abstract

Introduction
Hypolipidemic therapies are a cornerstone in the management of patients (pts) after an acute ST segment elevation myocardial infarction (STEMI). The efficacy of such therapies is based on clinical trials where pts are highly selected and closely monitored, perhaps not entirely reflecting a real world scenario.

Purpose
To evaluate efficacy of hypolipidemic therapy in a real world population of young pts with STEMI from an intermediate CV risk country.

Methods
Retrospective, single-center study of consecutive pts, aged below 50 years, who were admitted with STEMI and discharged under hypolipidemic therapy, between 2017 and 2021. Demographics, clinical characteristics, and outcomes were analyzed. Parametric and non-parametric tests were performed as appropriate.

Results
We included 306 pts, 81.7% men, mean age was 43.9 years, 52% had hypertension, 76% dyslipidemia, 20% diabetes, 70% were smokers and 63.8% were overweight. Most pts had one vessel disease, mainly anterior descending coronary artery.
Only 26pts were previously under statin therapy; at discharge, 63% of pts received high intensity statin, 33% moderate intensity and 4% ezetimibe concomitantly. During a mean follow-up (FUP) of 3.8 years, 35% of pts intensified medication, 55% received high intensity statin and 22% combination of high intensity statin and ezetimibe.
Patients under high intensity statin presented a significant reduction of cLDL (119±39 vs 82±33, p&lt;0.001) with a mean reduction of 30±41% - 20 percentual points inferior to the expected average reduction of 50%. Furthermore, only 26% of pts presented a 50% reduction of baseline cLDL and only 21.5% met the cLDL&lt;55mg/dl goal. Similarly, when analyzing pts under high intensity statin plus ezetimibe, a significant cLDL reduction was observed (118.7±33.5 vs 69.9±49.8, p=0.004), with an average reduction of 33±48%. Only 23.7% of these pts reached cLDL goal and 27% reduced cLDL above 50%.
During FUP 19 pts had a second coronary event, of these 21% were under high intensity statin strategy and 47.4% high intensity statin plus ezetimibe. Statin intolerance was present in only 2 pts and rhabdomyolysis was not reported. .

Conclusion
In this real-world population hypolipidemic therapy proved to be safe and effective in lowering cLDL, however average reduction was inferior to the one previously reported. Early up titration and aggressive LDL control with PCSK9i or inclisiran has to be implemented such as lifestyle measures.
The association between the remnant cholesterol and non-HDL-C with subclinical carotid atherosclerosis in patients with metabolic syndrome
Authors: Kostic S , Djordjevic D , Tasic I , Deljanin Ilic M , Stoickov V 
Published: June 2024

Abstract

Objective
This study evaluated the association between RC and Non-HDL-C with subclinical carotid atherosclerosis in patients with metabolic syndrome (MetSy) without cardiovascular disease.

Method
The study included 130 participants, without manifested cardiovascular disease. The patients were divided into 2 groups. The first group consisted of subjects with MetSy, n=65 (mean age: 53,92±8,36), the second group is control, without MetSy, n=65. For all patients was determined: presence of risk factors for cardiovascular disease (hypertension, hyperlipidemia, smoking, diabetes, obesity), laboratory analysis and anthropometric measurements. The carotid artery intima-media thickness and carotid atherosclerotic plaques were measured by B-mode ultrasound. Non-HDL-C was calculated by subtracting HDL-C from total cholesterol (TC). RC was calculated by subtracting LDL-C and HDL-C from TC.

Results
C-IMT were significantly higher in the group with MetSy (0,80±0,21 vs. 0,64±0,12, p&lt;0,001). The high C-IMT values (≥0.90) were observed in 26% patients with MetSy, p&lt;0,001. Patients with MetSy had more frequently one or more carotid plaques (p&lt;0,001), higher average number of carotid plaques (p&lt;0,001) and percentage of stenosis (p&lt;0,001). In MetSy group plaques were mostly fibrocalcified (28%), followed by fibrous (22%) and calcified, in non MetSy group were fibrous (14%). Subjects with MetSy had higher values of glycemia and glycated hemoglobin (HgA1C) in serum, higher levels of lipid parameters – total cholesterol, LDL-C, oxidized LDL-C, Non-HDL-C (5,70±1,31 vs. 4,59±1,07, p&lt;0,001), Remnant-C (1,21±0,75 vs. 0,55±0,31, p&lt;0,001) and triglycerides and lower values of HDL cholesterol (p&lt;0.001). Univariate regression analysis showed that C-IMT was significantly associated with lipid paremeters: Remnant-C (p&lt;0,05), oxidized LDL-C (p&lt;0,05), triglycerides (p&lt;0,01), HDL-C (p&lt;0,001), glycemia and HgA1C (p&lt;0,001). As the most important factors associated with carotid plaque regression analysis singled out: TC (p&lt;0,05), LDL-C (p&lt;0,05), Non-HDL-C (p&lt;0,01), Remnant-C (p&lt;0,1), HDL-C (p&lt;0,01), HgA1C (p&lt;0,05).

Conclusions
Our study showed a significant association between the RC and carotid intima-media thickness in patients without clinically evident cardiovascular disease. Elevated Non-HDL-C was associated with the presence of carotid plaques.
Cross-sectional associations between device-measured physical activity and atrial fibrillation
Authors: Heitmann K A , Loechen M L , Johansen K R , Morseth B 
Published: June 2024

Abstract

Background
Atrial fibrillation (AF) may lead to thrombosis and increased risk of stroke, myocardial infarction, heart failure, and premature death. AF increases substantially with age, and estimates indicate that one in three individuals ≥55 years in Europe will develop AF. Physical activity (PA) may contribute to the prevention of AF, as it improves overall cardiovascular health. However, the positive effect of PA on AF is mainly based on subjective self-reports of PA and the pattern of the association is still unclear. To our knowledge, few studies have so far examined the association between accelerometry-measured PA and AF.

Purpose
The aim of this study is to explore the association between accelerometry-measured PA and self-reported AF.

Methods
The seventh survey of a large population-based study was conducted in 2015-2016 and included 21083 men and women aged ≥40 years (65% attendance). Of these, a random sample of 5194 participants wore a triaxial accelerometer for at least ≥10 hours/day for ≥4 days to measure PA, in addition to having valid data on all covariates. Based on validated cut-points, the counts were averaged and categorized into moderate-to-vigorous PA (MVPA, ≥2690 counts/min). Steps were collected from accelerations on the vertical axis. AF was self-reported and dichotomized into no AF or current/previous AF. The associations between PA and AF were estimated by univariable and multivariable logistic regression analyses and are presented as odds ratio (OR) with 95% confidence intervals (CI). The multivariable model was adjusted for age, sex, body mass index, systolic blood pressure, alcohol, heart attack, and heart failure. The present study was approved by the Regional Committee of Health Research Ethics and was carried out in accordance with the Declaration of Helsinki.

Results
In an unadjusted model, the odds of having AF was reduced with 10% for every 10-minute increase in MVPA/day (OR 0.90, 95% CI 0.87-0.94), and 13% for every 1000 steps/day (OR 0.87, 95% CI 0.84-0.90) in a linear association. After adjustment, there was no significant association between MVPA and AF (OR 0.97, 95% CI 0.93-1.01), whereas the odds of having AF was reduced by 5% for every 1000 steps/day (OR 0.95, 95% CI 0.91-0.998) in a linear association. When stratified by sex, the odds of having AF was reduced by 10% for every 1000 steps/day in females (OR 0.90, 95% CI 0.84-0.97) in a linear association, whereas no statistical association between steps/day and AF was observed in males (OR 0.98, 95% CI 0.93-1.04), or between MVPA and AF in females (OR 0.94, 95% CI 0.87-1.02) or males (OR 0.99, 95% CI 0.94-1.03).

Conclusion
These results from a large population-based study showed that the odds of having AF decreased as the dose of PA increased, although not significantly in males. Further studies exploring longitudinal associations between PA and AF using objectively measured PA are warranted.
Prevalence of non-cardiometabolic chronic conditions between sexes in patients enrolled in cardiac rehabilitation
Authors: Gomes P , Miller S A , Chacin-Suarez A , Olson T P 
Published: June 2024

Abstract

Background
Patients enrolled in cardiac rehabilitation (CR) demonstrate a greater burden of co-occurring chronic conditions (CC) compared to the general population. Studies have shown that the prevalence of multimorbidity among noninstitutionalized, civilian US adults is higher among women compared to men. These CC are often grouped and categorized as Cardiometabolic, Somatic, and Mental Health based on the origin and organ system the condition affects. Importantly, sex differences between categorizations of CC in patients undergoing CR has not been examined.

Purpose
Because patients enrolled in CR are known to have multiple Cardiometabolic conditions, the aim of this study is to examine sex differences in the prevalence of non-cardiometabolic conditions in the CR population.

Methods
We extracted data on all 21 CC defined by the US Department of Health and Human Services using the local Epidemiology Project records-linkage system. Our study population included participants who attended (≥1) CR sessions from 1995 to 2019. The CC were categorized into cardiometabolic (CMC), Somatic, and Mental health groups (Table 1), and as CMC only, CMC + Somatic only, CMC + Mental health only, and CMC + Somatic + Mental health groups (Table 2). The sex differences in the number of CC within these groups were analyzed by Kruskal-Wallis test and prevalence were analyzed by Pearson’s Chi-squared test, where p&lt;0.05 was significant.

Results
We identified 13,056 CR patients (68.5% males) who were ≥18 years old with a mean age of 65.7±12.7 yrs (67.6±13.6 yrs in females and 64.8±12.1 yrs in males). Median [Q1, Q3] number of CC was 7 [5,9], with females having a greater number (7 [5, 9]) than males (6 [5,8]), p&lt;0.001. Both sexes had at least 1 CMC with a median of 5 [3,5] CMC and no differences between sexes (p&gt;0.05); however, females demonstrated more somatic and mental health conditions compared to males (p&lt;0.001, for both, Table 1). When grouping categories of CC, females demonstrated a higher number of CC in CMC + Somatic + Mental health as well as CMC + Somatic only groups (p&lt;0.001, for both, Table 2), with a higher prevalence in the former group only. While the number of CC in CMC + Mental health group was similar between sexes, the prevalence was lower in females. In contrast, the CMC only grouping demonstrated a higher number of CC and prevalence among males (p&lt;0.05).

Conclusion
Our data suggest that females enrolled in CR demonstrate a significantly higher number of CC compared to males. Although males have a higher prevalence of CMC, the prevalence of Somatic ± Mental health conditions in addition to CMC is significantly greater in females. These data demonstrate the importance of considering sex differences in the prevalence of non-CMC when formulating individualized treatment plans for CR patients.
How much protected? Assessment of cardiovascular risk factors in patients with previous cardiovascular events admitted for acute coronary syndrome
Authors: Gregorio Antunes Coelho R , Quintal J , Pohle C , Silva Ferreira J , Bernardes P , Goncalves S , Seixo F 
Published: June 2024

Abstract

Background
The 2021 ESC guidelines on cardiovascular disease prevention recommend that all patients with a prior history of atherosclerotic cardiovascular disease (ASCVD) - with a history of acute coronary syndromes, coronary heart disease, surgical or percutaneous myocardial revascularization, stroke or peripheral arterial disease - are considered to have very high risk of cardiovascular events (class I, level A evidence). Despite having an increased residual risk, optimization and control of cardiovascular risk factors (diabetes, dyslipidemia, high blood pressure and smoking) is often suboptimal.

Purpose
The aim of this study is to evaluate the control of modifiable cardiovascular risk factors in patients with history of cardiovascular disease and admitted for acute coronary syndrome. Furthermore, understand the impact of follow-up in primary care (vs hospital follow-up) on this control.

Methods
We retrospectively evaluated patients admitted for acute coronary syndrome between November 2021 and October 2022 with history of cardiovascular disease, with or without hospital follow-up. Previous control of the main cardiovascular risk factors was assessed, as well as compliance with other secondary prevention measures (smoking abstinence, compliance with antithrombotic therapy).

Results
Between November 2021 and October 2022, 395 patients were admitted to our center due to acute coronary syndrome. 111 (30%) had a previous history of cardiovascular events, and of these, 41 (37%) remained under hospital follow-up. 66 patients (59%) were taking statins, but only 15 (14%) had LDL cholesterol levels &lt;55 mg/dl and 28 (25%) LDL-C &lt;70 mg/dl. 41 patients (37%) were diabetic, but only 35 (85%) had a previous known diagnosis and 12 (29%) were under control (HbA1c &lt;7.0%). 97 patients (87%) had high blood pressure and 91 had systolic BP values &gt;135 mmHg (82%). 33 patients (30%) were former smokers but 20 (18%) maintained smoking habits. 26 patients (23%) were obese (BMI &gt;30 kg/m2). 28 patients (25%) were not taking any antithrombotic therapy.
The adherence to statins was higher in patients that kept hospital follow up (50% in primary care vs 76% in hospital follow-up; p = 0.008) with no diferences regarding other risk factos.

Conclusions
Patients with established cardiovascular disease are a subgroup at high risk of recurrent events. Despite this, compliance with control measures is often suboptimal. It's urgent to establish multidisciplinar care programs in order to reduce their residual risk.
High-dose statins are associated with increased aortic valve calcium load in patients with severe stenosis
Authors: Poggio P , Moschetta D , De Giorgi D , Rusconi V , Bertolini F , Massaiu I , Valerio V , Myasoedova V A 
Published: June 2024

Abstract

Background
AS represents the predominant valvular pathology, marked by the progressive fibro-calcific remodeling of aortic valve leaflets. This condition poses a significant clinical burden due to its association with increased morbidity and mortality. In recent years, emerging research has shed light on the potential role of statins in influencing the pathogenesis of AS. Statins, known primarily for their lipid-lowering properties, have been found to modulate the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism. This novel avenue of investigation into the interplay between statins, PCSK9, and aortic valve calcification holds considerable therapeutic implications and warrants further exploration for the development of targeted interventions in the management of AS.

Purpose
To investigate the dose-dependent impact of statins on aortic valve calcification in patients with AS.

Methods
We enrolled 194 AS patients (87 no, 34 low-dose, and 73 high-dose statins) who underwent contrast-enhanced computed tomography (CT). Atorvastatin (A:0.1uM and 1uM) and pravastatin (P:1uM and 100uM) treatments were used to evaluate valve interstitial cells (VIC) calcification potential and PCSK9 secretion.

Results
CT quantifications showed that patients taking high-dose statins had significantly higher AVC content compared to low-dose (903.8±601 vs.526.8±403 mm3/cm2, respectively; p&lt;0.0001), while no difference in AVC was observed between patients with low-dose statins and no-statins (p=0.226). Of note, low-density lipoprotein cholesterol (LDL-C) levels were comparable between low- and high-dose statins’ groups (p=0.255). We confirmed our observation in vitro, showing that treatment with low-dose satins did not stimulate calcification nor PCSK9 secretion. While high-dose statins significantly increased VICs extracellular calcification (A:+4.3±2.6 fold-change (FC), P:+3.2±1.2FC, respectively; p&lt;0.0001) and PCSK9 secretion (A:+3.3±1.9FC, P:+2.5FC, respectively; p&lt;0.0001).

Conclusion
Patients with severe AS who receive high-dose statins compared with those receiving low-dose statins, both of whom achieve the target for LDL-C, had higher AVC load. An in vitro model confirms increased intracellular calcification and PCSK9 secretion upon treatment with high-dose statins only. To achieve lipid targeting in AS patients, it is important to consider this phenomenon, giving preference to other types of drugs, which do not exhibit similar effects.
Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group B Streptococcus
Authors: Brissac Terry , Guyonnet Cécile , Sadouni Aymane , Hernández-Montoya Ariadna , Jacquemet Elise , Legendre Rachel , Sismeiro Odile , Trieu-Cuot Patrick , Lanotte Philippe , Tazi Asmaa , Firon Arnaud 
Published: June 2024

Abstract
Streptococcus agalactiae is among the few pathogens that have not developed resistance to ß-lactam antibiotics despite decades of clinical use. The molecular basis of this long-lasting susceptibility has not been investigated, and it is not known whether specific mechanisms constrain the emergence of resistance. In this study, we first report ß-lactam tolerance due to the inactivation of the c-di-AMP phosphodiesterase GdpP. Mechanistically, tolerance depends on antagonistic regulation by the repressor BusR, which is activated by c-di-AMP and negatively regulates ß-lactam susceptibility through the BusAB osmolyte transporter and the AmaP/Asp23/GlsB cell envelope stress complex. The BusR transcriptional response is synergistic with the simultaneous allosteric inhibition of potassium and osmolyte transporters by c-di-AMP, which individually contribute to low-level ß-lactam tolerance. Genome-wide transposon mutagenesis confirms the role of GdpP and highlights functional interactions between a lysozyme-like hydrolase, the KhpAB RNA chaperone and the protein S immunomodulator in the response of GBS to ß-lactam. Overall, we demonstrate that c-di-AMP acts as a turgor pressure rheostat, coordinating an integrated response at the transcriptional and post-translational levels to cell wall weakening caused by ß-lactam activity, and reveal additional mechanisms that could foster resistance.
Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients
Authors: Hernández-Vega Ana M , Llorente Itzel , Sánchez-Hernández Raúl , Segura Yayoi , Tusié-Luna Teresa , Morales-Buenrostro Luis E , García-Villegas Refugio , Islas León D , Rosenbaum Tamara 
Published: June 2024

Abstract
Polycystic kidney disease (PKD), a disease characterized by the enlargement of the kidney through cystic growth is the fourth leading cause of end-stage kidney disease world-wide. Transient receptor potential Vanilloid 4 (TRPV4), a calcium-permeable TRP, channel participates in kidney cell physiology and since TRPV4 forms complexes with another channel whose malfunction is associated to PKD, TRPP2 (or PKD2), we sought to determine whether patients with PKD, exhibit previously unknown mutations in TRPV4. Here, we report the presence of mutations in the TRPV4 gene in patients diagnosed with PKD and determine that they produce gain-of-function (GOF). Mutations in the sequence of the TRPV4 gene have been associated to a broad spectrum of neuropathies and skeletal dysplasias but not PKD, and their biophysical effects on channel function have not been elucidated. We identified and examined the functional behavior of a novel E6K mutant and of the previously known S94L and A217S mutant TRVP4 channels. The A217S mutation has been associated to mixed neuropathy and/or skeletal dysplasia phenotypes, however, the PKD carriers of these variants had not been diagnosed with these reported clinical manifestations. The presence of certain mutations in TRPV4 may influence the progression and severity of PKD through GOF mechanisms. PKD patients carrying TRVP4 mutations are putatively more likely to require dialysis or renal transplant as compared to those without these mutations.
Seismic and acoustic signals from the 2014 ‘interstellar meteor’
Authors: Fernando Benjamin , Mialle Pierrick , Ekström Göran , Charalambous Constantinos , Desch Steven , Jackson Alan , Sansom Eleanor K 
Published: June 2024

SUMMARY
We conduct a thorough analysis of seismic and acoustic data purported to be from the so-called ‘interstellar meteor’ which entered the Earth’s atmosphere off the coast of Papua New Guinea on 2014 January 08. Previous work had suggested that this meteor may have been caused by an alien spacecraft burning up in the atmosphere. We conclude that both previously reported seismic signals are spurious—one has characteristics suggesting a local vehicular-traffic-based origin; whilst the other is statistically indistinguishable from the background noise. As such, previously reported localizations based on this data are unreliable. Analysis of acoustic data provides a best-fitting location estimate which is very far ($\sim$170 km) from the reported fireball location. Accordingly, we conclude that material recovered from the seafloor and purported to be from this event is almost certainly unrelated to it, and is likely of more mundane (non-interstellar) origin.