bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete mesocolic excision for right colonic cancer: prospective multicentre study
Authors: Benz Stefan R , Feder Inke S , Vollmer Saskia , Tam Yu , Reinacher-Schick Anke , Denz Robin , Hohenberger Werner , Lippert Hans , Tannapfel Andrea , Stricker Ingo
Published: November 2022

Background

Complete mesocolic excision (CME) for right colonic cancer is a more complex operation than standard right hemicolectomy but evidence to support its routine use is still limited. This prospective multicentre study evaluated the effect of CME on long-term survival in colorectal cancer centres in Germany (RESECTAT trial). The primary hypothesis was that 5-year disease-free survival would be higher after CME than non-CME surgery. A secondary hypothesis was that there would be improved survival of patients with a mesenteric area greater than 15 000 mm2.

Methods

Centres were asked to continue their current surgical practices. The surgery was classified as CME if the superior mesenteric vein was dissected; otherwise it was assumed that no CME had been performed. All specimens were shipped to one institution for pathological analysis and documentation. Clinical data were recorded in an established registry for quality assurance. The primary endpoint was 5-year overall survival for stages I–III. Multivariable adjustment for group allocation was planned. Using a primary hypothesis of an increase in disease-free survival from 60 to 70 per cent, a sample size of 662 patients was calculated with a 50 per cent anticipated drop-out rate.

Results

A total of 1004 patients from 53 centres were recruited for the final analysis (496 CME, 508 no CME). Most operations (88.4 per cent) were done by an open approach. Anastomotic leak occurred in 3.4 per cent in the CME and 1.8 per cent in the non-CME group. There were slightly more lymph nodes found in CME than non-CME specimens (mean 55.6 and 50.4 respectively). Positive central mesenteric nodes were detected more in non-CME than CME specimens (5.9 versus 4.0 per cent). One-fifth of patients had died at the time of study with recorded recurrences (63, 6.3 per cent), too few to calculate disease-free survival (the original primary outcome), so overall survival (not disease-specific) results are presented. Short-term and overall survival were similar in the CME and non-CME groups. Adjusted Cox regression indicated a possible benefit for overall survival with CME in stage III disease (HR 0.52, 95 per cent c.i. 0.31 to 0.85; P = 0.010) but less so for disease-free survival (HR 0.66; P = 0.068). The secondary outcome (15 000 mm2 mesenteric size) did not influence survival at any stage (removal of more mesentery did not alter survival).

Conclusion

No general benefit of CME could be established. The observation of better overall survival in stage III on unplanned exploratory analysis is of uncertain significance.
‘People Here Are Their Own Gods’: The Migration of South African Social Workers to England
Authors: Hakak Yohai , Onokah Shirley , Shishane Kwanele
Published: November 2022

The migration of social workers has become an established trend internationally. Existing research largely ignored the impact of culture on this migration. The study presented here focused on the experiences of social workers who were trained in South Africa and migrated to England. South African-trained social workers had to adjust to significant cultural differences, ranging from the place of religion, the characteristics of the family and parenting, forms of interpersonal communication and what is considered polite and impolite behaviour. Whilst these issues have a wide societal impact, they also shape the daily reality of practising social workers. Implications for practice are discussed, and pre-migration education about the host country’s structures, a systemic induction process, mentorship and supervision with an emphasis on culture, is recommended.
The Connected Lives We Live: Autoethnographic Accounts of Disability, Mental Illness and Power
Authors: Pryer Shaylie , Davies Kate , Hislop Lauren
Published: November 2022

In this article, we use a collaborative approach to autoethnography to explore experiences of power in relation to our identities as people with disabilities and/or mental illnesses. We draw on elements of Bronfenbrenner’s ecological systems framework to consider how we enact our own power or struggle against systemic power in making meaning of our lives. As a team of lived experience researchers we wrote, shared and thematically analysed a series of narratives about our personal (microsystem) and institutional (macrosystem) relationships. Through this research process we were able to identify common experiences of being resilient in the face of institutions that dehumanised and problematised us and tried to render us voiceless—exerting ‘power over’. In contrast, reflections on our personal relationships highlighted experiences of reciprocity, respect and autonomy that energised our efforts towards meaningful and powerful identities—‘power with’. We conclude that by generating strength through our own advocacy, perseverance and caring relationships, we engage dynamics (mesosystem) of empowerment and identity to resist oppressive power at structural levels. This exemplifies the importance of person-centred social work premised on self-determination, autonomy and dignity, and socially just social work that advocates for equitability and fights structural discrimination.
Ethical challenges faced by Korean development practitioners in international community development practices
Authors: Noh Jae-Eun
Published: November 2022

Establishing development ethics is a rising concern for Korean NGOs with a relatively short history of engaging in international community development. This study explores the ethical challenges faced by Korean development practitioners. This study draws on in-depth interviews with 13 Korean development practitioners experienced in community development projects in Asia and Africa. The exploration of contexts affecting ethical practices suggests the influence of religion, professionalism and boundaries, neo-liberal and managerial culture. The findings of this study highlight the significance of reflective practices for development ethics by illustrating how development practitioners identified and constructed norms and principles through critical encounters with their emotions and challenges in practice. This study’s practical implications include drawing attention to emotions as a source of reflection by involving underpinning values and judgement. The importance of reflective practices warrants further exploration of building collective ethics to inform and challenge international community development practices.
Spectral specificity of gamma-frequency transcranial alternating current stimulation over motor cortex during sequential movements
Authors: Spooner Rachel K , Wilson Tony W
Published: November 2022

Motor control requires the coordination of spatiotemporally precise neural oscillations in the beta and gamma range within the primary motor cortex (M1). Recent studies have shown that motor performance can be differentially modulated based on the spectral target of noninvasive transcranial alternating current stimulation (tACS), with gamma-frequency tACS improving motor performance. However, the spectral specificity for eliciting such improvements remains unknown. Herein, we derived the peak movement-related gamma frequency in 25 healthy adults using magnetoencephalography and a motor control paradigm. These individualized peak gamma frequencies were then used for personalized sessions of tACS. All participants completed 4 sessions of high-definition (HD)-tACS (sham, low-, peak-, and high-gamma frequency) over M1 for 20 min during the performance of sequential movements of varying complexity (e.g. tapping adjacent fingers or nonadjacent fingers). Our primary findings demonstrated that individualized tACS dosing over M1 leads to enhanced motor performance/learning (i.e. greatest reduction in time to complete motor sequences) compared to nonspecific gamma-tACS in humans, which suggests that personalized neuromodulation may be advantageous to optimize behavioral outcomes.
Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization
Authors: Fomitcheva Ioulia V , Sword Jeremy , Shi Yang , Kirov Sergei A
Published: November 2022

High astroglial capacity for glutamate and potassium clearance aids in recovering spreading depolarization (SD)-evoked disturbance of ion homeostasis during stroke. Since perisynaptic astroglia cannot be imaged with diffraction-limited light microscopy, nothing is known about the impact of SD on the ultrastructure of a tripartite synapse. We used serial section electron microscopy to assess astroglial synaptic coverage in the sensorimotor cortex of urethane-anesthetized male and female mice during and after SD evoked by transient bilateral common carotid artery occlusion. At the subcellular level, astroglial mitochondria were remarkably resilient to SD compared to dendritic mitochondria that were fragmented by SD. Overall, 482 synapses in `Sham' during `SD' and `Recovery' groups were randomly selected and analyzed in 3D. Perisynaptic astroglia was present at the axon-spine interface (ASI) during SD and after recovery. Astrocytic processes were more likely found at large synapses on mushroom spines after recovery, while the length of the ASI perimeter surrounded by astroglia has also significantly increased at large synapses. These findings suggest that as larger synapses have a bigger capacity for neurotransmitter release during SD, they attract astroglial processes to their perimeter during recovery, limiting extrasynaptic glutamate escape and further enhancing the astrocytic ability to protect synapses in stroke.
An HPLC–MS/MS Method for Pharmacokinetic Study of Y-99: A Novel Diuretic Agent Targeting Urea Transporters
Authors: Xu Yue , Wang Shuyuan , Ma Wen , Li Jun , Lu Yingyuan , Abulizi Abudumijiti , Sun Jianguo , Yang Baoxue
Published: November 2022

Y-99, a promising first-in-class diuretic, is a novel urea transporter inhibitor with oral diuretic activity. However, little is known about the pharmacokinetic profiles of Y-99 in experimental animals. In this study, a method of quantitative determination of Y-99 in rat plasma based on high-performance liquid chromatography–tandem mass spectrometry was developed and validated in selectivity, linearity, recovery and matrix effect, accuracy and precision, stability, carry-over and dilution integrity. Chromatographic separation was conducted on an ACQUITY BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient elution at a 0.3 mL/min flow rate after protein precipitation. Mass spectrometry was performed by a positive electrospray ionization mass spectrometer in multiple reaction monitoring mode. The method showed standard-compliant linearity (1–1,000 ng/mL, r = 0.9991). The intra-day and inter-day accuracy (relative error < 11.2%) and precision (coefficient of variation <8.4%) were within acceptable criteria. The recovery and matrix effects were 97.3–110.7% and 103.7–107.5%, respectively. The stability, dilution integrity and carry-over of the method were also within the acceptable criteria. Pharmacokinetic profiles of Y-99 in rats were first investigated using this method, which was vital for developing novel diuretics without electrolyte imbalance targeting urea transporters.
Prevalence of anaemia in adults with chronic kidney disease in a representative sample of the United States population: analysis of the 1999–2018 National Health and Nutrition Examination Survey
Authors: Kovesdy Csaba P , Davis Jill R , Duling Ian , Little Dustin J
Published: November 2022

Background

Population-based estimates of anaemia prevalence in patients with chronic kidney disease (CKD) vary, and data on the prevalence of severe anaemia of CKD are limited. This study examined the prevalence of anaemia and anaemia eligible for erythropoiesis-stimulating agent (ESA) treatment in patients with CKD in the USA.

Methods

National Health and Nutrition Examination Survey (NHANES) data from 1999–2000 to 2017–18 were used to determine the prevalence of diagnosed anaemia (haemoglobin <12 g/dL in women; <13 g/dL in men) and anaemia eligible for ESA treatment (haemoglobin <10 g/dL) in survey participants aged ≥18 years with stage 3–5 non-dialysis-dependent CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The study objectives were to (i) obtain a more recent estimate of anaemia prevalence in patients with non-dialysis-dependent CKD and (ii) examine the characteristics of individuals with CKD and haemoglobin <10 g/dL.

Results

Of 51 163 eligible NHANES participants, 2926 (5.7%) with stage 3–5 CKD were included. In all participants, the weighted prevalences of anaemia and haemoglobin <10 g/dL were 25.3% and 1.9%, respectively. Mean haemoglobin levels decreased numerically between 1999 and 2012 and remained stable thereafter. The prevalence of anaemia and haemoglobin <10 g/dL increased with advancing CKD stage. The odds of haemoglobin <10 g/dL were significantly higher in stage ≥3B versus 3A and in non-Hispanic Blacks versus other races.

Conclusions

In our analysis, approximately 25% of individuals with stage 3–5 CKD in the USA had anaemia and approximately 2% had anaemia eligible for ESA treatment.
High salt intake activates the hypothalamic–pituitary–adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
Authors: Costello Hannah M , Krilis Georgios , Grenier Celine , Severs David , Czopek Alicja , Ivy Jessica R , Nixon Mark , Holmes Megan C , Livingstone Dawn E W , Hoorn Ewout J , Dhaun Neeraj , Bailey Matthew A
Published: November 2022

Aims

High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic–pituitary–adrenal axis activation and leads to sustained glucocorticoid excess.

Methods and results

In male C57BL/6 mice, high salt intake for 2–8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic–pituitary–adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic–pituitary–adrenal axis activation by high salt diet.

Conclusion

Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells.
Interspecific differences in plasma carotenoid profiles in nestlings of three sympatric vulture species
Authors: Blanco Guillermo , Hornero-Méndez Dámaso
Published: November 2022

Carotenoids are diet-based micronutrients important in health and coloration signaling. Related species with similar diets can differ in the kinds and levels of circulating carotenoids, which suggests specific physiological mechanisms to efficiently utilize these micronutrients, regardless of their availability. We explored whether diet and parental provisioning of unusual sources of carotenoids (fresh vegetal matter and vertebrate feces) can explain the occurrence and concentrations of carotenoids in the cinereous vulture Aegypius monachus, griffon vulture Gyps fulvus, and Egyptian vulture Neophron percnopterus nestlings, even when these pigments appear to not be deposited in their integumentary system. A greater diversity of wild prey in diet could be behind the profile of higher concentrations of carotenoids in the Egyptian vulture, the species with carotenoid-dependent coloration during adulthood, while differences in diet composition between cinereous and griffon vultures do not translate to different carotenoid profiles. The carotenoid profile appears to not be related to the ingestion of unusual matter rich in these compounds, although the infrequent occurrence of lycopene and unidentified γ-carotene-like compounds suggest that these vultures may be exploiting vegetal matter that left no identifiable unconsumed remains in the nest of Egyptian vultures. The consumption of green plant material by griffon vultures does not result in especially high levels of carotenoids when compared to the carotenoids found in cinereous vultures, which do not consume green plant material. Ungulate feces were not provisioned to Egyptian vulture nestlings, despite the fact they contain carotenoids that adults need for appropriate coloration. Overall, this study indicates that diet differences alone appear insufficient to explain contrasting interspecific carotenoid profiles, especially since all types of food consumed are considered to be poor in carotenoids, except vegetable matter. We suggest that nestling Egyptian vultures are comparatively efficient in uptaking carotenoids present in low concentrations in food when these compounds are not deposited in their integument, which suggests allocation to other functions.
Predictors of dominance rank and agonistic interactions in captive Livingstone’s fruit bats
Authors: Richdon Sarah , Price Eluned , Wormell Dominic , Jones Gareth , McCabe Grainne
Published: November 2022

Male dominance hierarchies have been studied in many animals but rarely in bats (Chiroptera). The dominance rank of social animals may dictate access to resources and mates; therefore, it has important implications for an individual’s fitness and is crucial for successful captive management. Between January and December 2018, at both Bristol Zoo Gardens (Bristol, UK) and Jersey Zoo (Jersey, British Isles), we observed 19 male Livingstone’s fruit bats Pteropus livingstonii using focal follows for 345 h overall, noting the outcome of all agonistic interactions. We recorded instigators of interactions, along with winners and losers, and analyzed these data using the R-package “EloRating” to create Elo-rating temporal plots of dominance ranks. We used generalized linear mixed models and multiple linear regression to analyze interaction data and test hypotheses regarding predictors of dominance rank, frequency of agonistic interaction, and choice of interaction partner. Age was positively correlated with dominance rank up to around year 9, when an asymptote was attained. Highly ranked bats instigated the most agonistic interactions, and largely directed these interactions at bats with much lower rankings than themselves. Hierarchies were extremely stable throughout the data collection period at both sites. We conclude that Livingstone’s fruit bats have a stable linear dominance hierarchy, with high-ranking, typically older males instigating the most interactions with lowest ranking males to secure dominance rank. This study adds to the limited discourse on Pteropus social behaviors, indicating that some bat species may have social systems similar in complexity to some nonhuman primates.
The Long-Term Effects of Student Absence: Evidence from Sweden
Authors: Cattan Sarah , Kamhöfer Daniel A , Karlsson Martin , Nilsson Therese
Published: November 2022

Despite the relatively uncontested importance of promoting school attendance in the policy arena, little evidence exists on the causal effect of school absence on long-run outcomes. We address this question by combining historical and administrative records for cohorts of Swedish individuals born in the 1930s. We find that elementary school absence significantly reduces contemporaneous academic performance, final educational attainment and labour income throughout the life cycle. The findings are consistent with a dynamic model of human capital formation, whereby absence causes small immediate learning losses, which cumulate to larger human capital losses over time and lead to worse labour market performance.
Sticky wages and the Great Depression: evidence from the United Kingdom
Authors: Lennard Jason
Published: November 2022

How sticky were wages during the Great Depression? Although classic accounts emphasise the importance of nominal rigidity in amplifying deflationary shocks, the evidence is limited. In this paper, I calculate the degree of nominal wage rigidity in the United Kingdom between the wars using new granular data covering millions of wages. I find that nominal wages changed infrequently but that wage cuts were more common than wage rises on average. Nominal wage adjustment fluctuated over time and by state, so that in 1931 amid falling output and prices more than one-third of workers received wage cuts.
‘Use of lipid-lowering therapy: the guidelines, the drugs or the patient?’
Authors: Borghi Claudio , Bragagni Alessio
Published: November 2022

The current step up approach in the therapy of dyslipidemias aims to reduce the amount of LDL cholesterol below a threshold that varies according to the patient's risk category, with a pharmacological approach that sees statins as a fundamental cornerstone. Although absolutely functional in reducing cardiovascular events, this therapeutic algorithm does not yet take into consideration the innumerable phenotypic variables that we can find in dyslipidemic subjects. The ever finer understanding of the pathophysiological mechanisms underlying dyslipidemias in combination with the novelties obtained through DNA genotyping will allow, in the near future, the development of a ‘tailor-made’ therapy for each category of patients. This article will summarize the most recent evidence regarding the therapy of dyslipidemias, with particular attention to the concept of cumulative exposure and some hypotheses on possible initial therapeutic proposals in patients with diabetes, vasculopathy, with hypertriglyceridaemia and with high levels of Lp (a).
Role of lipoprotein(a) in plaque progression
Authors: Ruscica Massimiliano , Rizzuto Alessandra S , Corsini Alberto
Published: November 2022

Identified by Berg in 1963, lipoprotein(a) represents a key contemporary residual risk pathway in atherosclerotic cardiovascular disease (ASCVD) secondary prevention. Indeed, epidemiological and genetic studies have undoubtedly demonstrated that lipoprotein(a) is one of the strongest causal risk factors of ASCVD. Although a risk threshold has been set between 30 and 50 mg/dL, depending on the ethnicity, a linear risk gradient across the distribution has been demonstrated. In the context of the atherosclerotic process, hyperlipoproteinaemia(a) contributes to the atherosclerotic plaque formation by deposition of cholesterol in the same manner as low-density lipoprotein (LDL) cholesterol, due to the LDL particle component of lipoprotein(a). Lipoprotein(a) accumulates in human coronary and carotid atherosclerotic lesions. High concentrations of lipoprotein(a) are associated with accelerated progression of the necrotic core, but not with coronary calcium score (CAC), although in the latter case, the evaluation of lipoprotein(a) can overcome the potential limitation of CAC to capture the totality of ASCVD risk in asymptomatic individuals. Finally, in the absence of a pharmacological approach to lower lipoprotein(a) to the extent required to achieve a cardiovascular benefit, implementation strategies that increase awareness among the population, patients, and healthcare providers on the importance of lipoprotein(a) in the development of ASCVD are eagerly needed.
The stent in the high-bleeding risk patient: antiplatelet monotherapy?
Authors: Capranzano Piera
Published: November 2022

Dual antiplatelet therapy (DAPT) is the recommended treatment after percutaneous coronary intervention (PCI). The introduction into clinical practice of new drug-eluting stents (DESs) with significantly improved safety profiles has made it possible to shorten the DAPT. Randomized studies have established the superiority of DES over bare metal stents in high-bleeding risk (HBR) patients treated with antiplatelet monotherapy after 1 month of DAPT from PCI. This regimen has been adopted in randomized trials comparing different DES in patients with HBR. Furthermore, antiplatelet monotherapy after 1 month of DAPT from PCI has been shown to reduce bleeding risk without increasing ischaemic events compared with a conventional DAPT regimen (3–12 months) in a recent randomized study that included HBR patients treated with DES. Parallel to the trend of shortening DAPT, there is growing debate about which antiplatelet monotherapy is optimal after discontinuation of DAPT, with some recent studies exploring the paradigm shift from aspirin monotherapy to P2Y12 inhibitor monotherapy. Finally, future studies are underway to evaluate the clinical effect of monotherapy with ticagrelor or prasugrel directly after implantation of DES thus eliminating DAPT.
Pollution and coronary risk: how much does it matter?
Authors: Muscente Francesca , de Caterina Raffaele
Published: November 2022

Air pollutants are a complex mixture of gaseous substances and particulate matter (PM). Each component potentially has specific harmful effects on human health, but several experimental and clinical studies have shown a strong impact of fine particles on major adverse cardiovascular events. Most of the available evidence concerns the effects of exposure to PM with a diameter of <2.5 µm (PM2.5) and the risk of developing coronary heart disease through inflammation and oxidative stress. While prolonged exposure to PM2.5 has been shown to be associated with the development of atherosclerosis and cardio-metabolic risk factors, short-term exposure has instead proved to be a trigger for acute coronary events, and especially in subjects with pre-existing coronary artery disease. As such, environmental PM2.5 is a major risk element for global public health. This underlines on the one hand not only the need to adopt and encourage preventive measures especially for individuals with a higher risk profile but also to practice environmental policies that are effective in promoting the reduction of exposure to pollutants.
The percutaneous coronary angioplasty gets better, but the surgical coronary artery bypass does not stay behind
Authors: De Paulis Ruggero , Folino Giulio , Scaffa Raffaele
Published: November 2022

Coronary artery bypass grafting remains one of the most frequently performed cardiac operations, with well-established prognostic benefits in patients with multivessel coronary artery disease and left main disease. Despite an increasingly higher patients’ risk profile, the results of this procedure have significantly improved over time, with an evident and striking decrease in operative mortality and peri-operative complications. A fair amount of technical and technological refinements has further improved the short- and long-term results of coronary artery bypass surgery. The improvements in the beating heart coronary surgery and aortic ‘no-touch’ technique, in the appropriate use of conduits (bilateral internal mammary artery, radial artery, and composite conduits configuration), and in the optimization of venous grafts’ patency are reviewed.
The link between influenza and myocardial infarction: vaccination protects
Authors: Bocale Raffaella , Necozione Stefano , Desideri Giovambattista
Published: November 2022

The association between influenza and cardiovascular disease has been known since the influenza pandemics of the early years of the last century. This association is more consistent and more lasting in the case of particularly severe infections. Several pathogens, including influenza viruses, can modulate the inflammatory response and influence the biology of atherosclerotic plaque to rupture it and cause a Type 1 myocardial infarction. Clinically relevant viral infections can also exacerbate pre-existing cardiovascular disease and contribute to the development of a Type 2 myocardial infarction through an increase in the metabolic demands of the myocardial tissue for fever and tachycardia and the possible induction of hypoxaemia. Evidence of a relevant protective efficacy of influenza vaccination provides further robust and convincing support for a causal link between influenza and myocardial infarction. Consistent cardiovascular protection linked to influenza vaccination has also been demonstrated in patients with recent myocardial infarction to suggest the possibility that this procedure may become an integral part of in-hospital management of acute coronary syndromes. Despite the solidity of these evidences, acknowledged by the guidelines that recommend influenza vaccination in patients at increased cardiovascular risk, still today an unacceptably high proportion of patients at high cardiovascular risk do not receive flu vaccination. Despite some potential limitations of the current flu vaccination, its advantages in terms of reducing cardiovascular events and related mortality are still such as to justify its wide use, especially, but not limited to, in patients with high cardiovascular risk.
Ischaemic stroke in the absence of documented atrial fibrillation: is there who could benefit from anticoagulant therapy?
Authors: Vassiliki’ Coutsoumbas Gloria , Di Pasquale Giuseppe
Published: November 2022

About 25% of ischaemic strokes are of cryptogenic origin and a significant proportion of them has a certain embolic nature, and for these patients the term embolic stroke of undetermined source (ESUS) has been coined. In the absence of subclinical atrial fibrillation (AF) identifiable through prolonged electrocardiogram monitoring, atrial cardiomyopathy, demonstrable through non-invasive cardiac imaging, aortic plaques and heart failure with preserved sinus rhythm, have been recognized among the potential causes of ESUS. In patients with ESUS, randomized clinical trials performed so far have failed to demonstrate a benefit of therapy with direct oral anticoagulants (DOACs). However, it is possible that in patients in whom the presence of atrial cardiomyopathy is ascertained there may be a benefit of anticoagulant therapy in secondary prevention after ESUS. In patients with aortic plaques associated with a thrombotic component and in those with heart failure and preserved sinus rhythm in the absence of AF but with a high congestive heart failure, hypertension age, diabetes, stroke, vascular disease (CHA2DS2-VASc) score, the decision on anticoagulant therapy with DOACs could be made in the individual patient even in the absence of evidence from clinical trials.
Iron deficiency in heart failure: diagnosis and clinical implications
Authors: Del Pinto Rita , Ferri Claudio
Published: November 2022

Iron deficiency is a widely prevalent finding in patients with heart failure, observed on average in 50% of outpatients and up to 80% of acute patients, regardless of the ejection fraction and the presence of anaemia, being an independent predictor of worst functional capacity and reduced survival. The definition of iron deficiency in heart failure considers the state of chronic inflammation that characterizes the pathology, recognizing a discriminating role for transferrin saturation. The studies conducted so far, which focused on the patient with heart failure with at least moderately reduced ejection fraction, have shown clinical benefit with intravenous supplementation of ferric carboxymaltose in terms of functional capacity, quality of life, laboratory markers of disease and inflammation, and possible reduction of re-hospitalizations, but not in terms of mortality. Based on this evidence, guidelines recommend intravenous ferric carboxymaltose in decompensated and iron-deficient patients, while research is at work to investigate the clinical impact of supplementation in contexts not yet examined, such as that of decompensation in patients with heart failure and preserved ejection fraction.
Is it possible that angioplasty does not improve the quality of life in patients with stable angina?
Authors: Golino Paolo
Published: November 2022

The scientific evidence in favour of percutaneous transcatheter coronary angioplasty (PTCA) in chronic ischaemic heart disease in terms of reduction of myocardial infarction and mortality is very scarce and controversial. However, for many years, the cardiology community has believed in the dogma that PTCA in chronic ischaemic heart disease could improve symptoms, especially when combined with effective medical therapy. A recent randomized controlled trial (ORBIT) has completely overturned this dogma, questioning much of what we have been taught about revascularization procedures in patients with stable coronary artery disease. In this article, the ORBITA study is discussed in depth, highlighting the lights and shadows of the study itself.
Post-infarct mitral insufficiency: when to resort to reparative surgery, when to the mitral clip
Authors: Gomez-Polo Juan Carlos , Buzzatti Nicola , Denti Paolo , Gatto Pamela , Scandroglio Mara , Aiello Silvia , Zangrillo Alberto , Maisano Francesco
Published: November 2022

Severe mitral insufficiency is a feared complication that develops in 10–12% of patients with myocardial infarction and ST elevation. It results from the rupture of the papillary muscle or is secondary to an acute remodelling of the left ventricle in its entirety or of the infarcted region. The mortality of patients with acute clinical onset reaches 50%. The ideal treatment of acute mitral insufficiency is controversial and still a source of debate. Most of these patients are at high surgical risk or inoperable; therefore, they are treated conservatively and have a poor prognosis. In these candidates, percutaneous treatment of insufficiency with percutaneous edge to edge can be considered an alternative.
Scenarios in precision medicine: proteomics in heart failure
Authors: Gentile Piero , Palazzini Matteo , Garascia Andrea , Oliva Fabrizio
Published: November 2022

Proteomics in heart failure (HF) is aimed to study and identify proteins involved in the pathophysiology of this clinical syndrome. Proteins have a role as diagnostic, prognostic and therapeutic markers. This review will unravel the developments and impact of proteomics in HF, focusing on its role in the diagnosis, prognosis and definition of new HF therapies. Proteomics promises to change our approach to HF in the near future, accepting the need for precision medicine, tailored on the characteristics of the single patient.
Is drinking wine in moderation good for health or not?
Authors: Poli Andrea
Published: November 2022

Drinking alcoholic beverages is associated with various health effects in the population. Generally speaking, the evidence from epidemiological studies suggest that moderate alcohol intake is associated with a reduction in the risk of cardiovascular events, such as myocardial infarction; the risk of cancer, on the other hand, tends to rise; whether an increase in the incidence of cancer is observed also in association with moderate consumption levels is yet not definitively ascertained. All these effects seem primarily to be associated with the amount of alcohol consumed; the role of the different alcoholic beverages, and of their minor components, in this regard is in fact not clearly defined. Due to the opposite direction of the association between alcohol consumption and cardiovascular and cancer events, the association with all-cause mortality is complex, and J-shaped, with a consumption window theoretically associated with a reduction in all-cause mortality, up to 25 g alcohol per day. However, this issue is the subject of intense scientific debate.
When Brugada syndrome is at risk of sudden death: clinical and anatomical aspects
Authors: Stazi Filippo , Battisti Paola
Published: November 2022

The current prognostic stratification of asymptomatic patients with Brugada syndrome is suboptimal. The so-called ‘Brugada burden’ concept is certainly emerging: the more extensive are the electrocardiographic alterations of the syndrome in space (peripheral as well as precordial derivations) and in time (persistence in the follow-up of electrocardiographic alterations), the greater the probability of arrhythmic events. Numerous clinical and electrocardiographic markers have been considered risk factors, but none of them alone is able to guide the choice of whether or not to implant a defibrillator, the only therapy so far proved effective in preventing SD (sudden death) in these patients. The prognostic value of the electrophysiology study also gradually decreased over time. Therapeutic decisions must therefore be taken, at the moment, considering a large number of variables, possibly included in risk scores to be validated prospectively and in large series. Magnetic resonance and the study of electro-anatomical alterations of the right ventricular outflow tract will most likely improve our prognostic stratification capacity in the future.
Clinical research methodology process: what has changed with COVID-19?
Authors: Tavazzi Luigi
Published: November 2022

The immediate repercussions of the pandemic on clinical research were the systematic interruption of ongoing studies and the explosion of tens of thousands of anti-COVID-19 research protocols reported in fragmented, uncoordinated, often technically insufficient international registers, from which almost nothing of significance was produced. In the first two years of intensive research, anti-inflammatory and anticoagulant benefits were identified, while the systemic nature of the viral disease was clearly manifested, but no specific antiviral drugs emerged. Subsequently, monoclonal antibodies and antiviral drugs such as Ritonavir-Boosted Nirmatrelvir (Paxlovid) have given way to more specific therapies, even if surprisingly little used. Finally, the new national Electronic Health Record (EHR-FSE2 Fascicolo Sanitario Elettronico 2 in Italian) was approved as a law, which will integrate the previous one, which is in fact not functional. The systematic, orderly and complete collection of the health data of each citizen constitutes a radical modification of the current National Health System, epidemiology and clinical research.
Polygenic risk score and age: an extra help in the cardiovascular prevention of the young?
Authors: Temporelli Pier Luigi
Published: November 2022

All major guidelines recommend assessing the risk of atherosclerotic cardiovascular disease (ASCVD) using risk scores. In fact, it has been shown that their use at the population level increases the accuracy of event prediction and facilitates the choice of strategies to be adopted in primary prevention. In fact, their use in clinical practice is far from optimal and their predictive ability on an individual level is not excellent. Our genetic heritage is substantially stable from birth and determines a ‘baseline risk’ on which external influences act. Genetic information therefore has the potential to be an early predictor of risk. Common diseases such as diabetes mellitus, ASCVD and neurodegenerative diseases are conditioned by different genetic variants with small individual effects, so that a reliable risk prediction requires careful examination of the aggregate impact of these multiple variants. The polygenic risk score (PRS) is a tool that potentially enables this complex assessment and provides a new opportunity to explore our risk of developing common diseases, including coronary artery disease (CAD). In the future, it is possible that a specific PRS could be used as an independent CAD screening tool, but this requires a detailed assessment of the practical implications, including the population to be investigated, and the consequent interventions that would then be offered.
Association between heart and dementia… keep an eye on the left atrium
Authors: Terrosu Pierfranco
Published: November 2022

Atrial fibrillation is associated with an increased risk of cognitive impairment and dementia. The mechanisms are not well known, but they are probably multifactorial and involve atrial myopathy, cardio-embolism, cerebral hypoperfusion, and comorbidities (systemic vascular sclerosis, disease of the small cerebral vessels, inflammation, etc.). Atrial fibrillation therapy could have a protective effect on dementia through diversified actions: (i) prevention of left atrial remodelling; (ii) prevention of cardio-embolism and silent (and not) cerebral infarcts; (iii) improvement of cardiac output and cerebral perfusion. Randomized trials will be needed to clarify the links between left atrium and dementia and to identify the most appropriate therapeutic strategies.
Genetics and clinics: together to diagnose cardiomyopathies
Authors: Urtis Mario , Di Toro Alessandro , Osio Roberto , Giuliani Lorenzo , Serio Alessandra , Grasso Maurizia , Fergnani Viola , Smirnova Alexandra , Aliberti Flaminia , Arbustini Eloisa
Published: November 2022

The diagnostic paths of hereditary cardiomyopathies (CMPs) include both clinical and molecular genetics. The first step is the clinical diagnosis that guides the decisions about treatments, monitoring, prognostic stratification, and prevention of major events. The type of CMP [hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy (ARVC)] is defined by the phenotype, and the genetic testing may identify the precise cause. Furthermore, genetic testing provides a pre-clinical diagnosis in unaffected family members and the basis for prenatal diagnosis. It can contribute to risk stratification (e.g. LMNA) and can be a major diagnostic criterion (e.g. ARVC). The test can be limited to a single gene when the pre-test diagnostic hypothesis is based on proven clinical evidence (e.g. GLA for Fabry disease). Alternatively, it can be expanded from a multigene panel to a whole exome or whole genome sequencing when the pre-test hypothesis is a genetically heterogeneous disease. In the last decade, the study of larger genomic targets led to the identification of numerous gene variants not only pathogenic (clinically actionable) but also of uncertain clinical significance (not actionable). For the latter, the pillar of the genetic diagnosis is the correct interpretation of the pathogenicity of genetic variants, which is evaluated using both bioinformatics and clinical-genetic criteria about the patient and family. In this context, cardiologists play a central role in the interpretation of genetic tests, performing the deep-phenotyping of variant carriers and establishing the co-segregation of the genotype with the phenotype in families.
Reduction of cerebrovascular and peripheral events with PCSK9 inhibitors: Does it just depend on the lowering of the low-density lipoprotein?
Authors: Cesaro Arturo , Acerbo Vincenzo , Raucci Giuseppe , Calabrò Paolo
Published: November 2022

Atherosclerotic cardiovascular disease is a systemic condition involving several vascular districts. The most involved vascular bed, beyond the coronary district, is represented by the peripheral arteries, whose involvement can give rise to cerebrovascular or peripheral events. PCSK9 inhibitors (PCSK9i) have established themselves as safe and effective drugs in reducing cholesterol linked to low-density lipoprotein (LDL-C), a causative factor of disease, with a consequent reduction in cardiovascular events. The two main studies on anti-PCSK9 antibodies, the FOURIER study for evolocumab and the ODYSSEY OUTCOMES study for alirocumab, highlighted the effectiveness in reducing LDL-C levels and its translation in a lower event rate of around 15%. Sub-analysis of these two trials showed how PCSK9i prevent cerebrovascular and/or peripheral events and how patients with already known cerebrovascular or peripheral disease benefit more from the action of these drugs than patients who do not have a widespread disease. Current evidence suggests that the preventive action of cerebrovascular and peripheral events is mainly expressed through reducing LDL-C levels. Although there are data regarding the association of PCSK9 levels and inflammatory status, propensity for thrombosis and platelet aggregation, these are currently less robust and do not justify a cardiovascular event reduction action that is independent of the action on LDL-C.
Some good reasons to proceed with the occlusion of the auricle
Authors: Casu Gavino , Merella Pierluigi , Lorenzoni Giovanni , Denurra Cristiana , Talana Giuseppe , Atzori Enrico
Published: November 2022

Atrial fibrillation (AF) is the most common arrhythmia. The most fearful complication of AF is represented by cardio-embolic stroke and 30% of ischaemic strokes are attributable to AF. The prevention of cardio-embolic risk is therefore based on oral anticoagulant therapy (OAT). Some categories of patients do not benefit from OAT. These are patients at increased bleeding risk and with varying degrees of contraindication to long-term anticoagulant therapy. On the opposite are those patients who develop an embolic event related to AF despite a well-conducted OAT. These types of patients benefit from an interventional approach, percutaneous closure of the left auricle (LAAO), aimed at eliminating what is the primary source of AF-related thrombo-embolism, precisely the left auricle. Percutaneous closure of the left auricle has proven to be an effective and safe procedure, significantly reducing the bleeding risks of patients who, after the procedure, will no longer have to take OAT. Furthermore, it has been shown to be effective in reducing cardio-embolic risk. Uncertainty still remains as to what is the optimal antithrombotic therapy after LAAO. In any case, LAAO represents a valid alternative to OAT for those patients in whom it is contraindicated or ineffective.
Sodium–glucose co-transporter 2 inhibitors for the treatment of cardio-renal syndrome
Authors: Cice Gennaro , Calo’ Leonardo , Monzo Luca
Published: November 2022

The 2021 guidelines of the European Society of Cardiology on the diagnosis and therapy of heart failure (HF) introduced relevant changes in the pharmacological treatment of chronic HF. Among these, certainly the most significant was the introduction in the therapeutic flow-chart (with the highest recommendation level) of the sodium glucose co-transporter 2 (SGLT2) inhibitors. In fact, SGLT2 inhibitors are responsible for major paradigm shifts in the care of patients with or at high risk for HF, progression of chronic kidney disease, or both. SGLT2 inhibition demonstrated to improve cardiovascular outcomes in patients with HF over a wide range of ejection fractions, regardless of diabetic status, and have a strong nephroprotective effect. There are several important interactions between heart disease and kidneys disease. Indeed, acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. The term ‘cardiorenal syndrome’ has been applied to these interactions. Since kidneys dysfunction in the setting of HF has a strong prognostic relevance, drugs that can slow down the decline of renal function are of utmost importance. Here, we discuss about the beneficial effects of SGLT2 inhibitors on the kidneys function in patients with HF and how these effects can improve both renal and cardiovascular outcomes.