Association of gut microbiome dysbiosis with the progression of atrial fibrillation: A systematic review

Objective

Many clinical and preclinical studies have implicated an association between atrial fibrillation (AF) and its progression to imbalances in the gut microbiome composition. The gut microbiome is a diverse and complex ecosystem containing billions of microorganisms that produce biologically active metabolites influencing the host disease development.

Methods

For this review, a literature search was conducted using digital databases to systematically identify the studies reporting the association of gut microbiota with AF progression.

Results

In a total of 14 studies, 2479 patients were recruited for the final analysis. More than half (n = 8) of the studies reported alterations in alpha diversity in atrial fibrillation. As for the beta diversity, 10 studies showed significant alterations. Almost all studies that assessed gut microbiota alterations reported major taxa associated with atrial fibrillation. Most studies focused on short-chain fatty acids (SCFAs), whereas three studies evaluated TMAO levels in the blood, which is the breakdown product of dietary l -carnitine, choline, and lecithin. Moreover, an independent cohort study assessed the relationship between phenylacetylglutamine (PAGIn) and AF.

Conclusion

Intestinal dysbiosis is a modifiable risk factor that might provide newer treatment strategies for AF prevention. Well-designed research and prospective randomized interventional studies are required to target the gut dysbiotic mechanisms and determine the gut dysbiotic-AF relationship.     

Prevalence,characteristics and outcomes of older patients with hereditary versus wild-type transthyretin amyloid cardiomyopathy

Aims

Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of transthyretin (TTR) variants among elderly patients diagnosed with ATTR-CM.

Methods and results

Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality. The study population consisted of 2029 patients with ATTR-CM (median age 79 years at diagnosis, 13.5% females, 80.4% Caucasian). Variant ATTR-CM (ATTRv-CM) was diagnosed in 20.7% (n = 421) of the study population of whom 327 (77.7%) carried V122I, 47 (11.2%) T60A, 16 (3.8%) V30M and 31 (7.3%) other pathogenic TTR variants. During a median (range) follow-up of 29 (12–48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p < 0.001). Univariable and multivariable logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p < 0.001), female sex (OR 2.73, p < 0.001), Afro-Caribbean ethnicity (OR 65.5, p < 0.001), atrial fibrillation (OR 0.65, p = 0.015), ischaemic heart disease (OR 0.54, p = 0.007), peripheral polyneuropathy (OR 5.70, p < 0.001) and orthostatic hypotension (OR 6.29, p < 0.001) to be independently associated with ATTRv-CM.

Conclusion

Up to 20.7% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age.     

Use of patient-reported outcomes in heart failure: from clinical trials to routine practice

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care.     

Complex high-risk percutaneous coronary intervention types,trends, and outcomes according to vascular access site

Background

Radial access is associated with improved outcomes following percutaneous coronary intervention (PCI); however, its role in complex, high-risk percutaneous coronary intervention (CHiP) remains poorly studied.

Methods

We studied retrospectively all registered patients's records from the British Cardiovascular Intervention Society dataset and compared the baseline characteristics, trends and outcomes of CHiP procedures performed electively between January 2006 and December 2017 according to the access site.

Results

Out of 137,785 CHiP procedures, 61,825 (44.9%) were undertaken via transradial access (TRA). TRA use increased over time (14.6% in 2006 to 67% in 2017). The TRA patients were older, with a greater prevalence of previous stroke, hypertension, peripheral vascular disease, and smokers. TRA was used more frequently in most CHiP procedures (elderly (51.6%), chronic renal failure (52.6%), poor left ventricular (LV) function (47.6%), left main PCI (48.0%), treatment for severe vascular calcification (50.3%); although transfemoral access (TFA) was used more commonly in those with prior history of coronary artery bypass graft surgery, and PCI to a chronic total occlusion and LV support patients. Following adjustment for differences in clinical and procedural characteristics, TFA was independently associated with higher odds for mortality [adjusted odds ratio (aOR): 1.3 (1.1–1.7)], major bleeding [aOR: 2.9 (2.3–3.4)], and MACCE (following propensity score matching) [aOR: 1.2 (1.1–1.4)]. The same was found with multiple accesses: mortality [aOR: 2.1 (1.5–2.8)], major bleeding [aOR: 5.5 (4.3–6.9)], and MACCE [aOR: 1.4 (1.2–1.7)].

Conclusion

TRA has become the predominant access site for CHiP procedures and is associated with significantly lower mortality, major bleeding and MACCE odds than TFA.     

Median canaliform nail dystrophy in a 2-year-old boy: Case report and review of the literature

Median canaliform nail dystrophy (MCD) is a rare nail abnormality with an unknown etiology. We report the case of MCD of both great toenails in a 2-year-old boy presenting with a fir tree nail pattern and longitudinal splits. MCD was treated with topical marigold therapy (Tagetes sp.). By 15 weeks, the proximal 50% of the MCD had normalized. The report highlights a potential new treatment of marigold therapy for MCD.     

Orexinergic neurons in the hypothalami of an Asiatic lion,an African lion,and a Southeast African cheetah

Employing orexin-A immunohistochemistry, we describe the distribution, morphology, and nuclear parcellation of orexinergic neurons within the hypothalami of an Asiatic lion (Panthera leo subsp. persica), an African lion (Panthera leo subsp. melanochaita), and a Southeast African cheetah (Acinonyx jubatus subsp. jubatus). In all three felids, the clustering of large, bipolar, and multipolar hypothalamic orexinergic neurons primarily follows the pattern observed in other mammals. The orexinergic neurons were found, primarily, to form three distinct clusters—the main, zona incerta, and optic tract clusters. In addition, large orexinergic neurons were observed in the ventromedial supraoptic region of the hypothalamus, where they are not typically observed in other species. As has been observed in cetartiodactyls and the African elephant, a cluster of small, multipolar orexinergic neurons, the parvocellular cluster, was observed in the medial zone of the hypothalamus in all three felids, although this parvocellular cluster has not been reported in other carnivores. In both subspecies of lions, but not the cheetah, potential orexin-immunopositive neurons were observed in the paraventricular hypothalamic nucleus, supraoptic nucleus, the lateral part of the retrochiasmatic area, and the inner layer of the median eminence. The distribution and parcellation of orexinergic neurons in the hypothalami of the three felids studied appear to be more complex than observed in many other mammals and for the two subspecies of lion may be even more complex. These findings are discussed in terms of potential technical concerns, phylogenetic variations of this system, and potentially associated functional aspects of the orexinergic system.     

Pericardial mesothelioma presenting as constrictive pericarditis

A 46-year-old woman underwent pericardiocentesis and pericardial window for recurrent pericardial effusion. She presented 17 months later with signs and symptoms consistent with constrictive pericarditis. Cardiac magnetic resonance imaging revealed an infiltrative mass surrounding the pericardium. A transcutaneous core needle biopsy of the pericardium confirmed the diagnosis of pericardial mesothelioma.     

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.     

Synthesis and evaluation of novel xanthene-based thiazoles as potential antidiabetic agents

A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase (α-Amy), and α-glycosidase (α-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC₅₀: 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for α-Gly, and 152.48 and 124.84 nM for α-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, α-Amy, and α-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme.