Pubblicazioni recenti - cardiac disease
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Apparent Mineralocorticoid Excess in Israel: A Case Series and Literature Review.
Eur J Endocrinol2024 Apr;():. doi: lvae049.
Lebel Asaf, Ben Shalom Efrat, Mokatern Rozan, Halevy Raphael, Zehavi Yoav, Magen Daniela,
Abstract
BACKGROUND AND OBJECTIVE:
Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature.
DESIGN:
Retrospective cohort study.
METHODS:
Clinical, laboratory, and molecular data from patients' records were collected.
RESULTS:
Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while two patients presented during late childhood with CKD. Molecular analysis revealed two novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only one showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those five patients who presented early exhibited normal eGFR and near-normal blood pressure, but two have hypertension complications. The two patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation.
CONCLUSIONS:
In this 11-year follow-up report of two Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment.
© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
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Is Reiki effective in reducing heart rhythm, cortisol and anxiety and improving biochemical parameters in individuals with cardiac disesase? Randomized placebo-controlled trial.
Eur J Cardiovasc Nurs2024 Apr;():. doi: zvae051.
Bektas Akpinar Nilay, Özcan Yüce Ulviye, Cans?z Gizem, Yurtsever Dilek, Özkanat Cemaynur, Unal Nursemin, Sabanoglu Cengiz, Alt?nbas Akkas Özlem, Yurtsever Sabire,
Abstract
AIMS:
The aim of this study was to examine the effect of Reiki in patients with cardiac disease.
METHODS AND RESULTS:
This study was a single-blind, pre-post-test, randomized, placebo-controlled study. Patients from the cardiology outpatient clinic of a training and research hospital were randomized into three groups: Reiki (n?=?22), sham (placebo) (n = 21), and control (no treatment) (n?=?22). Data were collected using a personal information form, biochemical parameters, cortisol levels, Beck Anxiety Inventory, and electrocardiography analysis. The Reiki group received Reiki to nine main points for 30?min, while the sham Reiki group received the same points during the same period without starting energy flow. On day two, performed Distance Reiki for 30?minutes. After one week, the researchers administered the Beck Anxiety Inventory, assessed the biochemical parameters and cortisol levels, and analyzed the electrocardiography again. Of the patients, 52.3% were male and 47.7% were female, and the mean age (years) is 60.45?±?9.67 years. The control group had a significantly higher posttest cortisol level than the other groups (p?=?0.002). According to the post-hoc analysis, there was a significant difference between the Reiki versus control groups and sham versus control groups (p?=?0.002). The control group had a significantly higher post-test cortisol level than the pre-test cortisol level (p?=?0.008). Reiki group had a significantly lower mean posttest Beck Anxiety Inventory score than the other groups (p?0.001). There was no difference between the electrocardiography results of the groups (p?>?0.05).
CONCLUSION:
Reiki reduces blood cortisol levels and anxiety levels in patient with cardiac diseases.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
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Eosinophilic Pleural Effusion Secondary to Trichinella spiralis Infection in a Patient with Systemic Sclerosis: A Case Report.
Am J Case Rep2024 Apr;25():e943420. doi: 10.12659/AJCR.943420.
Vulcan M?d?lina ?tefania, Dragne Andrei-Daniel, Badea Camelia Georgeta,
Abstract
BACKGROUND Scleroderma is a chronic autoimmune disease characterized by angiopathy, autoimmunity, and fibrosis. One form of scleroderma, systemic sclerosis, is characterized by diffuse skin lesions and visceral involvement. Eosinophilic pleural effusion is a rare complication attributed to a large array of diseases. We present a case of a man with underlying systemic sclerosis who developed eosinophilic pleural effusion as a complication of associated Trichinella spiralis infection. CASE REPORT A 49-year-old man presented for bilateral inflammatory radio-ulnar-carpal joint pain, paresthesia of the hands and forearms and a 2-week history of right posterior aching thoracic pain and night sweats. The physical examination revealed sclerodermatous skin involvement of the hands, forearms, and forehead, sclerodactyly, Raynaud's phenomenon, and telangiectasias, together with muffled cardiac sounds and right basal abolishment of the vesicular breath sounds. Imagistic evaluation showed the presence of pleuro-pericardial fluid. A thoracocentesis highlighted the presence of an exudative eosinophilic pleural effusion. Laboratory findings showed leukocytosis, with elevated neutrophil and eosinophil counts. The patient was tested for a parasitic infection, but initially the results were negative. He started anti-inflammatory treatment, but no reduction of the pleural fluid was observed. Subsequent evaluation revealed specific anti-trichinella IgG antibodies. Albendazole and corticosteroid therapy were initiated, which resulted in remission of the symptoms. CONCLUSIONS This report highlights the possibility of developing rare or even not-until-now seen complications when 2 etiologically different diseases are associated. The physician should carefully assess the situation to find and resolve the underlying causes.
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Identifying areas of Australia with high out-of-hospital cardiac arrest incidence and low bystander cardiopulmonary resuscitation rates: A retrospective, observational study.
PLoS One2024 ;19(4):e0301176. doi: 10.1371/journal.pone.0301176.
Doan Tan, Howell Stuart, Ball Stephen, Finn Judith, Cameron Peter, Bosley Emma, Dicker Bridget, Faddy Steven, Nehme Ziad, Heriot Natalie, Swain Andy, Thorrowgood Melanie, Thomas Andrew, Perillo Samuel, McDermott Mike, Smith Tony, Smith Karen, Belcher Jason, Bray Janet, ,
Abstract
AIM:
This study aims to explore regional variation and identify regions within Australia with high incidence of out-of-hospital cardiac arrest (OHCA) and low rates of bystander cardiopulmonary resuscitation (CPR).
METHOD:
Adult OHCAs of presumed medical aetiology occurring across Australia between 2017 and 2019 were mapped onto local government areas (LGA) using the location of arrest coordinates. Bayesian spatial models were applied to provide "smoothed" estimates of OHCA incidence and bystander CPR rates (for bystander-witnessed OHCAs) for each LGA. For each state and territory, high-risk LGAs were defined as those with an incidence rate greater than the state or territory's 75th percentile and a bystander CPR rate less than the state or territory's 25th percentile.
RESULTS:
A total of 62,579 OHCA cases attended by emergency medical services across 543 LGAs nationwide were included in the study. Nationally, the OHCA incidence rate across LGA ranged from 58.5 to 198.3 persons per 100,000, while bystander CPR rates ranged from 45% to 75%. We identified 60 high-risk LGAs, which were predominantly located in the state of New South Wales. Within each region, high-risk LGAs were typically located in regional and remote areas of the country, except for four metropolitan areas-two in Adelaide and two in Perth.
CONCLUSIONS:
We have identified high-risk LGAs, characterised by high incidence and low bystander CPR rates, which are predominantly in regional and remote areas of Australia. Strategies for reducing OHCA and improving bystander response may be best targeted at these regions.
Copyright: © 2024 Doan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Lack of mTORC2 signalling in CD11c+ myeloid cells inhibits their migration and ameliorates experimental colitis.
J Leukoc Biol2024 Apr;():. doi: qiae084.
Ignacio Aline, Cipelli Marcella, Takiishi Tatiane, Aguiar Cristhiane Favero, Fernandes Terra Fernanda, Ghirotto Bruno, Silva Eloisa Martins, Castoldi Angela, Magalhães Yuli Thamires, Antonio Tiago, Nunes Padovani Barbara, Ioshie Hiyane Meire, Andrade-Oliveira Vinicius, Forti Fabio Luis, Camara Niels Olsen Saraiva,
Abstract
The Mammalian Target of Rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRic?/?), this study investigated the role of mTOR complex 2 (mTORC2) signalling in dendritic cells (DCs) function in mice. We showed that upon DSS-induced colitis, lack of mTORC2 signalling CD11c+ cells diminishes colitis score, and abrogates dendritic cell (DC) migration to the mesenteric lymph nodes (MLN), thereby diminishing the infiltration of T helper (Th) 17 cells in the lamina propria (LP) and subsequent inflammation. These findings corroborate with abrogation of cytoskeleton organization and decreased activation of Rac1 and Cdc42 GTPases observed in CD11c+-mTORC2-deficient cells. Meta-analysis on colonic samples from ulcerative colitis (UC) patients revealed increased gene expression of pro-inflammatory cytokines which coincided with augmented expression of mTOR pathway, positive correlation between the DC marker ITGAX and IL-6, the expression of RICTOR, and CDC42. Together, this work proposes that targeting mTORC2 on DCs offers a key to hamper inflammatory responses and this way, ameliorates the progression and severity of intestinal inflammatory diseases.
© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
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Characteristics and Determinants of Pulmonary Long COVID.
JCI Insight2024 Apr;():. doi: e177518.
Patton Michael John, Benson Donald, Robison Sarah W, Raval Dhaval, Locy Morgan L, Patel Kinner, Grumley Scott, Levitan Emily B, Morris Peter, Might Matthew, Gaggar Amit, Erdmann Nathaniel,
Abstract
BACKGROUNDPersistent cough and dyspnea are prominent features of post-acute sequelae of SARS-CoV-2 (also termed 'Long COVID'); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFTs) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary Long COVID.METHODSThis single-center retrospective study included 1,097 patients with clinically defined Long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for ?1 month after resolution of primary COVID infection.RESULTSAfter exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified diffusion impairment and restriction as measured by percent predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Dyspnea was the predominant symptom in the cohort (78%) and had similar prevalence regardless of degree of diffusion impairment or restriction. Longitudinal evaluation revealed diffusion impairment (DLCO ?80%) and pulmonary restriction (TLC ?80%) in 51% of the cohort overall (n=479). In multivariable logistic regression analysis (adjusted odds ratio; aOR, 95% confidence interval [CI]), invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary Long COVID with diffusion impairment and restriction (aOR=10.9 [4.09-28.6]). Finally, a sub-analysis of CT imaging identified radiographic evidence of fibrosis in this patient population.CONCLUSIONSLongitudinal PFT measurements in patients with prolonged pulmonary symptoms after SARS-CoV-2 infection revealed persistent diffusion impaired restriction as a key feature of pulmonary Long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of patients with prolonged pulmonary symptoms after resolution of SARS-CoV-2. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary Long COVID patients.FUNDINGThis work was supported by the National Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), the National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund established by the Hugh Kaul Precision Medicine Network at the University of Alabama at Birmingham.
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Changes in Sleep Patterns, Genetic Susceptibility, and Incident Cardiovascular Disease in China.
JAMA Netw Open2024 Apr;7(4):e247974. doi: 10.1001/jamanetworkopen.2024.7974.
Diao Tingyue, Liu Kang, Lyu Junrui, Zhou Lue, Yuan Yu, Yang Handong, Wu Tangchun, Zhang Xiaomin,
Abstract
IMPORTANCE:
The associations of changes in sleep patterns with incident cardiovascular disease (CVD) are not fully elucidated, and whether these associations are modified by genetic susceptibility remains unknown.
OBJECTIVES:
To investigate the associations of 5-year changes in sleep patterns with incident CVD and whether genetic susceptibility modifies these associations.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study of the Dongfeng-Tongji cohort was conducted from 2008 to 2018 in China. Eligible participants included those with complete sleep information at baseline survey (2008-2010) and the first follow-up survey (2013); participants who had no CVD or cancer in 2013 were prospectively assessed until 2018. Statistical analysis was performed in November 2023.
EXPOSURES:
Five-year changes in sleep patterns (determined by bedtime, sleep duration, sleep quality, and midday napping) between 2008 and 2013, and polygenic risk scores (PRS) for coronary heart disease (CHD) and stroke.
MAIN OUTCOMES AND MEASURES:
Incident CVD, CHD, and stroke were identified from 2013 to 2018. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs.
RESULTS:
Among 15?306 individuals (mean [SD] age, 65.8 [7.4] years; 8858 [57.9%] female and 6448 male [42.1%]), 5474 (35.78%) had persistent unfavorable sleep patterns and 3946 (25.8%) had persistent favorable sleep patterns. A total of 3669 incident CVD cases were documented, including 2986 CHD cases and 683 stroke cases, over a mean (SD) follow-up of 4.9 (1.5) years. Compared with those with persistent unfavorable sleep patterns, individuals with persistent favorable sleep patterns over 5 years had lower risks of incident CVD (HR, 0.80; 95% CI, 0.73-0.87), CHD (HR, 0.84; 95% CI, 0.76-0.92), and stroke (HR, 0.66; 95% CI, 0.54-0.82) in the subsequent 5-year period. No significant effect modification by PRS was observed for sleep pattern change and CHD or stroke risk. However, sleep pattern changes and PRS were jointly associated with the CHD and stroke risk in a dose-dependent manner, with the lowest risk being among those with persistent favorable sleep patterns combined with low PRS (HR for CHD, 0.65; 95% CI, 0.52-0.82 and HR for stroke, 0.48; 95% CI, 0.29-0.79).
CONCLUSIONS AND RELEVANCE:
In this cohort study of middle-aged and older Chinese adults, individuals with persistent favorable sleep patterns had a lower CVD risk, even among those with higher genetic risk. These findings highlight the importance of maintaining favorable sleep patterns for CVD prevention.
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RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-?/NF-?B/NLRP3 Signaling Pathway through Inhibiting Calcineurin.
J Cardiovasc Transl Res2024 Apr;():. doi: 10.1007/s12265-023-10376-8.
Gao Yi, Li Shuai, Liu Xueyan, Si Daoyuan, Chen Weiwei, Yang Fenghua, Sun Huan, Yang Ping,
Abstract
The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-?/NF-?B/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-?/NF-?B/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-?/NF-?B/NLRP3 pathway.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Improvement in right heart function following kidney transplantation in esrd patients: insights from speckle tracking echocardiography analysis.
Int J Cardiovasc Imaging2024 Apr;():. doi: 10.1007/s10554-024-03103-0.
Khani Mohammad, Moradi Amir, Ghadirzadeh Erfan, Sari Seyed Pooria Salehi Mashhad, Akbari Tooba,
Abstract
Chronic kidney disease (CKD) is commonly associated with unfavorable cardiovascular outcomes and remains the leading cause of mortality in individuals with end-stage renal disease (ESRD). Despite substantial knowledge about the impact of CKD on the left heart, the right heart, which holds significant clinical relevance, has often been overlooked and inadequately assessed in ESRD patients who have undergone kidney transplant (KTx). This study aimed to evaluate the effects of KTx on the right heart chambers in ESRD patients. 57 adult KTx candidates were enrolled in this prospective longitudinal study, while 49 of them were included in the final assessment. Patients underwent a comprehensive cardiac assessment, including conventional echocardiography, speckle tracking echocardiography, and three-dimensional heart modeling both before and after surgery. Echocardiographic assessments showed significant increases in right ventricular (RV) ejection fraction, RV fractional area change (RVFAC), tricuspid annular plain systolic excursion, RV fractional shortening, right atrial (RA) reservoir, conduit, and booster strains, and RV global longitudinal strain (RVGLS). Moreover, significant reductions in RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume, RV end-diastolic diameter (RVEDD) in mid-cavity view, systolic pulmonary artery pressure was observed (all P values?0.05). However, no significant difference was found in S velocity, as well as RVEDD in basal and apex-to-annulus view. Moreover, pre-KTx measurements of RVGLS, RVEDD (apex-to-annulus diameter), RV fractional shortening, and S velocity were predictors of RVGLS after KTx. RA conduit strain was also identified as a predictor of RA conduit strain after KTx. Additionally, age, RVEDV, RVESV, RVFAC, and RA reservoir strain before KTx were identified as independent predictors of RA reservoir strain after KTx. The findings of this study demonstrate a significant improvement in right heart function following KTx. Furthermore, strain analysis can provide valuable insights for predicting right heart function after KTx.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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Cracking the heart code: using ChatGPT's Data Analyst feature for cardiovascular imaging research.
Int J Cardiovasc Imaging -
NASCI case of the month: desmoplakin cardiomyopathy masquerading as acute myocarditis.
Int J Cardiovasc Imaging2024 Apr;():. doi: 10.1007/s10554-024-03112-z.
Gowda Prateek C, Gasperetti Alessio, Zimmerman Stefan L,
Abstract
We present a case of a young patient with chest pain. Labs and cardiac imaging were suspicious for acute myocarditis. Genetic testing revealed a diagnosis of desmoplakin cardiomyopathy. Desmoplakin cardiomyopathy may be considered in patients with recurrent acute myocarditis or a family history of cardiac disease to avoid the potential for misdiagnosis.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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Correlations and discrepancies between cardiac ultrasound, clinical diagnosis and the autopsy findings in early deceased patients with suspected cardiovascular emergencies.
Int J Cardiovasc Imaging2024 Apr;():. doi: 10.1007/s10554-024-03107-w.
Stankovic Ivan, Zivanic Aleksandra, Vranic Ivona, Neskovic Aleksandar N,
Abstract
Cardiac ultrasound (CUS), either focused cardiac ultrasound (FoCUS) or emergency echocardiography, is frequently used in cardiovascular (CV) emergencies. We assessed correlations and discrepancies between CUS, clinical diagnosis and the autopsy findings in early deceased patients with suspected CV emergencies. We retrospectively analysed clinical and autopsy data of 131 consecutive patients who died within 24 h of hospital admission. The type of CUS and its findings were analysed in relation to the clinical and autopsy diagnoses. CUS was performed in 58% of patients - FoCUS in 83%, emergency echocardiography in 12%, and both types of CUS in 5% of cases. CUS was performed more frequently in patients without a history of CV disease (64 vs. 40%, p?=?0.08) and when the time between admission and death was longer (6 vs. 2 h, p?=?0.021). In 7% of patients, CUS was inconclusive. In 10% of patients, the ante-mortem cause of death could not be determined, while discrepancies between the clinical and post-mortem diagnosis were found in 26% of cases. In the multivariate logistic regression model, only conclusive CUS [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.30-7.39, p?=?0.044] and chest pain at presentation (OR 30.19, 95%CI 5.65 -161.22, p?0.001) were independently associated with congruent clinical and autopsy diagnosis. In a tertiary university hospital, FoCUS was used more frequently than emergency echocardiography in critically ill patients with suspected cardiac emergencies. Chest pain at presentation and a conclusive CUS were associated with concordant clinical and autopsy diagnoses.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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Fetal transposition of the great arteries: 3D virtual and physical models from ultrasound datasets.
Int J Cardiovasc Imaging2024 Apr;():. doi: 10.1007/s10554-024-03106-x.
Nieblas Caroline de Oliveira, Bravo-Valenzuela Nathalie Jeanne, Araujo Júnior Edward, Werner Heron,
Abstract
Transposition of the great arteries (TGA) is a cyanotic congenital heart disease characterized by ventriculoarterial discordance and atrioventricular concordance with the great arteries in a parallel relationship. Prenatal diagnosis of TGA has implications for postnatal outcomes, allowing for planned delivery and perinatal management. Three-dimensional virtual or physical models of fetal TGA allow better understanding of fetal cardiac anomalies by parents and interactive discussion among the multidisciplinary team (obstetricians, pediatricians, maternal-fetal specialists, pediatric cardiologists, and cardiovascular surgeons), as well as continuing medical education.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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Examining the contribution of Notch signaling to lung disease development.
Naunyn Schmiedebergs Arch Pharmacol2024 Apr;():. doi: 10.1007/s00210-024-03105-8.
Antar Samar A, ElMahdy Mohamed Kh, Darwish Ahmed G,
Abstract
Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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The thrombin receptor PAR4 supports visceral adipose tissue inflammation.
Naunyn Schmiedebergs Arch Pharmacol2024 Apr;():. doi: 10.1007/s00210-024-03097-5.
Kleeschulte Sonja, Fischinger Vivien, Öhlke Lisa, Bode Johannes, Kamler Markus, Dobrev Dobromir, Grandoch Maria, Fender Anke C,
Abstract
Thrombin inhibition suppresses adiposity, WAT inflammation and metabolic dysfunction in mice. Protease-activated receptor (PAR)1 does not account for thrombin-driven obesity, so we explored the culprit role of PAR4 in this context. Male WT and PAR-4 mice received a high fat diet (HFD) for 8 weeks, WT controls received standard chow. Body fat was quantified by NMR. Epididymal WAT was assessed by histology, immunohistochemistry, qPCR and lipase activity assay. 3T3-L1 preadipocytes were differentiated ± thrombin, acutely stimulated ± PAR4 activating peptide (AP) and assessed by immunoblot, qPCR and U937 monocyte adhesion. Epicardial adipose tissue (EAT) from obese and lean patients was assessed by immunoblot. PAR4 was upregulated in mouse WAT under HFD. PAR4 mice developed less visceral adiposity and glucose intolerance under HFD, featuring smaller adipocytes, fewer macrophages and lower expression of adipogenic (leptin, PPAR?) and pro-inflammatory genes (CCL2, IL-1?) in WAT. HFD-modified activity and expression of lipases or perilipin were unaffected by PAR4 deletion. 3T3-L1 adipocytes differentiated with thrombin retained Ki67 expression, further upregulated IL-1? and CCL2 and were more adhesive for monocytes. In mature adipocytes, PAR4-AP increased phosphorylated ERK1/2 and AKT, upregulated Ki67, CCl2, IL-? and hyaluronan synthase 1 but not TNF-? mRNA, and augmented hyaluronidase-sensitive monocyte adhesion. Obese human EAT expressed more PAR4, CD68 and CD54 than lean EAT. PAR4 upregulated in obesity supports adipocyte hypertrophy, WAT expansion and thrombo-inflammation. The emerging PAR4 antagonists provide a therapeutic perspective in this context beyond their canonical antiplatelet action.
© 2024. The Author(s).
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Treatment of transthyretin cardiac amyloidosis.
Curr Opin Cardiol2024 Apr;():. doi: 10.1097/HCO.0000000000001156.
Bampatsias Dimitrios, Wardhere Abdirahman, Maurer Mathew S,
Abstract
PURPOSE OF REVIEW:
Tafamidis is currently the only approved disease-modifying treatment for ATTR-CM. However, there have been important developments in the treatment of ATTR-CM, as the results of two phase 3 trials were published and several other trials are in their final stages. In this review, we summarize current and future therapies for ATTR-CM.
RECENT FINDINGS:
Recently, acoramidis, a TTR stabilizer has been proven to be effective in reducing mortality and morbidity compared to placebo in the ATTRibute-CM trial. Additionally, patisiran, an RNA silencer, preserved functional capacity and quality of life compared to placebo in the APOLLO-B trial. However, the FDA declined to approve patisiran for ATTR-CM. The results of phase 1 trial of ALXN2220, an antiamyloid antibody raise hope for reversal of myocardial damage by amyloid depletion. Phase 3 trials evaluating the efficacy of different RNA silencers, gene editing with CRISPR-Cas9, and other anti-amyloid antibodies are ongoing.
SUMMARY:
Therapies targeting different mechanism in the pathophysiology of ATTR-CM provide new alternatives for treating patients with ATTR-CM. Future research should focus on comparing their effectiveness, the potential of combined treatment with agents from different classes and on identifying the patients who will benefit most from each class of medication.
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
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Anti-cancer potential of zerumbone in cancer and glioma: current trends and future perspectives.
Med Oncol2024 Apr;41(5):125. doi: 10.1007/s12032-024-02327-3.
Soroush Alborz, Pourhossein Siavash, Hosseingholizadeh Dorrin, Hjazi Ahmed, Shahhosseini Reza, Kavoosi Haniyeh, Kermanshahi Nazgol, Behnamrad Parisa, Ghavamikia Nima, Dadashpour Mehdi, Karkon Shayan Sepideh,
Abstract
Plant-derived immunomodulators and antitumor factors have appealed lots of attention from natural product scientists for their efficiency and safety and their important contribution to well-designed targeted drug action and delivery mechanisms. Zerumbone (ZER), the chief component of Zingiber zerumbet rhizomes, has been examined for its wide-spectrum in the treatment of multi-targeted diseases. The rhizomes have been used as food flavoring agents in numerous cuisines and in flora medication. Numerous in vivo and in vitro experiments have prepared confirmation of ZER as a potent immunomodulator as well as a potential anti-tumor agent. This review is an interesting compilation of all the important results of the research carried out to date to investigate the immunomodulatory and anticancer properties of ZER. The ultimate goal of this comprehensive review is to supply updated information and a crucial evaluation on ZER, including its chemistry and immunomodulating and antitumour properties, which may be of principal importance to supply a novel pathway for subsequent investigation to discover new agents to treat cancers and immune-related sickness. In addition, updated information on the toxicology of ZER has been summarized to support its safety profile.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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[Max Reger and his early death: could it have been avoided? : Would he have lived longer with adequate intensive care?].
Med Klin Intensivmed Notfmed2024 Apr;():. doi: 10.1007/s00063-024-01144-w.
Trappe Hans-Joachim,
Abstract
BACKGROUND:
Max Reger was an organist, university teacher and composer whose life, illnesses, death and dying are not or hardly known to many.
OBJECTIVES:
Which illnesses determined Reger's life and did his lifestyle and illnesses influence his compositional work? Could his early death have been avoided? From today's point of view, could modern intensive care medicine have helped him?
MATERIAL AND METHODS:
A detailed analysis of Reger's diseases was performed using scientific databases (medline, pubmed). All published articles were evaluated and examined in detail.
RESULTS:
Max Reger was born in Brand in 1873 and received early lessons in violin, piano and organ playing. From 1890 he studied at the conservatory in Sondershausen, later at the conservatory in Wiesbaden. In 1901 he moved to Munich, and in 1907 to Leipzig, where he became university director and professor at the conservatory. Four years later he took over the court chapel in Meiningen, but ended this activity again in 1914. A year later he moved to Jena and wrote his late works in the "Jenaish style". Reger suffered from many illnesses, especially bipolar disorder with manic and depressive phases. He had metabolic syndrome with arterial hypertension, was overweight and smoked incredibly heavily. Overeating ("binge eating" syndrome) and polydipsia were other prominent findings. Reger's life was characterized by alcohol abuse, often aggravated by professional and/or human crises. In 1916 Reger died suddenly and unexpectedly in Leipzig of cardiovascular failure.
DISCUSSION:
Reger was an outstanding personality who left behind an extensive oeuvre. Among the highlights of Max Reger's oeuvre are his chorale fantasies such as on "Ein' feste Burg ist unser Gott" (op. 27) or also the "Fantasia and Fugue on B A C H" (op. 46), but other compositions such as the Mozart Variations (op. 132) and the Clarinet Quintet (op. 146) are also world-famous. His lifestyle certainly favored coronary heart disease, the consequences of which caused Reger's sudden, unexpected and much too early death. Today's modern intensive care medicine could probably have prolonged his life.
© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
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Macrophage-derived extracellular vesicles alter cardiac recovery and metabolism in a rat heart model of donation after circulatory death.
J Cell Mol Med2024 Apr;28(8):e18281. doi: 10.1111/jcmm.18281.
Graf Selianne, Biemmi Vanessa, Arnold Maria, Segiser Adrian, Müller Anja, Méndez-Carmona Natalia, Egle Manuel, Siepe Matthias, Barile Lucio, Longnus Sarah,
Abstract
Conditions to which the cardiac graft is exposed during transplantation with donation after circulatory death (DCD) can trigger the recruitment of macrophages that are either unpolarized (M0) or pro-inflammatory (M1) as well as the release of extracellular vesicles (EV). We aimed to characterize the effects of M0 and M1 macrophage-derived EV administration on post-ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20?min aerobic perfusion, followed by 27?min global, warm ischaemia or continued aerobic perfusion and 60?min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0-macrophage-dervied EV; (4) ischaemia with M1-macrophage-derived EV. Post-ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1-EV hearts, but not in M0-EV hearts, compared to non-ischaemic hearts (p?0.05). In parallel with the reduced functional recovery in M1-EV versus M0-EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0- and M1-macrophages differentially affect post-ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD.
© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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Personalized pulmonary vein isolation with very high-power short-duration lesions guided by left atrial wall thickness: the QDOT-by-LAWT randomized trial.
Europace2024 Mar;26(4):. doi: euae087.
Falasconi Giulio, Penela Diego, Soto-Iglesias David, Francia Pietro, Saglietto Andrea, Turturiello Dario, Viveros Daniel, Bellido Aldo, Alderete Jose, Zaraket Fatima, Franco-Ocaña Paula, Huguet Marina, Cámara Óscar, V?t??escu Radu, Ortiz-Pérez José-Tomás, Martí-Almor Julio, Berruezo Antonio,
Abstract
AIMS:
Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using very high-power short-duration (vHPSD) radiofrequency (RF) ablation proved to be safe and effective. However, vHPSD applications result in shallower lesions that might not be always transmural. Multidetector computed tomography-derived left atrial wall thickness (LAWT) maps could enable a thickness-guided switching from vHPSD to the standard-power ablation mode. The aim of this randomized trial was to compare the safety, the efficacy, and the efficiency of a LAWT-guided vHPSD PVI approach with those of the CLOSE protocol for PAF ablation (NCT04298177).
METHODS AND RESULTS:
Consecutive patients referred for first-time PAF ablation were randomized on a 1:1 basis. In the QDOT-by-LAWT arm, for LAWT ?2.5?mm, vHPSD ablation was performed; for points with LAWT > 2.5 mm, standard-power RF ablation titrating ablation index (AI) according to the local LAWT was performed. In the CLOSE arm, LAWT information was not available to the operator; ablation was performed according to the CLOSE study settings: AI ?400 at the posterior wall and ?550 at the anterior wall. A total of 162 patients were included. In the QDOT-by-LAWT group, a significant reduction in procedure time (40 vs. 70?min; P
CONCLUSION:
LAWT-guided PVI combining vHPSD and standard-power ablation is not inferior to the CLOSE protocol in terms of 1-year atrial arrhythmia-free survival and demonstrated a reduction in procedural and RF times.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
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