The heart in cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) patients experience pulmonary exacerbations and the three-minute step test (3-min step test) may be a simple and easy-to-perform functional test to help identify such episodes. The present study aimed to evaluate the association of the 3-min step test with the occurrence of pulmonary exacerbations in children with CF. METHODS: Cross-sectional study of CF patients aged 6 years and older. Pulmonary exacerbations were assessed using both the Fuchs criteria and the Kanga Score...

BACKGROUND: With improvements in care for people with Cystic Fibrosis (pwCF), total survival after Lung Transplantation (LTx) will be longer. Therefore, this population's up-to-date analysis of late-onset post-transplant metabolic and vascular complications will be more relevant in current clinical practice. METHODS: We studied 100 pwCF who underwent an LTx between 2001 and 2020 at the University Medical Centre Utrecht, the Netherlands. The median age at transplant was 31 years and 55 percent was male...

BACKGROUND: Therapeutically immunosuppressed transplant recipients exhibit attenuated responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. To elucidate the kinetics and variant cross-protection of vaccine-induced antibodies in this population, we conducted a prospective longitudinal study in heart and lung transplant recipients receiving the SARS-CoV-2 messenger RNA (mRNA) 3-dose vaccination series. METHODS: We measured longitudinal serum antibody and neutralization responses against the ancestral and major variants of SARS-CoV-2 in SARS-CoV-2-uninfected lung (n = 18) and heart (n = 17) transplant recipients, non-lung-transplanted patients with cystic fibrosis (n = 7), and healthy controls (n = 12) before, during, and after the primary mRNA vaccination series...

Microtubule-Associated Serine/Threonine (MAST) kinases represent an evolutionary conserved branch of the AGC protein kinase superfamily in the kinome. Since the discovery of the founding member, MAST2, in 1993, three additional family members have been identified in mammals and found to be broadly expressed across various tissues, including the brain, heart, lung, liver, intestine and kidney. The study of MAST kinases is highly relevant for unraveling the molecular basis of a wide range of different human diseases, including breast and liver cancer, myeloma, inflammatory bowel disease, cystic fibrosis and various neuronal disorders...

Choice of vector is the most critical step in gene therapy. Adeno-associated viruses (AAV); third generation vectors, are getting much attention of scientists to be used as vehicles due to their non-pathogenicity, excellent safety profile, low immune responses, great efficiency to transduce non-dividing cells, large capacity to transfer genetic material and long-term expression of genetic payload. AAVs have multiple serotypes and each serotype shows tropism for a specific cell. Different serotypes are used to target liver, lungs, muscles, retina, heart, CNS, kidneys, etc...

Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients...

BACKGROUND: sodium-dependent glucose cotransporter 1 and 2 (SGLT1/2) belong to the family of glucose transporters, encoded by SLC5A1 and SLC5A2, respectively. SGLT-2 is almost exclusively expressed in the renal proximal convoluted tubule cells. SGLT-1 is expressed in the kidneys but also in other organs throughout the body. Many SGLT inhibitor drugs have been developed based on the mechanism of blocking glucose (re)absorption mediated by SGLT1/2, and several have gained major regulatory agencies' approval for treating diabetes...

BACKGROUND: Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. METHODS: We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data)...

BACKGROUND: Whether functional status is associated with survival to pediatric lung transplant is unknown. We hypothesized that completely dependent functional status at waitlist registration, defined using Lansky Play Performance Scale (LPPS), would be associated with worse outcomes. METHODS: Retrospective cohort study of pediatric lung transplant registrants utilizing UNOS STAR files (2005-2020). Primary exposure was completely dependent functional status, defined as LPPS score of 10-40...

The human ether-a-go-go-related gene (hERG) encodes for the pore-forming subunit of the channel that conducts the rapidly activating delayed K+ current (IKr ) in the heart. The hERG channel is important for cardiac repolarization, and reduction of its expression in the plasma membrane due to mutations causes long-QT syndrome type 2 (LQT2). As such, promoting hERG membrane expression is a strategy to rescue mutant channel function. In the present study, we applied patch clamp, Western blots, immunocytochemistry, and Quantitative Reverse Transcription PCR (RT-qPCR) techniques to investigate the rescue effects of two drugs, remdesivir and lumacaftor, on trafficking defective mutant hERG channels...

BACKGROUND: Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation. METHODS: This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days...

Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms...

BACKGROUND: Gastroesophageal reflux (GER) has been associated with poor outcomes after lung transplantation for chronic lung disease, including increased risk of chronic rejection. GER is common in cystic fibrosis (CF), but factors influencing the likelihood of pre-transplant pH testing, and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown. AIM: To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF...

MasR is a critical element in the RAS accessory pathway that protects the heart against myocardial infarction, ischemia-reperfusion injury, and pathological remodeling by counteracting the effects of AT1R. This receptor is mainly stimulated by Ang 1-7, which is a bioactive metabolite of the angiotensin produced by ACE2. MasR activation attenuates ischemia-related myocardial damage by facilitating vasorelaxation, improving cell metabolism, reducing inflammation and oxidative stress, inhibiting thrombosis, and stabilizing atherosclerotic plaque...

INTRODUCTION: Absence from school is more frequent for children with chronic health conditions (CHCs) than their peers and may be one reason why average academic attainment scores are lower among children with CHCs. METHODS: We determined whether school absence explains the association between CHCs and academic attainment through a systematic review of systematic reviews of comparative studies involving children with or without CHCs and academic attainment. We extracted results from any studies that tested whether school absence mediated the association between CHCs and academic attainment...

BACKGROUND: Right heart functions are affected in patients with bronchiectasis as a result of pulmonary hypertension induced by chronic hypoxemia. Pulmonary artery wall thickness has recently been introduced as a sign of intensive and prolonged inflammation. The aim of this study was to analyze right ventricular and right atrial functions and to mea-sure pulmonary artery wall thickness in patients with cystic fibrosis-bronch iecta sis in comparison to those with noncystic fibrosis-bronchiectasis and healthy individuals...

Tachypnoea in the newborn is common. It may arise from the many causes of the respiratory distress syndrome such as hyaline membrane disease, transient tachypnoea of the newborn, meconium aspiration etc. Congenital heart disease rarely presents with early tachypnoea on day one or two, in contrast to the early presentation of cyanosis, unless there is "pump" (ventricular) failure such as may occur in a cardiomyopathy/myocarditis, or as a result of severe obstruction to either ventricle. Space-occupying lesions within the chest, for example from a diaphragmatic hernia or a congenital cystic adenomatoid malformation, may present with early tachypnoea, as can a metabolic cause resulting in acidosis...

Fibrosis, or tissue scarring, develops as a pathological deviation from the physiological wound healing response and can occur in various organs such as the heart, lung, liver, kidney, skin, and bone marrow. Organ fibrosis significantly contributes to global morbidity and mortality. A broad spectrum of etiologies can cause fibrosis, including acute and chronic ischemia, hypertension, chronic viral infection (e.g., viral hepatitis), environmental exposure (e.g., pneumoconiosis, alcohol, nutrition, smoking) and genetic diseases (e...

INTRODUCTION: Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly...

OBJECTIVE: To evaluate the validity and reliability of the modified shuttle 25-level test (MST-25) in children with cystic fibrosis (CF). METHODS: A prospective single center study in clinically stable children with CF. Participants undertook two testing conditions on different days: (1) 2xMST-25 tests; (2) cardiopulmonary exercise test (CPET). Test order was randomized. Nadir oxygen saturation (SpO2 ), peak heart rate (HR), breathlessness (modified Borg), rate of perceived exertion (RPE), energy expenditure (EE) and metabolic equivalents (MET) from the MST-25 and CPET were compared to assess validity, while outcomes from 2xMST-25 tests were compared for reliability...