The conventional sequence of guideline-directed medical therapy (GDMT) initiation in heart failure with reduced ejection fraction (HFrEF) assumes that the effectiveness and tolerability of GDMT agents mirror their order of discovery, which is not true. In this review, the authors discuss flexible GDMT sequencing that should be permitted in special populations, such as patients with bradycardia, chronic kidney disease, or atrial fibrillation. Moreover, the initiation of certain GDMT medications may enable tolerance of other GDMT medications. Most importantly, the achievement of partial doses of all four pillars of GDMT is better than achievement of target dosing of only a couple.

Congenital heart disease (CHD) is the most common global congenital defect affecting over 2.4 million individuals in the United States. Ongoing medical and surgical advancements have improved the survival of children with CHD leading to a shift where, as of 2010, adults constitute two-thirds of the CHD patient population. The increasing number and aging of adult congenital heart disease (ACHD) patients present a clinical challenge due to heightened complexity, morbidity, and mortality. Studies indicate that 1 in 13 ACHD patients will develop heart failure (HF) in their lifetime. ACHD-HF patients experience more frequent emergency department visits, higher hospitalization rates, longer hospital stays, and higher mortality compared to non-ACHD patients with heart failure (non-ACHD-HF). Despite HF being the leading cause of death in ACHD patients, there is a notable gap in evidence regarding treatment. While guideline-directed medical therapy (GDMT) has been extensively studied in non-ACHD-HF, research specific to ACHD-HF individuals is limited. This article aims to comprehensively review available literature addressing the pharmacological treatment of ACHD-HF.

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OBJECTIVE: Antihypertensive medications increase osteoblasts differentiation and bone mineral formation. Osseointegration of dental implants depends on new bone formation and remodelling. Consequently, improved osseointegration may be speculated in patients receiving antihypertensive drugs. Aim - Asses the effect of antihypertensive medications on osseointegration of dental implants.
METHODS: Retrospective cohort study. All individuals (792) who received at least one dental implant during a 6-year period at a single medical centre. The cohort was divided into three groups: normotensive (74.8% - 593) patients (NT group), hypertensive (23.4% - 185) patients using antihypertensive medications (HTN +med group), and hypertensive patients not using (1.8% - 14) antihypertensive medications (HTN -med group). Interventions-Installation of dental implants by experienced oral and maxillofacial surgeons with or without bone augmentation. Main measures - Early implant failure (EIF) (≤12 months from loading) reflects lack of new bone formation or excessive bone turnover during osseointegration.
RESULTS: The study included 792 individuals, 14 in the HTN-med group, 185 in the HTN +med group and 593 in the NT group. At the patient level, the HTN -med group were most likely (P = .041) to experience EIF 28.60% (4/14 patients). Due to the small sample of the HTN -med group, an additional analysis was carried out excluding this group. EIF of 9.70% (18/185 patients) in the HTN +med group was significantly (P = .047) lower than the NT group 14.50% (86/593 patients). 2971 implants were inserted in all study groups, 71.4% (2123) in the NT group, 26.4% (784) in the HTN +med group and 2.2% (64) in the HTN -med group. Collectively, EIF was recorded for 114 (3.84%) implants. In the HTN -med group, EIF of 6.25% (4 implants), was significantly (P < .001) higher than the two other groups. The EIF rate of the HTN +med group was 2.29% (18 implants) which was significantly less than that of the NT group 4.33% (92 implants). Controlling modifying parameters, using antihypertensive medication yielded lower EIF with marginal significance (P = .059) and OR = 0.618.
CONCLUSIONS: Based on statistically significant lower EIF rate found in the HTN +med group, antihypertensive medications may decrease the EIF rate of dental implants.
CONCLUSIONS: Clinicians should be encouraged to treat hypertensive patients with implant-supported prostheses, provided patient compliance regarding medications intake is good.

The pathway for pollutant degradation involving reactive oxygen species (ROS) in the rhizosphere is poorly understood. Herein, a rootchip system was developed to pinpoint the ROS hotspot along the root tip of Iris tectorum. Through mass balance analysis and quenching experiment, we revealed that ROS contributed significantly to rhizodegradation for beta-blockers, ranging from 22.18 % for betaxolol to 83.83 % for atenolol. The identification of degradation products implicated ROS as an important agent to degrade atenolol into less toxic transformation products during phytoremediation. Moreover, an active production of ROS in rhizosphere was identified by mesocosm experiment. Across three root-associated regions aquatic plants inhabiting the rhizosphere accumulated the highest •OH of ∼1200 nM after 3 consecutive days, followed by rhizoplane (∼230 nM) and bulk environment (∼60 nM). ROS production patterns were driven by rhizosphere chemistry (Fe and humic substances) and microbiome variations in different rhizocompartments. These findings not only deepen understanding of ROS production in aquatic plants rhizosphere but also shed light on advancing phytoremediation strategies.

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Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.

OBJECTIVE: Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR).
METHODS: Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger\'s regression tests.
RESULTS: Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes.
CONCLUSIONS: In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

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