Augmentation of natriuretic peptide (NP) receptor A and B (NPR-A and NPR-B) and cyclic guanosine monophosphate (cGMP) signalling as a therapeutic strategy in heart failure.

INTRODUCTION: Heart failure is a complex, debilitating condition and despite advances in treatment, it remains a significant cause of morbidity and mortality worldwide. Therefore, the need for alternative treatment strategies is essential. In this review, we explore the therapeutic strategies of augmenting natriuretic peptide receptors (NPR-A and NPR-B) and cyclic guanosine monophosphate (cGMP) in heart failure. AREAS COVERED: We aim to provide an overview of the evidence of preclinical and clinical studies on novel heart failure treatment strategies. Papers collected in this review have been filtered and screened following PubMed searches. This includes epigenetics, modulating enzyme activity in natriuretic peptide (NP) synthesis, gene therapy, modulation of downstream signaling by augmenting soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) inhibition, nitrates, c-GMP-dependent protein kinase, synthetic and designer NP and RNA therapy. EXPERT OPINION: The novel treatment strategies mentioned above have shown great potential, however, large randomized controlled trials are still lacking. The biggest challenge is translating the results seen in preclinical trials into clinical trials. We recommend a multi-disciplinary team approach with cardiologists, geneticist, pharmacologists, bioengineers, researchers, regulators, and patients to improve heart failure outcomes. Future management can involve telemedicine, remote monitoring, and artificial intelligence to optimize patient care.

Alcohol and Heart Failure.

Alcohol is the most frequently consumed toxic substance in the world and remains a major global public health issue, with one in three adults consuming it worldwide. Alcohol use is a leading risk factor for disease, contributing to over 60 acute and chronic health conditions, with a particularly complex association with cardiovascular disease. Chronic excessive alcohol consumption is associated with a range of cardiac complications, including decreased myocardial contractility, hypertension, arrhythmias, MI and heart failure. However, low-level alcohol consumption is believed to have a protective effect against ischaemic heart disease and diabetes. In most cohort studies, small to moderate amounts of alcohol consumption have not been linked to heart failure, indicating a threshold effect of alcohol with individual (possibly genetic) predisposition rather than a continuous effect of exposure. This review article explores the potential benefits of alcohol on the heart, the association between alcohol use and alcoholic cardiomyopathy and the epidemiology, clinical correlates and management of alcoholic cardiomyopathy.

The effect of changing to Bictegravir on lipids using real world data: A brief report.

WHAT IS KNOWN AND OBJECTIVE: Cardiovascular disease is of increasing concern in patients living with HIV. The significant advancement in antiretroviral treatment has ensured that patients are now succumbing to traditional diseases of ageing. First generation antiretroviral therapy caused multiple side effects including significant dyslipidaemia. Despite the advancement and improving safety profile of treatment concerns remain about antiretroviral induced dyslipidaemia. We sought to investigate the real-world effect on lipids in patients switching to a Bictegravir based regime. METHODS: We conducted a retrospective analysis in patients switching therapy to Biktarvy at the Royal Liverpool University Hospital. Data was collected from the HIV database that is established for clinical use, as an electronic patient record, and audit purposes. Lipid data was cross checked with the Trust electronic reporting system. Participants were included if they were HIV-positive, >18 years and had switched to Biktarvy Patients were also required to have a lipid profile available 52 weeks prior to switching and 100 weeks post switching. Summary statistic were calculated and multiple regressions models were constructed to assess the independent predictors of lipid change. We also performed one way analysis of covariance (ANCOVA) to assess the impact of switching therapy on each quartile of the baseline lipid panel. RESULTS AND DISCUSSION: There were 135 patients included in the analysis with a mean age of 47. The majority of the population were male (80%). At a mean follow up of 42 weeks post switch there was no significant difference in total cholesterol (p = 0.64), triglyceride (p = 0.64) or high density lipoprotein (HDL) cholesterol (p = 0.08). In the regression analysis the highest quartile of baseline total cholesterol and triglyceride were independently associated with improvement in lipid markers. Switching from protease inhibitor therapy was also significantly associated with improvement in triglyceride. In addition, the ANCVOA demonstrated that the highest quartiles of total cholesterol, triglyceride and the lowest quartile of HDL were associated with significant improvement in lipid markers after switching to Bictegravir. WHAT IS NEW AND CONCLUSION: We demonstrated that patients with the most adverse lipid profiles at baseline had significant improvements in lipid profiles. In addition, patient switching away from protease inhibitor therapy also had significant improvements in triglyceride.

Viability and antibacterial efficacy of four root canal disinfection techniques evaluated using confocal laser scanning microscopy.

BACKGROUND: Several disinfection techniques have been recently introduced with the main objective of improving root canal disinfection in the inaccessible areas of the root canal system. This in vitro study was done to evaluate the antimicrobial effect and viability of Enterococcus faecalis biofilms using conventional irrigation, EndoActivator (Dentsply, Tulsa Dental, USA), diode laser irradiation and photon-initiated photoacoustic streaming (PIPS). MATERIALS AND METHODS: Root canals of 130 single rooted mandibular premolars, standardized to a uniform length of 20 mm were instrumented until finishing file, F1 (Universal Protaper Rotary System, Dentsply, Tulsa Dental Specialties, USA). After smear layer removal and sterilization, five teeth were randomly selected to assure sterility before bacterial inoculation. The remaining 125 samples were contaminated with E. faecalis suspension, incubated for 21 days and divided into five groups (n = 25). In Group 1; untreated group (positive control), the root canals were not subjected to any disinfection procedure. Sampling was performed within the canals and the colony-forming unit count was evaluated for 20 samples. Five samples were selected to visualize the pattern of colonization at Level 1 (4 mm from the apex) and Level 2 (1 mm from the apex) by confocal laser scanning microscopy. Samples in Groups 2-5 namely conventional needle irrigation, EndoActivator, diode laser and PIPS were subjected to their respective disinfection procedures. Postdisinfection sample evaluation criteria was followed for all groups as same as that for Group 1. RESULTS: Diode laser displayed the highest antibacterial efficacy and least viable bacteria than the other three disinfection techniques. CONCLUSION: Diode laser group showed better antibacterial efficacy and least viable bacteria when compared to conventional needle irrigation, PIPS and EndoActivator groups in minimally instrumented, experimentally infected root canals.

Imaging features of micropapillary DCIS: correlation with clinical and histopathological findings.

RATIONALE AND OBJECTIVES: The aim of this study was to describe the mammographic, sonographic, and magnetic resonance imaging (MRI) findings of micropapillary ductal carcinoma in situ. MATERIALS AND METHODS: Between May 2004 and April 2008, the pathology database of a single institution was reviewed for patients diagnosed with histologically proven DCIS with a predominant micropapillary component. Clinical data and preoperative imaging studies, including mammography, sonography, and/or MRI, were reviewed. RESULTS: Forty-one patients (mean age, 55 years; range, 33-82 years) with 42 tumors were included in this study. Most tumors (n = 32 [76%]) were detected on screening mammography, with a mean tumor size of 4.7 cm (range, 0.5-13 cm). Of 42 tumors, seven (16%) were multicentric, and 23 (54%) were high nuclear grade. Calcifications were identified in 36 tumors (86%) on mammography, most frequently with pleomorphic morphology (15 tumors [42%]). Sonography was frequently normal (17 of 36 [47%]). When abnormal, irregular mass and angular margins were the most common sonographic features. All four tumors with MRI showed non-mass-like enhancement and showed the best correlation with pathologic size. CONCLUSIONS: Micropapillary ductal carcinoma in situ is a unique subset of in situ cancer that is frequently clinically occult but has a large mean size at diagnosis and demonstrates highly suspicious features at imaging including pleomorphic calcifications on mammography and an irregular mass at sonography. MRI may be the imaging modality of choice for delineation of disease extent and warrants further validation.

Primary breast cancer in men: clinical, imaging, and pathologic findings in 57 patients.

OBJECTIVE: The purpose of our study was to describe the imaging findings in primary breast cancer in men. MATERIALS AND METHODS: Male patients from a single pathology database with the histologic diagnosis of breast cancer who had undergone preoperative mammography or sonography were included in this study. The mammograms and sonograms were retrospectively reviewed according to the American College of Radiology BI-RADS lexicon. Patients who did not have films available but had imaging reports available for review were also included. Sonograms of the regional nodal basins, including axillary, infraclavicular, internal mammary, and supraclavicular regions, were noted. Histopathology subtype of breast cancer and axillary nodal status were documented. RESULTS: A total of 57 patients with imaging and 187 patients without imaging were included. The median age was 62 years (range, 19-80 years). Forty-nine patients had undergone both mammography and sonography; six, mammography alone; and two, sonography alone. Ninety-five percent (54/57) of patients presented with a palpable mass and 4% (2/57) with nipple inversion. At mammography, 69% (38/55) of cancers showed a mass; 29% (16/55), mass with microcalcifications; and 2% (1/55), microcalcifications. Gynecomastia was noted in 22 (40%) of 55 patients. Mammographic features included an irregular mass with spiculated or indistinct margins. Calcifications were typically pleomorphic and segmental. Sonographic features were typically an irregular mass with microlobulated margins. Axillary nodal involvement was present in 47% of patients. Most cancers were ductal carcinoma, either invasive or in situ. CONCLUSION: Breast cancer in men characteristically presents as an irregular subareolar mass with spiculated or indistinct margins on mammography and can be associated with calcifications and gynecomastia. Sonography has a role in regional staging of lymph nodes.