SGLT2-inhibitors: Should they be considered anti-remodeling drugs?

Heart failure (HF) is a complex syndrome characterized by multiple aetiologies and a progressive clinical course with a strong impact in terms of morbidity, mortality and public health costs. According to the neurohormonal hypothesis, HF with reduced ejection fraction (HFrEF) is considered a neurohormonal disease and HF patients benefit from the use of medications that interfere with and modulate the negative effects of neurohormonal systems (i.e. permanent renin–angiotensin–aldosterone system activation). The foundation of HF treatment includes the combination of well-known neurohormonal antagonists such as angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. However, recently, Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-i) have emerged as a new additional cornerstone of HF treatment – they are now regarded as one of the four keystone drugs to be introduced as first line therapy in HFrEF (class I recommended drug). Moreover, SGLT2-i have been shown to decrease combined endpoints of cardiovascular mortality and worsening HF regardless of ejection fraction (EF), and also to prevent the onset of HF in patients who are at high cardiovascular risk. The pathophysiologic mechanisms that may explain the benefit in clinical outcomes of the SGLT2-i in patients with HF are still incompletely understood. Therefore, it is of great interest to analyze the biological changes, which may occur in patients taking SGLT2-i because this may be helpful to elucidate how SGLT2-i may lead to improved cardiovascular outcomes. In this context, the metanalysis published in the European Journal of Internal Medicine by Fan et al. is timely and relevant because it evaluates the potential structural and functional impact of SGLT2-i in human heart giving possible translational understandings of the biologic consequences caused by SGLT2-i

Editorial: Proceedings and predictions in cardiac amyloidosis: unsolved mysteries and challenges for the future

Perceptions of amyloidosis have changed dramatically over the recent years following major advances in diagnosis and therapeutic strategies, especially in the field of cardiac amyloidosis

A paradigm of extreme rainfall pluvial floods in complex urban areas: The flood event of 15 July 2020 in Palermo (Italy)

In the last few years, some regions of the Mediterranean area have witnessed a progressive increase in extreme events, such as urban and flash floods, as a response to the increasingly frequent and severe extreme rainfall events, which are often exacerbated by the ever-growing urbanization. In such a context, the urban drainage systems may not be sufficient to convey the rainwater, thus increasing the risk deriving from the occurrence of such events. This study focuses on a particularly intense urban flood that occurred in Palermo (Italy) on 15 July 2020; it represents a typical pluvial flood due to extreme rainfall on a complex urban area that many cities have experienced in recent years, especially in the Mediterranean region. A conceptual hydrological model and a 2D hydraulic model, particularly suitable for simulations in a very complex urban context, have been used to simulate the event. Results have been qualitatively validated by means of crowdsourced information and satellite images. The experience of Palermo, which has highlighted the urgent need for a shift in the way stormwater in urban settlements is managed, can be assumed to be a paradigm for modeling pluvial floods in complex urban areas under extreme rainfall conditions. Although the approaches and the related policies cannot be identical for all cities, the modeling framework used here to assess the impacts of the event under study and some conclusive remarks could be easily transferred to other, different urban contexts

HEAT SHOCK PROTEINS AND ULCERATIVE COLITIS: THE START OF A NEW ERA?

We read with great interest the article written by Abou El Azm and coworkers, published in the last issue of the Arab Journal of Gastroenterology [1]. In this article, the authors investigated the molecular expression of heat shock proteins (HSP) 70 and 90 in relation to the grades of inflammation and dysplasia in patients with ulcerative colitis (UC) before and after treatment. In this study, in agreement with other published studies [2–4], the authors not only found a potential role for HSP 70 and HSP 90 for assessment of the activity and prognosis of UC, but also such markers predicted the presence of dysplasia and differentiated it from reactive atypia [1]. HSP had been found not only a marker of active disease, thus considering UC as a ‘‘chaperonopathy by mistake’’, but also show a key role in the psychosocial setting in which inflammatory bowel diseases manifest themselves [5]. Furthermore, they could represent a new diagnostic tool to differentiate the different phenotypes of UC, thus allowing to tailor a targeted approach to better manage UC patients [6]. However, some unresolved issues still remain about the potential roles of HSP in both the acute and the longstanding disease. First, it should be interesting to assess the role of HSP in the infections associated to UC flares, like Clostridium difficile and Cytomegalovirus (CMV) infections. In fact, HSP could be investigated as a further marker of inflammation in case of severe and steroid-refractory disease; with regard to CMV infection, mucosal levels of HSP could differentiate when CMV plays a role of direct pathogen or when it represents merely a ‘‘silent bystander’’. Second, in longstanding UC, an integrated approach of colorectal cancer surveillance, by using the advanced endoscopic imaging together with mucosal markers, like HSP, could result in being markedly helpful, both to clinicians and pathologist. In fact, current guidelines recommend that image-enhanced endoscopy (IEE) may increase the yield of detection of dysplasia, thus representing a reasonable alternative to the random sampling of colon using standard white light [7]. The use of both IEE and new biomarkers, like HSP, predicting future occurrence of colonic neoplasia, could lead to a more centralised approach of UC patients, in which a ‘‘biomarker-based surveillance’’ might play a pivotal rol

Breakthrough advances enhancing care in ATTR amyloid cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) has been traditionally considered a rare and inexorably fatal condition. ATTR-CM now is an increasingly recognized cause of heart failure (HF) and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CM, which is now possible without recourse to endomyocardial biopsy in ≈70 % of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CM and more accurate prognostic stratification. Although radionuclide scintigraphy with 'bone' tracers has an established diagnostic value, the diagnostic performance of the bone tracers validated for non-invasive confirmation of ATTR-CM may not be equal. Characterising the wider clinical phenotype of patients with ATTR-CM has enabled identification of features with potential for earlier diagnosis such as carpal tunnel syndrome. Therapies able to slow or halt ATTR-CM progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional HF medications. Cutting-edge research in the field of antibody-mediated removal of ATTR deposits compellingly suggest that ATTR-CM is a truly reversible disorder, bringing hope for patients even with advanced disease. A wide horizon of possibilities is unfolding and awaits discovery

COLORECTAL CANCER IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: PRELIMINARY RESULTS FROM AN ONGOING CASE-CONTROL STUDY

Background and Aim:Understanding the risk factors for colorectal cancer (CRC) is crucial to the development of effective strategies for its prevention. meta-analysis and epidemiological studies have already shown that type 2 diabetes mellitus (DM) is associated with an increased risk of CRC and have provided data to support a positive relationship between these diseases. Material and Methods: We retrospectively evaluated 741 consecutive caucasian patients with type 2 DM who underewnt colonoscopic screening cof CRC and followed in our tertiary referrral center in 200-208 for incidence of CRC. Patients were stratified based on gender, age, body mass index (MBI), alchool and NSAIDS assumption, family history for cancer blood glycated hemoglobin levels, hypertension, hypertrigliceridemia, age at diabetes onset and duration, treatment with insulin or other hypoglicemic drugs. A total of 257 consecutive control patients were selected from a cohort of patients followed as outpatients for thyroid diseases. Results: At a median follow-up of 132,5 months (range 33,3-175,7) 56 cases of cancer (prevalence 7,56%) occurred; among these, 14 cases of CRC were reported (prevalence 18,8%) among the diabetic patients, while only one case (prevalence 0,004%) occurred in the control group, although this difference is not statistically significant (chi-square 2,9, P=0,08). Median duration of DM to CRC diagnosis was 156 months (range 1-768). At the univariate analysis older age (p=0,001), and diabetes duration (p=0,001) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0,058). in the subset of patients with CRC, older age (p=0,001) and diabetes duration (p=0,001) were related to higher risk of CRC, such as treatment with sulphonylureas (p=0,01). Conclusions: Our preliminbar data show that the prevalence of CRC in the cohort of patients with type 2 DM was higher compared to that from our control group, and to that from the National Tumor Register up 2010 (0,5%). Furthermore we could interestingly hypotize that sulphonylureas may play a role in CRC carcinogenesis altering the physiological insulin secretion

Breakthrough advances enhancing care in ATTR amyloid cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) has been traditionally considered a rare and inexorably fatal condition. ATTR-CM now is an increasingly recognized cause of heart failure (HF) and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CM, which is now possible without recourse to endomyocardial biopsy in ≈70 % of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CM and more accurate prognostic stratification. Although radionuclide scintigraphy with 'bone' tracers has an established diagnostic value, the diagnostic performance of the bone tracers validated for non-invasive confirmation of ATTR-CM may not be equal. Characterising the wider clinical phenotype of patients with ATTR-CM has enabled identification of features with potential for earlier diagnosis such as carpal tunnel syndrome. Therapies able to slow or halt ATTR-CM progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional HF medications. Cutting-edge research in the field of antibody-mediated removal of ATTR deposits compellingly suggest that ATTR-CM is a truly reversible disorder, bringing hope for patients even with advanced disease. A wide horizon of possibilities is unfolding and awaits discovery

Molecular and Cellular Mechanisms in Heart Failure

Pathophysiology and treatment of pediatric heart failure (HF) is poorly understood. A growing body of literature demonstrates age-related differences in mechanisms and in therapies efficacy. HF results from ventricular dysfunction due to volume or/and pressure overload. Circulatory, neurohormonal, and molecular alterations promote the progression of HF and ventricular remodeling; they include inflammation, oxidative stress, mitochondrial dysfunction, loss of cardiomyocytes, and fibrosis. Children and young affected by cardiomyopathies have the greatest risk of HF and heart transplantation. Genetic mutations of sarcomere, cytoskeleton, cell membrane proteins, and ion channels have been recognized as the main causes of many cardiomyopathy phenotypes. In particular, sarcomeric and cytoskeleton genes mutations seem to have an important role in the progression of HF. Prognostic stratification and clinical management could benefit from identification of biomarkers such as inflammatory mediators or microRNA (miRNA). miRNA and myocardial regenerative strategies are under investigations as potential novel therapeutic approaches