Fabry disease: a rare disorder calling for personalized medicine.

Fabry Disease (FD) is a genetic disease caused by a deficiency in the activity of lysosomal galactosidase A (α-GalA), an enzyme responsible for the catabolism of globotriaosylceramide (Gb3). Since lysosomes are present throughout the body and play a crucial role in catabolism and recycling of cytosolic compounds, FD can affect multiple organs and result in various symptoms, including renal, cardiovascular, neurological, cutaneous, and ophthalmic manifestations. Due to the nonspecific symptoms and the rarity of FD, it is often diagnosed late in life. However, introducing targeted therapies such as enzyme replacement therapy (ERT) and chaperone therapy has significantly improved FD's natural history and prognosis by restoring α-GalA enzyme activity. Despite the advancements, there are limitations to the currently available therapies, which has prompted research into new potential treatments for FD, including alternative forms of enzyme replacement therapy, substrate reduction therapy, mRNA therapy, and genetic therapy. In this review, we analyze the epidemiology, pathophysiology, and treatment of FD, with particular emphasis on promising therapeutic opportunities that could shift the treatment of this rare disease from a standardized to a personalized approach soon.

The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in Patients with Chronic Kidney Disease.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.

The many faces of interstitial pneumonia: a case of presumed SARS-CoV-2 infection.

We present the case of an oncology patient admitted to our hospital during the current COVID-19 pandemic with clinical and radiological features strongly suggestive of interstitial pneumonia. Multiple laboratory tests were negative for SARS-CoV-2 (polymerase chain reaction testing of nasopharyngeal swabs, and of induced sputum and stool samples, investigation of serum immunoglobulins G and M). In the setting of an immunocompromised status due to recent chemotherapy cycles for lung adenocarcinoma and prolonged corticosteroid therapy (due to frequent exacerbations of chronic obstructive pulmonary disease in recent months), we actively searched for the pathological agent and found it to be Pneumocystis jirovecii. The patient started specific antibiotic treatment but finally had a negative outcome due to the progression of the lung adenocarcinoma. The importance of differential diagnostics in clinical practice should be a given, especially during times of pandemic. The novel coronavirus infection introduced new guidelines for and approaches to the investigation of immunocompromised patients, so it is especially important not to forget the basis of differential diagnosis, to and adopt a thorough approach when assessing these complex patients. We want to stress the importance of thorough investigation to avoid misdiagnosis of atypical pathogens in the current setting of SARS-CoV-2 pandemic.

Supraventricular Arrhythmias in Patients With Pulmonary Arterial Hypertension.

The onset of supraventricular arrhythmias (SVA) may be associated with clinical worsening in patients with pulmonary arterial hypertension (PAH). However, limited data have been reported, especially at long-term follow-up. Aim of this study was to investigate the incidence of SVA in our patients with PAH, the risk factors correlated to their onset and the prognostic impact. All consecutive patients with PAH without history of SVA were enrolled. Incidence of new SVA was investigated and also the risk factors for SVA. Primary end point of the study was the impact of SVA on a composite of all-cause mortality and re-hospitalization, whereas mortality was the secondary end point. Seventy-seven patients were enrolled. No significant differences in the clinical or instrumental baseline characteristics between the 2 study groups were reported. During a median follow-up of 35 months (interquartile range 21.5 to 53.5), 17 (22%) patients experienced SVA. Development of SVA was associated with worsening of prognostic parameters at the follow-up: increasing of World Health Organization (WHO) functional class (p = 0.005) and N-terminal-pro-brain natriuretic peptide (NT-proBNP) (p = 0.018) and reduction of 6-minute walking distance (p = 0.048), tricuspid annular plane systolic excursion (TAPSE) (p = 0.041), and diffusing capacity of the lung for carbon monoxide (p = 0.025). The primary end point occurred in 13 patients (76%) in the SVA group and in 22 patients (37%) in the group without SVA (p = 0.004), whereas 9 patients (53%) among those with SVA died during the follow-up compared with 8 (13%) among those without (p = 0.001). At multivariate analysis, development of SVA was independently associated with an increased risk to meet the both primary (hazard ratio 2.13; 95% confidence interval 1.07 to 4.34; p = 0.031) and secondary (hazard ratio 4.1; 95% confidence interval 1.6 to 10.6; p = 0.004) end points. In conclusion, during the 3-year follow-up period, 1/3 of patients with PAH developed SVA, which was related to worsening of hemodynamic and functional parameter and independently predicted adverse prognosis.

High prevalence at computed coronary tomography of non-calcified plaques in asymptomatic HIV patients treated with HAART: a meta-analysis.

INTRODUCTION: Asymptomatic patients with human immunodeficiency virus (HIV) infection are at increased risk of vascular disease. Whether asymptomatic HIV patients have increased prevalence or structural differences in coronary artery plaques is not clear. METHODS: Pubmed, Cochrane and Google Scholar were searched for articles evaluating asymptomatic HIV patients evaluated with coronary computed tomography. The prevalence of coronary stenosis (defined as >30% and >50%), of calcified coronary plaques (CCP) viewed as more 'stable' plaques, and of non-calcified coronary plaques (NCP) viewed as more 'vulnerable' plaques were the end points of interest. RESULTS: 9 studies with 1229 HIV patients and 1029 controls were included. No significant differences were detected about baseline cardiovascular risk profile. The prevalence of significant coronary stenosis>30% or >50% did not differ between HIV+ and HIV- patients (42% [37-44] and 46% [35-52] with an Odds Ratio [OR] of 1.38 [0.86-2.20] for >30% stenosis) and (15% [9-21] and 14% [7-22] with an OR of 1.11 [0.81-1.52]), respectively. The prevalence of calcified coronary plaques (CCP) (31% [24-32] and 21% [14-30] with an OR of 1.17 [0.63-2.16]) also did not differ among HIV+ and HIV- patients. On the contrary rates of NCP were >3-fold higher in HIV-positive patients [58% (48-60) and 17% (14-27) with an OR of 3.26 (1-30-8.18)], with an inverse relationship with CD4 cell count at meta-regression (Beta -0.20 [-0.35-0.18], p 0.04). CONCLUSION: Asymptomatic HIV patients present a similar burden of coronary stenosis and calcified coronary artery plaques but significantly higher rates of non-calcific coronary plaques at computed tomography. The association between HIV infection, reduced CD4 cell counts and higher prevalence on non-calcific coronary artery plaques may shed light into the pathogenesis in HIV-associated coronary artery disease, stressing the importance of primary prevention in this population.

Heart failure in patients with human immunodeficiency virus: a review of the literature.

Coronary artery disease represents the leading cause of death for HIV patients treated with highly active antiretroviral treatment. Besides this, an extensive amount of data related to the risk of overt heart failure and consequently of atrial fibrillation and sudden cardiac death (SCD) in this population has been reported. It seems that persistent deregulation of immunity in HIV-infected patients is a common pathway related to both of these adverse clinical outcomes. Despite the fact that atrial fibrillation and heart failure are relatively common in HIV, few data are reported about screening, diagnosis, and potential treatment of these conditions.