Immobiliare Casa Sollievo Della Sofferenza SpA

The introduction of tenofovir (TFV) alafenamide (TAF) into clinical practice will be a further revolution in antiretroviral therapy. Currently available HIV-1 regimens are wide enough to allow diversified usage in different settings. Despite the fact that TAF is not capillary accessible, even in industrialized countries, ultimate International Guidelines have already included TAF in backbone or in single-tablet regimens. Due to a better safety profile, TAF will progressively replace TFV disoproxil fumarate, both in naïve and experienced patients. However, therapeutic innovations have to deal with budget constraints and different global spending-review patterns. The aim of this article is to give a comprehensive agenda of TAF use in naïve and experienced HIV-1 infected patients, providing a full review of the studies present in the literature and contextualizing these findings into daily clinical practice.

Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder caused by inactivating variants of the calcium-sensing receptor gene (CASR), GNA11, and AP2S1 genes, which lead to decreased intracellular receptor activity. Typical biochemical features include hypercalcemia and hypocalciuria, while PTH serum levels may be inappropriately normal or high. Despite the finding of hypercalcemia, the disorder has a benign course and patients usually do not require any therapeutical intervention. We describe a man with FHH caused by a previously unreported missense variant, c.496A>C, p.(Ser166Arg), located in exon 4 of CASR. The same variant was subsequently found in the father who presented with asymptomatic hypercalcemia. The variant was classified as “likely pathogenic.” In silico analysis predicted that the variant destabilizes for the tertiary structure of the protein and may induce conformational changes. An in vitro functional assay on HEK293-transfected cells demonstrated that the variant likely disrupts calcium binding and transport by CaSR. The present case expands the mutational spectrum of CASR and reinforces the clinical utility of multidisciplinary assessment for adults presenting with unexplained hypercalcemia.

Of the wide range of symptoms affecting patients with chronic kidney disease (CKD) on haemodialysis, CKD-associated pruritus is one of the most common and burdensome, occurring at moderate-to-severe intensity in 31%–40% of patients, significantly impacting multiple aspects of quality of life, and associated with increased healthcare utilization. Despite the distressing nature of this symptom, clinicians frequently underestimate its prevalence and it is under-reported by patients who may be unaware of the availability of effective treatment options. The identification and management of CKD-associated pruritus should form an essential aspect of patient-centred care; however, patients with CKD may have multiple causes of chronic itch including those of dermatological, systemic, neuropathic and psychogenic origin, and CKD-associated pruritus must be distinguished from these. Together with its highly variable presentation in patients on haemodialysis, the range of potential causes of itch makes differential diagnosis of CKD-associated pruritus challenging. The presence of bilaterally symmetrical and non-dermatomally distributed itching, commonly affecting the back, limbs, chest and head is characteristic of CKD-associated pruritus, although approximately 50% of patients report generalized pruritus. Secondary skin lesions (including excoriation, crusts, impetigo, lichenifications and prurigo also seen in dermatological conditions) may or may not be observed, and xerosis (dry skin) that may exacerbate itching is common. Here, we provide a pragmatic approach to the identification and differential diagnosis of chronic itching in CKD-associated pruritus with the aim of supporting the effective management of this highly distressing symptom in clinical practice.