Clinico-immunological outcomes of HCV-cured cryoglobulinemia: Lower relapse rate with interferon-based than interferon-free therapy.

Sustained virological response (SVR) obtained with interferon (IFN) or with direct-acting antivirals (DAAs) is commonly followed by response of hepatitis C virus (HCV)-associated mixed cryoglobulinemia vasculitis (MCV), but relapse of MCV despite SVR has been reported in several patients after DAAs and rarely after IFN. Since relapses could have been overlooked in studies with IFN, we retrospectively compared the outcomes of MCV in SVR patients treated with DAAs (n = 70) or IFN (n = 39) followed-up, respectively, for 30.5 (range 11-51) or 48 months. Groups were comparable for demographics and clinics and response rates of MCV were similar (92% and 86%); however, DAA-treated patients less efficiently reduced cryoglobulins (P = .006) and circulating B-cell clones (P = .004), and had more frequently relapses of MCV (18% vs 3%, P = .028) and need for rituximab therapy (P = .01). Although largely inferior on an intention-to-treat basis, IFN may be superior to DAAs on clinico-immunological outcomes possibly owing to its antiproliferative activity.

Vaccination in PADs.

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.

Comparisons of skin microvascular changes in patients with primary aldosteronism and essential hypertension.

The aim of our cross-sectional study was to evaluate skin microvascular alterations in patients with hypertension secondary to primary aldosteronism (PA) and in subjects with essential hypertension (EH). Skin microcirculation was detected by nailfold videocapillaroscopy (NVC) and laser Doppler perfusion imaging (LDPI), both noninvasive techniques for the evaluation of digital capillaroscopic damage and hand skin blood perfusion. From September 2018 to April 2019, we consecutively enrolled 80 patients, of whom 42 had PA and 38 had EH. A morphological and structural study of cutaneous microcirculation was carried out through NVC, while functional evaluation of the peripheral microcirculation was carried out with LDPI. Using LDPI indices, dermal perfusion gradients were calculated in various regions of interest at the level of the back of the hand (ROI1 and ROI2). No differences between the two groups in NVC parameters were found. In contrast, LDPI showed worse skin perfusion parameters in patients with PA compared with patients with EH (ROI1: 143.9 ± 29.9 pU vs 163.3 ± 35.2 pU, p = 0.01; perfusion gradient ROI1-ROI2: 62.4 ± 28.8 pU vs 79.3 ± 33.5 pU, p = 0.019). Furthermore, the ROI1-ROI2 (proximal-distal) perfusion gradient was negatively correlated with aldosterone plasma levels (r -0.269; p = 0.017). Multivariate analysis showed that aldosterone was significantly associated with the ROI1-ROI2 perfusion gradient (b -0.220; p = 0.044). Patients with PA showed altered skin perfusion and greater microvascular dysfunction compared with the EH group. Our results are consistent with the hypothesis that aldosterone may have a pathophysiological role in microvascular remodeling in patients with PA, with predominant functional dysfunction.

A Perspective of Immunotherapy for Prostate Cancer.

In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa.

Beyond the Immune Suppression: The Immunotherapy in Prostate Cancer.

Prostate cancer (PCa) is the second most common cancer in men. As well in many other human cancers, inflammation and immune suppression have an important role in their development. We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression. Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapies.