Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial.

Background: The primary analysis of the phase III NIBIT-M2 study showed a 41% 4-year overall survival (OS) of melanoma patients with asymptomatic brain metastases treated with ipilimumab plus nivolumab.

Methods: Here, we report the 7-year efficacy outcomes and the Health-Related Quality of Life (HRQoL) analyses of the NIBIT-M2 study.

Results: As of May 1, 2023, at a median follow-up of 67 months (mo), the median OS was 8.

Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19.

Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single-administration GRAd-COV2 vaccine candidate in the context of the phase-1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T-cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

The kinetic of calcium silicate hydrate formation from silica and calcium hydroxide nanoparticles.

Hypothesis: The mechanism of calcium silicate hydrate (CSH) formation, a relevant component of cement, the largest used material by mankind, is well documented. However, the effects of nano-sized materials on the CSH formation have not yet been evaluated. To this aim, a kinetic study on CSH formation via the "pozzolanic reaction" of nanosilica and calcium hydroxide nanoparticles, and in the presence of hydroxypropyl cellulose (HPC) as hydration regulator, is reported in this paper.

Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases.

Purpose: Phase II trials have shown encouraging activity with ipilimumab plus fotemustine and ipilimumab plus nivolumab in melanoma brain metastases. We report the primary analysis and 4-year follow-up of the NIBIT-M2 study, the first phase III trial comparing these regimens with fotemustine in patients with melanoma with brain metastases.

Patients And Methods: This phase III study recruited patients 18 years of age and older with wild-type or mutant melanoma, and active, untreated, asymptomatic brain metastases from nine centers, randomized (1:1:1) to fotemustine, ipilimumab plus fotemustine, or ipilimumab plus nivolumab.

The carbonation kinetics of calcium hydroxide nanoparticles: A Boundary Nucleation and Growth description.

Hypothesis: The reaction of Ca(OH) with CO to form CaCO (carbonation process) is of high interest for construction materials, environmental applications and art preservation. Here, the "Boundary Nucleation and Growth" model (BNGM) was adopted for the first time to consider the effect of the surface area of Ca(OH) nanoparticles on the carbonation kinetics.

Experiments: The carbonation of commercial and laboratory-prepared particles' dispersions was monitored by Fourier Transform Infrared Spectroscopy, and the BNGM was used to analyze the data.

Hybrid nano-composites for the consolidation of earthen masonry.

Hypothesis: Earth is one of the oldest silicate-based materials in stone heritage, still largely used in architecture worldwide. Earthen materials are highly susceptible to wind and water erosion, leading to loss of cohesion and crumbling. Conventional consolidants (alkoxysilanes, synthetic or natural polymers) lack physico-chemical compatibility or effectiveness, and can promote degradation.

Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy.

Background: Immune checkpoint blockade antibodies (imAbs), such as the anti Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) ipilimumab (IPI) raised overall survival (OS) in metastatic melanoma (MM). Further, long-term OS is a crucial endpoint in MM. Thymosin alpha-1 (Tα1) with dacarbazine (DTIC) showed activity in a phase II trial and a compassionate use program (EAP).

Historical review of thymosin α 1 in infectious diseases.

Introduction: Thymosin α 1 (Tα1) is a peptidic biological response modifier, which plays a significant role in activating and regulating various cells of the immune system. For the above-mentioned activities it is expected to exert a clinical benefit in the treatment of diseases where the immune system is altered.

Areas Covered: Several clinical trials have been carried out with Tα1 for treatment or prevention of many different infectious diseases such as hepatitis B and C, sepsis and Aspergillosis in bone marrow-transplanted patients.

Historical review on thymosin α1 in oncology: preclinical and clinical experiences.

Introduction: Thymosin α1 (Tα1) is a naturally occurring polypeptide that regulates immune cell development and function, and is also capable of interacting with multiple target cells with relevant biological effects. The rationale of Tα1 use in cancer treatment stems from the consideration that tumor progression is favored by a failure of the immune response and in turn induces immune suppression. This paper will review the historical background of Tα1 use in oncology, aiming to highlight the importance of Tα1 as an immunotherapeutic tool to be used in combination with chemotherapy, a concept that is not yet fully established in clinic.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature.

Objectives: Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues.

Thymosin α1 continues to show promise as an enhancer for vaccine response.

Thymosin α1 (Tα1) is an immune-modulating peptide that can be expected to improve response to vaccinations, as stimulated dendritic cells and T cells can act in concert to increase antibody production along with an improved cytotoxic response from the T cells themselves. Tα1 demonstrated efficacy in preclinical studies; subsequently, it was shown to enhance response to vaccinations in difficult-to-treat populations, including individuals immune suppressed due to age or hemodialysis, and leading to a decrease in later infections. During the 2009 pandemic outbreak of H1N1 influenza, mouse and ferret studies confirmed that the use of higher doses of Tα1 allowed for fewer injections than those used in the previous clinical studies.

Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?

This study was conducted to determine whether the adding thymosin alpha-1 to standard of care for re-treatment of nonresponding hepatitis C infections can improve sustained viral response (SVR) rates. Patients (n = 552) with hepatitis C infections not responding to the combination of Peginterferon alfa-2a or 2b with ribavirin (RBV)were randomized to receive peginterferon alfa-2a 180 mg/week with RBV 800-1200 mg/daily plus either thymosin alpha-1 1.6 mg SC twice weekly (n = 275) or placebo (n = 277) for 48 weeks.

Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.

Background: Although influenza vaccination is widely recommended for immunosuppressed people, the same immune dysfunction that can increase the risk of contracting influenza might also compromise vaccine effectiveness, especially during pandemics. Clinical data have highlighted the role of adjuvants in improving vaccine efficacy. As uremic patients are especially vulnerable to infections, it is recommended that they should be vaccinated yearly against influenza.

Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.

Influenza constitutes a serious problem for healthcare and social services worldwide, owing to its pattern and the severity of its complications in some categories of subjects at risk, such as the elderly and immunocompromised individuals. The only really effective means of combating influenza is vaccination. The elderly and immunocompromised subjects are refractory or low responders to vaccination.

Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment.

Background: Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells.

Aim: To evaluate efficacy and safety of colon-release propionyl-L-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy.

Methods: In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo.

Current adjuvants and new perspectives in vaccine formulation.

Given the important role of adjuvants in prophylactic vaccines, identification and development of new adjuvants with enhanced efficacy and safety is necessary. The use of adjuvants with immunopotentiating properties that can direct the immune responses to humoral or cell-mediated immunity and can induce T-cell responses has made it possible to design more protective vaccines. Although current regulations focus on traditional adjuvants, notably aluminum and calcium salts, advances have been made in regulatory considerations.

The effect of thymosin treatment of venous ulcers.

Venous ulcers are responsible for about 70% of the chronic ulcers of the lower limbs. Standard of care includes compression, dressings, debridement of devitalized tissue, and infection control. Thymosin beta 4 (Tbeta4), a synthetic copy of the naturally occurring 43 amino-acid peptide, has been found to have wound healing and anti-inflammatory properties, and is thought to exert its therapeutic effect through promotion of keratinocyte and endothelial cell migration, increased collagen deposition, and stimulation of angiogenesis.