Negative Pressure Wound Therapy and Traditional Dressing: An Italian Health Technology Assessment Evaluation.

This evaluation shows the main advantages related to the introduction of negative pressure wound therapy (NPWT) in Italian clinical practice for the management of incisions in vascular surgery in patients suffering from peripheral arterial disease (PAD) and at risk of postoperative complications, compared to treatment with traditional dressings. A health technology assessment (HTA) activity was conducted assuming the hospital perspective, within a 12-month time horizon. The nine EUnetHTA Core Model dimensions were deeply explored, using scientific evidence on the topic, real-life data, and healthcare professionals' perceptions. The evaluation shows that the use of NPWT has had a positive impact in terms of higher clinical effectiveness and safety profile. The process mapping highlights how NPWT allows a reduction of 2.5 hospitalization days compared with standard dressing, with the consequent benefits considering economic, organizational, and social aspects. A significant economic saving per patient emerged, with an overall optimization of the patient's clinical pathway, impacting positively on the hospital's capacity. The budget impact analysis shows that the higher number of patients treated with NPWT, the higher the economic advantages. Furthermore, assuming the patient's perspective, it would generate an overall reduction in social costs of 28%. In conclusion, the results of this study provide helpful evidence-based information to policymakers through examinations of the relative values of intervention, thus supporting the overall hospital and institutional decision-making process to define appropriate areas of investments, leading to the achievement of not only higher clinical outcomes, but also important social, economic, and organizational advantages.

Monoclonal antibodies for the treatment of COVID-19 patients: An umbrella to overcome the storm?

The world is facing up the most considerable vaccination effort in history to end the Coronavirus disease 2019 (COVID-19) pandemic. Several monoclonal antibodies (mAbs) direct against the Receptor binding domain of the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received an Emergency Use Authorization for outpatient management of mild to moderate manifestation from COVID-19. MAbs could prevent the transmission SARS-CoV-2 infection and protect individuals from progression to severe disease. Under the pressure of different treatment strategies, SARS-CoV-2 has been demonstrated to select for different sets of mutations named "variants" that could impair the effectiveness of mAbs by modifying target epitopes. We provide an overview of both completed and unpublished, or ongoing clinical trials of mAbs used and review state of art in order to describe clinical options, possible indications, and the place in therapy for these agents in the treatment of COVID-19 with a particular focus on anti-spike agents. Then, we reassume the current evidence on mutations of the SARS-CoV-2 that might confer resistance to neutralization by multiple mAbs.

Severe neuropathy after diphtheria-tetanus-pertussis vaccination in a child carrying a novel frame-shift mutation in the small heat-shock protein 27 gene.

Mutations in small heat-shock protein 27 and small heat-shock protein 22 genes were found in association with Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. We searched for mutations in small heat-shock protein 27 gene in an Italian family with peripheral neuropathy and intrafamilial phenotypic variability. A novel heterozygous frame-shift mutation c.476_477delCT was found while point mutations in most genes associated with hereditary neuropathies were ruled out. In the proband, who showed a severe early onset peripheral neuropathy, an independent pathogenetic effect on the peripheral nervous system secondary to the tetanus toxoid injection may be supposed. This is the first truncating nonsense mutation in the small heat-shock protein 27 gene identified so far and the clinical, neurophysiologic, and neuropathological findings are discussed.

Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease.

X-linked Charcot-Marie-Tooth disease (CMT1X) is a peripheral neuropathy transmitted in a dominant manner and caused by mutations in the Connexin 32 (Cx32) gene (GJB1, gap junction beta 1). Here we report the mutation analysis of the GJB1 gene in 76 subjects with possible CMT1 and absence of 17p11.2 duplication, and in 38 CMT2 patients without mutations in CMT2-associated-genes, selected from a cohort of 684 patients with peripheral sensory-motor neuropathy. The analysis was performed by direct sequencing of the coding sequence and exon/intron boundaries of the GJB1 gene. The mutation screening identified 22 mutations in GJB1, eight of which have not been previously published: six point mutations (c.50C > G, c.107T > A, c.545C > T, c.545C > G, c.548G > C, c.791G > T) and two deletions (c.84delC, c.573_581delCGTCTTCAT). The GJB1 mutation frequency (19.3%) and the clinical heterogeneity of our patients suggest searching for GJB1 mutations in all CMT cases without the 17p11.2 duplication, regardless of the gender of the proband, as well as in CMT2 patients with possible X-linked inheritance.