Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.

Introduction: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is predicted to provide functional FVIII activity in patients with congenital haemophilia A with inhibitors (CHAWI).

Aims: To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing invasive procedures.

Methods: This phase 3, multicentre, single-arm, open-label study (NCT02895945) enrolled males aged 12-75 years with severe/moderately severe CHAWI who required surgical/invasive procedures.

IDEAL study: A real-world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX-FP) in patients with haemophilia B in Italy.

Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.

Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.

Translational readthrough at nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association.

In hemophilia A, F8 nonsense variants, and particularly those affecting the large factor VIII (FVIII) B domain that is dispensable for coagulant activity, display lower association with replacement therapy-related anti-FVIII inhibitory antibodies as retrieved from multiple international databases. Since null genetic conditions favor inhibitor development, we hypothesized that translational readthrough over premature termination codons (PTC) may contribute to immune tolerance by producing full-length proteins through the insertion of amino acid subset(s). To quantitatively evaluate the readthrough output in vitro, we developed a very sensitive luciferase-based system to detect very low full-length FVIII synthesis from a wide panel (n=45; ~60% patients with PTC) of F8 nonsense variants.

In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A.

In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production.

Stapled fascial suture: ex vivo modeling and clinical implications.

Background: Recently, in the field of abdominal wall repair surgery, some minimally invasive procedures introduced the use of staplers to provide a retromuscular prosthetic repair. However, to the knowledge of the authors, there are little data in the literature about the outcomes of stapled sutures adoption for midline reconstruction. This study aims to investigate the biomechanics of stapled sutures, simple (stapled), or oversewn (hybrid), in comparison with handsewn suture.

Complete pathological response of colorectal peritoneal metastases in Lynch syndrome after immunotherapy case report: is a paradigm shift in cytoreductive surgery needed?

Background: We report the first case of a patient affected by peritoneal metastases from colon cancer, arising in the context of Lynch syndrome with pathological complete response. The patient was treated with immunotherapy and cytoreductive surgery. This paper discusses the implications of these novel therapies for the management of PM.

F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.

Background: Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels.

Objectives: To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK).

Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.

Background: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging.

Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature.

Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs).

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

Purpose: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice.

Serum uric acid levels and the risk of recurrent venous thromboembolism.

Essentials Increase in serum uric acid (SUA) levels has been widely associated with higher risk of cardiovascular disease. We investigated the link between SUA levels and the risk of venous thromboembolism (VTE) recurrence. Patients with SUA levels ≥ 4.

Use of homologous bone for alveolar crest reconstruction in 483 patients with 5 years' outcomes post implantation.

Purpose: The purpose of this study was to evaluate the clinical course of bone reconstruction of the alveolar crest using homologous fresh-frozen bone harvested from deceased donors.

Methods: A retrospective survey was based on the Castelfranco Veneto Hospital database, in which 3264 clinical records with a primary or secondary diagnosis of alveolar atrophy were collected over a 10-year period. A random sample of 483 patients with at least 5 years' follow-up was included in the survey.

Phase 1, single-dose escalating study of marzeptacog alfa (activated), a recombinant factor VIIa variant, in patients with severe hemophilia.

Unlabelled: Essentials Marzeptacog alfa (activated) [MarzAA] is a novel variant of activated human factor VII. A phase 1 dose escalation trial of MarzAA was conducted in subjects with severe hemophilia. MarzAA was safe and tolerated at intravenous doses up to 30 μg kg Data observed support further trials for hemophilia patients with inhibitors to factors VIII/IX.

Rate and appropriateness of polypharmacy in older patients with hemophilia compared with age-matched controls.

Background: In older people, multiple chronic ailments lead to the intake of multiple medications (polypharmacy) that carry a number of negative consequences (adverse events, prescription and intake errors, poor adherence, higher mortality). Because ageing patients with haemophilia (PWHs) may be particularly at risk due to their pre-existing multiple comorbidities (arthropathy, liver disease), we chose to analyse the pattern of chronic drug intake in a cohort of PWHs aged 60 years or more.

Patients And Methods: S + PHERA is a multicentre observational study, with the broad goal to evaluate prospectively the health status and medication intake in 102 older patients with severe haemophilia A or B compared with 204 age- and residence-matched controls chosen randomly from the same general practices of PWHs.

Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients.

The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected.

"In vitro" correction of the severe factor V deficiency-related coagulopathy by a novel plasma-derived factor V concentrate.

Introduction: Severe congenital factor V (FV) deficiency is a rare bleeding disorder characterized by very low/undetectable levels of FV. Fresh frozen plasma is the standard treatment for bleeding manifestations. Recently, a novel plasma-derived FV concentrate has been developed.

High resolution melting for F9 gene mutation analysis in patients with haemophilia B.

Background: Since 2001, we have used conformation sensitive gel electrophoresis (CSGE) as our first choice for F9 gene mutation screening, leading to the identification of about 300 mutations causing haemophilia B (HB). To circumvent the disadvantages of CSGE, we recently evaluated high-resolution melting analysis (HRM), which represents the next-generation mutation scanning technology.

Materials And Methods: In order to explore and validate HRM as a new screening method, we analysed 26 HB patients with previous CSGE-detected mutations, 22 patients with CSGE-undetectable mutations and 13 HB patients who had not been previously investigated.

Multiplex ligation-dependent probe amplification as first mutation screening for large deletions and duplications in haemophilia.

Introduction: Molecular characterization has shown a wide mutational spectrum underlying haemophilia A (HA) and haemophilia B (HB). Different molecular assays have allowed laboratories to perform genetic testing for F8 and F9 mutations.

Aim: Recently, multiplex ligation-dependent probe amplification (MLPA), a simple technique for relative quantitation of targeted genomic regions, has been introduced in HA and HB for detection of large deletions and duplications.

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS).

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here.

Methods: Thirty-two clinical centers are involved in the survey.

Patterns and determinants of use of pharmacological therapies for intermittent claudication in PAD outpatients: results of the IDOMENEO study.

Background: Peripheral arterial disease (PAD) usually presents with intermittent claudication (IC). The aim of the present study was to assess, in clinical practice, the pattern of use of pharmacological therapies for IC in stable PAD outpatients.

Methods: A propensity analysis was performed using data from the IDOMENEO study, an observational prospective multicenter cohort study.

Clinical relevance of isolated prolongation of the activated partial thromboplastin time in a cohort of adults undergoing surgical procedures.

Background: Coagulation screening prior to surgery is performed routinely worldwide to identify patients at risk of bleeding during the procedure. Evidence from medical and surgical literature suggests that the activated partial thromboplastin time (aPTT) alone is suitable for predicting individual bleeding risk during surgery and it is current practice in our hospital to measure this parameter.

Materials And Methods: We retrospectively reviewed aPTT ratio results in 8,069 consecutive adult subjects undergoing elective surgery from January 1 to December 31, 2014 to confirm the validity of this approach.