Haemophilia B: Where are we now and what does the future hold?

Research has been lacking on the natural history, complications, and treatment of haemophilia B, which is less common than haemophilia A and was recognized as a distinct clinical entity in 1947. Although the two diseases share the same clinical manifestations, they differ in causative mutation, risk of inhibitor development, and patient quality of life. Frequently debated is whether haemophilia B is as clinically severe as haemophilia A, with much of the published data on overall and haemophilia-specific health outcomes suggesting that haemophilia B may have a less severe clinical phenotype.

Biodistribution of Liver-Derived Mesenchymal Stem Cells After Peripheral Injection in a Hemophilia A Patient.

Background: With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia.

Deficits of ankle muscle strength not found in children, adolescents and young adults with haemophilic ankle arthropathy.

Objectives: Adequate management of haemophilia patients requires early detection of joint impairment in relatively asymptomatic patients. This study sought to quantify the impact of the ankle's structural impairment on muscle strength in children, adolescent and young adults with haemophilia (CAAwH).

Methods: Twenty-three CAAwH underwent bilateral magnetic resonance imaging (MRI) assessing the anatomical status of tibiotalar joint (TTJ) and subtalar joint (STJ) using the International Prophylaxis Study Group MRI scale.

Towards Prognostic Profiling of Non-Small Cell Lung Cancer: New Perspectives on the Relevance of Polo-Like Kinase 1 Expression, the Mutation Status and Hypoxia.

: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required.

Clinical Signs, Pathophysiology and Management of Cutaneous Side Effects of Anti-Tumor Necrosis Factor Agents.

Approximately one in four patients treated with anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab, and golimumab) develops cutaneous adverse events, typically months to years after the initiation of treatment, with xerosis cutis, eczema (often psoriasiform), psoriasis, palmoplantar pustulosis, cutaneous infections, alopecia, and skin cancer being the most frequently encountered. The typical skin lesion of anti-tumor necrosis factor (TNF)-treated patients is orange-red psoriasiform eczema affecting the flexures, genitalia, scalp, or face, with high susceptibility to bacterial superinfection with Staphylococcus aureus. When adequate dermatological treatment is administered to patients with skin lesions receiving anti-TNF treatment, the discontinuation of anti-TNF agents is only rarely required.

Successful Management of Acquired Hemophilia A Associated with Bullous Pemphigoid: A Case Report and Review of the Literature.

. Acquired hemophilia A (AHA) is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions.

Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

Unlabelled: Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk.

Current Practice of Therapeutic Drug Monitoring of Biopharmaceuticals in Psoriasis Patients.

The high prevalence of psoriasis and the high spending on pharmaceuticals motivate a more evidence-based and cost-effective usage of biopharmaceuticals. A growing body of evidence exists that the implementation of therapeutic drug monitoring for biopharmaceuticals in psoriasis patients optimizes patient management and clinical outcome and enhances their efficacy. Therefore, the aim of this review was to give an overview of the literature on therapeutic drug monitoring of biopharmaceuticals in the treatment of psoriasis and to provide the useful information to dermatologists to improve health care in psoriasis patients.

Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.

Background: Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis.

Outcome measures for adult and pediatric hemophilia patients with inhibitors.

Recent advancements in almost all aspects of hemophilia treatment have vastly improved patient care and management, and new and emerging treatments hold the promise of further progress. However, there remains a scarcity of data on long-term outcomes in hemophilia, particularly among those patients with inhibitors, for whom no validated outcome assessment tools are currently available. At the 15 Zürich Haemophilia Forum, an expert panel reviewed the most important outcome measures in inhibitor patients and considered the challenges associated with assessing outcomes in this population.

Biomechanical markers and theoretical concepts related to haemophilic ankle and subtalar joint arthropathy: introducing the term 'haemophilic tarsal pan-arthropathy'.

Background: Although regular factor replacement can reduce the incidence of joint bleeds and slow down the development of haemophilic arthropathy, the ankle joint remains particularly vulnerable even in children with haemophilia on primary or secondary prophylaxis and is now the primary joint affected. The heterogeneity in the pathoaetiology of haemophilic ankle arthropathy means that the functional consequences of early stage of ankle arthropathy are difficult to define as early morphological and structural changes can be observed in clinically asymptomatic ankles. In this context, understanding biomechanics of the normal and arthritic foot is complex and difficult to quantify unless considering the foot as multiple functional segments using more sophisticated assessment tools such as multisegment foot models.

Modeling the photoperiodic entrainment of the plant circadian clock.

The circadian clock is an endogenous 24 hour rhythm that helps organisms anticipate and adapt to daily and seasonal variations in environment, such as the day/night cycle or changing temperatures. The plant clock is a complex network of transcription factors that regulate each other, forming interlocked feedback loops. Most of its components are light-regulated in some way, making the system highly sensitive to changes in light conditions.

Deep sequencing of the TP53 gene reveals a potential risk allele for non-small cell lung cancer and supports the negative prognostic value of TP53 variants.

The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non-small cell lung cancer, this study conducted further research, particularly focusing on subtype and tumor stage. Therefore, we determined the TP53 status of 97 non-small cell lung cancer adenocarcinoma patients using next generation deep sequencing technology and defined the prognostic value of frequently occurring single nucleotide polymorphisms and mutations in the TP53 gene.

Ultrasound-guided approach to nerves (direct vs. tangential) and the incidence of intraneural injection: a cadaveric study.

This study evaluated the incidence of nerve puncture and intraneural injection based on the needle approach to the nerve (direct vs. tangential). Two expert operators in regional anaesthesia performed in-plane ultrasound-guided nerve blocks (n = 158) at different levels of the brachial plexus in cadavers, aiming either directly for the nerve (n = 77) or tangentially inferior to the nerve (n = 81).

Double-Balloon Endoscopy in Overt and Occult Small Bowel Bleeding: Results, Complications, and Correlation with Prior Videocapsule Endoscopy in a Tertiary Referral Center.

Background/aims: Videocapsule endoscopy (VCE) and double-balloon endoscopy (DBE) allow deep exploration in patients with suspected small bowel pathology. VCE is often performed as an initial small bowel examination to explore whether an intervention by DBE is indicated and to determine insertion route. The study aim was to evaluate the correlation between DBE and VCE in patients with obscure or overt bleeding or anemia, as well as intervention frequency, and complications.

Postural control of typical developing boys during the transition from double-leg stance to single-leg stance.

Unlabelled: Literature is lacking information about postural control performance of typically developing children during a transition task from double-leg stance to single-leg stance. The purpose of the present study was therefore to evaluate the clinical feasibility of a transition task in typical developing age groups as well as to study the correlation between associated balance measures and age.Thirty-three typically developing boys aged 6-20 years performed a standard transition task from DLS to SLS with eyes open (EO) and eyes closed (EC).

3D Multi-segment foot kinematics in children: A developmental study in typically developing boys.

Background: The relationship between age and 3D rotations objectivized with multisegment foot models has not been quantified until now. The purpose of this study was therefore to investigate the relationship between age and multi-segment foot kinematics in a cross-sectional database.

Methods: Barefoot multi-segment foot kinematics of thirty two typically developing boys, aged 6-20 years, were captured with the Rizzoli Multi-segment Foot Model.

Outcome measures in European patients with haemophilia: Survey of implementation in routine clinical practice, perception of relevance and recommendations by European treaters in the EHTSB.

Introduction: This study was conducted to evaluate the current implementation of outcome measures in routine clinical haemophilia practice and to explore and appreciate the perception of the relevance of such measures by treaters.

Methods: A survey was completed by 19 of the 26 physicians involved in the European Haemophilia Therapy Strategy Board (EHTSB). Employing an extensive inventory of outcome measures used in patients with haemophilia, information was collected about the frequency of data collection and the subjective appreciation of their importance during clinic review.

Pain and pain management in haemophilia.

Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception.

European retrospective study of real-life haemophilia treatment.

Introduction: Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available.

Aim: To provide an overview of the FVIII/FIX treatment practice and outcome for patients with haemophilia A (HA) or haemophilia B (HB) across Europe.

Methods: Non-interventional, 12-month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom.