Primary chemoradiation versus neoadjuvant chemotherapy followed by surgery as treatment strategy for locally advanced vulvar carcinoma (VULCANize2).

Background: Current treatment options for patients with locally advanced vulvar cancer are limited and associated with high morbidity. Therefore, it is important to develop new and safe treatment strategies for this vulnerable patient group.

Primary Objective: To compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery with definitive chemoradiation in patients with locally advanced vulvar cancer.

Combining CRISPR-Cas9 and TCR exchange to generate a safe and efficient cord blood-derived T cell product for pediatric relapsed AML.

Background: Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft.

Risk factors for deliberate self-poisoning among children and adolescents in The Netherlands.

Introduction: In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center.

Methods: A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning.

Significant Increase in Deliberate Self-Poisonings Among Adolescents During the Second Year of the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic.

Methods: A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs.

Estimation of the risk of local and systemic effects in infants after ingestion of low-concentrated weak acids from descaling products.

Introduction: The accidental ingestion of diluted household descaling products by infants is a phenomenon that poison control centers regularly encounter. Feeding infants with baby milk prepared with water from electric kettles still containing descaler is a common way of exposure. This study aimed to determine the risks related to ingestion of (diluted) descalers by infants.

Treatment-related risk factors for inhibitor development in non-severe hemophilia A after 50 cumulative exposure days: A case-control study.

Background: Non-severe hemophilia A patients have a life-long inhibitor risk. Yet, no studies have analyzed risk factors for inhibitor development after 50 factor VIII (FVIII) exposure days (EDs).

Objectives: This case-control study investigated treatment-related risk factors for inhibitor development in non-severe hemophilia A and assessed whether these risk factors were different for early versus late inhibitor development.

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case-control study.

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case-control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients.

Pain-related fear in adolescents with chronic musculoskeletal pain: process evaluation of an interdisciplinary graded exposure program.

Background: For studying the effectiveness of treatment, it is important to check whether a new treatment is performed as originally described in the study-protocol.

Objectives: To evaluate whether an interdisciplinary graded exposure program, for adolescents with chronic musculoskeletal pain reporting pain-related fear, was performed according to protocol, and whether it is feasible to implement the program in rehabilitation care.

Methods: A process evaluation where quantitative and qualitative data on participant characteristics (adolescents, parents and therapists), attendance and participants' opinion on the program were collected, by means of registration forms, questionnaires and group interviews.

Colistin methanesulfonate infusion solutions are stable over time and suitable for home administration.

The stability of colistin methanesulfonate (CMS) was determined in quadruplicate in elastomeric home infusion pumps containing 1, 2 or 3 MU CMS and in infusion bags with 2 MU CMS all in 100 mL normal saline. Infusions were stored at room temperature (20°C-24°C) with or without exposure to natural light or refrigerated (4°C-8°C) and protected from light up to 2 weeks. In the initial solution of 2 MU CMS in 100 mL saline sampled immediately after reconstitution and dilution, 1.

Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis: A randomized, crossover study.

Aims: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis.

Methods: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg).

Dexamethasone promotes durable factor VIII-specific tolerance in hemophilia A mice via thymic mechanisms.

The development of inhibitory antibodies to factor VIII is the most serious complication of replacement therapy in hemophilia A. Activation of the innate immune system during exposure to this protein contributes to inhibitor development. However, avoidance of factor VIII exposure during innate immune system activation by external stimuli (e.

Desmopressin in moderate hemophilia A patients: a treatment worth considering.

Desmopressin increases endogenous factor VIII levels in hemophilia A. Large inter-individual variation in the response to desmopressin is observed. Patients with a lower baseline factor VIII activity tend to show a reduced response, therefore, desmopressin is less frequently used in moderate hemophilia A patients (baseline factor VIII activity 1-5 international units/deciliter), even though factor VIII levels may rise substantially in some of them.

Early cellular interactions and immune transcriptome profiles in human factor VIII-exposed hemophilia A mice.

Unlabelled: Essentials Initial immune cell interactions leading to factor (F) VIII immunity are not well characterized. We assessed cellular interactions and expression profiles in hemophilia A mice. MARCO+, followed by SIGLEC1+ and SIGNR1+ macrophages co-localize most with human FVIII.

To serve and protect: The modulatory role of von Willebrand factor on factor VIII immunogenicity.

Hemophilia A is a bleeding disorder characterized by the absence or dysfunction of blood coagulation factor VIII (FVIII). Patients are treated with regular infusions of FVIII concentrate. In response to treatment, approximately 30% of patients with severe hemophilia A develop inhibitory antibodies targeting FVIII.

Minerals and Sarcopenia; The Role of Calcium, Iron, Magnesium, Phosphorus, Potassium, Selenium, Sodium, and Zinc on Muscle Mass, Muscle Strength, and Physical Performance in Older Adults: A Systematic Review.

Introduction: Minerals may contribute to prevent and treat sarcopenia, the age-related loss of muscle mass, muscle strength, and physical performance. So far, there is no comprehensive review on the impact of minerals on sarcopenia outcomes. The aim of this systematic review is to evaluate the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults.

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.

Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations.

Unlabelled: Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels.

Emerging Issues in Diagnosis, Biology, and Inhibitor Risk in Mild Hemophilia A.

Mild hemophilia A (MHA) is an X-linked bleeding disorder defined by factor VIII (FVIII) levels between 5 and 40 U/dL. Diagnosis occurs later in life compared with severe or moderate disease. Although bleeding episodes are especially posttraumatic, their unexpected occurrence may be potentially life threatening if diagnosis is missed or delayed.

Pharmacokinetics and Tolerability of Once Daily Double Dose Tobramycin Inhalation in Cystic Fibrosis Using Controlled and Conventional Nebulization.

Background: Better treatment outcomes in cystic fibrosis (CF) may be expected by changing standard twice daily (BID) tobramycin inhalation with the conventional nebulizer to once daily (OD) inhalation at double the standard BID dose with a controlled-inhalation nebulizer. We aimed to determine the pharmacokinetics and tolerability of inhaled double-dose tobramycin with the controlled-inhalation AKITA(®) and conventional PARI-LC(®) Plus nebulizer in patients with CF.

Methods: Randomized, open label, crossover study.

The incidence and treatment of bleeding episodes in non-severe haemophilia A patients with inhibitors.

The development of an inhibitory antibody in non-severe haemophilia A patients may aggravate the bleeding phenotype considerably. Effective treatment of bleeding episodes may be challenging, with ensuing severe complications. At present, evidence is scarce for optimal treatment of bleeding episodes in this patient group.

Inhibitor development and mortality in non-severe hemophilia A.

Background: The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications.

Inhibitors in nonsevere haemophilia A: outcome and eradication strategies.

In nonsevere haemophilia A (HA) patients the presence of an inhibitor may exacerbate the bleeding phenotype dramatically. There are very limited data on the optimal therapeutic approach to eradicate inhibitors in these patients. We aimed to describe inhibitor eradication treatment in a large cohort of unselected nonsevere HA patients with inhibitors.