BackgroundBAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance.ObjectivesTo demonstrate superiority of prophylaxis vs. on-demand therapy with BAY 81-8973 in patients with severe hemophilia A.Patients/MethodsIn this multinational, randomized, open-label crossover study (LEOPOLD II; ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20–30 IU kg−1), 3-times-weekly prophylaxis (30–40 IU kg−1), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs) and immunogenicity were also assessed.ResultsEighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, anova). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0; 3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported.ConclusionsTwice-weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.

Background: Hyperprolactinemia is the most common disturbance in pituitary gland secretion. Functional diversity of prolactin action is responsible for different initial clinical expressions of hyperprolactinemia. Patients and Methods: We investigated causes of hyperprolactinemia in 11 children and adolescents (6 females and 5 males), aged from 1.5 to 17.5 years. Children with primary hypothyroidism, iatrogenic hyperprolactinemia and adolescents with polycystic ovaries were excluded. Results: Four patients had short stature or growth deceleration, the same number were clinically obese, 2 adolescent girls had secondary amenorrhea, 1 girl had premature thelarche and gynecomastia, and hypogonadism was the indication for the endocrinologic examination of two adolescent boys. Delayed pubertal development was present in both sexes. Hyperprolactinemia was also found in the youngest girl with multiple ovarian cysts. A very high prolactin (PRL) level was documented in the PRL profile of all patients (mean 2,553.00 ± 1,020.97 mU/l). MRI of the pituitary was indicated and revealed 4 microprolactinomas, one congenital hypophyseal cyst and one tumor of the hypothalamus. Dopamine agonist treatment was efficacious in almost all the patients. Conclusion: Hyperprolactinemic children expressed a wide variety of initial clinical presentations. The most common were growth and puberty disorders and obesity. PRL determination should be included in investigation protocols of obese and short stature children.

At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

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Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2). Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.