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Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature-stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven ® ), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature-stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.

Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50-75 IU/kg twice weekly; bleeds were treated with 20-75 IU/kg. Half-life was estimated for the patients' previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients' previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.

Objective: The incidence of bronchiectasis has decreased significantly in developed countries due to successful control of childhood infections. However, the surgical treatment of this disease still plays an important role in thoracic surgical practice in underdeveloped and developing countries. The aim of this retrospective study was to present our surgical experience in patients with bronchiectasis, including our surgical treatment strategies and the results of long-term follow-up., Methods: A retrospective chart review was conducted of 339 patients who underwent surgical resection for bronchiectasis between January 1992 and December 2009. The patients' demographic features, the symptoms, etiologies and resection types, morbidity, mortality and outcomes after surgical management were analyzed., Results: There were 301 (88.8 %) male and 38 (11.2 %) female patients; the average patient age was 22.4 years (range 15-50 years). The most common presenting symptoms were productive cough in 197 (58.1 %) patients. There were 21 (6.2 %) asymptomatic patients. Two hundred and thirty of the 339 patients (67.8 %) had had previous medical therapy before admission to our department. The most common etiology of bronchiectasis was childhood infections in 101 (29.8 %) patients. In most patients, bronchiectasis was found on the left side (n = 225, 66.4 %). Thirty-five patients underwent a second operation for bilateral disease. There were two (0.6 %) early postoperative mortalities including one myocardial infarction and one respiratory insufficiency. Complications occurred in 43 patients (12.7 %). The median follow-up was 13.6 months. Symptoms disappeared in 201 patients (71 %), and 66 patients (23.3 %) experienced an improvement, while 16 patients (5.7 %) continued to be symptomatic., Conclusion: Although improvements in medical treatment have resulted in a significant decrease in the number of patients with bronchiectasis, surgical management is still very important in developing countries. Surgical resection can be performed with acceptable morbidity and mortality rates. The aim should be the resection of all involved bronchiectatic sites, even in patients with bilateral disease, if the pulmonary reserve is adequate., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: After surgical correction of thoracic wall deformities, promoting neochondrogenesis in the perichondrial bed is very important for obtaining a flexible chest wall. In this experimental study, we aimed to investigate the effects of human amniotic fluid on cartilage regeneration in the costal perichondrial bed in a rabbit model., Methods: Fifty-four adult New Zealand rabbits were divided into three groups, with 18 rabbits in each group. The third and fifth costal cartilages were excised totally on the right side and partially excised on the left side in all groups. Group 1 served as controls. All rabbits in group 1 underwent closure of the perichondrium of the third costal cartilage and closure of the perichondrium of the fifth costal cartilage with reimplantation of reshaped cartilage into the fifth costal perichondrial bed. Rabbits in group 2 underwent closure of the perichondrium of the third and fifth costal cartilages after the administration of human amniotic fluid into the perichondrial bed. Group 3 rabbits received both human amniotic fluid and underwent cartilage reimplantation. The third and fifth costal perichondriums in group 3 rabbits were closed after the administration of human amniotic fluid and the reimplantation of reshaped cartilages. Rabbits were sacrificed at two, eight and 12 weeks after operation., Results: Numerical scores for the right perichondrial bed were significantly higher for group 2 compared to group 1 ( P < 0.05). But the difference was not significant for the left perichondrial bed ( P > 0.05). The diameter of chondrogenesis also did not differ significantly between left and right perichondrial bed for all groups., Conclusion: Our study shows that administration of human amniotic fluid into the perichondrial bed increases chondrogenesis in adult rabbits, an important finding which may contribute to improving chest wall flexibility after the surgical correction of pectus excavatum., (© Georg Thieme Verlag KG Stuttgart · New York.)

Von Willebrand disease (VWD) is caused by a deficiency or dysfunction of Von Willebrand factor (VWF). The pathophysiology, classification, diagnosis, and management of VWD are relatively complex, but their understanding is important for proper diagnosis and management of patients with VWD. There are inherent difficulties in both the identification and classification of VWD because of clinical uncertainty and the limitations in the test processes and test panels typically used by laboratories. The most common test panel employed by laboratories, particularly in the geographic regions covered by the mutational studies, would comprise factor VIII coagulant (FVIII:C), VWF protein (antigen; VWF:Ag), and ristocetin cofactor (VWF:RCo). In our center, use of a desmopressin challenge with our core four-test panel (i.e., VWF:Ag, VWF:RCo, FVIII:C, and PFA-100) is expected to further assist laboratory diagnosis of VWD in Turkey. Molecular genetics is a rather new approach for Turkey, with gene analyses related to VWD being initiated in one center and the results used for confirmation of diagnosis in limited cases., (© Thieme Medical Publishers.)

Extra-adrenal paragangliomas are uncommon tumors arising from neuroectodermal-derived paraganglionic tissue. There are very few case reports on primary pulmonary paraganglioma in the literature. We present the case of a 21-year-old man who was treated with chemotherapy for Hodgkin's lymphoma. Only a partial response was noted so he underwent additional chemotherapy and involved field radiotherapy. PET-CT showed pathological activity in the lung parenchyma. Subsequent bronchoscopic biopsy showed paraganglioma and the patient underwent a left lower lobectomy., (Georg Thieme Verlag KG Stuttgart New York.)

Objective: The purpose of this study was to review 97 patients with giant pulmonary hydatid cysts and assess the clinical features and results of different operative techniques over a 27-year period., Material and Methods: Between January 1981 and December 2007, 590 patients were operated on for pulmonary hydatidosis and 97 (17 %) of these patients had giant pulmonary hydatid cyst. We retrospectively reviewed the medical records of these 97 patients. The diameter of the hydatid cysts were measured using radiological methods and intraoperatively., Results: Seventy-eight patients were male (80 %) and 19 were female (20 %). The median age was 23.4 years (range: 15-63 years). The most common symptoms were chest pain (54 %), cough (43 %) and dyspnea (41 %). Fourteen patients were asymptomatic (14 %). The diameters of the cyst ranged between 10 and 25 cm (mean 13.8 cm). The cysts were located in the right hemithorax in 52 (54 %) patients, in the left hemithorax in 44 (45 %) patients and bilaterally in one patient (1 %). Five patients had more than one cyst. The procedures consisted of cystotomy and capitonnage in 53 patients, enucleation and capitonnage in 27 patients and simple cystotomy or enucleation in 8 patients. Anatomical resection was performed in 9 patients. Prolonged air leakage of more than 7 days occurred in five patients; one patient underwent an operation and a Heimlich valve was placed in two patients. There was no postoperative mortality. Recurrence was not detected at follow-up after 6 months and 27 months., Conclusion: The higher lung tissue elasticity and delayed symptoms due to localizations of the cyst are the reasons for the occurrence of giant hydatid cysts in the lung. A parenchyma-saving operation should be performed instead of anatomical resection because of the low complication rates and because most complications can be treated conservatively.

Background: Pulmonary sequestration is the term used to describe a rare embryonic mass of lung tissue which has no bronchial communication with the normal tracheobronchial tree., Methods: In this study, we reviewed the medical records of 14 patients who underwent surgical resection for pulmonary sequestration between January 1992 and December 2006., Results: Nine patients were symptomatic with recurrent respiratory tract infections and five patients were asymptomatic with a suspected lesion revealed incidentally during imaging investigations for other indications. Pulmonary sequestration was diagnosed with preoperative diagnostic procedures in eight patients and the other six cases were diagnosed after histopathological examination of the resected specimen. All patients were treated surgically. No postoperative complications were observed., Conclusions: We conclude that the optimal treatment of pulmonary sequestration is surgical resection to avoid infection and destruction of the normal pulmonary parenchyma, even in asymptomatic cases. Moreover, in the case of pulmonary infection and the destruction of normal tissue, major resection such as lobectomy or pneumonectomy may be considered, instead of limited resection.

The aim was to evaluate the efficacy and safety of two recombinant factor VIIa (rFVIIa) dose regimens for treating haemarthroses in patients with congenital haemophilia A or B and inhibitors. This was a multicentre, randomised, cross-over, double-blind trial. Patients were randomly allocated to treat a first joint bleeding episode with one 270 microg/kg rFVIIa dose followed by two doses of placebo at 3-hour intervals and a second joint bleed with three single doses of 90 microg/kg rFVIIa at 3-hour intervals, or vice versa. Efficacy was evaluated using a novel and robust treatment response-rating scale based on patient-assessment of pain and joint mobility. Outcome was rated at different timepoints, and an effective or ineffective treatment response was determined. Treatment "preference" was defined as effective treatment with one regimen and ineffective with the other. Patients with equally effective or ineffective treatments had no "preference". Treatment was rated as effective for 65% of patients using the 270 microg/kg dose versus 70% for the 90 microg/kg x 3 regimen. An equal "preference" was noted for the two regimens (21% for each; p = 0.637); most patients (58%) had no "preference". 37/42 bleeding episodes (88%) were successfully treated with rFVIIa; additional haemostatic medications were administered for five episodes. No safety issues were identified. Administration of rFVIIa as a single 270 microg/kg dose to treat haemarthroses in patients with haemophilia and inhibitors was at least as efficacious and safe as the 90 microg/kg x 3 regimen.