Hematopoietic stem cell mobilization for gene therapy of adult patients with severe β-thalassemia: results of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects

The safety and efficacy of hematopoietic stem cell (HSC) mobilization was investigated in adult splenectomized (SPL) and non-SPL patients with thalassemia major, in two clinical trials, using different mobilization modes: granulocyte-colony-stimulating factor (G-CSF)-alone, G-CSF following pretreatment with hydroxyurea (HU), plerixafor-alone. G-CSF-mobilization was both safe and effective in non-SPL patients. However, in SPL patients the procedure resulted in excessive response to G-CSF, expressed as early hyperleukocytosis necessitating significant dose reduction, and suboptimal CD34(+) cells yields. One-month HU-pretreatment prevented hyperleukocytosis and allowed successful CD34(+) cell collections when an optimal washout period was maintained, but it significantly prolonged the mobilization procedure. Plerixafor resulted in rapid and effective mobilization in both SPL and non-SPL patients and was well-tolerated. For gene therapy of thalassemia, G-CSF or Plerixafor could be used as mobilization agents in non-SPL patients whereas Plerixafor appears to be the mobilization agent of choice in SPL adult thalassemics in terms of safety and efficacy.     

Bronchopleural fistula repair during Clagett closure utilizing a collagen matrix plug

We describe a 65-year-old man who was treated for an empyema after a right middle and lower lobectomy for adenocarcinoma with a Clagett procedure who subsequently had a bronchopleural fistula develop. After adequate debridement of the cavity through dressing changes, the right bronchus intermedius bronchopleural fistula was closed using a collagen porcine plug (Surgisis anal fistula plug [Cook Medical Inc, Bloomington, IN]) placed through the cavity into the fistula along with the placement of omentum into the cavity. This case report illustrates the utility of collagen plugs to close bronchopleural fistulas.     

Unusual case of hemoptysis 13 years after bilobectomy

We describe a 68-year-old man with recurrent episodes of hemoptysis. The patient had undergone right upper and middle lobectomies for a benign cystic lesion 13 years ago and coronary artery bypass grafting for ischemic heart disease immediately before the onset of hemoptysis. Diagnostic work-up revealed that pulmonary arterial flow to the remaining right lower lobe had been inadvertently compromised by prior ligation of the right main pulmonary artery during the time of his bilobectomy, with the development of a robust collateral blood supply derived from bronchial and intercostals arteries. Successful treatment required percutaneous embolization of the dominant bronchial collaterals, followed by completion pneumonectomy.     

Treatment of pityriasis rubra pilaris with pimecrolimus cream 1%

Pityriasis rubra pillaris is an uncommon idiopathic dermatosis considered both a keratinization and an inflammatory disorder. Treatment is largely based on the information presented in case reports. We report the case of a young man with pityriasis rubra pillaris limited to the scalp and face, which cleared completely after application of pimecrolimus 1% cream for 2 weeks.     

Improving the Subcutaneous Mouse Tumor Model by Effective Manipulation of Magnetic Nanoparticles-Treated Implanted Cancer Cells

Murine tumor models have played a fundamental role in the development of novel therapeutic interventions and are currently widely used in translational research. Specifically, strategies that aim at reducing inter-animal variability of tumor size in transplantable mouse tumor models are of particular importance. In our approach, we used magnetic nanoparticles to label and manipulate colon cancer cells for the improvement of the standard syngeneic subcutaneous mouse tumor model. Following subcutaneous injection on the scruff of the neck, magnetically-tagged implanted cancer cells were manipulated by applying an external magnetic field towards localized tumor formation. Our data provide evidence that this approach can facilitate the formation of localized tumors of similar shape, reducing thereby the tumor size’s variability. For validating the proof-of-principle, a low-dose of 5-FU was administered in small animal groups as a representative anticancer therapy. Under these experimental conditions, the 5-FU-induced tumor growth inhibition was statistically significant only after the implementation of the proposed method. The presented approach is a promising strategy for studying accurately therapeutic interventions in subcutaneous experimental solid tumor models allowing for the detection of statistically significant differences between smaller experimental groups.