Functional Assessment of Pluripotent and Mesenchymal Stem Cell Derived Secretome in Heart Disease.

OBJECTIVES: Cell-based therapies have demonstrated variable degrees of success in the management of myocardial infarction and heart failure. By inducing a myocardial infarction in a rat model, the effects of secretome from human induced pluripotent stem cells (HiPSCs) and human mesenchymal stem cells (hMSCs) on cardiac function and remodeling were investigated. METHODS: HiPSCs and hMSCs were cultured and after 12 cycles, secretome was collected. The quantification of stem cell growth factors was measured using the ELISA test. Thirty female Lewis rats underwent surgical ligation of the left coronary artery. The rats were then randomized (n=10/group) to receive one of three treatments injected into the peri-infarct area; normal saline, HiPSC and hMSC. Left ventricular ejection fraction (LVEF), fractional shortening (FS), histology and serum proteomics were evaluated in a blinded fashion both pre-operatively and at 2, 4 and 6 weeks. RESULTS: ELISA studies revealed, Platelet-derived growth factor (PDGF) concentration of 3.35± 0.031 ng/ml (0.68± 0.027ng/ml) for MSC-CM group, 3.44± 0.042 ng/ml (0.78± 0.03 ng/ml) for the HiPSC-CM group, 3.2± 0.107 ng/ml (0.64±0.013 ng/ml) for the MSC-pre-group, 3.1± 0.075 ng/ml (0.71± 0.013 ng/ml) for the HiPSC-pre group and 3.3± 0.047 ng/ml (0.71± 0.014ng/ml) for the HiPSC-pre-r group at 60 min in comparison to at (0 min).Compared to non-treated (NT), HiPSC and hMSC, treated rats demonstrated significant improvement in LVEF and FS, and significant reduction in scar size (p<0.05) at 4 and 6 weeks. Proteomic analysis detected the presence of Vascular endothelial growth factor (VEGF) in the serum of rats receiving HiPSC, which was absent in the NT and hMSC groups. CONCLUSION: The current study demonstrated a significant improvement of cardiac function and remodeling in response to secretome from HiPSCs and hMSCs. These findings suggest that secretome from HiPSCs may have potential therapy for acute myocardial infarction (MI) without the need of stem cell harvesting and implantation.

Percutaneous sclerotherapy for congenital venous malformations in the extremities.

Between January 1991 and January 1998, a total of 15 patients underwent direct injection sclerotherapy for painful peripheral venous malformations. Duplex ultrasonography or venography was used in all cases for the detection and localization of tortuous venous structures. Direct injection with absolute ethyl alcohol was performed in 12 patients, and Sotradecol or sodium morrhuate was used in 5 patients. Provocative lidocaine testing was used in 2 patients in whom major nerves were in proximity to the malformations. All patients underwent follow-up in the clinic with duplex examination after each sclerotherapy. Clinical symptoms of all patients improved during average follow-up of 2.5 years (range: 3 months to 6 years.) Duplex examination was useful in detecting the venous component including the size and course of veins, which were often less well seen on magnetic resonance imaging. Duplex study was helpful in follow-up after sclerotherapy in all patients. Direct injection sclerotherapy is an acceptable treatment modality for venous malformations. Complications are manageable, and regular follow-up with Duplex is helpful.

Refractory abdominal-cutaneous fistulas or leaks: percutaneous management with a collagen plug.

BACKGROUND: We report the results of abdominal-cutaneous fistula tract occlusion with a collagen plug in a series of patients with fistulas or leaks refractory to conservative therapy. STUDY DESIGN: Seven patients were found to have persistent fistula or leak after percutaneous drainage of abdominal pelvic fluid collections. All patients but one were refractory to surgical or percutaneous drainage. Under fluoroscopic guidance, modified Vasoseal (Datascope Inc, Montvale, NJ) collagen plugs were deployed into the fistulas using catheter-directed techniques. The plugs were split longitudinally to fit into an 8F or 9F peel-away sheath, placed into the fistula, and deployed. Results were tabulated and patients were followed up. RESULTS: Six of seven patients undergoing fluoroscopically guided, catheter-directed tract occlusion had resolution of the fistula, with no evidence of fistula or abscess recurrence from 30 to 180 days after closure. There were no procedural complications. The technique was unsuccessful in dosing a gastrocutaneous fistula after removal of a large-bore gastrostomy tube; this failure was believed to be secondary to the short length and large caliber of the tract in a patient with hypercortisolemia. CONCLUSIONS: Closure of abdominal-cutaneous fistula tracts by occlusion with a modified Vasoseal collagen plug shows promise in the management of fistulas refractory to catheter drainage.

Fluoroscopically guided percutaneous placement of large-bore gastrostomy and gastrojejunostomy tubes: review of 109 cases.

PURPOSE: To evaluate our experience with percutaneous placement, management, and complications of large-bore (20-24 F) gastrostomy and gastrojejunostomy feeding tubes. MATERIALS AND METHODS: A retrospective review was performed on 109 consecutive patients who underwent placement of percutaneous large-bore feeding tubes between January 1994 and May 1998. Data were collected with respect to underlying illness, technical success, number of replaced tubes, and immediate and late complications. No patient had a small-bore tube placed during this series. RESULTS: A total of 109 cases were reviewed. Immediate follow-up within the first 2 weeks was available for all 109. Follow-up after 2 weeks was available for 61 (56%) patients. Tubes were placed in patients aged 15 to 94 years. Neurologic dysfunction from a variety of causes was the most common underlying illness and occurred in 52% of patients. There were nine (8.3%) immediate, treatable complications: three major and six minor. There was one procedure-related death (0.9%). Persistent fistula tracts following tube removal occurred in three patients (4.9%). Balloon rupture was the most common reason for tube exchange (40.7%). CONCLUSION: Percutaneous large-bore gastrostomy and gastrojejunostomy tubes are safe to place and have technical success, morbidity, and mortality rates comparable to those of tubes placed surgically or endoscopically as well as small-bore tubes placed with fluoroscopic guidance.

Clinical outcomes of patients after a negative spiral CT pulmonary arteriogram in the evaluation of acute pulmonary embolism.

PURPOSE: To examine 6-month clinical outcomes of patients after acquisition of a spiral computed tomography (CT) pulmonary arteriogram interpreted as negative for acute pulmonary embolism (PE). MATERIALS AND METHODS: A retrospective review was performed on a consecutive series of 143 patients who underwent spiral CT pulmonary arteriography for possible acute PE during a 19-month period. All studies were performed on a HiSpeed Scanner with use of 3-mm collimation with a pitch between 1.3 and 2.0, depending on patient size. All imaging was performed during dynamic contrast material injection at rates between 3.0 and 4.0 mL/sec, timed to peak pulmonary arterial enhancement. For the studies interpreted as negative for PE through the segmental (fourth order) pulmonary arteries, follow-up data were collected by telephone interviews with patients or surviving relatives, and by medical record reviews. RESULTS: Among 143 patients, 22 studies (15%) were positive for PE, eight (6%) were suboptimal to exclude PE to the segmental artery level, and 113 (79%) were interpreted as negative for acute PE. Among the 113 negative studies, 13 patients were lost to follow-up, leaving a study population of 100 patients. Eighty-one patients were alive a minimum of 6 months after acquisition of a negative spiral CT pulmonary arteriogram (mean, 9 months; range, 6-24 months) and were without interim diagnosis of PE. Nineteen patients died within the follow-up period after a negative spiral CT pulmonary arteriogram (mean, 3 months; range, 0-8 months); however, in none of these cases was acute pulmonary embolus reported as the cause of death. No documented PE was identified by subsequent imaging studies or autopsy within the study population. CONCLUSION: A series of 100 patients with a negative spiral CT pulmonary arteriogram did not experience significant morbidity and mortality as a result of pulmonary embolic disease within a 6-month follow-up period.