Autologous micro-fragmented adipose tissue for the treatment of diabetic foot minor amputations: a randomized controlled single-center clinical trial (MiFrAADiF).

BACKGROUND: The diabetic foot ulcer (DFU) is one of the most prevalent complications of diabetes mellitus and often develops severe effects that can lead to amputation. A non-healing "minor" amputation often precedes a major amputation resulting in a negative impact on the function and quality of life of the patients. Stem cell-based therapies have emerged as a promising option to improve healing, and the adipose tissue is an abundant and easy to access source. The injection of autologous micro-fragmented adipose tissue at the amputation stump of a diabetic population undergoing a lower limb minor amputation was evaluated and compared with the standard care. METHODS: In this randomized controlled trial with two arms (parallel assignment) and no masking, 114 patients undergoing a lower limb minor amputation were randomized to standard of care or to micro-fragmented adipose tissue injection prepared using a minimal manipulation technique (Lipogems®) in a closed system. Clinical outcomes were determined monthly up to 6 months. Primary endpoint of the study was the evaluation of the healing rate and time after the minor amputation. Secondary endpoints included the assessment of safety, feasibility, technical success, relapse rate, skin tropism, and intensity of pain. RESULTS: At 6 months, 80% of the micro-fragmented adipose tissue-treated feet healed and 20% failed as compared with the control group where 46% healed and 54% failed (p = 0.0064). No treatment-related adverse events nor relapses were documented, and technical success was achieved in all cases. The skin tropism was improved in the treatment group, and the pain scale did not differ between the two groups. CONCLUSION: The results of this randomized controlled trial suggest that the local injection of autologous micro-fragmented adipose tissue is a safe and valid therapeutic option able to improve healing rate following minor amputations of irreversible DFU. The technique overcomes several stem cell therapy-related criticisms and its potential in wound care should be better evaluated and the therapeutic indications could be expanded. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03276312. Date of registration: September 8, 2017 (retrospectively registered).

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

New Conception of Relining in the Endovascular Aneurysm Sealing Era: A Monocentric Case Series Study.

Over 20 years from the first endovascular aortic repair, endoleaks still represent a common problem, even with newer endograft generation. Numerous procedures can be adopted to manage these complications; relining of the endoprosthesis is a rational technique to treat type III and IV endoleaks. The absence of dedicated materials for these procedures forces the vascular surgeon to perform complex hybrid or endovascular interventions. In this case report, we aimed to evaluate our relining experience using the Nellix device in 5 consecutive cases.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Durability and efficacy of tibial arterial stent placement for critical limb ischemia.

PURPOSE: To analyze the efficacy and durability of long-term tibioperoneal arterial stent placement for selected cases of symptomatic chronic limb ischemia (CLI). MATERIALS AND METHODS: From January 2005 to June 2012, 168 limbs (155 patients) were treated with percutaneous transluminal angioplasty (PTA)/stent placement for de novo tibial stenosis or occlusion in at least one tibial artery. Most patients (92.9%) were classified with severe disease (Rutherford category 5/6). Concomitant interventions were performed in 58%. Bare metal (84%) and drug-eluting (16%) stents were used. Indications for stent placement were residual stenosis after PTA (> 30%), elastic recoiling, and dissection. Primary endpoints were freedom from symptomatic intrastent restenosis, target lesion revascularization (TLR), major amputation, and overall survival (OS). RESULTS: Technical success rate was 99%. Within 30 days, five deaths (3.2%) occurred, and a 1.8% (95% confidence interval [CI], 0.1%-27.2%) major adverse cardiac event rate, 3.6% (95% CI, 0.1%-22.1%) major adverse limb event rate, and 1.8% (95% CI, 0%-27.5%) amputation rate were recorded. Mean follow-up was 33 months (range, 1-96 mo). Symptomatic intrastent restenosis occurred in 20 limbs (12%) at a mean of 10.3 months ± 11.27; this was identified as a prognostic factor for limb loss (P = .045). TLR was necessary in 10.8% of limbs, for a limb salvage rate of 89.2%. OS was influenced by age (> 75 y; P < .001), diabetes (P = .048), and renal insufficiency and/or dialysis (P < .001). Estimated survival rate was 63% at 36 months (hazard ratio, 1.63; 95% CI, 54%-70%). CONCLUSIONS: Stent placement offers promising short- to long-term restenosis and patency rates, even in cases of multilevel symptomatic disease. Rigorous follow-up is vital.

Anakinra treatment in drug-resistant Behcet's disease: a case series.

The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

Preoperative diagnosis of orbital cavernous hemangioma: a 99mTc-RBC SPECT study.

PURPOSE: This study aimed to describe 99mTc-labeled RBC scintigraphy as a diagnostic method for orbital cavernous hemangiomas and to evaluate this diagnostic tool according to surgical outcomes. METHODS: Fifty-five patients with clinical and radiological (US, CT, and/or MRI) suspicion of unilateral cavernous hemangioma of the orbit underwent 99mTc-RBC SPECT study.Qualitative and semiquantitative evaluations were performed, and results were statistically analyzed. RESULTS: SPECT images showed focal uptake in the orbital mass in 36 of 55 patients. Nineteen patients had a negative scintigraphic pattern, with concordance of early and late absence of uptake of 99mTc-RBC.Our procedure showed 100% sensitivity and 88.9% specificity for the diagnosis of orbital cavernous hemangioma, with a positive predictive value of 90.9% and a negative predictive value of 100%. CONCLUSIONS: 99mTc-RBC imaging is safe, easy to perform, and highly accurate in providing adequate clinical and surgical management. As a noninvasive and highly specific method for diagnosing orbital hemangioma, 99mTc-RBC scintigraphy can avoid more invasive imaging or biopsy.

Urgent carotid artery stenting with technical modifications for patients with transient ischemic attacks and minor stroke.

PURPOSE: To evaluate the safety and efficacy of urgent carotid artery stenting (CAS) with technical modifications in patients with recent (<24 hours) initial or recurrent (≥2 episodes in 24 hours) transient ischemic attacks (TIA) or with minor stroke. METHODS: A single-center, prospective, observational study was begun in March 2005 to assess an urgent CAS protocol for the treatment of selected high-risk patients with carotid artery disease who presented within 24 hours of an initial or recurrent TIA or minor stroke. Up to June 2011, 78 patients (59 men; mean age 76 years) with TIA (n=57) or minor stroke (n=21) underwent urgent CAS (within 48 hours) for severe internal carotid artery stenosis. Outcome measures were major adverse cardiac and cerebrovascular events (MACCE), modifications in the National Institutes of Health Stroke Scale (NIHSS) values for minor stroke patients, and postoperative stroke and death rates. RESULTS: Technical and procedural success rates were 100% and 97.4%, respectively; 1 intraoperative minor stroke occurred due to stent thrombosis. At 30 days, 2 patients had recurrent minor stroke; one subsequently died after a hemorrhagic brain infarction. The MACCE rate was 3.8%. There were no cases of myocardial infarction or access-related complications. Of the 20 surviving minor stroke patients, 14 showed improvement in neurological deficit on the NIHSS scale at 30 days, while 5 remained stable and one was neurologically impaired. CONCLUSION: Urgent CAS in selected patients with symptomatic carotid stenosis was satisfactory in preventing the recurrence of TIA and stroke in this study. Urgent CAS with careful patient selection, contemporary tools (medical and technical), and expert technique may represent a possible solution for some patients with recent or recurrent TIA or minor stroke.

Use of combined thoracic and abdominal endografts for proximal severe neck angulation in abdominal aortic aneurysms.

PURPOSE: To evaluate endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) with severe neck angulation (SNA) utilizing a thoracic endograft placed proximal to a bifurcated endograft. METHODS: A retrospective review was conducted of 28 consecutive EVAR patients (25 men; mean age 71 years, range 62-86) with proximal SNA ≥60° treated electively between December 2006 and May 2011. The average AAA neck diameter was 23 mm (range 22-28), with a mean length of 25 mm (range 10-51) and a mean maximum sac diameter of 63 mm (range 55-98). The mean neck angulation was 73° (range 60-92). All patients received an endograft designed for the thoracic aorta (Relay) placed as a proximal extension above a bifurcated abdominal aortic endograft (IntuiTrak Powerlink). RESULTS: Technical success was achieved in 100% of cases. An intraoperative type I proximal endoleak was successfully treated with stent deployment, and 2 type II endoleaks spontaneously resolved within 30 days. In all 28 patients, endograft integrity and correct positioning were confirmed at the latest imaging follow-up (mean 23.7 months, range 6-43). Fifteen (56%) aneurysm sacs were stable and 13 (46%) were reduced in size. Two patients died of unrelated causes during follow-up. CONCLUSION: The unique morphology of SNA requires the development of a precise proximal fixation technology for successful endovascular repair. This hybrid solution exploits the technological advances of the thoracic aortic endograft and the stability of an anatomically fixed bifurcated endograft. This device combination may be an alternative solution for patients with SNA who are unsuitable for traditional surgery.