MicroRNA Microarray Profiling in Infantile Hemangiomas.

Objective: MicroRNAs are short, noncoding RNA molecules that negatively regulate the stability and translational efficiency of target mRNAs. They are critical regulators of growth and development. Our aim was to identify microRNAs involved in the growth and regulation of infantile hemangiomas. In addition, we searched for the presence of Piwi-interacting RNAs in hemangioma tissue as another regulator of infantile hemangiomas. Methods: RNA was extracted from hemangioma specimens from 3 clinical, age-based categories: proliferative (N = 16), quiescent (N = 8), and involuting (N = 9). RNAs from human dermal microvascular endothelial cells were used as controls. MicroRNA microarray was performed, and the expression profiles of the hemangiomas and endothelial cells were compared using the t test. 5' End-labeling of RNA of our hemangioma specimens was performed for Piwi-interacting RNA detection. Results: Analysis confirmed statistically significant downregulated (N = 18) and upregulated (N = 15) microRNAs. Piwi-interacting RNA analysis did not detect Piwi-interacting RNA transcripts in the hemangioma specimens. Conclusions: The differential expression of microRNAs found in our hemangioma specimens provides insight into the regulation of hemangioma formation and proliferation, quiescence, and fibrofatty involution. Piwi-interacting RNA transcripts were not detected in the hemangioma specimens. These novel findings will help in establishing new therapeutic and diagnostic initiatives for these tumors.

A Common Polymorphism within the IGF2 Imprinting Control Region Is Associated with Parent of Origin Specific Effects in Infantile Hemangiomas.

Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states.

Infantile hemangiomas exhibit neural crest and pericyte markers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.

Facial angiofibromas in a mosaic pattern tuberous sclerosis: A case report.

Tuberous sclerosis is a rare genetic disorder presenting clinically with multiple hamartomas in different organs including the skin. The cutaneous manifestations include facial angiofibromas, hypopigmented macules (ash leaves), connective tissue nevi (shagreen patches), and periungual fibromas (Koenen tumors). We present a case of facial angiofibromas in a mosaic pattern tuberous sclerosis in an 11-year-old boy.

Minimally invasive groin dissection.

INTRODUCTION: Melanoma of the lower extremity with a positive sentinel lymph node biopsy (SLNB) mandates a groin dissection. This procedure has been associated with numerous complications; therefore we devised a modified approach. METHODS: All patients presenting with lower extremity melanomas that met criteria for SLNB had this procedure performed through an incision in the inguino-femoral region. In the event of a positive SLND, this same incision was used for the minimally invasive groin dissection (MIGD). A lighted retractor was used to improve visualization and a Ligasure (Valley-lab) was used to prevent seroma formation. RESULTS: Twenty patients met criteria for this investigation and five underwent MIGD. All patients tolerated the procedure well. There was no incidence of flap necrosis nor wound dehiscence. There was one case of seroma and cellulitis, one seroma, and one patient with lymphedema. All patients preferred the MIGD incision over traditional incisions. CONCLUSIONS: This new algorithm utilizing MIGD is well tolerated in patients. Complications appear to be minimal and patient satisfaction superior to traditional groin dissection.

An unusual log-splitter injury leading to radial artery thrombosis, ulnar artery laceration, and scapholunate dissociation.

A log splitter is a gasoline- or diesel-powered machine that uses a hydraulic-powered cutting wedge to do the work of an axe. Log-splitter injuries that do not result in amputation of digits or limbs are uncommon and not well described in the literature. We present a unique case of a patient who sustained a log-splitter injury that resulted in thrombosis of the radial artery and avulsion laceration of the ulnar artery leading to acute hand ischemia, in addition to scapholunate ligament disruption leading to a DISI deformity. In this case, thrombolytic therapy was contraindicated and surgical revascularization was the best possible treatment option. Our case illustrates the pitfalls of using this modality in a crush injury, since the use of thrombolytics in this instance would have resulted in severe hemorrhage. An important clinical caveat is the potentially misleading arteriographic diagnosis of thrombosis and/or spasm.

rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

STUDY DESIGN: The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. OBJECTIVE: To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). SUMMARY OF BACKGROUND DATA: rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. METHODS: Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. RESULTS: Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. CONCLUSIONS: The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

Chondral resurfacing of articular cartilage defects in the knee with the microfracture technique. Surgical technique.

BACKGROUND: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. METHODS: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m(2). Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.

Necrotizing infection of the spine.

STUDY DESIGN: Case report of multifocal necrotizing fasciitis with lumbar involvement. OBJECTIVES: To raise awareness of an unusual, but potential, focus of a multifocal necrotizing infection in a diabetic patient. SUMMARY OF BACKGROUND DATA: Necrotizing fasciitis is a rapidly spreading infection of the soft tissue and fascia. These infections can be polymicrobial, are challenging to treat, and often have grave consequences. The spine may rarely be involved in such infections. METHODS: We describe a patient with long-standing diabetic foot ulcers, which evolved to a necrotizing infection. This infection spread hematogenously to several noncontiguous locations, including the lumbar spine, and was heralded by gas production at the sites of involvement. The spine was treated aggressively and infection eradicated at this site. RESULTS: Despite eradicating the spinal component of this infection, other sites were challenging to clear, and the patient went on to die of multisystem organ failure. CONCLUSIONS: Necrotizing infections rarely involve the spine. Heightened awareness of this potential focus of infection may facilitate its detection. As with other sites, aggressive surgical debridement of this potentially fatal condition is imperative.

The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study.

BACKGROUND: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. METHODS: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m(2). Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.

Complications following hamstring anterior cruciate ligament reconstruction with femoral cross-pin fixation.

Cross-pin fixation of hamstring grafts for anterior cruciate ligament reconstruction was developed with hopes of improving on potential problems associated with interference screw and button fixation methods. However, cross-pins are a relatively new method of graft fixation and there are limited data on this technique. We report 2 cases in which reoperation was necessary after complications associated with cross-pin fixation. In one case, the cross-pin was left too proud and in the other it penetrated the medial side of the femur and was prominent. Surgeons who use cross-pin fixation should pay close attention so as not to leave the cross-pin proud laterally or medially to avoid the necessity of reoperation for hardware removal.