Supermicrosurgical treatment for lymphedema: a systematic review and network meta-analysis protocol

Background Lymphedema is a condition that affects up to 130 million subjects worldwide. Since it is related to several complications and a significant reduction in terms of quality of life, it is a heavy burden not only to the patients but also for the healthcare system worldwide. Despite the development of supermicrosurgery, such as vascularized lymph node transfer (VLNT) and lymphovenous anastomosis LVA, the indications and outcomes of these complex groups of interventions remain a controversial topic in the field of reconstructive plastic surgery. Methods This systematic review and network meta-analysis aims to assess the evidence of outcomes of LVA and VLNT in patients with lymphedema. Secondary aims of the project are to determine if for any outcomes, LVA or VLNT is superior to conservative therapy alone, and whether the available evidence favors any kind of supermicrosurgical interventions for lymphedema patients. This study will include original studies of patients with lymphedema on the extremities indexed in PubMed, EMBASE, CENTRAL, PASCAL, FRANCIS, ISTEX, LILACS, CNKI, and IndMED that reported microsurgery (supermicrosurgery) of all techniques aiming the re-functionalization of the lymphatic system. As comparators, mere observation, conservative treatment of any kind, and the other subgroups of supermicrosurgery are planned. The primary outcome of this systematic review and network meta-analysis is the difference of the limb volume, while the secondary outcomes of interest will be erysipelas rates, major and minor complications, postoperative necessity of continuous compression garments, and patient satisfaction, measured by already published and validated scores for quality of life. Discussion We will provide an overview and evidence grade analysis of the scientific literature available on the effectiveness of the subcategories of supermicrosurgical interventions for lymphedema

Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction

Aims: Whether and how iron affects the progression of atherosclerosis remains highly debated. Here, we investigate susceptibility to atherosclerosis in a mouse model (ApoE-/- FPNwt/C326S) which develops atherosclerosis in the context of elevated non-transferrin bound serum iron (NTBI). Methods and Results: Compared to normo-ferremic ApoE-/- mice, atherosclerosis is profoundly aggravated in iron-loaded ApoE-/-FPNwt/C326S mice, suggesting a pro-atherogenic role for iron. Iron heavily deposits in the arterial media layer, which correlates with plaque formation, vascular oxidative stress and dysfunction. Atherosclerosis is exacerbated by irontriggered lipid profile alterations, vascular permeabilization, sustained endothelial activation, elevated pro-atherogenic inflammatory mediators and reduced nitric oxide availability. NTBI causes iron overload, induces ROS production and apoptosis in cultured vascular cells, and stimulates massive MCP-1-mediated monocyte recruitment, well-established mechanisms contributing to atherosclerosis. NTBI-mediated toxicity is prevented by transferrin- or chelatormediated iron scavenging. Consistently, a low-iron diet and iron chelation therapy strongly improved the course of the disease in ApoE-/-FPNwt/C326S mice. Our results are corroborated by analyses of serum samples of hemochromatosis patients, which show an inverse correlation between the degree of iron depletion and hallmarks of endothelial dysfunction and inflammation. Conclusions: Our data demonstrate that NTBI-triggered iron overload aggravates atherosclerosis and unravel a causal link between NTBI and the progression of atherosclerotic lesions. Our findings support clinical applications of iron restriction in iron-loaded individuals to counteract iron-aggravated vascular dysfunction and atherosclerosis

Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity