Refinements in Tear Trough Deformity Correction: Intraoral Release of Tear Trough Ligaments: Anatomical Consideration and Clinical Approach.

BACKGROUND: Correction of tear trough (TT) deformity is a crucial aspect of facial rejuvenation. Because the anatomical origins of TT deformity lie in the TT ligaments, which firmly attach the dermis to the periosteum, the release of TT ligaments should be considered when performing an etiological correction. The aim of this paper is to propose an alternative method for TT deformity correction, comprising use of filler together with the release of TT ligaments. This technique was compared to the procedure of only percutaneous filler. METHODS: From January 2014 to December 2015, 10 patients were enrolled in the study for recurrence of TT deformity. All the patients underwent TT ligament release and filler injections; all had been previously treated with percutaneous hyaluronic acid injection without ligament release. Under local anesthesia, the TT ligaments were detached using a blunt cannula introduced directly in the supra periosteal plane through an intraoral access. Once the ligament was released, the TT depression was evenly recontoured with a very small amount of filler. The clinical data, digital images, evaluations of outcomes, including patient satisfaction rates were collected and compared. RESULTS: Adding the procedure of TT ligament release to filler injections showed satisfactory results, avoiding an unnatural puffy appearance. The comparison between the two different methods showed improved outcomes and increased patient satisfaction with minor patient discomfort among those who underwent TT ligament release. CONCLUSION: Because TT ligaments are among the etiologic factors of TT deformity, they have a strong impact on procedures that are designed to improve TT deformity; therefore, TT ligament release should always be considered to obtain satisfactory, natural results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Study of the tendinous vascularization for the compound radial forearm flap plus flexor carpi radialis tendon.

PURPOSE: The aim of this study was to explore the tendinous vascularization of flexor carpi radialis (FCR) and investigate the anatomical basis for harvesting the compound radial forearm flap (free or pedicled) with the vascularized tendon for the reconstruction of cutaneotendinous defects. METHODS: The area of the radial forearm flap was studied in seventeen forearms of fresh cadavers injected with red latex. A lozenge-shaped flap about 9 cm long and 4 cm wide was raised along the axis of the radial artery. Dissection of the flap was carried out subfascially. We searched perforators going into the flap and the nutritive branches for the tendon sheath of FCR were dissected up to their origin from the radial artery. Their distance from the scaphoid tubercle was recorded. RESULTS: We found nutritive branches for all the length of the tendon. The mean number of perforators going into the tendon sheath was 9.5 (range 8-12). Constant sizeable branches larger than 0.2 mm were identified from the scaphoid tubercle to the myotendinous junction; their distance from the scaphoid tubercle ranged between 0.5 and 12.5 cm. We found an average 0.8 perforators/cm of tendon (range 0.7-1). The donor sites were always closed primarily. CONCLUSIONS: Nutrient branches of the radial artery for the tendon of FCR were constantly found. Our anatomical findings confirm the possibility of raising a compound radial forearm flap including a sure vascularized tendon of FCR. Its clinical application provides a quick and straightforward single-stage option for the reconstruction of complex cutaneotendinous defects.

Radial forearm flap plus Flexor Carpi Radialis tendon in Achilles tendon reconstruction: Surgical technique, functional results, and gait analysis.

BACKGROUND: Wound dehiscence, infection, and necrosis of tendon and overlying skin are severe complications after open repairs of Achilles tendon. A simultaneous reconstruction should be provided in a single stage operation. We evaluated the outcomes of one of the possible options: the radial forearm free flap with Flexor Carpi Radialis (FCR) tendon. METHODS: Between 2006 and 2014, six patients affected by infection and necrosis after Achilles tendon open repair underwent multi-tissutal reconstruction by a composite radial forearm free flap including a vascularized FCR tendon. The mean skin and tendon defect was respectively 9.8 cm × 4.7 cm and 6.5 cm. After reconstruction, patients underwent clinical examination, including the Achilles Tendon Total Rupture Score (ATRS) questionnaire, DASH score, MRI study, and a computer-assisted gait analysis. RESULTS: All flaps survived and no complications were recorded. Full weightbearing was allowed within 2 months after surgery. The mean follow-up was 36.2 months (range 12-96). MRI showed an optimal reconstruction of the tendon. Range of motion was minimally reduced if compared to the contralateral side. Gait analysis showed the recovery of a nearly symmetrical stance phase, time to heel off, and step length of the gate. ATRS and DASH score improved to a mean value of 85.2 (range 83-88) and 8.0 (range 3-15) respectively. CONCLUSIONS: This procedure provided an anatomical reconstruction of the Achilles tendon and skin achieving good and objective functional results; donor site morbidity was limited to the sacrifice of the radial artery, which, in our opinion, is a minor drawback if compared to the quality of the results.

Inhibiting angiotensin-converting enzyme promotes renal repair by limiting progenitor cell proliferation and restoring the glomerular architecture.

We previously reported that angiotensin-converting enzyme inhibitor (ACEi) renoprotection in Munich Wistar Frömter (MWF) rats, which develop progressive glomerular injury, was associated with podocyte repopulation and preservation of glomerular architecture. Here, we studied the time course of the lesions, their cellular components, and the effect of ACEi. Early glomerular lesions were synechiae, followed by extracapillary crescents and glomerulosclerosis. The majority of cells forming crescents were claudin1(+) parietal epithelial cells and, to a lesser extent, WT1(+) podocytes, both in active proliferation. In crescents, cells expressing the metanephric mesenchyme marker NCAM were also found. Three distinct populations of parietal epithelial cells were identified in the rat Bowman's capsule: NCAM(+)WT1(-) cells, also expressing progenitor cell marker CD24, and NCAM(+)WT1(+) and NCAM(-)WT1(+) cells, the latter population representing parietal podocytes. After exposure to inductive medium, cultured parietal epithelial cells that were obtained by capsulated glomeruli generated podocytes, documenting their progenitor nature. Mitotic activity of cultured renal progenitors was induced by angiotensin II through the down-regulation of cell cycle inhibitor C/EBPδ expression. Treatment with ACEi reduced number and extension of crescents and glomerulosclerosis in MWF rats. Renoprotection was accomplished through the limitation of NCAM(+) progenitor proliferation via the modulation of C/EBPδ. Thus, chaotic migration and proliferation of the Bowman's capsule progenitor cells pave the way to crescent formation and subsequent sclerosis. ACEi, by moderating progenitor cell activation, restores glomerular architecture and prevents renal disease progression.

Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing.

BACKGROUND: Duchenne and Becker Muscular dystrophies (DMD/BMD) are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions and duplications account for approximately 75% of mutations in DMD and 85% in BMD. The implementation of techniques allowing complete gene sequencing has focused attention on small point mutations and other mechanisms underlying complex rearrangements. METHODS: We selected 47 patients (41 families; 35 DMD, 6 BMD) without deletions and duplications in DMD gene (excluded by multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction analysis). This cohort was investigated by systematic direct sequence analysis to study sequence variation. We focused our attention on rare mutational events which were further studied through transcript analysis. RESULTS: We identified 40 different nucleotide alterations in DMD gene and their clinical correlates; altogether, 16 mutations were novel. DMD probands carried 9 microinsertions/microdeletions, 19 nonsense mutations, and 7 splice-site mutations. BMD patients carried 2 nonsense mutations, 2 splice-site mutations, 1 missense substitution, and 1 single base insertion. The most frequent stop codon was TGA (n=10 patients), followed by TAG (n=7) and TAA (n=4). We also analyzed the molecular mechanisms of five rare mutational events. They are two frame-shifting mutations in the DMD gene 3'end in BMD and three novel splicing defects: IVS42: c.6118-3C>A, which causes a leaky splice-site; c.9560A>G, which determines a cryptic splice-site activation and c.9564-426 T>G, which creates pseudoexon retention within IVS65. CONCLUSION: The analysis of our patients' sample, carrying point mutations or complex rearrangements in DMD gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects and dystrophin functional domains. These data can have a prognostic relevance and can be useful in directing new therapeutic approaches, which rely on a precise definition of the genetic defects as well as their molecular consequences.

Mutations of FUS gene in sporadic amyotrophic lateral sclerosis.

BACKGROUND: Mutations in the FUS gene have recently been discovered to be a major cause of familial amyotrophic lateral sclerosis (FALS). OBJECTIVE: To determine the identity and frequency of FUS gene mutations in a large cohort of Italian patients enriched in sporadic cases (SALS). METHODS: Exons 5, 6, 14 and 15 of the FUS gene were screened for mutations in 1009 patients (45 FALS and 964 SALS). The genetic analysis was extended to the entire coding sequence of FUS in all the FALS and 293 of the SALS patients. RESULTS: Seven missense mutations (p.G191S, p.R216C, p.G225V, p.G230C, p.R234C, p.G507D and p.R521C) were identified in nine patients (seven SALS and two FALS), and none in 500 healthy Italian controls. All mutations are novel except for the p.R521C mutation identified in one SALS and one FALS case. Both patients showed a similar unusual presentation, with proximal, mostly symmetrical, upper limb weakness, with neck and axial involvement. With the exception of p.G507D and p.R521C, the mutations identified in SALS patients are all localised in the glycine-rich region encoded by exon 6. In addition, eight different in-frame deletions in two polyglycine motifs were detected, the frequency of which was not significantly different in patients and controls. CONCLUSIONS: The results show that FUS missense mutations are present in 0.7% of Italian SALS cases, and confirm the previous mutational frequency reported in FALS (4.4%). An unusual proximal and axial clinical presentation seems to be associated with the presence of the p.R521C mutation.

Perforator-based Reverse Radial Teno-Adipo-Fascial Flap: Surgical Technique and Case-report for the Functional Reconstruction of the Dorsum of the Hand.

BACKGROUND: Dorsal complex cutaneotendinous lesions of the hand represent a reconstructive challenge. The use of composite microvascular flaps and vascularized tendon grafts represent the gold-standard. The radial anti-brachial region can still represent an excellent donor site, to the detriment of the possible sacrifice of the radial artery. The reverse radial anti-brachial flap can be either perforator-based, thus saving the radial artery or raised as an adipo-fascial flap, to spare the skin. PATIENTS AND METHODS: A case of post-traumatic highly contaminated dorsal cutaneotendinous defect of the second ray of the hand was reported. An original surgical reconstructive technique with a Revers Radial Teno-Adipo-Fascial Flap (RRTAFF) plus vascularized Palmaris Longus was described, preserving the radial artery. A simple partial thickness skin graft was performed a second time to complete dorsal cutaneous coverage. A subsequent infection was managed by trusting the complete vascularization of the tissues used for the reconstruction. RESULTS: The hand healed well with containment of the infection. The dorsal healed skin appeared elastic and pliable enough. Passive and active motion of interphalangeal and metacarpofalangeal joints were very satisfying. The donor site was well healed, with almost no morbidity. CONCLUSIONS: This reconstructive strategy provides a quick and straightforward single-stage option for the reconstruction of complex cutaneotendinous defects of the dorsum of the hand. Such a reconstruction, with a completely vascularized procedure, is particularly indicated in cases of high contamination or infection of the recipient site.