25-year Follow-up of Primary Tibial Periosteal Graft for Hard Palate Repair in Cleft Lip and Palate: Outcomes, Concerns and Controversies.

OBJECTIVE: This study evaluates long-term outcomes in adults with Unilateral and Bilateral Cleft Lip and Palate (UCLP/BCLP) treated during the period 1992 to 1995 with tibial periosteal graft in primary repair. DESIGN: Retrospective study. SETTING: Department of Plastic and Maxillofacial Surgery, Children's Hospital Bambino Gesù (Italy). PATIENTS: The study included 52 patients with non-syndromic BCLP/UCLP who met the inclusion criteria. INTERVENTIONS: All patients underwent a standardized surgical protocol using a tibial periosteal graft as primary repair of the hard palate. MAIN OUTCOME MEASURE(S): Long-term outcomes on maxillary growth, residual oronasal fistula, and leg length discrepancy. RESULTS: About <2% of patients showed oral-nasal communication. Mean value of maxillary depth was 86° ± 4.5°. The lower value for maxillary retrusion was 76.8° in relation to the Frankfurt plane. At the x-ray control, 12.2% of patients showed leg discrepancy with a difference of always <2 cm. CONCLUSIONS: The rate of maxillary retrusion obtained was the same if compared to other techniques. Tibial periosteal graft reduces the risk of fistula and the need for reintervention after secondary bone graft. The study did not observe negative impacts on leg growth after 25 years.

Male Lower Extremity Sculpting.

BACKGROUND: The muscular sculpture (MS) is a new technique of male body contouring to achieve: tight skin that very well reveals muscular bulk, a male muscular and athletic body, minimal observable scars and even patients who are not, nor have been in. With this study, we describe the new technique for sculpting of lower extremities. In literature are not described techniques to accomplish a sound aesthetic result in sculpting surgery about lower extremities. METHODS: For this surgical procedure, we illustrate the technique that was obtained from 5 male patients (principles outlined in the Declaration of Helsinki have been followed). We describe this surgery with six steps: defatting step; MS; internal scar removal; irregularity removal; dermal grasping; last residues of fat removing. RESULTS: We obtain a high satisfaction rate as high as 100% for short and long term. Compared to the complications more described in literature (infection, hematoma, seroma, wound dehiscence, hypertrophic scars, sensory nerve injury and recurrent skin laxity, Monarca and Rizzo in Aesthetic Plast Surg 39(2):199-202, 2015), we have not had complications. We had no major complications. We observed, with our other studies, a direct relationship between complications and smoking habit. Successful body-contouring surgery requires a patient to embrace positive lifestyle habits: exercise, a proper diet and other positive lifestyle changes (Monarca et al. in Plast Reconstr Surg 123(5):1637-1638, 2009), and a high compliance and to avoid all the excesses. CONCLUSIONS: We obtain amazing aesthetic results with total patient satisfaction without complications. There are not enough studies in the literature about body sculpting, and is necessary to deepen this technique in order to obtain increasingly encouraging results. LEVEL OF EVIDENCE V: Sculpting surgery, Body contouring, 41 leg surgery, adipose tissue. 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 .

Optimal care for rhino-orbital mucormycosis in child with myeloblastic leukemia. Case report and literature review.

Mucormycosis is an opportunistic and aggressive fungal infection that mainly affects immunocompromised patients who generally suffer from diabetes mellitus, immune impairment, hematological disease. It is a life-threatening infection and the management is not standardized. The literature proposes aggressive and early surgical approach, even at the expense of mutilation. We report a case of rhino-orbital mucormycosis in a child with myeloblastic leukemia and the successful treatment using the instill negative pressure wound therapy combined with reconstructive surgery in order to reduce mortality and to avoid disfigurement. KEY WORDS: Amphotericin B, Apex syndrome, Forehead flap, Instill NPWT, Myeloaplasia Mucormycosis.

Detection of circulating tumor cells in patients with laryngeal cancer using ScreenCell: Comparative pre- and post-operative analysis and association with prognosis.

The presence of circulating tumor cells (CTCs) in the blood of patients with metastatic breast, colorectal and prostate cancer have been widely investigated; however, few studies have examined CTCs in patients with laryngeal cancer. The present pilot study aimed to detect pre- and postoperative CTCs in the blood of patients with laryngeal cancer and evaluate the association with prognosis. Eight patients with laryngeal squamous cell carcinoma (LSCC) at stage III were included in the present study and underwent total or subtotal laryngectomy and radical bilateral neck lymph node dissection. Blood samples were collected from all patients before and after surgery at different time-points. The following processing steps were followed; preoperative blood sampling, surgery, postoperative blood sampling at 3, 6 and 12 month follow-ups, and prognostic association analysis. CTCs were retained on ScreenCell filters for cytological characterization. The presence of CTCs was associated with a less favorable prognosis, whereas a decrease of CTCs in the postoperative sampling was observed in patients who exhibited an improved therapeutic response. The results of the present pilot study revealed a possible association between the presence of CTCs and a less favorable prognosis in patients with LSCC; therefore, these preliminary findings may encourage further research into the incorporation of a liquid biopsy in the management of LSCC, as this may help identify patients with occult metastatic disease earlier and in a non-invasive manner. In addition, this approach may represent novel independent prognostic factor for use in the clinical evaluation of patients with LSCC.

Volumetric analysis of cleft lip deformity using 3D stereophotogrammetry.

PURPOSE: To quantify and compare pre-operative and post-operative volumetric adjustments of the upper lip tissues in patients with cleft lip. METHODS: The authors performed an anthropometric study and a quantitative analysis of the differences based on three-dimensional morphology of the nasolabial area. Twenty facial images using the three-dimensional stereophotogrammetry were taken from ten selected subjects on two separate occasions, sitting in natural head position. Facial landmarks were marked and measurements recorded, in order to calculate the volumetric adjustments in the soft tissues of the upper lip, comparing the preoperative and postoperative results. Student test and p-Value were performed for statistical analysis. RESULTS: The analysis of the 3D images showed variability with the pre- and postoperative volumes of the nasolabial area with: an increase of upper lip volume all patients; a complete view of the severity in the preoperative; and an improvement of the appearance in the postoperative. The amount of increase of the upper lip volume was established about 29,7%. For all measurements, the variability between pre- and post-operative was significant (p < 0.01). CONCLUSION: The 3D stereophotogrammetry technique allows a detailed preoperative evaluation and an accurate assessment of the surgical outcomes. The study provides a value of volumetric variation of the upper lip in individuals with cleft lip. KEY WORDS: Cleft lip, Nasolabial area, 3D Morphological Analysis, 3D Stereophotogrammetry, Upper lip volume.

Lay People Esthetic Evaluation of Primary Surgical Repair on Three-Dimensional Images of Cleft Lip and Palate Patients.

Background and Objectives: Previous literature has disclosed that facial attractiveness affects the esthetic evaluation of nose and lip deformity on frontal and lateral photographs. However, it has never been debated if the removal of the external facial features on three-dimensional (3D) models ("cropped assessment bias") could provide a considerable usefulness in the interpretation and comparison of the results. Additionally, it has been assumed on two-dimensional (2D) studies that esthetic assessment biases with respect to observer gender, and it is not acknowledged if and to the extent that "gender assessment bias" may be influenced by a three-dimensional layout. The aim of this study is to investigate if facial traits and observers' gender may affect the esthetic ratings of unilateral cleft lip and palate (UCLP) patients after soft tissue reconstruction. Materials and Methods: Three-dimensional images of ten UCLP patients' images were acquired before the intervention (T0), one-month (T1) and six-months (T2) postoperative. Geomagic® software (version 2014; 3D Systems, Rock Hill, SC, USA) was used to remove the external facial features of 3D surface models. Five-point scale developed by Asher-McDade et al. was used to rate both nasolabial attractiveness and impairment for full-face (FF) and cropped-face (CF) 3D images. Forty-three judges (21 males, 22 females) were enrolled for the esthetic evaluation. Intraclass correlation coefficient (ICC) was used to test intra- and inter-examiner reliability; a value of 0.7 was set as the minimum acceptable level of reliability. Results: When comparing the 2 sets of observations (FF and CF), the ICC ranged from 0.654 to 0.823. Concerning gender assessment bias, the ICC ranged from 0.438 to 0.686 and from 0.722 to 0.788 for males and females, respectively. Concerning inter-examiner reliability, ICC for questions 2-7 ranged from 0.448 to 0.644 and from 0.659 to 0.817 at T0 and T2, respectively. Conclusions: The removal of external facial features provides subtle differences on the esthetic assessment of UCLP patients. Moreover, based on our data, examiners' gender differences may affect esthetic assessment of UCLP patients. Despite the subjectivity of esthetic judgments, a reliable, validated and reproducible scoring protocol should consider the influence of gender differences on 3D esthetic assessment of UCLP patients.

How to eliminate bilateral cleft lip stigmata 30 year experience.

PURPOSE: To report a surgical algorithm for the treatment of bilateral cleft lip stigmata. METHODS: The investigators designs a retrospective study composed of patients with bilateral cleft lip stigmata. The surgical approach is on the basis of the severity of the deformity and of course the age of the patient. It consists in Simple scar revision with orbicularis muscle synthesis; Two dermal flaps tunneled in the central vermilion; Abbe flap. The investigators analyzes early and late complications, and performs the evaluation of the cosmetic appearance by a parent or patient himself/herself, a surgeon and a blinded third party observer. RESULTS: The sample was composed of 351 patients. At short-term follow-up, viability of the flaps, function and morphology are good. At long-term follow-up, we observed significant improvement of the characteristics and profile of the patient's face and a normal function of the lips. We recorded a good scarring and a high satisfaction rate by evaluation of patients/ surgeon/ blinded third party observer. CONCLUSION: The results of this study suggest that a surgical algorithm on the basis of the severity of the deformity and of course the age of the patient can represent an option of choice for most patients with bilateral cleft lip stigmata. KEY WORDS: Abbe flap, Bilateral cleft lip stigmata, Cleft lip, Dermal flaps, Orbicularis muscles.

Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease.

Hypertrophic pachymeningitis (HP) is a rare disorder that causes thickening of the dura mater. Inflammatory lesions may be located in the cerebral or spinal dura mater or, less frequently, in both locations simultaneously. Numerous clinico-pathological entities cause thickening of the pachymeninges. Indeed, HP is a potential manifestation of many different diseases, but the diagnosis often remains uncertain. Cases in which the pachymeningitis has no known aetiology are termed "idiopathic" HP (IHP). Recently, it has been suggested that IgG4-related disease represents a subset of cases previously diagnosed as idiopathic hypertrophic pachymeningitis. Little is known regarding the pathogenic events of IHP. In a general theory, the inflammatory infiltrate, mainly consisting of B and T lymphocytes, activates fibroblasts and induces collagen deposition, leading to tissue hypertrophy and increased dural thickness. Clinical manifestations of IHP depend upon the location of the inflammatory lesions and compression of the adjacent nervous structures. Three central pathological features are lymphoplasmacytic infiltration, obliterative phlebitis, and storiform fibrosis. MRI is the examination of choice for the preliminary diagnosis of IHP. Histopathological examination of a biopsy specimen of the dura mater would finally confirm the diagnosis. The differential diagnosis for HP is broad and includes infections, autoimmune disorders, and neoplasia. Currently, there is no consensus about treatment for patients with IHP. There is a preference for glucocorticoid treatment on diagnosis followed by the addition of other immunosuppressive agents in the event of a recurrence. Rituximab is used in patients who did not respond to glucocorticoids or to conventional steroid-sparing agents.

Glaucoma: recent advances in the involvement of autoimmunity.

Glaucomatous optic neuropathy is the most commonly acquired optic neuropathy encountered in clinical practice. It is the second leading cause of blindness globally, after cataracts, but it presents a greater public health challenge than cataracts, because the blindness it causes is irreversible. It has pathogenesis still largely unknown and no established cure. Alterations in serum antibody profiles, upregulation, and downregulation have been described, but it still remains elusive if the autoantibodies seen in glaucoma are an epiphenomenon or causative. Hypertension, diabetes, and hearing disorders also are associated. This review is a glaucoma update with focus about the recent advances in the last 15 years.

Parkinson's disease: Autoimmunity and neuroinflammation.

Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and warrant further investigation.

Emerging Concepts in Glaucoma and Review of the Literature.

Glaucoma is the most commonly acquired optic neuropathy. It represents a public health challenge because it causes an irreversible blindness. Emerging evidence indicates that the pathogenesis of glaucoma depends on several interacting pathogenetic mechanisms, which include mechanical effects by an increased intraocular pressure, decreased neutrophine-supply, hypoxia, excitotoxicity, oxidative stress, and the involvement of autoimmune processes. In particular, alterations in serum antibody profiles have been described. However, it is still unclear whether the autoantibodies seen in glaucoma are an epiphenomenon or causative. Oxidative stress appears to be a critical factor in the neurodestructive consequences of mitochondrial dysfunction, glial activation response, and uncontrolled activity of the immune system during glaucomatous neurodegeneration. In addition, hearing loss has been identified in association with glaucoma. A higher prevalence of antiphosphatidylserine antibodies of the immunoglobulin G class was seen in normal-tension glaucoma patients with hearing loss in comparison with normal-tension glaucoma patients with normacusis. This finding suggests a similar pathological pathway as a sign for generalized disease.

Cancer stem cells in laryngeal cancer: what we know.

Cancer stem cells (CSCs) are a group of cells with eternal life or infinite self-renewal ability, which have high migrating, infiltrative, and metastatic abilities. Though CSCs only account for a small proportion in tumors, the high resistance to traditional therapy exempts them from therapy killing and thus they can reconstruct tumors. Previous studies found that heterogeneity of cancer cells extensively exists in head and neck cancers. Our current knowledge, about CSCs in the laryngeal cancer (LC), largely depends on head and neck studies. Given the lack of systematic data about CSCs in LC, we propose a review of the literature, reporting the evidences of CSCs in tumorigenesis of LC, with the purpose to provide new insights into the prevention and/or treatment of laryngeal carcinoma.

The prognostic role of E-cadherin and ß-catenin overexpression in laryngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Epithelial-to-mesenchymal transition (EMT) consists of a rapid and reversible change in the cellular phenotype toward the mesenchymal cell phenotype that facilitates cell migration and invasion of the tumor into surrounding tissues followed by metastasis. In the present study, we sought to determine the clinical significance of E-cadherin, N-cadherin, ß-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin in a cohort of patients with stage I to IVA laryngeal squamous cell carcinoma (LSCC) treated with surgery with or without adjuvant therapy using immunohistochemical analyses. STUDY DESIGN: Individual retrospective cohort study. METHODS: E-cadherin, N-cadherin, ß-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated in a cohort of 82 patients with stages I to IVA LSCC. The Fisher exact test was used for categorical variables, and the Mann-Whitney test where appropriate for continuous variables. Survival comparisons was performed using the log-rank test. A multivariate analysis using the Cox proportional hazards model was performed and considered all EMT markers. RESULTS: In multivariate analysis, T stage was an independent risk factor for adverse disease-specific survival (DSS) and overall survival (OS) (P = .025 and .019, respectively). Cytoplasmic ß-catenin overexpression was independently associated with a longer DSS (P = .0007), and E-cadherin overexpression was found to be an independent risk factor for poor OS (P = .030). CONCLUSIONS: E-cadherin and ß-catenin pathways could represent future therapeutic targets in the treatment of LSCC. However, validation of our results in prospective cohorts of patients with LSCCs is required before their clinical implementation. LEVEL OF EVIDENCE: NA.

Autoimmune epilepsy.

Despite the fact that epilepsy is the third most common chronic brain disorder, relatively little is known about the processes leading to the generation of seizures. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Besides, recent studies show that epilepsy and autoimmune disease frequently co-occur. Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid and responsiveness to immunotherapy. An autoimmune cause is suspected based on frequent or medically intractable seizures and the presence of at least one neural antibody, inflammatory changes indicated in serum or spinal fluid or on MRI, or a personal or family history of autoimmunity. It is essential that an autoimmune etiology be considered in the initial differential diagnosis of new onset epilepsy, because early immunotherapy assures an optimal outcome for the patient.

Microscopic polyangiitis: Advances in diagnostic and therapeutic approaches.

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies.

Kawasaki disease: an evolving paradigm.

Kawasaki disease (KD) is a self-limited childhood systemic vasculitis that exhibits a specific predilection for the coronary arteries. KD predominantly affects young children between the ages of 6months and 4years. Incidence rates in Asians are up to 20 times higher than Caucasians. The aetiology of KD is not known. One reasonable open hypothesis is that KD is caused by an infectious agent that produces an autoimmune disease only in genetically predisposed individuals. The typical presentation of KD is a young child who has exhibited a high swinging fever for five or more days that persists despite antibiotic and/or antipyretic treatment. The lips are dry and cracked. There is a characteristic strawberry tongue, and a diffuse erythema of oropharyngeal mucosal surfaces. Lymphadenopathy is usually unilateral and confined to the anterior cervical triangle. Coronary aneurysms generally appear during the convalescence phase (beginning during the second week). The absence of any laboratory tests for KD means that the diagnosis is made by the presence of a constellation of clinical features. The aim of echocardiography is to assess the presence of coronary artery dilatation or aneurysm formation. Effective therapies exist for most patients with acute KD, but the exact mechanisms of action are not clear. Treatment with aspirin and intravenous immunoglobulins (IVIG) are first-line therapies. However, options are plentiful for the children who fail this treatment, but these treatments are not as beneficial. Some centres attempt to salvage resistant patients using intravenous pulsed doses of methylprednisolone. Other centres use infliximab or combinations of these approaches.

Goodpasture's syndrome: a clinical update.

Goodpasture's syndrome (GS) is a rare and organ-specific autoimmune disease that is mediated by anti-glomerular basement membrane (anti-GBM) antibodies and has pathology characterized by crescentic glomerulonephritis with linear immunofluorescent staining for IgG on the GBM. It typically presents as acute renal failure caused by a rapidly progressive glomerulonephritis, accompanied by pulmonary hemorrhage that may be life-threatening. It was first described as a distinctive syndrome by Pasture in 1919. Autoimmune Inner Ear Disease (AIED) may be associated. The etiology of GS is unknown. Researchers hypothesized a genetic predisposition HLA-associated. Complex immunological mechanisms are in the pathogenesis. The disease is caused by autoantibodies against the NC1 domain of the alpha 3 chain of type IV collagen. The limited presence of this molecule in the body explains the interest confined to specific target organs, such as the lung and kidney. It occurs when the immune system attacks the walls of the lungs and the tiny filtering units in the kidneys. Without prompt diagnosis and treatment, the disease can lead to bleeding in the lungs, kidney failure, and even death.