Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Conventional progesterone receptors (PR) B and PRA are expressed by human chondrocytes and can be involved in the pathogenesis of osteoarthritis.

To evaluate the expression, location and role of progesterone receptors (PRs) A and B in human chondrocytic cell lines, Western blotting, real time PCR analyses, transmission electron microscopy and immunogold assays were performed. By transfection and co-transfection assays, the influence of progesterone (OHPg) on estrogen receptor alpha (ERα) promoter activity was investigated. MTT and pAKT documented OHPg effects on chondrocytes survival. The PR-B and PR-A were both observed in human chondrocytes. The PR-B was evidenced both in the nucleus and in the cytosol of the cells. OHPg, through PR-B, induced ERα expression by acting at the ER promoter level affecting chondrocytes survival. We reported for the first time the expression of PRs in human chondrocytes. Interestingly, we described a novel mechanism via progesterone induction of ERα, which may explain, at least in part, the dramatic rise in OA prevalence among postmenopausal women.

Custom made onlay implants in peek in maxillofacial surgery: a volumetric study.

PURPOSE: Facially malformed patients often present a variable degree of facial imbalance even after basal bone correction, and resolution of the residual hard- and soft-tissue deficiencies and asymmetries of the face are of great importance for achieving a satisfactory post-implant procedure result. The use of polyether ether ketone (PEEK) implants for maxillofacial reconstruction has been documented in the literature, but the number of patients who have received them is limited. The aim of this study was to evaluate the overall volumetric results in patients with facial imbalance after onlay custom implant positioning for mandible and fronto-orbital reconstructions. Analysis was performed by confronting volumes with the use of three-dimensional (3D) photogrammetry. METHODS: Fifteen patients were eligible for PEEK implant placements, eight for mandibular angle reconstruction, and seven for fronto-orbital reconstruction. Pre- and post-surgical 3D images of each patient's face were acquired. Facial asymmetry was analyzed by comparing each face with its mirrored copy. RESULTS: Three-dimensional analyses have shown that some degree of volume imbalance was still present in the patients with only 1.32 ± 1.02 mm residual discrepancy after treatment. CONCLUSION: Results of the study were found to fall within clinically acceptable limits since an asymmetry rate of < 3 mm is considered to fall into the norm.

Tantalum monoblock cups in total hip arthroplasty: clinical results and outcome predictors.

This study aims to report the minimum 2-year follow-up results of the tantalum monoblock cup in primary THA and to identify possible outcome predictors. Eighty-eight porous tantalum monoblock acetabular cup in primary THA were reviewed. The Harris Hip Score (HHS) and the Short Form-36 Health Survey (SF-36) were used for the evaluation of outcomes. Radiographic evaluation included acetabular component orientation, presence of bone gaps, radiolucent lines, new bone formation and heterotopic ossifications. After a mean follow-up of 55.4±19.5 months, no component revision was noted. The HHS improved from 43.6±14.6 to 88.3±8.4 (P less than 0.001). The mean physical domain of the SF-36 did not significantly differ from that of age-matched, healthy subjects (P=0.072); the mean mental component of the SF-36 was significantly higher than that of age-matched, healthy subjects (P less than 0.001). Negative determinants of postoperative HHS (total adjusted R2=0.328) using tantalum monoblock cups were age at surgery (R2=0.164, P less than 0.001), female sex (R2=0.103, P less than 0.001), and acetabular inclination (R2=0.084, P equals 0.003).

Reinfusion-drains reduce blood transfusions in total joint arthroplasty.

This study aims to evaluate the effect of postoperative blood recovery with reinfusion drains on hematologic parameters and blood transfusion rate in patients undergoing total joint arthroplasty. Three-hundred-and-forty-four patient records were reviewed and 271 patients were included in the study; 56.8% of patients were treated with postoperative cell salvage procedure using reinfusion drains (PCS) and 43.2% had closed-suction drain (CSD) postoperatively. In comparison to the CSD group, the PCS group showed higher hemoglobin (Hb) levels on the first and second days postoperatively but no statistical differences were noted at the day of discharge. 75.2% and 37.7% of patients required blood transfusions in the CSD and PCS groups, respectively. The PCS group had a lower number of blood transfusions than the CSD group. At multivariate analysis, Hb loss rate was related to preoperative Hb values, total amount of drained blood and chronic antiplatelet therapy. The number of blood transfusions was related to preoperative Hb values, closed-suction drains, preoperative platelet count, TKA surgery and BMI. This study supports the use of PCS with reinfusion drains after THA and TKA at least for the short-term.

C3f is a potential tool for the staging of osteoarthritis.

An attractive method for osteoarthritis (OA) staging is the measurement of biochemical markers in biological fluids, which could reflect dynamic and quantitative changes in joint remodeling and therefore disease progression. Proteome analysis has been recognized as one of the most effective tools to explore biomarkers as it can furnish a wealth of information in both diagnosis and prognosis of diseases. We have recently described an innovative tool for peptidome and lipidome profiling of fluids based on mesoporous aluminosilicate (MPAS) and Matrix-Assisted Laser Desorption/Ionization time-of-flight Mass Spectrometry (MALDI-TOF MS). The aim of this study was to analyze peptide profiles of human synovial fluid in patients with different grade of OA using MALDI-TOF-MS technique in order to identify potential markers of disease progression. Twenty-five patients older than 50 years and affected by primary knee OA diagnosed according to clinical and radiological criteria were enrolled. For each patient a synovial fluid sample was aspirated from the affected knee and analyzed using MALDI-TOF-MS technique. A statistically significant difference in the normalized area of two peaks (m/z=1865 and m/z=2021) was detected among different stages of OA. The 2 peaks were identified as Complement C3 peptide fragments: C3f and C3f Des-Arg. The expression levels of these two peptides (m/z=1865 and 2021) decreased with the progression of OA degrees severity (ρs=-0.434, p=0.03, and ρs=-0.532, p=0.006, respectively). This marker may be a useful tool for assessing the severity of knee OA and it may be a novel target for drug discovery, specifically for the development of disease modifying OA drugs. However further studies are required to clarify the role of C3f in OA pathogenesis.

Progression-free survival as surrogate end point for overall survival in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer.

BACKGROUND: The gold standard end point in randomized clinical trials in metastatic breast cancer (MBC) is overall survival (OS). Although therapeutics have been approved based on progression-free survival (PFS), its use as a primary end point is controversial. We aimed to assess to what extent PFS may be used as a surrogate for OS in randomized trials of anti-HER2 agents in HER2+ MBC. METHODS: Eligible trials accrued HER2+ MBC patients in 1992-2008. A correlation approach was used: at the individual level, to estimate the association between investigator-assessed PFS and OS using a bivariate model and at the trial level, to estimate the association between treatment effects on PFS and OS. Correlation values close to 1.0 would indicate strong surrogacy. RESULTS: We identified 2545 eligible patients in 13 randomized trials testing trastuzumab or lapatinib. We collected individual patient data from 1963 patients and retained 1839 patients from 9 trials for analysis (7 first-line trials). During follow-up, 1072 deaths and 1462 progression or deaths occurred. The median survival time was 22 months [95% confidence interval (CI) 21-23 months] and the median PFS was 5.7 months (95% CI 5.5-6.1 months). At the individual level, the Spearman correlation was equal to ρ = 0.67 (95% CI 0.66-0.67) corresponding to a squared correlation value of 0.45. At the trial level, the squared correlation between treatment effects (log hazard ratios) on PFS and OS was provided by R(2) = 0.51 (95% CI 0.22-0.81). CONCLUSIONS: In trials of HER2-targeted agents in HER2+ MBC, PFS moderately correlates with OS at the individual level and treatment effects on PFS correlate moderately with those on overall mortality, providing only modest support for considering PFS as a surrogate. PFS does not completely substitute for OS in this setting.

PTEN ELEVATION, AUTOPHAGY AND METABOLIC REPROGRAMMING MAY BE INDUCED IN HUMAN CHONDROCYTES DURING STEROIDS OR NUTRIENT DEPLETION AND OSTEOARTHRITIS.

The exact mechanisms controlling the development and progression of osteoarthritis have not yet been clarified. Our aim was to investigate new pathomechanisms, with an emphasis on novel molecular targets that might regulate human chondrocytes in osteoarthritis. As a model for studying cell survival and metabolism, C-28/I2 and T/C-28a4 human chondrocytes were grown in complete medium, in dex-tran-coated charcoal treated medium and in serum-free medium. Healthy and osteoarthritic human cartilage samples were obtained from discarded surgical material. Cell survival, PTEN, AKT, Beclin1, AMBRA, AMPK and glucose/triglyceride metabolism were evaluated by immunoblotting and spectro-photometric assays. Starvation and steroids depletion decreased cell survival concomitantly with PTEN elevation, repression of the PI3K/AKT signaling axis and autophagy activation. These experimental conditions promoted the accumulation of glucose, decreased levels of G6PDH and resulted in differen-tial expression of OXPHOS complexes. Furthermore, they induced the expression of AMPK, reduced triglyceride levels and increased lipase activity, which was accompanied by a change in chondrocytes toward a fibroblast-like morphology. In osteoarthritic human cartilage, increased PTEN, AMPK and autophagy reflected the chondrocyte responses observed during starvation and steroids depletion. In conclusion, we defined the metabolic phenotype of human chondrocytes, in which both starvation and steroids depletion induce the activation of PTEN, AMPK and autophagy signaling, concomitant with metabolic reprogramming. Our data may aid in the development of novel in vitro models for the discovery and design of drugs or nutraceuticals capable of ameliorating the course of osteoarthritis.

Dermatological consultations in an observation unit of an emergency department in Italy.

BACKGROUND: Dermatological emergencies exist and should not be underestimated. On the other hand, many accesses to the emergency department (ED) of patients with dermatological conditions are unjustified. OBJECTIVE: Our main objective is to describe dermatological conditions seen in an ED observation unit (EDOU). Secondly, our aim is to identify alarm symptoms and signs of 'true emergencies'. METHODS: We conducted a prospective study, including dermatological patients admitted to EDOU of the University Hospital of San Martino, Genoa, Italy, in 3 years. RESULTS: Overall 372 patients were studied. The most common condition seen was infection (41.67%) (mainly bacterial), followed by atypical exanthem (13.98%) and vasculitis (11.29%). The highest rate of cases peaked in May (13%); infectious diseases showed two peaks (spring and autumn). CONCLUSION: Given constraints involved in health care today, it is crucial to understand which dermatological presentations are 'true emergencies'. In such a scenario knowing the epidemiology of dermatological emergencies and the alarming skin signs and symptoms might be useful.

Vasculitis associated with connective tissue diseases.

Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

Trismus-pseudocamptodactyly syndrome: a 20 year follow-up.

BACKGROUND: Trismus-Pseudocamptodactyly Syndrome (TPS) is a rare autosomal syndrome characterised by the inability to open the mouth fully, pseudocamptodactyly, short stature and foot deformities. The maxillofacial feature entails hyperplasia of the coronoid processes which mechanically interfere with the zygomatic processes during mouth opening. CASE REPORT: A 22-year- old girl affected by a severe form of TPS was followed from the age of three years. Bone reossification was observed after two coronoidotomies of both hyperplasic coronoid processes. After the decision to perform a coronoidectomy, the four-year follow-up showed a favourable outcome. Meanwhile the patient developed an anterior open bite which was treated with a fourth orthognathic surgery. The follow-up underscores how the correction of malformation leads to the generation of EMG activity of the masticatory muscles after many years of passiveness.

Pyoderma gangrenosum: a systematic review.

Pyoderma gangrenosum (PG) is a rare, chronic neutrophilic dermatosis of unknown etiology. The world wide incidence is estimated to be around 3-10 cases per million population per year. In 50-70% of cases inflammatory bowel diseases, hematological malignancies or rheumatologic disorders are associated to PG. Although the etiology is uncertain, the dysregulation of the immune system appears to be implied. Pathergy is the most important triggering factor of PG. Indeed, 20-30% of patients report the onset of PG following trivial trauma. Four main variants of PG have been described, namely classic, pustular, bullous, and vegetative forms. The classic form of PG is characterized by ulcers with a raised, undermined, inflammatory border. Intense pain is generally associated to PG. The diagnosis is mainly clinical and of exclusion. The differential diagnosis should take into account infections, vascular disorders and malignancies. The clinical course can be explosive and rapidly progressive or indolent and gradually progressive. Often patients develop only one episode and the overall prognosis is good but extremely influenced by the underlying disorders. Local therapy, mainly with topic steroids is used for mild to moderate lesions. For severe forms of PG a systemic therapy with glucocorticoids and/or other drugs such as tacrolimus, cyclosporine, etc. is needed. This paper is a systematic review of literature on PG.

The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial.

OBJECTIVE: We investigated the effects of celecoxib, diclofenac, and ibuprofen on the disease-specific quality of life, synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis (OA). DESIGN: Ninety patients scheduled for a total knee arthroplasty (TKA) were randomized to six groups that were treated with low and high dosages of celecoxib, diclofenac or ibuprofen. At the time of the first admission (T0) and at surgery (T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs (NSAIDs)), samples of knee synovial fluid were obtained from each patient for analysis. During the surgery the synovial tissue was harvested from the knee of patients. The Western Ontario and McMaster universities (WOMAC) score was used to evaluate the patient disease-specific quality of life at T0 and T1. Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)-alpha, Interleukin-6 (IL-6), IL8 and Vascular endothelial growth factor (VEGF) concentration in the synovial fluid. Western blot assays evaluated the effects of NSAIDs on MAP kinase (MAPK) signal transduction pathway in the synovial membrane. RESULTS: NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6, VEGF and TNF-alpha concentration in the synovial fluid. Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid. Inhibition of MAPKs was noted after NSAID treatment. CONCLUSION: Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA. Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs. ClinicalTrial.gov: NCT01860833.

OSAS treatment with oral appliance: assessment of our experience through the use of a new device.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is defined as repeated episodes of obstruction of the upper airway and oxygen desaturation of the arterial hemoglobin. OSAS is associated with loud snoring, excessive daytime sleepiness, cardiovascular and neurocognitive disease, increase risk of road accidents. AIM: The aim of this study is to evaluate non-surgical therapy for OSAS using a mandibular advancement device (MAD) that provides for lower jaw protrusion and for an adequate vertical opening, that allows for greater airflow. MATERIALS AND METHODS: The device was assembled using the working principles of "Herbst-like" appliances and splints of neuromuscular deprogramming of the "Federici" type used for gnathologic treatments. We selected 17 males and 4 females, with an average age of 42 years, and an average BMI of 29. Eighteen patients were treated with our oral appliance, 1 patient was treated with the orthesis proposed by Schmidt-Nowara et al and 2 patients were treated with the oral appliance proposed by Johal and Battagel. All patients used the appliance for at least 6 months. RESULTS: After treatment with the oral appliance, the posterior airway space increased (p = 0.0002); no statistically significant difference for the improvement degree of OSAS severity (p = 0.1085) was shown; an improvement was found in: AHI (p = 0.0028); Nadir O2 (p = 0.0035); TO2 < 90% (p = 0.0140); 2 patients presented with temporomandibular joint (TMJ) discomfort. CONCLUSIONS: Our MAD has proved effective in improving the polysomnographic and radiographic parameters and assures good TMJ compliance.

Reconstruction of severe atrophic jaws with Fresh Frized Bone Allografts: clinical histologic and histomorphometric evaluation.

OBJECTIVES: Rehabilitation of maxillary edentulism with implant-supported prostheses has come into common clinical practice. Although autologous bone has osteoinductive, osteoconductive and osteogenetic properties, its use is subject to certain disadvantages such as: Increased morbidity Limited amount of bone harvested from each donor site. AIM: The aim of this study is to analyze clinical, histological and histomorphometric results of homologous bone for implantoprosthetic rehabilitation in severe atrophic jaws. PATIENTS AND METHODS: Twenty consecutive patients, 14 female and 6 males, were treated with homologous bone bank. Treatment protocol consist of: first surgycal step, trasversal and vertical volume restore, second surgycal step: screw remove, specimen biopsy and insert implant fixtures. RESULTS: Data show that Fresh Frozen Bone Allografts (FFBA) could be a valuable substitute for autologous bone, in as much as histological and histomorphometric results are widely overlapping. CONCLUSIONS: Homologous bone is a valuable option for its large availability with a low cost, good versatility, no morbidity at the donor site, shorter surgical time and hospital stay.