Ultrasound as a diagnostic tool for femoral head containment disorders in children between one and 12 years of age.

PURPOSE: Ultrasound has been used to diagnose hip dysplasia in neonates and to screen until the end of their first year. For older children, femoral head containment disorders such as developmental dysplasia of the hip, Legg-Calvé-Perthes disease or cerebral palsy are usually diagnosed with plain radiographs. The aim of the present study was to evaluate ultrasound in comparison with radiographic imaging in children up to age 12 years and to determine reference values for sonographic containment parameters. METHODS: Hip ultrasound and radiographic imaging were acquired on the same day and then compared. As a reference, normal acetabular angle and acetabulum head index were determined on radiographs. Lateral cartilage distance (LCD), lateral head distance (LHD) and femoral head extrusion angle (HA) were measured on ultrasound images. RESULTS: We included 96 patients with 167 healthy hips in the study. A total of 55 patients were female and 41 male. The mean age was 5.2 years (sd 3.3; 1.0 to 11.9). LCDultrasound, LHDultrasound and HAultrasound correlated significantly with radiographic parameters. The following ultrasound values were calculated as limits for impending loss of containment: LCDultrasound ≥ 6.5 mm, LHDultrasound ≥ 3.3 mm and HAultrasound ≥ 27.6°. CONCLUSION: Ultrasound is a simple, radiation-free diagnostic tool to detect femoral head containment disorders, even in children older than one year. This study provides reference values for hip ultrasound in children up to 12 years. LEVEL OF EVIDENCE: III.

Recurrence types 3 years after endovenous thermal ablation in insufficient saphenofemoral junctions.

OBJECTIVE: Although many studies have demonstrated that endovenous therapies have comparable efficacy to crossectomy and stripping, few studies have been published regarding the classification and recurrence patterns of varicose veins after endovenous therapy. This study attempted to provide an objective scheme for the definition and classification of recurrence. Moreover, it describes the types and rates of recurrence after endovenous thermal ablation, as well as factors associated with recurrence. METHODS: This prospective cohort study comprised a cohort of 449 patients with saphenofemoral junction (SFJ) insufficiency who underwent endoluminal varicose vein treatment for the first time in the limb between October 2013 and January 2015. The treatments were performed by a team of three experienced phlebologists. For endovenous laser ablation, Biolitec ELVeS was used with bare, radial or radial slim fibers. Radiofrequency ablation was performed with VNUS ClosureFAST (Medtronic, Deggendorf, Germany). The patients were consecutively scheduled for 3-year follow-up examinations. Detailed ultrasound findings were collected by two experienced phlebologists who classified the observed duplex ultrasound recurrence into different recurrence types. RESULTS: Clinically relevant recurrence was found in only 5.1% of cases. Examining only the recanalizations requiring reintervention resulted in a recurrence rate of 2.6%. However, if every new varicose vein that occurred postoperatively was considered a recurrence, the resultant recurrence rate was almost 54%. Preliminarily, we defined a recurrence as newly developed varicose veins within the region of the SFJ or along the course of the former treated vein distal to the SFJ. According to this definition, we obtained a clinically relevant recurrence rate of 5.3%, thus indicating that neovascular vessels were the largest recurrence type (57.7% within the region of the SFJ and 9.9% distal to the SFJ), followed by recanalization (8.9% within the region of the SFJ and 9.4% distal to the SFJ) and a refluxing anterior accessory saphenous vein (7.5%). We also developed a modified classification of progression to better understand recurrence after treatment of chronic venous insufficiency; the scheme included method failure (recanalization), neovascularizations, and disease progression (refluxing untreated vessels and new varicose veins occurring outside the treated region). The diameter of the treated vein (P = .001) and the clinical class according to CEAP classification (P = .008) were significant predictors of recurrence. CONCLUSIONS: Endoluminal therapies are efficient methods for the treatment of varicose veins, which result in low recurrence rates after 3 years. Several factors influence the development of recurrence. This study provides a practice-oriented classification and description of recurrence with clinical relevance, through making distinctions among technical error, progression of the underlying disease and actual recurrence.

Practice Patterns for Prophylaxis and Treatment of Venous Thromboembolism in German Cancer Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious threat for cancer patients. Guidelines recommend low-molecular-weight heparin (LMWH) for prophylaxis and treatment, but it is unknown to what extent specialists adhere to these recommendations. This survey assesses the current approach to patients with cancer-associated VTE in Germany. MATERIALS AND METHODS: A questionnaire was sent out to members of the DGHO (Deutsche Gesellschaft für Hämatologie und Onkologie), the BNHO (Berufsverband Niedergelassener Hämatologen und Onkologen) and the DGP (Deutsche Gesellschaft für Phlebologie). For most questions, more than 1 answer was possible; therefore, the total sum of percentages may exceed 100%. RESULTS: 275 specialists responded. 76% of them treat acute VTE with LMWH while 22% switch to oral treatments (vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs)) during the acute phase. For the next 3-6 months, 55% of the specialists continue LMWH, while 31% switch to VKAs and 33% to NOACs. Among those who continue LMWH for 3-6 months, 37% continue at the full dose, 26% reduce to 75% of the initial dose, and 40% even to 50%. Important factors guiding treatment decisions were the need for injections and the availability of a partner/spouse (LMWH), the need for laboratory controls (VKAs), and the number of other oral medications (NOACs). CONCLUSION: This survey reveals that practice patterns often do not follow the guideline recommendations with respect to the use of LMWH for long-term treatment of VTE in cancer patients.

Decorin expression with stump recurrence and neovascularization after varicose vein surgery--a pilot study.

BACKGROUND: An evaluation of the reason for saphenofemoral recurrence (SFR, technical error vs neovascularization) after surgery is necessary to improve the method or find purchase for new therapies. Currently, differentiation by the surgeon or ultrasound are unsatisfying; histology depends mainly on the physician's experience. Decorin, an extracellular matrix component, is up-regulated in angiogenesis with antiangiogenetic effects on neovascularization. OBJECTIVE: To determine whether decorin is a reliable marker to distinguish neovascularization and stump recurrence. METHODS: Twenty specimens obtained in re-operation of patients with duplex-detected SFR were stained with hematoxylin and eosin, Elastica van Gieson, and decorin antibody. An experienced pathologist reviewed specimens for stump recurrence or neovascularization. An independent physician analyzed the specimens semiquantitatively for expression of decorin (0=none to 3=strong). RESULTS: Only low expression of decorin was found around residual stumps (1.4±0.5), but extensive expression was detectable around neovascularization (2.4±0.3, p=.001). In one specimen with neovascularization and a residual stump, decorin was a capable marker to divide the two zones. Correlation of histological and decorin-based diagnosis was 100%, but differentiation was much easier with decorin. CONCLUSION: Decorin is a marker for any easy differentiation of stump recurrence and neovascularization and can support further investigation in SFR and improvement of the primary therapy.

Immunohistochemical expression patterns of the microRNA-processing enzyme Dicer in cutaneous malignant melanomas, benign melanocytic nevi and dysplastic melanocytic nevi.

Dicer is an essential cytosolic enzyme necessary for processing pre-microRNAs into mature microRNAs (miRNAs). Although a variety of malignancies have been attributed to perturbations in the miRNA machinery, there has been little research conducted on the role of miRNAs in cutaneous malignant melanoma and its premalignant lesions. In this small pilot study, we therefore investigated the distribution of Dicer by immunohistochemistry in cutaneous malignant melanomas, as well as in benign and dysplastic melanocytic nevi. Dicer was assessed in ten cutaneous malignant melanomas (CMM), benign melanocytic nevi (BMN), and dysplastic melanocytic nevi (DMN), by standard immunohistochemical staining. Semiquantitative analyses determined expression indices (EIs), which associate the conventional area fraction of labeled cells with immunostaining intensity scores, based on visual qualitative examination by two independent observers. Mean EI scores were significantly higher in the CMM group compared to those in the BMN group (p < 0.05). However, EI differences between BMN and DMN as well as between CMM and DMN were not significant (p > 0.05). For CMM we observed a significant correlation of Breslow tumor thickness and Dicer EI (r â€Š=  0.84, p â€Š=  0.022). For all three groups investigated, Dicer-positive staining was primarily located in the epidermis, specifically in melanocytes. By immunohistochemistry, Dicer staining was significantly higher in melanoma cells than in benign melanocytes. This preliminary study indicates that alterations in the miRNA machinery could exist and should be subject of further investigation.

Upregulation of cathepsin S in psoriatic keratinocytes.

Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human/mouse skin. In normal human skin CATS-immunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T- and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased in the dermis. But only in psoriasis, CATS-immunostaining is also detectable in keratinocytes. We show that cocultivation with T-cells as well as treatment with cytokines can trigger expression and secretion of CATS, which is involved in MHC II processing in keratinocytes. Our data provide first evidence that CATS expression (i) is selectively induced in psoriatic keratinocytes, (ii) is triggered by T-cells and (iii) might be involved in keratinocytic MHC class II expression, the processing of the MHC class II-associated invariant chain and remodeling of the extracellular matrix. This paper expands our knowledge on the important role of keratinocytes in dermatological disease.

Histological and clinical findings in different surgical strategies for focal axillary hyperhidrosis.

INTRODUCTION: Although a variety of different surgical strategies for focal axillary hyperhidrosis (FAH) have proven effective, little is known of intraoperative and postoperative histologies of different surgical methods. OBJECTIVE: The objective was to use pre-, intra-, and postoperative histologic findings to evaluate different surgical procedures for FAH in establishing a possible correlation between the interventions and clinical outcome. MATERIAL AND METHODS: A total of 40 patients underwent surgery with 15 undergoing liposuction-curettage (LC), 14 radical skin excision (RSE) with Y-plasty closure, and 11 a skin-sparing technique (SST). Before surgery, density and ratio of eccrine and apocrine sweat glands were evaluated with routine histology. Further biopsies were taken directly after surgery in the RSE and SST groups and 1 year postoperatively in all patients. Additionally, gravimetry was performed, side effects were documented, and patients were asked to evaluate the aesthetic outcome of the surgical method by using an analogue scale. RESULTS: Preoperatively, the mean density of eccrine glands was 11.1/cm(2) compared to 16.9/cm(2) apocrine glands (apocrine/eccrine ratio, 1.6). Biopsy specimen directly after surgery showed remaining sweat glands in 7/15 (46.7%) LC patients and in 4/11 (36.4%) of the SST patients. One year after surgery, sweat gland density was significantly reduced in the LC (79.1%) and the SST (74.9%) groups. In the RSE group, only scar formation was present. Gravimetry showed significantly reduced sweat rates 12 months after surgery in all groups (LC, 66.4%; SST, 62.9%; RSE, 65.3% [p<.05]). Most frequent side effects were hematoma (LC, n=3; SST, n=2; RSE, n=3), subcutaneous fibrotic bridles (LC, n=8; SST, n=3; RSE, n=0), skin erosion (LC, n=3; SST, n=4; RSE, n=0), focal hair loss (LC, n=9; SST, n=11; RSE, n=14), and paresthesia (LC, n=4; SST, n=3; RSE, n=5). CONCLUSION: Histologic distribution and density of sweat glands were comparable to previous studies. All three surgical procedures evaluated are effective in the treatment of FAH. RSE and SST techniques are associated with a higher risk of side effects and cause more extensive scarring. However, one LC patient (n=1; 6.7%) did not respond to treatment.

Prevention of epidural scarring after microdiscectomy: a randomized clinical trial comparing gel and expanded polytetrafluoroethylene membrane.

A randomized clinical trial compared two materials used to prevent epidural scarring after microdiscectomy. To determine whether ADCON-L Gel (ALG) or Preclude Spinal Membrane (PSM) was more effective in preventing scarring, reducing pain, and improving quality of life postoperatively. Postdiscectomy syndrome may result from epidural scarring. Various materials have been used in attempts to prevent this problem, but none have provided optimal results. Previous laboratory and clinical studies have found ALG and PSM to be effective, but none compared the two materials. Thirty-one patients undergoing primary microdiscectomy were randomly assigned to receive either ALG or PSM. Postoperatively, patients were evaluated by magnetic resonance imaging (MRI), with contrast, for volume and rostral-caudal extent of scar tissue and nerve root involvement. Back and leg pain and quality of life were assessed by neurologic examinations and standardized patient surveys. Findings at any reoperations were recorded. Results in the PSM (n = 18) and ALG (n = 13) groups were compared statistically. No operative or postoperative complications occurred. Two patients in each group required reoperation. MRI at 6 months showed no, mild or mild-moderate scarring in most patients, with no significant differences between the ALG and PSM groups in scar volume and extent or nerve root involvement. Neurologic examinations and patient surveys showed substantial reductions in pain over time in both groups but no significant differences between groups. PSM was easy to see and remove at reoperation. PSM and ALG are equally effective in preventing epidural scarring associated with postdiscectomy syndrome.

Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma.

OBJECTIVE: To evaluate the efficacy of pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy in patients with severe localized scleroderma (LS). DESIGN: A prospective, nonrandomized, open pilot study. SETTING: Dermatology department at a university hospital in Bochum, Germany. Patients Fifteen patients with histologically confirmed severe LS. Interventions Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months. MAIN OUTCOME MEASURES: Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. RESULTS: One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean +/- SD clinical score from 10.9 +/- 5.3 at the beginning to 5.5 +/- 2.5 at the end of therapy was observed (P < .001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted. CONCLUSIONS: These data suggest that pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

Modulation of endothelial dysfunction and apoptosis: UVA1-mediated skin improvement in systemic sclerosis.

UVA1-mediated effects regarding vascular dysregulation as a primary pathogenetic factor of systemic sclerosis skin lesions have so far not been investigated. Pre- and posttherapy skin biopsies of four patients were evaluated immunohistochemically for angiostatic, angiogenic and angioapoptotic features. Immunohistochemistry revealed a partial pretherapy loss of endothelial CD31 and CD34 expression accompanied by a posttherapy increase of CD34(+) cells. Simultaneously, VEGF and M30 CytoDEATH immunolabeling demonstrated UVA1-induced neovascularization and decreased endothelial apoptosis. Our results suggest that UVA1 irradiation exerts its positive effects by a modulation of endothelial regulation/transformation beside the proposed induction of T cell apoptosis and collagenases.

Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: case report.

BACKGROUND: Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. CASE PRESENTATION: We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. CONCLUSIONS: Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

UVA1-induced decrease in dermal neuron-specific enolase (NSE) in acrosclerosis.

Besides its role in small-cell carcinoma of the lung, elevated serum levels of neuron-specific enolase (NSE) have recently been reported to be associated with autoimmune rheumatic disorders such as systemic sclerosis. Serum NSE seems to correlate with disease activity as well as Rodnan skin score. The aim of the study was to assess the neuromodulatory effects of conventional UVA1 phototherapy on acrosclerosis as an additional mechanism besides an assumed T cell apoptosis, collagenase induction and angiogenesis. Punch skin biopsies of acrosclerotic skin lesions taken before and after treatment from four patients were evaluated immunohistochemically for the presence of NSE, S100 and neurofilament. Immunolabeling revealed a UVA-induced decrease in dermal NSE expression. In contrast, no alteration in neurofilament+ cells could be detected. In line with the findings of a previous investigation, a high number of S100+ cells were detected in most specimens. We demonstrated a UVA1-induced reduction in dermal NSE levels correlating with a softening of former sclerotic lesions. Even though the origin and the functional mechanisms remain obscure, NSE might be relevant directly within sclerotic skin lesions and may possibly be used as a diagnostic marker at least in SSc-associated acrosclerotic skin.

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Monitoring of Containment in Perthes' Disease: Can Ultrasonography be Helpful?

Background. Prevention of loss of containment has become an accepted principle in the treatment of Perthes' disease. The pre-requisite is early recognition. It is based on evaluation of plain radiographs and more recently, on the study of Magnetic Resonance (MR) images which allow discrimination of early cartilaginous changes. Ultrasonography (US) allows visualisation of the lateral cartilaginous portion of the femoral head and the acetabular rim including the labrum and measurement of femoral head protrusion/lateralisation. The purpose of this paper is to highlight its potential for monitoring of containment . Materials and methods. We present typical MR and US images to demonstrate the anatomic landmarks of the normal hip joint and to define the parameters of protrusion in Perthes' disease. We selected three illustrative cases that had undergone routine imaging of both hip joints by MR imaging and ultrasound for evaluation of containment. Radiographs of the hips were also available. In radiographs we assessed the coverage of the femoral head, i.e. containment, by the well established Acetabulum-Head Index (AHI) and in MR imaging by the Cartilaginous Acetabulum-Head Index (CAHI). In US we assessed the uncoverage, i. e. protrusion, by the Lateral Cartilage Distance (LCD). Changes in the important morphological MR containment features were also noted. Results. There was a significant increase in the LCD in all Perthes hips (6.2, 7.4, 11.6 mm) when compared to the unaffected side (5.2, 5.1, 4.1 mm) and also when compared to the published mean normal value (5.4 +/- 0.9 mm). Correspondingly, the CAHI values were significantly decreased (75, 69, 67% versus 87, 79, 81%), also in comparison to the published limits (77, 75, and 73% respectively). As for the AHI only the value of 71 % in the third case represented a definite decrease below published normal limits (86 and 80.7% respectively). In the 1st case we diagnosed adequate containment, in the 2nd containment at risk, and in the 3rd loss of containment. In the 2nd case the AHI of 90 % suggested adequate containment whereas considerable protrusion/lateralisation was evident in MR imaging and US. The CAHI was only 69%. It showed that assessment by plain radiographs is less reliable because the cartilaginous portion of the hip joint is not included in interpretation. We were able to demonstrate a good agreement between LCD and CAHI in our cases. Conclusion. US can be helpful for monitoring of containment in Perthes' disease allowing a closer follow-up and a reduction of serial radiographs and MR exams.