Occlusion rate, venous symptoms and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®): are there differences between the great and the small saphenous veins?

BACKGROUND: Previous studies on the therapy of insufficient saphenous veins mainly compare different treatment methods. Only a few investigate differences of a specific treatment option between the great (GSV) and the small saphenous vein (SSV). The aim of this study was to evaluate the efficacy, clinical improvement and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®) with regard to the treated vein. PATIENTS AND METHODS: We included 65 patients (40 women, 25 men; mean age 54.75 years) who were treated with RFITT® for incompetent saphenous veins (n = 83: 62 GSV, 21 SSV). Occlusion rates were determined by duplex-sonography. Additionally, we performed a prospective analysis of venous symptoms and signs by means of a standardized questionnaire and of patient satisfaction using a semi-quantitative rating (1 = very good, 6 = insufficient). RESULTS: The GSV group showed a significantly greater reduction of venous symptoms in comparison to the SSV group (p = 0.005) despite no significant differences in long term occlusion rates (mean time after operation: 22 months) of 90 % in the GSV group and 81.8 % in the SSV group (p = 0.598). Following the procedure, detailed analysis revealed significantly more swelling (p = 0.022), feeling of heavy legs (p = 0.002) and nightly calf cramps (p = 0.001) in the SSV group. Additionally, RFITT® led to a significant improvement in patient satisfaction in the GSV group (from 1.93 at day 1 - 3 to 1.41 after 6 - 12 months, p = 0.009) but not in the SSV group (from 2.29 to 2.07, p = 0.43). CONCLUSIONS: With regard to the improvement of venous symptoms and patient satisfaction, the benefit of RFITT® is greater for patients with incompetent GSV compared to those with incompetent SSV.

Fumarate treatment in progressive forms of multiple sclerosis: first results of a single-center observational study.

OBJECTIVES: Therapeutic options in progressive forms of multiple sclerosis (MS) are still limited. Dimethyl fumarate (DMF) has immunomodulatory properties but may also exert antioxidative cytoprotective effects. Hence, it may be a therapeutic option for progressive MS. The aim of this observational study was to evaluate safety, adherence and efficacy of fumarates in patients with primary progressive MS (PPMS) or secondary progressive MS. METHODS: Patients with progressive MS whose condition had failed to respond to standard therapies and had worsened received the fumarate mixture Fumaderm, licensed for psoriasis therapy in Germany, or DMF by pharmaceutical preparation (Bochum ethics approval no. 4797-13). At regular follow-up visits, tolerability and disease course were assessed. RESULTS: Twenty-six patients [age 54 ± 7.8 years; female = 13 (50%); PPMS = 12 (46.2%); Expanded Disability Status Scale (EDSS) = 6.0 ± 0.4 (range 3.5-8.0); disease duration = 14.1 ± 8.7 years] were initiated on treatment with Fumaderm (n = 18) or pharmacy-prepared DMF (n=8). During a mean follow-up period of 13.2 ± 7.5 months (range 6-30) only five patients (19.2%) reported minor complaints. In 15 patients (57.7%) EDSS remained stable. In five cases (19.2%) there was even a decrease in EDSS while in six patients (23.1%) there was an increase in EDSS of more than 0.5 points, reflecting deterioration. Laboratory values were controlled for lymphopenia, renal and hepatic values, without any safety problems. We observed no significant differences between the two pharmaceutical forms. CONCLUSION: Our pilot data indicate that fumarate therapy appears to be safe and well tolerated by patients with progressive MS. In more than 75% of cases no further disease progression was evident. However, controlled studies are warranted to evaluate the detailed therapeutic potential of fumarates and their long-term effects in progressive MS.

[Seafood allergy in cooks: a case series and review of the literature]. / Allergie gegen Meeresfrüchte bei Köchen: Fallserie und Literaturübersicht.

BACKGROUND: Seafood is a very potent allergen. Epidemiological studies of seafood allergy in the highly exposed cooking profession are lacking. The objective of this first case series was to demonstrate the high relevance and consequences of seafood allergy in cooks. PATIENTS UND METHODS: Retrospective analysis of all the case files sent in which the presence of an occupational disease according to no. 5101 of the appendix of the German ordinance on industrial disease was to be clarified. RESULTS: Thirty cooks (men 70 %) with an occupational seafood allergy were assessed between January 2008 and April 2014. Seafood allergy was observed in youngish workers(median age 24.7 yrs.) with an early manifestation of the disease (after 1.7 yrs. of occupation in median). In all except one (96.7 %) onset was localized on the hands.Most commonly documented were immediate sensitizations to cod, salmon, trout,and herring. Emergency treatment due to an anaphylactic shock at the workplace became necessary in 5 cases (16.7 %). In 27 cases (90 %) discontinuation of occupation was needed and was carried out after 6.3 yrs. of occupation in median. CONCLUSIONS: Seafood allergy in cooks is mostly characterized by a quick progressive course of disease, already at the start of the cooking career. The prognosis for continuance in occupation is poor and an occupational disease is to be considered at a nearly stage. An emergency kit with an epinephrine auto-injector should be provided for life by the responsible accident insurer.

A novel epidermal growth factor--containing wound dressing for the treatment of hard-to-heal venous leg ulcers.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of a novel wound dressing containing epidermal growth factor (EGF) in a collagen-gel matrix on hard-to-heal venous leg ulcers. PATIENTS AND METHODS: The authors included 33 hard-to-heal venous leg ulcers found on 31 patients. The EGF-containing dressing was applied 3 times while best practice conservative wound treatment was continued. Patients were followed up with after 1, 2, and 3 months to evaluate (a) the wound size, (b) the ease of application and dissolution of the dressing, and (c) the wound dressing by means of a scale ranging from 1 to 5 (1 = best, 5 = worst). RESULTS: The protocol was completed by 25 of 31 patients. The reasons for discontinuation were wound infection, pain, and lost to follow-up (n = 2 each, respectively). After 3 months, the average wound surface was significantly reduced (from 33.69 cm to 18.94 cm, P = .023). On a scale from 0 to 100, the wound dressing was evaluated as very easy to apply and highly dissolvable (mean value of 97.14 and 98.11, respectively; 100 = very easy to apply or 100% dissolution). The dressing was generally well tolerated and scored a mean overall rating of 2.16 by healthcare specialists and 2.40 by patients. CONCLUSION: The authors' results demonstrate that the novel EGF-containing wound dressing was generally well tolerated and safe. Combined with the significant wound surface reduction, it can be regarded as an adequate novel treatment option for patients with hard-to-heal venous leg ulcers.

Efficacy and comfort of medical compression stockings with low and moderate pressure six weeks after vein surgery.

OBJECTIVE: The first two authors contributed equally to this work. A prospective, randomized study to evaluate efficacy, safety, and comfort of thigh-high, round knitted medical compression stockings (MCSs) with different pressure six weeks after vein surgery. METHODS: Female patients undergoing vein surgery were randomized for a compression therapy with low (18-21 mmHg, group A) or moderate (23-32 mmHg, group B) pressure MCSs. Follow-up was done by a phlebological experienced, blinded physician (pressure control, clinical aspect, duplex scan, and questionnaire) one and six weeks after surgery. RESULTS: Totally, 88 patients (41 in group A and 47 in group B) were analyzed. One week after surgery, patients of group B had significantly lower edema scores than patients of group A either in the clinical assessment (0.7 vs. 0.3; p = 0.016) or in the B-mode scan (0.9 vs. 0.4; p = 0.013). Significant less patients of group B had a feeling of "tightness" (p = 0.01) and significant more a reduction of discomfort (p = 0.01) after week 1 but with no significance in week 6. There was no significant difference according to other clinical and ultrasound findings such as hematoma, infection, hyperpigmentation, cording, or thrombosis after one or six weeks. In week 1 and week 6, more patients suffered from pain in group A (week 1 p = 0.24, week 6 p = 0.063). Application of the MCSs was easier in group A in week 1 but similar in groups A and B in week 6. Muscle vein thrombosis occurred in one patient of group A. CONCLUSION: Compression stockings with a pressure of 23-32 mmHg facilitate a faster resolution of clinical and ultrasound verified edema and the subjective feelings of pain, tightness, and discomfort of the leg in the early period after surgery but have no difference in the longer post-surgical period compared to stockings with a pressure of 18-21 mmHg.

Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin and autoimmune dermatoses.

BACKGROUND: Regulatory T cells (Tregs) play an important role in autoimmune diseases. In skin, the presence of Tregs is thought to be mandatory for suppression of autoreactive T cells. Here, we assess the number of Tregs in skin of healthy subjects and patients with an autoimmune dermatosis. METHODS: Immunohistochemical stainings for CD3 and FOXP3 on skin biopsies of healthy subjects and subjects with psoriasis, vitiligo, pemphigus vulgaris, bullous pemphigoid, and halo nevus to assess the number of T and regulatory T cells, respectively. RESULTS: Low numbers of CD3+ and FOXP3+ cells were seen in the skin of healthy controls (median = 0.5%). A significantly higher frequency of Tregs was seen in lesional skin of patients with psoriasis (median = 12.4%) and patients with bullous pemphigoid (median = 10.1%) as compared to controls. In vitiligo (median = 0.0%), pemphigus vulgaris (median = 5.2%), and halo nevi (median = 5.4%), no significant difference in number of FOXP3+ cells was observed when compared to controls. CONCLUSIONS: As confirmed in the literature, few Tregs were seen in healthy skin. A high number of Tregs were present in lesional skin from patients with psoriasis and bullous pemphigoid. These results support the hypothesis that not a decrease in number but rather a decrease in function of Tregs would be at the basis of autoimmune skin diseases, which could result in unrestrained activation autoreactive T cells in skin of patients with autoimmune dermatoses.

Clinical characteristics and survival data of melanoma patients with nevus cell aggregates within sentinel lymph nodes.

Histopathologic differentiation of nevus cell aggregates and metastatic melanoma in lymph nodes is challenging. Patients with melanoma who had undergone sentinel lymph node (SLN) biopsy were evaluated using univariate and multivariate analyses as well as Kaplan-Meier statistics. Of the 651 patients, 50 (7.7%) had a nodal nevus in the SLN. In the logistic regression model, primary melanoma on the lower extremities proved to be the strongest independent negative predictor of nodal nevi with an odds ratio of 0.11 (95% confidence interval, 0.034-0.36; P = .0002). Overall 5-year survival (P = .17) and 5-year disease-free survival (P = .45) of patients with nodal nevi did not significantly differ from that of patients with negative SLNs. The frequency and anatomic localization of nodal nevi observed in the present study are in line with previous studies. Our 5-year survival data clearly demonstrate that nevus cell aggregates in lymph nodes have to be considered a benign condition even though it occurs in patients with melanoma. This study provides an indirect proof of validity and accuracy of current histopathologic methods for differentiation between nodal nevi and melanoma metastasis.

Foam sclerotherapy with enoxaparin prophylaxis in high-risk patients with postthrombotic syndrome.

BACKGROUND: According to the current guidelines for sclerotherapy hypercoagulability and thrombophilia with or without deep venous thrombosis are seen as relative contraindication for this treatment. But often such patients have an indication for a sclerotherapy. Recommendations for additional anticoagulation for sclerotherapy are missing. PATIENTS AND METHODS: In this retrospective analysis (2009 - 2010), 54 patients with deep venous thrombosis and/or pulmonal embolism in their medical history that had had foam-sclerotherapy of truncal or tributary veins with polidocanol 0.5 - 3 % without prior anticoagulation therapy were included. In addition to compression treatment (23 - 32 mmHg) for 3 weeks patients were treated with enoxaparin 40 mg once a day for 3 days after sclerotherapy. Clinical and duplex controls were conducted before every treatment and 2 - 3 weeks after the last injection. RESULTS: Sclerotherapy was done on one (30/54) or on both (24/54) legs. In 2/54 legs a truncal vein and in all patients tributaries were treated. The volume per treatment session averaged 3.3 ml foam (2 - 6 ml). The patients had undergone an average of 4.9 treatments (1 - 11); altogether 262 sessions. There were no cases of deep venous thrombosis or symptomatic pulmonary embolism. In 7/262 treatments (2.7 %) symptomatic localized phlebitis occurred and in 2/262 (0.8 %) patients an ascending phlebitis beyond the sclerotherapy region was observed. CONCLUSIONS: Based on current data, foam sclerotherapy can be regarded as safe in patients with anamnestic thromboembolism when co-treated with compression therapy (23 - 32 mmHg) and enoxaparin 40 mg once per day for 3 days post sclerotherapy. The current study is the first with a standardized regime. In view of the limitations of this study there should be further randomized controlled trials.

Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

Thick legs - not always lipedema.

Due to its increased presence in the press and on television, the diagnosis of lipedema is on the way to becoming a trendy diagnosis for those with thick legs. Despite this, one must recognize that lipedema is a very rare disease. It is characterized by disproportional obesity of the extremities, especially in the region of the hip and the legs, hematoma development after minimal trauma, and increased pressure-induced or spontaneous pain. Aids for making the correct diagnosis are (duplex) sonography, the waist-hip index or the waist-height index and lymphoscintigraphy. Important differential diagnoses are constitutional variability of the legs, lipohypertrophy in obesity, edema in immobility, edema in chronic venous insufficiency and rheumatic diseases. The symptom-based therapy of lipedema consists of conservative (compression, manual lymphatic drainage, exercise) and surgical treatments (liposuction). Until now there is no curative therapy. Obesity is an important risk factor for the severity and prognosis of lipedema. Further studies for a better understanding of the pathogenesis of lipedema and in the end possible curative treatments are urgently needed.

Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.

Lichen sclerosus is a relatively common chronic inflammatory skin disease that predominantly affects the anogenital area. Accumulating evidence indicates that lichen sclerosus in women may be associated with other autoimmune disease, whereas this association seems to lack in male patients. We retrospectively evaluated the prevalence of autoimmune diseases and serological parameters indicative for autoimmunity in male and female patients with lichen sclerosus. Of the 532 patients (396 women, 136 men; 500 adults, 32 children; mean age: 49 years; range 1-89 years; female:male ratio 3:1), 452 (85%) had genital and 80 (15%) had extragenital disease. In women, lichen sclerosus was significantly more often associated with at least one autoimmune disease as compared to men (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.9-9.6; p<0.0001). Moreover, female patients with lichen sclerosus had sinificantly more often associated autoimmune thyroid diseases (OR 4.7, 95% CI 1.8-11.9; p<0.0002), antithyroid-antibodies (OR 2.7, 95% CI 1.1-6.5; p=0.023), and elevated autoantibodies (OR 4.1, 95% CI 1.9-9.3; p<0.0001) as compared to male patients. This observation is suggestive for a different pathogenetic background in male and female patients.

MicroRNA in non-melanoma skin cancer.

MicroRNAs (miRNAs) are a fairly novel class of 17- to 23-nucleotide (nt), short, non-coding RNA molecules that have revolutionized our understanding of gene regulation and opened new possibilities in the future of gene therapy. Here, we review the potential role of miRNAs in non-melanoma skin cancer (NMSC) and summarize the current studies available in this new aspect of NMSC research.

Acne inversa: evaluating antimicrobial peptides and proteins.

BACKGROUND: Acne inversa is a chronic, suppurative relapsing inflammatory skin disease that primarily affects the axillae, perineum and inframammary regions. Evidence suggests that the innate immune system is involved in the pathogenesis of acne inversa. OBJECTIVE: To investigate the role of the innate immune system in acne inversa. METHODS: Skin biopsies were obtained from inflammatory skin lesions (n=17) and from non-lesional skin (intraindividual control, n=17) of patients with acne inversa. Additional skin lesions were taken from patients with chronic venous leg ulcers (interindividual control, n=5). Quantitative real-time reverse transcription-polymerase chain reaction was used to determine the mRNA levels of antimicrobial peptides and proteins (AMPs), including human ß-defensin (hBD)-1, hBD-2 and hBD-3, LL-37 (cathelicidin) and Ribonuclease 7 (RNase 7). mRNA levels were also determined for inflammatory and anti-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-1 (MMP1), interleukin (IL)-1ß, IL-6, IL-8 and IL-10. RESULTS: The mRNA levels of hBD-2, LL-37, IL-1ß, IL-6, IL-8, IL-10 and MMP1 were significantly higher in acne inversa lesions compared to non-lesional skin (p<0.05). A significant positive correlation expression was observed between hBD-2 mRNA expression and LL-37 (ρ=0.53, p=0.03), and between hBD-2 and RNAse 7 (ρ=0.68, p=0.006). When compared to the chronic venous leg ulcer lesions, acne inversa lesions showed a significantly higher expression of RNase 7 mRNA, while IL-1 ß, IL-6, IL-8, TNF-α and MMP1 mRNA expression was significantly higher in the chronic venous leg ulcer lesions (p<0.05). CONCLUSION: The AMP, cytokine milieu and tissue proteases in acne inversa lesions differ significantly from non-lesional skin and chronic venous leg ulcers. The positively correlating up-regulation of AMPs in acne inversa indicates an important role of the innate immune system in the pathogenesis of this disorder.

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma.

BACKGROUND: MicroRNAs (miRNAs) are a novel class of short RNAs that are capable epigenetically regulating gene expression in eukaryotes. MicroRNAs have been shown to be dysregulated in a variety of cancers. The data on miRNA expression in cutaneous squamous cell carcinoma (cSCC) are very limited, and microarray-based miRNA expression profiles of cSCC have not yet been determined. OBJECTIVE: To describe differentially expressed miRNAs in cSCC. METHODS: Seven patients with cSCC were enrolled in the present study. Tumor biopsies (n=7) were taken from the center of each tumor. Adjacent healthy skin (n=7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimens were detected by microarray miRNA expression profiling based on miRBAse 16 scanning for 1205 potential human miRNA target sequences. The microarray results were confirmed by TaqMan quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Non-stringent filtering with a non-adjusted p ≤ 0.05 revealed thirteen up-regulated and eighteen down-regulated miRNAs. Non-stringent filtering with a non-adjusted p ≤ 0.01 revealed three up-regulated (hsa-miR-135b, hsa-miR-424 and hsa-miR-766) and six down-regulated (hsa-miR-30a*, hsa-miR-378, hsa-miR-145, hsa-miR-140-3p, hsa-miR-30a and hsa-miR-26a) miRNAs in cSCC. CONCLUSION: This study reveals differentially expressed miRNAs that may play a role in the molecular pathogenesis of cSCC and that are excellent candidates for further validation and functional analysis.