The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival.

INTRODUCTION: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. PATIENTS AND METHODS: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 106 lymph node cells, i.e. the disseminated cancer cell density (DCCD). RESULTS: We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCDNSN = DCCDSNc/101-c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCDSN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCDSN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs. CONCLUSION: The assessment of DCCDSN renders CLND for staging purposes unnecessary.

Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis.

Objectives: Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. Methods: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR. Results: The placebo group consisted of 44 patients and the TCZ group had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, 'Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?' showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023). Conclusion: PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice.

Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate).

OBJECTIVES: Assess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study. METHODS: Patients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96. RESULTS: Overall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was -3.1 (6.3 (-5.4 to -0.9)) for placebo and -5.6 (9.1 (-8.9 to-2.4)) for tocilizumab at week 48 and -9.4 (5.6 (-8.9 to -2.4)) for placebo-tocilizumab and -9.1 (8.7 (-12.5 to -5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period. CONCLUSIONS: Skin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab. TRIAL REGISTRATION NUMBER: NCT01532869; Results.

Europäische Leitlinien (S1) für die Anwendung von hochdosierten intravenösen Immunglobulinen in der Dermatologie.

HINTERGRUND UND ZIELE: Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hochdosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg-Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Wegen der hohen Kosten für IVIg im First-Line-Einsatz wurden die ersten klinischen Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet. METHODEN: Diese europäischen Leitlinien wurden von einer Gruppe durch das EDF und die EADV benannter Experten erarbeitet. Die Leitlinien wurden erstellt, um die derzeit als wirksam erachteten Behandlungsindikationen zu aktualisieren und die für die Anwendung von IVIg bei dermatologischen Autoimmunerkrankungen und TEN vorliegenden Daten zusammenzufassen. ERGEBNISSE UND SCHLUSSFOLGERUNG: Die vorliegenden Leitlinien repräsentieren die einvernehmlichen Meinungen und Definitionen von Experten zur Anwendung von IVIg, die die aktuell publizierten Daten widerspiegeln, und sollen als Entscheidungshilfe für den Einsatz von IVIg bei dermatologischen Erkrankungen dienen.

European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology.

BACKGROUND AND OBJECTIVES: Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011. METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the EDF and EADV. The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.

Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial.

BACKGROUND: Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis. METHODS: We did this double-blind, placebo-controlled study at 35 hospitals in Canada, France, Germany, the UK, and the USA. We enrolled adults with progressive systemic sclerosis of 5 or fewer years' duration from first non-Raynaud's sign or symptom. Patients were randomly assigned (1:1) to weekly subcutaneous tocilizumab 162 mg or placebo. The primary endpoint was the difference in mean change from baseline in modified Rodnan skin score at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT01532869. FINDINGS: We enrolled 87 patients: 43 assigned to tocilizumab and 44 assigned to placebo. The least squares mean change in modified Rodnan skin score at 24 weeks was -3·92 in the tocilizumab group and -1·22 in the placebo group (difference -2·70, 95% CI -5·85 to 0·45; p=0·0915). The least squares mean change at 48 weeks was -6·33 in the tocilizumab group and -2·77 in the placebo group (treatment difference -3·55, 95% CI -7·23 to 0·12; p=0·0579). In one of several exploratory analyses, fewer patients in the tocilizumab group than in the placebo group had a decline in percent predicted forced vital capacity at 48 weeks (p=0·0373). However, we detected no significant difference in disability, fatigue, itching, or patient or clinician global disease severity. 42 (98%) of 43 patients in the tocilizumab group versus 40 (91%) of 44 in the placebo group had adverse events. 14 (33%) versus 15 (34%) had serious adverse events. Serious infections were more common in the tocilizumab group (seven [16%] of 43 patients) than in the placebo group (two [5%] of 44). One patient died in relation to tocilizumab treatment. INTERPRETATION: Tocilizumab was not associated with a significant reduction in skin thickening. However, the difference was greater in the tocilizumab group than in the placebo group and we found some evidence of less decline in forced vital capacity. The efficacy and safety of tocilizumab should be investigated in a phase 3 trial before definitive conclusions can be made about its risks and benefits. FUNDING: F Hoffmann-La Roche, Genentech.

Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients.

OBJECTIVE: Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. METHODS: The data of 3248 patients with SSc were analyzed. RESULTS: Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. CONCLUSION: These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. OBJECTIVES: To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). METHODS: The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. RESULTS: Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. CONCLUSIONS: These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.

Quantitative measurement of melanoma spread in sentinel lymph nodes and survival.

BACKGROUND: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. METHODS AND FINDINGS: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories. CONCLUSIONS: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study.

The exact prevalence of psoriatic arthritis (PsA) among patients with psoriasis is still not conclusive. Data in the literature vary between 5.8 and 30 %. Objective of this study was to gain more information on the prevalence of PsA among patients with psoriasis in Germany. Between 09/2010 and 05/2011, consecutive patients from dermatological private practices and a university hospital with psoriasis were asked to fill out the validated German Psoriatic Arthritis Diagnostic (GEPARD) Questionnaire. Patients who answered ≥4 questions with "yes" were invited to come for a rheumatological check up. Those patients who refused a rheumatological examination were counted as "absence of PsA". Laboratory tests for inflammatory markers as well as the severity of skin manifestations were assessed. The diagnosis of PsA was made according to the CASPAR criteria, and imaging was performed in addition. A total of 404 questionnaires were evaluated; 50.5 % answered ≥4 questions positively; 19.3 % had a history of PsA confirmed by a rheumatologist; and in 10.9 %, PsA or spondyloarthritis was newly diagnosed during the present study. This leads to an overall prevalence of PsA in patients with psoriasis of 30.2 %. The frequency of psoriatic arthritis in the present study is higher than expected from previous studies in Germany. The prevalence is consistent with findings of a large observational survey from Scandinavia. Using the CASPAR criteria and imaging in all patients, certainty of the diagnosis is very high. The GEPARD Questionnaire is a helpful tool to identify people at risk for psoriatic arthritis.

Treatment of pyoderma gangrenosum with topical factor XIII.

Pyoderma gangrenosum (PG) is a severe ulcerative skin disease. Despite systemic immunosuppressive therapy, PG ulcers often progress and can develop into life-threatening conditions. In this case series, we treated 6 patients suffering from recalcitrant PG with topical coagulation factor XIII, which has been shown to exert beneficial effects on tissue regeneration and wound healing. All 6 patients showed a positive response to treatment with a marked reduction in wound size that was maintained during a 3-month follow-up period. The treatment was well tolerated with no remarkable adverse effects or complications. Topical factor XIII has potential in combination with standard immunosuppressive therapy for the treatment of PG.

Safety and efficacy of daptomycin as first-line treatment for complicated skin and soft tissue infections in elderly patients: an open-label, multicentre, randomized phase IIIb trial.

BACKGROUND: Daptomycin has proven efficacy in patients with Gram-positive complicated skin and soft tissue infections (cSSTIs), including those caused by Staphylococcus aureus, regardless of methicillin susceptibility. OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of daptomycin in elderly patients. STUDY DESIGN: This was an open-label, multicentre, randomized phase IIIb study conducted in hospitalized patients PATIENTS: Patients aged ≥65 years with a diagnosis of Gram-positive cSSTIs with or without bacteraemia were included. In addition, infections were required to be of sufficient severity to require inpatient hospitalization and treatment with parenteral antibiotics for at least 96 h. The main exclusion criterion was the presence of a non-complicated SSTI that could heal by itself or be cured by surgical removal of the site of infection. INTERVENTION: Patients were randomized (2:1) to intravenous daptomycin or pooled intravenous standard therapies (semi-synthetic penicillin or vancomycin, referred to as the 'comparator'). Duration of treatment was between 5 and 14 days for cSSTIs without bacteraemia and between 10 and 28 days for cSSTIs with bacteraemia. MAIN OUTCOME MEASURE: The primary objective was descriptive comparison of clinical success in clinically evaluable patients at test of cure, 7-14 days post treatment. Secondary objectives were microbiological outcome, duration of treatment and safety. RESULTS: In total, 120 patients were randomized (81 to daptomycin; 39 to the comparator) and 102 patients completed the study. Baseline characteristics were similar between the two groups. Common infections included cellulitis, ulcers and abscesses; six patients had bacteraemia [five documented (daptomycin, n = 3; comparator, n = 2); and one suspected (daptomycin, n = 1)]. Test-of-cure clinical success rates were numerically higher for daptomycin than for the comparator [89.0 % (65/73) vs. 83.3 % (25/30); odds ratio 1.65 (95 % confidence interval 0.49-5.54)]. For patients with S. aureus infections, cure rates were 89.7 % (35/39) versus 69.2 % (9/13), respectively; percentage points difference, 20.5 (95 % confidence interval -12.2 to 50.9)]. Rates of adverse events (AEs) and serious AEs were similar in both treatment arms; however, discontinuation rates for AEs/serious AEs were lower for daptomycin than for the comparator (3.8 % vs. 10.0 %). Three serious AEs were considered to be related to the study drug: one case each of pancytopenia (semi-synthetic penicillin), renal failure (vancomycin) and asymptomatic increase in creatine phosphokinase concentrations (daptomycin). CONCLUSION: In elderly patients, for whom data were previously limited, the efficacy and safety of daptomycin have been confirmed, including for infections caused by S. aureus, regardless of methicillin susceptibility.

Response evaluation of musculoskeletal involvement in patients with deep morphea treated with methotrexate and prednisolone: a combined MRI and clinical approach.

OBJECTIVE: The purpose of this article is to explore the role of MRI in monitoring musculoskeletal involvement in patients with morphea who are undergoing treatment with methotrexate and prednisolone. SUBJECTS AND METHODS: Twenty-two consecutive patients (six men and 16 women; median age, 52 years) with systemic scleroderma and deep morphea prospectively underwent whole-body MRI twice, before treatment (time 1) and during follow-up after 6-12 months (time 2). Images were evaluated for abnormal signal intensity or thickening of sub-cutaneous fatty tissue septa, muscular fasciae, intramuscular perifascial septa, muscle signal intensity, and articular or tendon sheath synovial abnormalities on STIR and gadolinium-enhanced scans. For clinical assessment, the localized scleroderma (morphea) severity index and a 0-6 pain score were applied. RESULTS: From a clinical point of view, none of our patients had progression of the disease, 12 patients were responders (defined as an improvement of localized scleroderma severity index and pain score ≥ 50%), and 10 patients had stable disease. Among responders, the number of patients with subcutaneous septal thickening (time 1, n = 9; time 2, n = 2), fascial enhancement (time 1, n = 8; time 2, n = 3), and articular synovitis (time 1, n = 5; time 2, n = 1) decreased more than in the stable disease group (subcutaneous septal thickening: time 1, n = 9; time 2, n = 8; fascial enhancement: time 1, n = 5; time 2, n = 5; articular synovitis: time 1, n = 8; time 2, n = 6). Subcutaneous thickening, fascial thickening, and fascial enhancement were scored significantly lower at follow-up MRI in responders. CONCLUSION: MRI findings were sensitive to changes in musculoskeletal manifestations in patients with deep morphea undergoing systemic treatment with methotrexate and prednisolone. Thus, MRI can be recommended as an additional tool for response monitoring.

Enteric-coated mycophenolate sodium for progressive systemic sclerosis--a prospective open-label study with CT histography for monitoring of pulmonary fibrosis.

The purpose of this study was to assess the impact of enteric-coated mycophenolate sodium (EC-MPS) on skin and pulmonary manifestations of patients with progressive systemic sclerosis (Ssc). A prospective, open-label single-centre trial with EC-MPS 2 × 720 mg/day over 12 months and a long-term follow-up of 50 months were conducted. Modified Rodnan skin score (mRSS) was used to assess the skin and pulmonary function tests to assess the pulmonary involvement. In order to quantify the extent of alveolitis/fibrosis via densitometry, the high attenuation value, median lung density and percentiles of lung tissue densities were obtained by high-resolution computed tomography. Eleven patients were included. Three patients had to stop medication before month 6 (2× side effects, 1× progression). For the remaining eight patients, the median mRSS was non-significantly reduced from 13.5 at baseline to 11 at month 12. According to the CT histography, median lung density and high attenuation values remained stable. However, the course of percentiles -200 to -300 and particularly -300 to -400 Hounsfield units slightly increased in seven of eight patients after 12 months, suggesting worsening of pulmonary involvement. Accordingly, median diffusing capacity for carbon monoxide showed a tendency to decline (75.1 % vs. 70.2) while forced vital capacity non-significantly improved (78.0 vs. 85.5 %) during the study. Four patients are still on EC-MPS without clinical signs of progression after 50 months follow-up. EC-MPS showed non-significant improvement of the skin. Pulmonary fibrosis remained stable with only a slight tendency towards progression which might be ascribed to the medication as well as the natural course of the disease. CT histography appears to be a sensitive method for the detection of progression of pulmonary fibrosis and therefore should be considered for further studies in Ssc.

Magnetic resonance imaging findings in patients with systemic scleroderma and musculoskeletal symptoms.

OBJECTIVE: To explore the role of whole-body magnetic resonance imaging (MRI) in detecting musculoskeletal involvement in patients with systemic scleroderma and musculoskeletal symptoms. METHODS: Eighteen consecutive patients (8 men, 10 women) with systemic scleroderma (median age 46 years) presenting with musculoskeletal complaints underwent whole-body MRI at 1.5 T. Images were evaluated for abnormal signal intensity and/or thickening of subcutaneous fatty tissue septa, muscular fasciae, intramuscular perifascial septa, muscle signal intensity and articular or tendon sheath synovial abnormalities on STIR and post-gadolinium scans. Additionally, C-reactive protein, creatinine kinase and the modified Rodnan skin score were determined. RESULTS: MRI indicated evidence of fasciitis, articular synovial inflammation, and subcutaneous thickening in 16 (89 %) patients. MRI findings were compatible with myopathy or myositis in 14 (78 %) patients, tenosynovitis in 11 (61 %) patients and enthesitis in 10 (56 %) patients. Typically, these manifestations were distributed symmetrically and mostly generalised. We only found few correlations with modified Rodnan skin score, C-reactive protein and creatinine kinase. CONCLUSION: In patients with systemic scleroderma experiencing musculoskeletal symptoms, whole-body MRI is able to detect involvement of muscles, fasciae, joints and entheses more confidently compared with clinical and laboratory parameters.

Long-term life and partnership satisfaction in infertile patients: a 5-year longitudinal study.

OBJECTIVE: To describe the long-term effects of infertility on life and partnership satisfaction. DESIGN: Longitudinal cohort study. SETTING: A university outpatient andrology and gynecology infertility clinic. PATIENT(S): 275 men and 272 women treated for infertility between August 2000 and December 2001. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The Life Satisfaction Questionnaire (FLZ), the Partnership Questionnaire (PFB), and sociodemographic items at baseline (T1) and 5 years later (T2). RESULT(S): Compared with a representative sample, our male and female participants had higher Finance and Partnership scores and lower Health scores on the FLZ at T1. They also had markedly higher PFB scores, with the exception of Conflict Behavior. After 5 years (T2), 101 men and 113 women rated the Partnership and Sexuality FLZ subscales as well as all the PFB subscales statistically significantly lower than at baseline. Only the women rated the Self-esteem FLZ subscale lower than at baseline (T1). Participants who became parents had lower Leisure and Partnership FLZ subscale scores, and fathers had lower Finance FLZ subscale scores. CONCLUSION(S): Satisfaction declined over 5 years for both men and women, but only in the partnership-related domains. Women were more affected than men. The success of infertility treatment had only a minor influence on a couple's future satisfaction.

Localized scleroderma: MR findings and clinical features.

PURPOSE: To describe musculoskeletal manifestations seen at magnetic resonance (MR) imaging in patients with localized scleroderma (LS) and to examine the relationship of MR findings to clinical subtypes and clinically suspected musculoskeletal features. MATERIALS AND METHODS: Institutional review board approval was obtained. Forty-three patients (30 female, 13 male; mean age, 42 years) with LS underwent MR imaging with a 1.5-T MR imager between November 2005 and June 2010. Findings were classified into clinical subtypes according to recently published consensus criteria. Images were evaluated for morphologic changes and signal abnormalities of subcutaneous fat septa, muscle fasciae, intramuscular septa, joint and/or tendon sheath synovia, entheses, and bone marrow. Clinically suspicious features of musculoskeletal manifestations-such as articular or periarticular pain, joint contractures, swelling, and increased warmth of the joints or extremities-were recorded. RESULTS: Musculoskeletal involvement was detected with MR imaging in 32 (74%) of 43 patients. It was detected with MR imaging in 26 (96%) of 27 patients in whom it was clinically suspected and in six (38%) of 16 patients in whom it was not clinically suspected. We found fascial thickening (26 [60%] of 43 patients), increased fascial enhancement (23 [53%] of 43 patients), articular synovitis (17 [40%] of 43 patients), tenosynovitis (nine [21%] of 43 patients), perifascial enhancement (seven [16%] of 43 patients), myositis (six [14%] of 43 patients), enthesitis (three [7%] of 43 patients), bone marrow involvement (two [5%] of 43 patients), and subcutaneous septal thickening (28 [65%] of 43 patients). The highest prevalence of musculoskeletal involvement was seen in patients with pansclerotic morphea. CONCLUSION: MR imaging reveals musculoskeletal involvement in patients with localized scleroderma.

Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: a pilot study.

PURPOSE: To evaluate whether tumour therapy for malignant uveal melanoma leads to a shedding of melanoma cells into the systemic circulation. METHODS: Ninety-four peripheral blood samples from 81 patients with malignant uveal melanoma were collected before and after different tumour therapies and the number of circulating melanoma cells (CMCs) was investigated (seven patients with enucleation, 49 patients with stereotactic radiotherapy, 19 patients with endoresection of the tumour, 15 patients with ruthenium-brachytherapy and four patients with transpupillary thermotherapy). A cellular approach was used to detect CMCs through an immunocytological assay with tumour cell enrichment by immunomagnetic cell sorting. The number of CMCs was analysed further according to specific patient characteristics, tumour parameters and the development of metastasis. RESULTS: There was no significant difference between the number of CMCs before and after the different therapies (p = 0.78). There was also no significant association between established prognostic parameters of primary uveal melanoma and the detection of CMCs (all p >0.05). The number of CMCs was not related to the development of metastasis in a short median follow-up time of 16 months (p > 0.05). CONCLUSION: No changes in CMC values were observed before and after different tumour therapies. In the majority of cases therapy does not lead to a shedding of detectable melanoma cells into the systemic circulation.