Petra Buttner

Eating disorder behaviors are increasing: findings from two sequential community surveys in South Australia

Background Evidence for an increase in the prevalence of eating disorders is inconsistent. Our aim was to determine change in the population point prevalence of eating disorder behaviors over a 10-year period. Methodology/Principal Findings Eating disorder behaviors were assessed in consecutive general population surveys of men and women conducted in 1995 (n = 3001, 72% respondents) and 2005 (n = 3047, 63.1% respondents). Participants were randomly sampled from households in rural and metropolitan South Australia. There was a significant (all p<0.01) and over two-fold increase in the prevalence of binge eating, purging (self-induced vomiting and/or laxative or diuretic misuse) and strict dieting or fasting for weight or shape control among both genders. The most common diagnosis in 2005 was either binge eating disorder or other “eating disorders not otherwise specified” (EDNOS; n = 119, 4.2%). Conclusions/Significance In this population sample the point prevalence of eating disorder behaviors increased over the past decade. Cases of anorexia nervosa and bulimia nervosa, as currently defined, remain uncommon.

Primary cutaneous melanoma. Prognostic classification of anatomic location

Background. Anatomic location has been identified by several investigators as a significant prognostic factor for patients with primary cutaneous melanoma (CM). However, the best determination of higher and lower risk sites is still controversial, and the biologic significance of tumor site in the course of primary CM is unknown. The aim of the present study was to identify higher and lower risk sites based on multivariate analysis.

BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site

Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun‐induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF‐mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF‐mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.

Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells

Purpose: To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared with functional tumor antigen–specific T cells in patients with melanoma with distant metastasis. Experimental Design: The percentage of CD14+CD11b+HLA-DR−/low MDSCs, CD4+CD25+FoxP3+ Tregs, and the presence of NY-ESO-1- or Melan-A–specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan–Meier and log-rank tests. Multivariate analyses were performed using Cox regression models. Results: NY-ESO-1–specific T cells, the M-category, and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1–specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of >11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months versus 8 months for others (P < 0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma antigen–specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs. Conclusions: Circulating CD14+CD11b+HLA-DR−/low MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen–specific T cells in patients with advanced melanoma. Our findings provide a rationale to investigate MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches. Clin Cancer Res; 20(6); 1601–9. ©2013 AACR.

First- or second-degree atrioventricular block as a risk factor in idiopathic dilated cardiomyopathy

To evaluate the significance of clinical, hemodynamic and electrocardiographic risk factors in idiopathic dilated cardiomyopathy 94 patients were followed prospectively for 49 +/- 37 months. During follow-up, 30 patients died, 13 died suddenly, 13 died of congestive heart failure and 4 of other causes. Follow-up was completed in 85 patients, and overall cardiac mortality was 31%. Univariate analysis revealed left ventricular ejection fraction among 20 variables as the major indicator of risk of both cardiac death of all causes and sudden cardiac death separately. Multivariate overall analysis determined 3 independent risk factors in the following order for all causes of cardiac death: Ventricular pairs > 40/24 hours (RR 7.2, p < 0.0001), left ventricular ejection fraction < or = 35% (RR 6.5, p < 0.001) and first- or second-degree atrioventricular (AV) block (RR 3.1, p < 0.05). In the subset of patients with ejection fraction < or = 35% ventricular pairs > 40 per 24 hours (RR 10.7, p < 0.001), AV block (RR 3.9, p < 0.05), and the missing administration of vasodilators (RR 3.3, p < 0.05) were the most important. The chief risk factors for sudden cardiac death were age (RR 7.4, p < 0.01) and AV block (RR 4.6, p < 0.05) by adjustment for age, and ejection fraction < or = 35% (RR 7.1, p < 0.01) and AV block (RR 4.2, p < 0.05) if not adjusted for age. A differentiation into 4 risk groups was attempted. The additional independent prognostic importance of AV block was shown, especially in combination with reduced ejection fraction or a high incidence of ventricular pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients.

The prognostic value of the TNM classifications of the UICC dated 1978 and 1987, was investigated in a population of 2,495 patients who were followed up over the long term. In the case of primary melanoma, Breslows tumour thickness proved to be the most powerful predictor of patient survival in multivariate analysis, while the significance of Clarks level ranged after that of both localisation of the primary tumour and the sex of the patient. The continuous proportional relationship between tumour thickness and risk of death makes it possible to regrade thickness groups. Grading cutoffs at 1, 2 and 4 millimetres, with no account being taken of depth of invasion, proved to be particularly favourable for a classification in accordance with prognostic criteria. In advanced stages of the disease, the outcome of locoregional and distant metastasis is significantly different; and furthermore in the case of locoregional metastasis, in-transit and satellite metastases exert a significantly better prognosis than regional lymph node involvement. Isolated juxtaregional lymph node metastases occurred primarily or during the course of the observation period in only 19 patients of our group, and, in comparison with visceral metastases, proved to have only an insignificantly better prognosis. For this reason, it would appear meaningful to assign them to a common stage. On the basis of these results, proposals are made for modifications of the TNM classification.

Thrombus volume is associated with cardiovascular events and aneurysm growth in patients who have abdominal aortic aneurysms

BACKGROUND Patients with abdominal aortic aneurysms (AAA) are predisposed to cardiovascular events and often experience continual expansion of their aneurysm. Cardiovascular events and expansion rates are positively correlated with aneurysm size. AAA is usually associated with intraluminal thrombus, which has previously been implicated in AAA pathogenesis. This study prospectively assessed the association of infrarenal abdominal aortic thrombus volume with cardiovascular events and AAA growth. METHODS Ninety-eight patients with AAAs underwent computed tomography angiography (CTA). The volume of infrarenal aorta thrombus was measured by a previously validated technique. Patients were monitored prospectively for a median of 3 years (interquartile range [IQR], 2.0-3.6 years), and cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, coronary revascularization, amputation, and cardiovascular death) were recorded. Of the original patients, 39 underwent repeat CTA a median of 1.5 years (IQR, 1.1-3.3 years) after entry to the study. Kaplan-Meier and Cox proportional analysis were used to examine the association of aortic thrombus with cardiovascular events and average weighted AAA growth. RESULTS There were 28 cardiovascular events during follow-up. The incidence of cardiovascular events was 23.4% and 49.2% for patients with small (smaller than the median) and large (median or larger) volumes of aortic thrombus, respectively, at 4 years (P = .040). AAA thrombus volume of median or larger was associated with increased cardiovascular events (relative risk [RR] 2.8, 95% confidence interval [CI], 1.01-5.24) independent of other risk factors, including initial AAA diameter, but was only of borderline significance when patients were censored at the time of AAA repair (RR, 2.35; 95% CI, 0.98-5.63). In the subset of patients with CTA follow-up, the median annual increase in AAA volume was 5.1 cm³ (IQR, 0.8-10.3 cm³). Annual AAA volume increase was positively correlated with initial AAA diameter (r = 0.44, P = .006) and thrombus volume (r = 0.50, P = .001). Median or larger aortic thrombus volume was associated with rapid AAA volume increase (≥ 5 cm/y), independent of initial aortic diameter (RR, 15.0; 95% CI, 1.9-115.7; P = .009). CONCLUSION In this small cohort, infrarenal aortic thrombus volume was associated with the incidence of cardiovascular events and AAA progression. These results need to be confirmed and mechanisms underlying the associations clarified in large further studies.

Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis

Background:Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis.Methods:We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan–Meier survival probabilities and multivariate Cox hazard regression analysis.Results:Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).Conclusion:The serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis. Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values.

Das Zentralregister Malignes Melanom der Deutschen Dermatologischen Gesellschaft in den Jahren 1983–1993 Epidemiologische Entwicklungen und aktuelle therapeutische Versorgung des malignen Melanoms der Haut**

ZusammenfassungDas Zentralregister Malignes Melanom der Deutschen Dermatologischen Gesellschaft hat seine Arbeit 1983 aufgenommen und sich seitdem zu einem kontinuierlich fortgeführten multizentrischen Projekt entwickelt. Insgesamt wurden bis Juni 1994 die Daten von 19.250 Patienten aus 41 Kliniken der alten Bundesländer, 14 Kliniken der neuen Bundesländer, zwei Kliniken aus Österreich und einer Klinik aus der Schweiz gemeldet. Die Auswertung der Daten läßt mehrere epidemiologische Trends im Zeitraum von 1983–1993 erkennen. a) Es fand sich eine kontinuierliche Zunahme des Anteils der Männer an den Melanom-Patienten, der im Mittel von 38% im Jahre 1983 auf 46% im Jahre 1993 anstieg. b) Die Früherkennung maligner Melanome wurde im untersuchten Zeitraum verbessert. Die Diagnosen im Stadium des Primärtumors stiegen im untersuchten Zeitraum an. Die mittlere Tumordicke nach Breslow nahm in den alten Bundesländern von 1,8 mm auf 1,3 mm und in den neuen Bundesländern von 2,5 mm auf 1,7 mm ab. Entsprechend verringerte sich der Anteil nodulärer Melanome in den alten Bundesländern im Mittel von 29,3% auf 14,1% und in den neuen Bundesländern von 40,6% auf 22,6%. In den Jahren 1990–1993 wurden in den alten Bundesländern 64% und in den neuen Bundesländern 34,2% aller primären malignen Melanome zweizeitig operiert. Insgesamt wurden 73,7% der Patienten in Lokalanästhesie operiert. In den letzten Jahren wurde vermehrt in Lokalanästhesie und zweizeitig operiert, wobei entsprechend der Abnahme der Tumordicke die endgültige Versorgung häufiger mit kleinerem Sicherheitsabstand erfolgte. Die vorliegende Analyse zeigt, daß das Zentralregister Malignes Melanom ein wichtiges Instrument zur Untersuchung von Entwicklungen der klinischen Epidemiologie und der Therapie des malignen Melanoms im deutschsprachigen Raum ist.SummaryThe Central Malignant Melanoma Registry of the German Dermatological Society was founded in 1983 and has meanwhile developed into a major continuously updated multicentre project. Up to June 1994, 19250 reports of cutaneous melanoma had been received, from 41 departments of dermatology in the former Federal Republic of Germany, from 14 departments in the former German Democratic Republic, from 2 departments in Austria, and from 1 department in Switzerland. Analysis of the data revealed some epidemiological trends over time during the years 1983 to 1993. (1) During the last 10 years the percentage of male patients has steadily increased, from an average of 38% in the year 1983 to 46% in 1993. (2) Early diagnosis of malignant melanoma improved during the period of time investigated. The percentage of diagnoses of primary tumour alone increased between 1983 and 1993. The mean tumour thickness (Breslow) decreased in the West Germany from 1.8 mm to 1.3 mm and in East Germany from 2.5 mm to 1.7 mm. The proportion of nodular melanoma decreased correspondingly from 29% to 14% in the former Federal Republic of Germany and from 40.6% to 22.6% in the former Germany Democratic Republic. During the years 1990 and 1993, 64% of melanoma patients with the primary tumour alone were operated on in two consecutive sessions in the former Federal Republic of Germany and 34.2% of those in the former Germany Democratic Republic. During this period 73.7% of all melanoma patients were operated on under local anaesthesia. In recent years surgical operations were more often performed in two consecutive sessions, mostly under local anaesthesia and with decreasing safety margins, in keeping with the decrease in tumour thickness. The present analysis shows that the Central Malignant Melanoma Registry is an important instrument for investigating trends in clinical epidemiology and treatment of malignant melanoma in the German-speaking countries.

Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

BACKGROUND Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. METHODS Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. FINDINGS Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes. INTERPRETATION Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.