Influence of a 7-day Transalpine Trail Run on cardiac biomarkers and myocardial function.

Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7-day trail-running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs-TnT, NT-proBNP, and suppression of tumorigenicity-2 protein (ST2)) at baseline, after each stage and 24-48 h post-race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT-proBNP increased significantly (3.6-fold, p = 0.009) during the first stage and continued to increase during the race. Hs-TnT revealed an incremental trend during the first day (2.7-fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post-race. NT-proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = -0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post-race. In summary, this study shows that prolonged, repetitive, high-volume exercise induced a transient, significant increase in NT-proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.

Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration.

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.

How Does Dietary Intake Relate to Dispositional Optimism and Health-Related Quality of Life in Germline BRCA1/2 Mutation Carriers?

Background: The Mediterranean diet (MD) is an anti-inflammatory diet linked to improved health-related quality of life (HRQoL). Germline (g)BRCA1/2 mutation carriers have an increased risk of developing breast cancer and are often exposed to severe cancer treatments, thus the improvement of HRQoL is important. Little is known about the associations between dietary intake and HRQoL in this population. Methods: We included 312 gBRCA1/2 mutation carriers from an ongoing prospective randomized controlled lifestyle intervention trial. Baseline data from the EPIC food frequency questionnaire was used to calculate the dietary inflammatory index (DII), and adherence to MD was captured by the 14-item PREDIMED questionnaire. HRQoL was measured by the EORTC QLQ-C30 and LOT-R questionnaires. The presence of metabolic syndrome (MetS) was determined using anthropometric measurements, blood samples and vital parameters. Linear and logistic regression models were performed to assess the possible impact of diet and metabolic syndrome on HRQoL. Results: Women with a prior history of cancer (59.6%) reported lower DIIs than women without it (p = 0.011). A greater adherence to MD was associated with lower DII scores (p < 0.001) and reduced odds for metabolic syndrome (MetS) (p = 0.024). Women with a more optimistic outlook on life reported greater adherence to MD (p < 0.001), whereas a more pessimistic outlook on life increased the odds for MetS (OR = 1.15; p = 0.023). Conclusions: This is the first study in gBRCA1/2 mutation carriers that has linked MD, DII, and MetS to HRQoL. The long-term clinical implications of these findings are yet to be determined.

Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Feasibility of a 12-Month Exercise Intervention in Postsurgical Colorectal Cancer Patients.

Background: Extensive physical activity (PA; ≥18 MET∗h/week, MET metabolic equivalent of tasks hours) postcancer diagnosis has shown favorable effects on colorectal cancer disease-free survival. However, the feasibility of introducing this high volume of PA in this patient group is unclear. Therefore, the aim of the F-PROTECT study was to evaluate the feasibility of extensive and prolonged PA (≥18 MET∗h/week over 12 months) in colorectal cancer patients with the primary objectives to (1) recruit 50 patients within 12 months and (2) reach an attendance rate of ≥70%. Methods: Single-armed, bicentric, prospective intervention study in colorectal cancer patients (≤80 years; UICC II/III Union for International Cancer Control) after histopathological confirmed R0-resection who were consecutively recruited from visceral surgery units of 10 clinics in Germany. Recruitment rates were calculated using screening logs. Intervention was a 12-month endurance-focused exercise program with supervised and home-based training. Attendance rates defined as ≥70% participation in training sessions were calculated by training diaries. Results: Out of 521 patients who were screened for eligibility, 50 (23 female; 59 ± 10 years, UICC 44% II, 56% III; adjuvant chemotherapy 60%) were recruited within 15 months. Mean duration between surgery and first training was 103 ± 57 days. Training attendance rate was 64% (including 9 dropouts). Six (12%) participants reached ≥18 MET∗h/week in ≥70% of training sessions between 4-12 months. 28 adverse events (n = 9 serious) occurred, however, were not assessed as training related. Conclusions: The present intervention involving a combination of supervised and home-based exercise training in postsurgical colorectal cancer patients was not feasible. Strategies specifically designed for this patient group must be developed and investigated to motivate long-term PA. Registration. The study was prospectively registered at clinicaltrials.gov (NCT01991847).

Determinants of oxygen utilization in breast cancer: Similarities between heart failure with preserved ejection fraction.

Reduced exercise tolerance and fatigue are hallmark features in both breast cancer (BC) and heart failure with preserved ejection fraction (HFpEF) and are associated with decreased physical function and quality of life. This brief review focuses on the mechanisms of exercise intolerance in women with BC across the survivorship continuum and highlights how these disturbances within the oxygen transport cascade are similar to that of HFpEF patients. Specifically, the role that impaired cardiac, peripheral vascular and skeletal muscle function play in limiting peak oxygen uptake are discussed. We propose that women with BC are at increased risk of developing HFpEF potentially due to the adverse effects of chemotherapy and concurrent adverse lifestyle behaviors on cardiovascular and skeletal muscle function.

Paediatric familial hypercholesterolaemia screening in Europe: public policy background and recommendations.

Familial hypercholesterolaemia (FH) is under-recognized and under-treated in Europe leading to significantly higher risk for premature heart disease in those affected. As treatment beginning early in life is highly effective in preventing heart disease and cost-effective in these patients, screening for FH is crucial. It has therefore now been recognized by the European Commission Public Health Best Practice Portal as an effective strategy. Model programmes exist in Europe to identify young individuals with FH, which are based on cascade screening of first-degree relatives of affected individuals, universal screening for high cholesterol, opportunistic screening of high-risk individuals, or a combination of the above approaches. Recommendations presented herein to improve identification of FH emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system, governments should provide financial support for these programmes and related care, and further research to optimize care and implementations should be conducted.

Long-term outcomes of implant-based immediate breast reconstruction with and without radiotherapy: a population-based study.

BACKGROUND: Radiotherapy (RT) is a risk factor for impaired outcomes after implant-based immediate breast reconstruction (IBR). Large studies including long-term follow-up are relatively scarce. The purpose of this analysis was to assess long-term effects of RT in implant-based IBR, distinguishing between implant removal because of postoperative complications versus patient preference. METHODS: This population-based cohort study included all patients with breast cancer who underwent implant-based IBR in Stockholm between 2005 and 2015. Data were collected through national registers and medical charts. The main endpoint was implant removal owing to postoperative complications (wound breakdown, infection, bleeding) or patient preference (dissatisfaction, pain, capsular contracture), with or without conversion to autologous reconstruction. RESULTS: Some 1749 implant-based IBRs in 1687 women were included. Median follow-up was 72 (range 1-198) months. Reconstructions were divided according to receipt of RT: No RT (n = 856, 48.9 per cent), adjuvant RT (n = 749, 42.8 per cent), and previous RT (n = 144, 8.2 per cent). Implant removal occurred after 266 reconstructions (15.2 per cent); 68 (7.9 per cent) in the no RT, 158 (21.1 per cent) in the adjuvant RT, and 40 (27.8 per cent) in the previous RT group. Implant removal was because of postoperative complications in 152 instances (57.1 per cent) and was most common in the first 3 years. This was especially observed in the previous RT group, where 15 of 23 implant removals occurred during the first 6 months. Implant removal owing to patient preference (114 of 266, 42.9 per cent) became more common with increasing follow-up. CONCLUSION: Implant removal after implant-based IBR is significantly associated with RT. The reason for implant removal shifts over time from postoperative complications to patient preference.

Irradiation of the chest wall after breast removal and implant placement (reconstruction) increases the risk of complications. These may lead to removal of the implant. Some women then choose a new breast reconstruction without an implant. The aim of this project was to find out how much irradiation affects complications after breast reconstruction using implants. This work used information on women who had a breast reconstruction with implants in Stockholm, Sweden, from 2005 to 2015. The main focus was on removal of the implant. This could be due to complications or patient preference. Implant removal could be with or without a new breast reconstruction. Of 1749 reconstructed breasts in 1687 women, 266 implants were removed. This was most often because of a complication, especially in the first years after surgery, but nearly as often due to patient wish. Implant removal owing to patient wish occurred later. Irradiation was a major factor increasing the risk of implant removal, together with, for example, smoking and obesity.

Associations of Plasma Bioactive Adrenomedullin Levels with Cardiovascular Risk Factors in BRCA1/2 Mutation Carriers.

Background Cardiovascular disease (CVD) is an important cause of morbidity and mortality in breast cancer survivors. Effective screening modalities to identify CVD risk are lacking in this population. Adrenomedullin (ADM) has been suggested as a biomarker for subclinical cardiac dysfunction in the general population. Levels of ADM have been proven to be responsive to lifestyle changes that lead to improved cardiovascular health. As BRCA1/2 mutation carriers are deemed to be at an increased risk for CVD, the aim of this study was to examine plasma ADM levels in a cohort of BRCA mutation carriers and to assess their association with cardiovascular risk factors. Methods Plasma ADM concentrations were measured in 292 female BRCA1/2 mutation carriers with and without a history of breast cancer. Subjects were classified into high versus low ADM levels based on the median ADM level in the entire cohort (13.8 pg/mL). Logistic regression models were used to estimate the odds ratios (OR) of having elevated ADM levels by several cardiovascular risk factors. Results Of all women (median age: 43 years), 57.5% had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was three years (range: 0 - 32 years). Women presenting with metabolic syndrome had 22-fold increased odds of having elevated ADM levels (p < 0.001). Elevated ADM levels were associated with lower cardiorespiratory fitness (OR = 0.88, p < 0.001) and several parameters of obesity (p < 0.001). ADM levels were higher in women who have ever smoked (OR = 1.72, p = 0.02). ADM levels were not associated with a previous diagnosis of breast cancer (p = 0.28). Conclusions This is the first study in BRCA mutation carriers that has linked circulating ADM levels to traditional cardiovascular risk factors. The long-term clinical implications of these findings are yet to be determined.

Peak O2 -pulse predicts exercise training-induced changes in peak V̇O2 in heart failure with preserved ejection fraction.

AIMS: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2 -pulse (V̇O2  × HR-1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2 , is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. METHODS AND RESULTS: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2 , peak O2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2 -pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2 -pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2 -pulse was associated with a decreased mean change in peak V̇O2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). CONCLUSIONS: In patients with HFpEF, the easily measurable peak O2 -pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2 -pulse, patients with high O2 -pulse may need to use additional therapies to significantly increase peak V̇O2 .

The COVID-19 Pandemic Consequences on Microsurgical Reconstructions: A Single Center's Shift of Indications.

Background: Since its outbreak, the COVID-19-pandemic has had a tremendous impact on healthcare systems worldwide. We conducted a comparative study to analyze the pandemic's consequence on microsurgical reconstructions at a reconstructive plastic surgery center in Sweden. Method: All free flaps performed at a single center between March 2019 and 2021 were analyzed. The patient cohort was divided into two groups, with a period of 1 year in each group: non-COVID-19 year and COVID-19 year. The periods were compared regarding the number and type of surgeries and patient characteristics. Results: In the year prior to the pandemic, 123 free flap surgeries were performed, compared with 103 surgeries during the COVID-19 year. There was a significant shift in the most common site for free flap reconstruction: from the breast [which decreased by 42% (66-38)] to head and neck [which increased by 22% (41-50); OR 0.53 (P = 0.02)]. This was also reflected by a significant increase in hospital stay for free flap patients during the COVID-19 year (P = 0.02). Conclusions: During the COVID-19 pandemic, a shift was seen from breast reconstructions toward head and neck reconstructions as the most common free flap procedure performed. An increasing backlog of elective breast reconstructions demands increased resources and tougher priorities, which challenge the healthcare system in the post-COVID-19 era.

Mandibular resection in patients with head and neck cancer: acute and long-term complications after reconstruction.

BACKGROUND: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient. AIMS/OBJECTIVES: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions. MATERIAL AND METHODS: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24). RESULTS: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication. CONCLUSIONS: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts. SIGNIFICANCE: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.

EAPC Core Curriculum for Preventive Cardiology.

Preventive cardiology encompasses the whole spectrum of cardiovascular disease (CVD) prevention, at individual and population level, through all stages of life. This includes promotion of cardiovascular (CV) health, management of individuals at risk of developing CVD, and management of patients with established CVD, through interdisciplinary care in different settings. Preventive cardiology addresses all aspects of CV health in the context of the social determinants of health, including physical activity, exercise, sports, nutrition, weight management, smoking cessation, psychosocial factors and behavioural change, environmental, genetic and biological risk factors, and CV protective medications. This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe. It will be the basis for dedicated fellowship programmes and a European Society of Preventive Cardiology (EAPC) subspecialty certification for cardiologists, with the intention to improve quality and outcome in CVD prevention.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology.

Background: Exercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). Methods: The Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60-70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90-95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results: 215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. Conclusions: Etiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration­URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Free Flap Surgery Outcome Related to Antithrombotic Treatment Regime: An Analysis of 1000 Cases.

Autologous free tissue transfer is today an integral part of reconstructive plastic surgery, but still lacks generally accepted guidelines regarding antithrombotic agents. We hypothesized that the overuse of antithrombotic agents could be a risk factor for free flap complications and therefore studied a treatment protocol adjustment. METHODS: Consecutive free flaps between 2005 and 2020 at a single center were analyzed for complications in relation to the use of pre- and intraoperative treatment with three different antithrombotic agents. The use of preoperative low molecular weight heparin (LMWH), intraoperative heparin, and dextran were analyzed in relation to outcome variables, thromboembolic events, or reexploration for hematoma. RESULTS: Nine hundred thirty-one patients underwent 1000 microvascular free flaps for breast (n = 487), head and neck (n = 365), and extremity (n = 148) reconstruction. Within the first postoperative week, 44 cases had a thromboembolic event and 58 cases underwent hematoma-related reexploration. In the multivariate analysis, thromboembolic events were associated with extremity reconstruction (P = 0.02) and smoking (P = 0.02). Hematoma-related reexploration was more common with triple antithrombotic therapy compared with all other treatment regimes (P < 0.05). The number of antithrombotic agents used perioperatively was linearly decreased, from three to none, over the elapsed time period (P < 0.001). CONCLUSIONS: Hematoma was the most common reason for reexploration and was further associated with the use of multiple antithrombotic agents. Cessation of triple treatment was associated with less hematomas and further reduction of antithrombotic agents did not result in any increase of thromboembolic events. Evidence-based guidelines are warranted for antithrombotic regimes in standard free flap surgery.

Changes of omentin-1 and chemerin during 4 weeks of lifestyle intervention and 1 year follow-up in children with obesity.

AIMS: Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce. METHODS: In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs). RESULTS: Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p < 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p < 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p < 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p < 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p < 0.001). CONCLUSION: Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss. TRIAL REGISTRATION: ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.

Beyond the 21-cm Notch-to-nipple Myth: Golden Proportions in Breast Aesthetics.

BACKGROUND: The 21-cm notch-to-nipple distance has been accepted without academic scrutiny as a key measure in breast aesthetics. The Fibonacci sequence and phi ratio occur frequently in nature. They have previously been used to assess aesthetics of the face, but not the breast. This study aims to assess if the static 21-cm measure or the proportional phi ratio is associated with ideal breast aesthetics. METHOD: Subclavicular-breast height and breast width were used to calculate the aesthetic ratio. Subjects were subsequently aesthetically rated. A one-sample t-test was used to determine if the ratio for each breast differed from phi. Breast scores with one, both, or no breasts were compared with an optimal phi ratio. Analysis of variance was performed. Tukey-Kramer adjustment for multiple comparisons was used when pairwise comparisons were conducted. RESULTS: Five subjects (14%) had bilateral optimal phi ratio breasts. Four subjects (11%) had one breast with an optimal phi ratio. Subjects with bilateral optimal phi ratios had significantly higher overall breast scores than those with only one optimal breast (Δ = 0.86, P = 0.025) or no optimal breast (Δ = 0.73, P = 0.008). Distance from optimal Fibonacci nipple position was moderately to strongly correlated with aesthetic score (-0.630, P = 0.016). No correlation was found between 21-cm notch-to-nipple distance and aesthetic score. CONCLUSION: The bilateral optimal phi ratio is correlated with high overall aesthetic scores, as is the optimal Fibonacci nipple position. No correlation was found between 21-cm notch-to-nipple distance and overall aesthetic score.

Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: results of the lifestyle intervention pilot study LIBRE-1.

PURPOSE: Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations. METHODS: Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups. RESULTS: The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = - 0.70; q = 0.0018). Baseline physical fitness (assessed as VO2peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871). CONCLUSION: Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.

Considerations on the Demography of BIA-ALCL in European Countries Based on an E(A)SAPS Survey.

BACKGROUND: A growing body of evidence indicates that breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is associated with the use of certain breast implants. Regional variations have been reported, and a genetic susceptibility has also been suggested. However, large variations in the ability to correctly diagnose BIA-ALCL and to further report and register cases exist between countries and may in part explain variations in the demography. MATERIAL AND METHODS: A survey was conducted by The European Association of Societies of Aesthetic Plastic Surgery E(A)SAPS and sent to 48 European countries. The primary aim was to identify the total number of confirmed cases of and deaths from BIA-ALCL in each country during four consecutive measurements over a two-year period. RESULTS: An increase in BIA-ALCL cases during four repeated measurements from a total of 305 in April 2019 to 434 in November 2020 was reported by 23 of the 33 responding countries. A nearly 100-fold variation in the number of cases per million inhabitants was noted, where Netherlands had the highest rate (4.12) followed by Finland (1.99). Countries with the lowest reported rates were Austria (0.078), Romania (0.052) and Turkey (0.048). CONCLUSION: The current study displays a notable variation ßin the number of confirmed BIA-ALCL cases across Europe, even for countries with established breast implant registers. Variations in diagnosis and reporting systems may explain the differences, but the influence of genetic variations and the prevalence of high-risk implants cannot be excluded. Incomplete sales data along with medical tourism preclude an absolute risk assessment. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .