"Normal" breast dimensions in obese women-reference values and the effect of weight loss.

BACKGROUND: Breast hypertrophy may cause significant suffering, such as back- and breast pain, painful shoulder groves, and eczemas. Furthermore, women with breast hypertrophy may have lower quality of life than women without breast hypertrophy. Although 50% of the women undergoing breast reduction in the US have body mass index (BMI) >30 kg/m2, the current standard of normality is based on studies focusing on women <40 years of age and BMIs <25 kg/m2. This study aimed to present reference values for breast measurements for women with obesity and to investigate the relationship between BMI loss and each breast measurement. MATERIALS AND METHODS: One hundred and six women underwent laparoscopic Roux-en-Y gastric bypass in Gothenburg, Sweden. The participants' breast anthropometrics were measured before and after bariatric surgery and their perception of the skin on their breasts was measured using the Sahlgrenska Excess Skin Questionnaire. RESULTS: Breast volume, sternal notch to nipple (SNN) distance, and ptosis increased significantly with increasing BMI. For instance, women with BMIs between 30-34.9 kg/m2 have a mean breast volume of approximately 770 ml, those with BMIs of 40-44.9 kg/m2 have approximately 1150 ml, and those with BMIs above 50 kg/m2 have approximately 1400 ml. Furthermore, the percent change in the respective breast measurements relative to percent BMI change can be predicted, for instance, with a 20% reduction in BMI, the breast volume, SNN-distance, and ptosis decrease by 25%, 4%, and 20% respectively. CONCLUSIONS: This article presents the first standard of normality for breast anthropometrics in women with obesity and a model for predicting the change in breast anthropometrics relative to BMI. CLINICAL TRIAL REGISTRATION: This is a longitudinal observation study, registered https://fou.nu/is/gsb/ansokan/49651, No: VGFOUGSB-49651. Trial registry name: "Överskottshud efter överviktskirurgi - dess utveckling samt behov och effekt av plastikkirurgi" ("Excess skin after bariatric surgery - its development and the need and effect of plastic surgery").

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial.

BACKGROUND: In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. METHODS: NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. FINDINGS: Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2-34·9) versus 38·5 months (27·6-not reached; hazard ratio [HR] 1·52 [95% CI 1·00-2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46-67) in the neoadjuvant FOLFIRINOX group versus 70% (55-83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2-34·9) versus 34·4 months (19·4-not reached; HR 1·46 [95% CI 0·99-2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. INTERPRETATION: This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven. FUNDING: Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.

SESQ, a patient-reported outcome instrument addressing excess skin; report on the updated version and the validation process.

Excess skin after weight loss is perceived as a major problem for the majority of the bariatric patients, between 68 and 90% desire additional reconstructive surgery. However, only about 20% of the patients actually have the possibility to undergo these procedures. Reliable and valid patient-reported outcome instruments, PROM, are required in order to consider the patients' perspective of excess skin when discussing reconstructive surgery. The aim of this study was to present the updated version of Sahlgrenska Excess Skin Questionnaire, SESQ and to report on the validation process. The material for the process to evaluate internal consistency and known group validity was based on four different studies conducted at the Department of Plastic Surgery at Sahlgrenska University Hospital, Sweden. Internal consistency was high in all four groups examined; the normal population, the obese patients, the post-bariatric patients and the post-abdominoplasty patients. Values for Cronbach's alpha were >0.86 in all groups, and the highest value was seen in the obese patients (0.92). Furthermore, regarding known group validity, there were strong significant differences between the answers from the normal population in comparison with most of the other studies. In conclusion, patients thought that the questions in SESQ were easy to understand, that they covered all appropriate aspects of excess skin and the patients did not think that SESQ overlooked any questions or aspects concerning excess skin. SESQ is a valid questionnaire addressing excess skin in post-bariatric patients. The updated version of the SESQ is both accurate and user-friendly.

Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures.

Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects against obesity-induced systemic disease in mice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularly well to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generating enzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.

Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components.

Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.

Physical activity with hindrances: a qualitative study of post bariatric patients' experiences of physical activity in relation to excess skin.

A common side effect after massive weight loss is excess skin. Knowledge about the experience of excess skin in relation to physical activity is limited. The aim of this study was therefore to investigate how post bariatric surgery patients experience physical activity in relation to excess skin. Fifteen semi-structured interviews were performed with individuals who experienced excess skin after massive weight loss after bariatric surgery. The interviews were transcribed, and data were analyzed by qualitative content analysis. An overall theme emerged, that the body was still a hindrance for physical activity but now because of excess skin. There were major changes in the participants' ability to be active after the weight loss, but there were still obstacles and some of them remained from the time when they were obese. The analysis resulted in three main categories containing the participants' knowledge about, changes in and wishes for physical activity after weight loss, factors that affected the ability and the role of mental processes. The result contributes to increased knowledge about post bariatric patients' experiences of excess skin in relation to physical activity. After weight loss, the body was still a hindrance for physical activity but now because of excess skin. As physical activity is important for general health, excess skin inhibiting physical activity ought to be an indicator for reconstructive surgery.

Translation and validation of a Swedish version of the BODY-Q: a patient-reported outcome instrument for weight loss and body contouring surgery.

BODY-Q is self-administered questionnaire that evaluates appearance, function and symptoms related to bariatric- and body contouring surgery. The purpose of this article was to describe the translation process of a Swedish version of BODY-Q and to evaluate its criterion validity to the Swedish questionnaire Sahlgrenska Excess Skin Questionnaire, SESQ. MATERIALS AND METHODS: BODY-Q was translated according to International Society for Pharmacoeconomics and Outcome Research's guidelines. The test of validity was made between parts which were comparable to SESQ. Both questionnaires were responded by 30 subjects who were suffering from excess skin after massive weight loss following bariatric surgery or dieting. RESULTS: The correlation between the two questionnaires varied. The parts of BODY-Q evaluating excess skin on the whole body and parts of the body had higher correlations (rs 0.328-0.766) than the parts evaluating side effects of excess skin and body-image (rs 0.103-0.574). CONCLUSION: The Swedish version of BODY-Q has a good criterion validity and can be recommended in the healthcare for patients with excess skin after massive weight loss and for evaluation of the outcomes from reconstructive surgical procedures.

Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets-Data from a Randomized Cross-Over Study in Healthy Subjects.

Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.

Challenges in PhD education due to COVID-19 - disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students.

BACKGROUND: It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data. METHODS: An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support. RESULTS: PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups. CONCLUSIONS: It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor's emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.

Excess skin after weight loss following bariatric surgery: focus on the abdomen.

BACKGROUND: The majority of postbariatric patients experience major problems from excess skin, with most desiring abdominoplasty. OBJECTIVES: To present visual assessments and objective measurements of excess abdominal skin; analyze relationships between patient-reported outcomes, objective measurements of excess skin, and visual assessments; and discuss criteria for reconstructive abdominal surgery in public healthcare. SETTING: An academic hospital in Sweden. METHODS: This is a secondary analysis of a prospective, longitudinal study that included 200 obese patients undergoing bariatric surgery, with 147 of these patients participating in follow-up 18-months postsurgery. Patients rated their symptoms related to excess skin and quality of life (QoL) according to the Sahlgrenska Excess Skin Questionnaire and EuroQol-5 D before and after bariatric surgery. Abdominal ptosis was measured at different anatomic locations. RESULTS: Waist circumference and ptosis were significantly reduced at all anatomic locations after weight loss, and abdominal ptosis was significantly larger laterally than at the midline (P < .001). The majority of patients had a ptosis ≥3 cm following bariatric surgery and had significantly more symptoms related to excess skin relative to those reported preoperation (P < .05). Additionally, the number of patients experiencing discomfort from excess skin increased along with increased ptosis size, but the correlation between ptosis size and QoL was low. Reconstructive abdominal surgery was requested by 70% of patients, all having significantly larger ptosis and significantly more symptoms than those not desiring surgery. CONCLUSION: Criteria for abdominal reconstruction should be based on both patient-reported symptoms and objective measures to ensure more patient-centered care than is possible only using objective measurements.

Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.

The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.

Aspects of excess skin in obesity, after weight loss, after body contouring surgery and in a reference population.

BACKGROUND: Excess skin is well known after massive weight loss but, there is missing knowledge from various groups. OBJECTIVES: To describe and compare excess skin in a reference population during obesity, after obesity surgery, and after reconstructive abdominoplasty. SETTING: University hospital, Sweden. METHODS: The following 6 groups were included: the reference population, obese adults before obesity surgery, obese adults after obesity surgery, adolescents after obesity surgery, super-obese adults after obesity surgery, and adults after abdominoplasty. All groups filled in the Sahlgrenska Excess Skin Questionnaire (SESQ). Some groups also underwent measurements of ptosis/excess skin on 4 body parts. RESULTS: All groups scored significantly higher experience of and discomfort from excess skin compared with the reference population. SESQ scores were significantly higher for obese adults (10.5 ± 8.5) and even higher for adults and adolescents (12.3 ± 8.1 versus 14.4 ± 7.7) after obesity surgery compared with the reference population (1.5 ± 3.5). Abdominoplasty resulted in significantly reduced scores (2.9 ± 5.2). Those undergoing obesity surgery and weight loss had significantly less excess skin measured on arms, breasts, and abdomen compared with before surgery, except for the upper arms on the adolescents. Excess skin increased on inner thighs in both age groups after weight loss. Correlations between objectively measured ptosis/excess skin and the patients' experience of and discomfort were .16 to .71, and the highest correlations were found among adolescents. CONCLUSION: Excess skin is not a problem for the vast majority of the normal population but is linked to obesity and massive weight loss. The SESQ score illustrates major problems related to excess skin both for obese adults and after obesity surgery for adults and for adolescents, who have problems similar to or worse than adults. Abdominoplasty markedly decreases symptoms.

Self-image after bariatric surgery and its relationship to gender, excess skin and health-related quality of life.

Introduction: There is limited knowledge about self-image in relation to excess skin after bariatric surgery. The aim of this study was therefore to explore self-image after massive weight loss and its relationship to gender, weight loss, discomfort regarding excess skin and health-related quality of life. Methods: Eighteen months after obesity surgery, 131 patients filled in questionnaires about self-image (Som jag ser mig själv), excess skin (Sahlgrenska Excess Skin Questionnaire, SESQ) and quality of life (EQ-5D and SF-36). In addition, maximal ptosis was measured on their abdomen, arms and thighs. Results: There were no differences in self-image or quality of life between the genders. Participants who scored low discomfort on SESQ had a significantly better overall self-image, in all subscales, compared to those with high discomfort scores (p < .05). They also had a significantly higher quality of life on the EQ-5D VAS (p = .045). Correlations were low, if any, between self-image, excess skin, quality of life and ptosis. There were moderate correlations between the SESQ score and the self-image subscore 'physical well-being', and in self-image and quality-of-life scores. Conclusions: Self-image is lower among those who experience a high degree of discomfort of excess skin after bariatric surgery. Its correlation to weight loss, measured excess skin and quality of life is weak.

Increased joint pain after massive weight loss: is there an association with joint hypermobility?

BACKGROUND: Obesity is associated with an increased risk of pain in weight-bearing joints. Although pain often decreases after obesity surgery, this is the reverse for some patients. Hypermobility is described as an excessive range of motion in joints and has been suggested to be a possible cause of joint pain. It is not known whether there is an association between increased joint pain after weight loss and hypermobility. OBJECTIVES: The objective of this study was to investigate whether there is an association between hypermobility and increased joint pain after massive weight loss. SETTING: University hospital, Sweden. METHODS: A survey including a screening questionnaire about hypermobility and questions about joint pain was sent to 149 people who had previously undergone bariatric surgery. Ninety-three people (72 women and 21 men) completed the questionnaire. RESULTS: Nineteen of the respondents fulfilled the criteria for hypermobility. There were no significant differences between the groups with and without hypermobility regarding pain in weight-bearing joints before or after surgery. There was a significant difference between the groups with increased or novel pain in the ankles, shoulders, hands, and feet (P<.05) after the weight loss. Furthermore, the patients with hypermobility had increased or novel pain in a significantly higher number of weight-bearing joints, other joints, and joints in total (P< .05). CONCLUSION: Even with a small sample size, a tendency can be seen for people with hypermobility to experience increased joint pain after weight loss compared with those without hypermobility.

AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin.

AIMS/HYPOTHESIS: In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. METHODS: Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 µg/g) three times/week from weeks 4-12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35-50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry. RESULTS: AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p < 0.05), urinary H2O2 (p < 0.05) and renal superoxide levels (p < 0.01) in both wild-type and Adipoq -/- mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq -/- mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients. CONCLUSIONS/INTERPRETATION: AICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02322073.

Understanding excess skin in postbariatric patients: objective measurements and subjective experiences.

BACKGROUND: Excess skin is a well-known side effect of massive weight loss after bariatric surgery. However, there is a lack of longitudinal follow-ups. OBJECTIVES: The primary aims of this study were to investigate the development and amount of excess skin after laparoscopic Roux-en-Y gastric bypass and to relate objective results to subjective experiences. SETTING: University hospital. METHODS: From 2009 to 2012, 200 patients were included and assessed with respect to excess skin before and 18 months after bariatric surgery. Patients were measured according to a standardized protocol and completed a questionnaire regarding their subjective experience of excess skin. RESULTS: A follow-up visit was completed in 149 patients (78%). All ptosis measurements decreased after weight reduction except for ptosis on the thighs. When comparing objective measurements with patients' subjective experience and discomfort from excess skin, we found little or low correlation in most body parts (rs .03-.67). The prediction analysis indicated that, for every centimeter of ptosis on the abdomen preoperatively, there was a 2-fold greater probability of having a postoperative ptosis on the abdomen of>3 cm (OR = 2.32, 1.76-3.07). CONCLUSION: The objective measurement of excess skin provides unique information in postbariatric patients' body habitus. Although the measured excess skin decreased compared with preoperative measurements, patients seem to become more aware of and disturbed and discomforted by it after the weight loss. Importantly, the objectively assessed measurements of excess skin correlated fairly with the perceived discomfort.

Objective measurements of excess skin in post bariatric patients--inter-rater reliability.

BACKGROUND: An ability to reliably assess excess skin after massive weight loss using well-described and transferrable methods is important. The aim of this trial was to evaluate inter-rater reliability of ptosis and circumference measurements in patients with excess skin after bariatric surgery. MATERIALS AND METHODS: Twenty-five postbariatric patients were included in the study, and their excess skin was measured 18 months after surgery. A protocol was designed to measure excess skin in a standardised way. To evaluate the inter-rater reliability in the measuring protocol, all patients were measured twice, by a specialist nurse and a specialist physiotherapist. RESULTS: All circumference measurements on different body parts had an ICC > 0.9, indicating high reliability. Furthermore, all breast and abdominal ptosis measurements had high reliability. In contrast, visual evaluation of abdominal ptosis had poor reliability. Measurements of ptoses on different body parts had an ICC > 0.6. There were no systematic differences between the results of the two testers, except for measurements of the buttocks and maximal knee circumference. CONCLUSION: The measuring protocol presented in this study has high reliability and, therefore, represents a useful instrument to provide a consistent and objective assessment of excess skin in the postbariatric patient.

Therapeutic ultrasound treatment for excessive skin on the upper arms due to extensive weight loss after bariatric surgery: A single blind, randomised, controlled trial.

BACKGROUND: Excessive skin is a side-effect of massive weight loss. The only evidence-based treatment for excessive skin is plastic surgery. Non-invasive treatments, therefore, need to be evaluated. The aim of this study was to investigate effects of therapeutic ultrasound treatment on excess skin on the upper arms after bariatric surgery. METHOD: Fourteen patients were randomised to receive five treatments, each lasting for 30 minutes with active ultrasound treatment by CellsonicTM (Cellsonic Ltd) on one arm. The other arm served as control. The effect was evaluated objectively by measuring arm volume, circumference, and ptosis, and subjectively by a questionnaire where the patients assessed the effect of the treatment and amount and/or discomfort of the excess skin. RESULT: No statistical differences were observed in the objectively measured variables. Some patients reported perceived effects and a majority reported positive experiences of the treatment. No side-effects were reported. CONCLUSION: This study could not find any objectively measured effect of ultrasound treatment on excessive skin after bariatric surgery. However, participants experienced relief of symptoms associated with excess skin, such as pain, looseness, and decreased skin burst, which indicates that ultrasonic treatment of patients with excessive skin should be further investigated.

Experience of excess skin after gastric bypass or duodenal switch in patients with super obesity.

BACKGROUND: There is a lack of knowledge about the patient's experience of excess skin after bariatric surgery in patients with body mass index, (BMI)>50 kg/m(2). The objective of this study was to evaluate experience of excess skin after laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS) or laparoscopic Roux-en-Y gastric bypass (LRYGB) and explore possible gender differences. Another aim was to analyze possible correlation between the reported experiences of excess skin with changes in weight, BMI, and hip and waist circumference after surgery. METHODS: One and/or 2 years after gastric bypass or duodenal switch surgery 57 patients responded to a specific questionnaire. The questionnaire included questions about the amount of excess skin and how much discomfort it caused. Furthermore, the patients were measured concerning weight and waist and hip circumference. RESULTS: One year after surgery, a majority of the patients experienced excess skin scored as>2 ("a lot of" or "very much"). The patients in the BPD/DS group experienced significantly more excess skin compared to patients in the LRYGB group. Women experienced more excess skin and discomfort on several body parts than men. The correlations between changes in BMI and the reported experience and discomfort of excess skin were low. There was a low to moderate correlation between changes in waist and hip circumference measures and the experience of excess skin on stomach and buttocks. CONCLUSION: Weight loss after LRYGB and BPD/DS in super-obese patients is associated with substantial discomfort from excess skin. Women reported more discomfort and experienced more excess skin than men. There was a low correlation between experience of excess skin and changes in weight, BMI, and circumference measures.

Sahlgrenska Excess Skin Questionnaire (SESQ): a reliable questionnaire to assess the experience of excessive skin after weight loss.

There is a lack of knowledge and reliable measurement instruments to assess excess skin after massive weight loss. The purpose of this study was to test the reliability of a new self-administered questionnaire. A self-administered questionnaire, the Sahlgrenska Excess Skin Questionnaire (SESQ) was designed to assess excess skin after weight loss. The questionnaire includes 30 questions about demographic data, activity and daily life and excess skin on specific body parts and the body as a whole. Forward and backward translations were made by two independent professional translators, from Swedish to English and then back to Swedish. The questionnaire was tested on 10 patients from Sweden and England and was followed by an interview with each patient. Minor corrections were made. A test-retest was carried out to evaluate the reliability by sending the Swedish questionnaire to 46 subjects with weight loss after obesity surgery, dieting, or medication. The test-retest reliability of questions concerning activity and daily life between the two occasions had a Percentage Of Agreement (POA) of 49%-76% and a weighted Kappa of 0.44-0.78. The questions about the degree of excess skin on specific body parts had a POA of 50%-76% and a weighted Kappa of 0.53-0.81. Excess skin perceived as causing problems had a POA of 32%-57 %, an adjusted POA of 63%-87%, and an Intra-Class Correlation of 0.72-0.92. The SESQ is reliable for evaluating patients' experience of excess skin after massive weight loss.