The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial.

BACKGROUND: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown. METHODS: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated. RESULTS: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis. CONCLUSION: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

Fifteen-year changes in health-related quality of life after bariatric surgery and non-surgical obesity treatment.

BACKGROUND: Evidence on the long-term (≥10 years) development of health-related quality of life (HRQoL) following bariatric surgery is still limited and mainly based on small-scale studies. This study aimed to investigate (1) 15-year changes in mental, physical, social, and obesity-related HRQoL after bariatric surgery and non-surgical obesity treatment; and (2) whether sociodemographic factors and pre-operative health status are associated with 15-year HRQoL changes in the surgery group. METHODS: Participants were from the non-randomized, prospective, controlled Swedish Obese Subjects study. The surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual obesity care. Recruitment took place in 1987-2001 and measurements (including six HRQoL scales) were administered before treatment and after 0.5, 1, 2, 3, 4, 6, 8, 10 and 15 years. Multilevel mixed-effect regression models using all observations for estimation were conducted. RESULTS: Surgical patients experienced greater 15-year improvements in perceived health and overall mood, and greater reductions in depression, obesity-related problems, and social interaction limitations than controls (all p < 0.001, adjusted for baseline differences). Effect size (ES) was classified as large only for obesity-related problems (ES = 0.82). At the 15-year follow-up, surgical patients reported better perceived health (p < 0.001) and less obesity-related problems (p = 0.020) than controls. In the surgery group, patients with baseline diabetes had smaller 15-year reductions in social interaction limitations (p < 0.001) and depression (p = 0.049) compared to those without baseline diabetes. Although surgical patients with a history of psychiatric disorder reported lower HRQoL than those without such history over the 15-year follow-up, there were no significant differences in the long-term improvements between the two groups (p = 0.211-0.902). CONCLUSIONS: Over 15 years, surgical patients experienced more positive development of HRQoL compared to those receiving usual care. This difference was large for obesity-related problems, but otherwise the differences were small. Patients with pre-operative diabetes might be at increased risk for smaller long-term HRQoL improvements.

Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study.

BACKGROUND: Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear. METHODS: We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population. RESULTS: In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery. CONCLUSIONS: Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).

Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.

OBJECTIVES: To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study. METHODS: The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n = 265), banding (n = 376), or vertical banded gastroplasty (n = 1369). The control group (n = 2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n = 392 surgery patients/n = 305 controls) or non-T2D (n = 1609 surgery patients/n = 1726 controls) during a median follow-up 26 years. RESULTS: In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR) = 0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p = 0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR = 0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p = 0.516)). CONCLUSIONS: Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.

Management of complications after skin surgery relevant for melanoma in the trunk and extremities during the COVID-19 pandemic: a case series report.

BACKGROUND: Patients with melanoma have been found to be at greater risk of adverse outcomes including mortality after contacting COVID-19. Management of postsurgical complications presented additional challenges by potentially increasing exposure to COVID-19 through repeated inpatient admissions to hospital during the pandemic. We report four cases for which skin flaps, lymph ligation, and split-thickness skin graft (STSG) were successfully used in the treatment of complications in the trunk and extremities after wide local excision (WLE). This study details the operative experience in management of postsurgical complications for melanoma in the trunk and extremities during a 6-month period at the height of the COVID-19 pandemic. CASE PRESENTATION: We present 4 cases detailing management of complications that occurred after wide local excisions performed for melanoma during Feb. to Oct. 2020. Case 1: A 90-year-old man who experienced wound dehiscence and necrosis on the shoulder after non-radical excision for an aggressive melanoma and underwent the side-to-side closure after ellipse formed WLE with modified tangent-to-circle method. Case 2: An 80-year-old man who had undergone excision for melanoma in his left upper arm and histopathology did not show radically. Two weeks after the excision, he underwent a WLE and direct reconstruction with double rotation skin flap. Case 3: A 55-year-old man that experienced a large wound dehiscence on his back due to WLE. He underwent an advanced double skin flap operation. Case 4: A 36-year-old woman who had a lymphorrhea and graft necrosis after WLE and STSG on the right lower leg. A combination of micro lymph ligation and re-STSG was performed. One month after the operation, all wounds had healed. There was no clinical evidence of tumor recurrence after 8 months post procedure. CONCLUSIONS: Severe complications (e.g., large wound dehiscence, necrosis, or lymphorrhea) following wide local excision of melanoma are infrequent but must be swiftly and appropriately managed, especially during the COVID-19 pandemic to decrease the likelihood of COVID-19 infection and impaired oncology outcomes from delaying systemic cancer therapy due to the complications in primary interventions.

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.

BACKGROUND: Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. METHODS: We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. RESULTS: A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity. CONCLUSION: Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

Prediction of Suicide and Nonfatal Self-harm After Bariatric Surgery: A Risk Score Based on Sociodemographic Factors, Lifestyle Behavior, and Mental Health: A Nonrandomized Controlled Trial.

OBJECTIVE: To identify preoperative sociodemographic and health-related factors that predict higher risk of nonfatal self-harm and suicide after bariatric surgery. BACKGROUND: Evidence is emerging that bariatric surgery is related to an increased risk of suicide and self-harm, but knowledge on whether certain preoperative characteristics further enhance the excess risk is scarce. METHODS: The nonrandomized, prospective, controlled Swedish Obese Subjects study was linked to 2 Nationwide Swedish registers. The bariatric surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual care. Participants were recruited from 1987 to 2001, and information on the outcome (a death by suicide or nonfatal self-harm event) was retrieved until the end of 2016. Subhazard ratios (sub-HR) were calculated using competing risk regression analysis. RESULTS: The risk for self-harm/suicide was almost twice as high in surgical patients compared to control patients both before and after adjusting for various baseline factors [adjusted sub-HR = 1.98, 95% confidence interval (CI) = 1.34-2.93]. Male sex, previous healthcare visits for self-harm or mental disorders, psychiatric drug use, and sleep difficulties predicted higher risk of self-harm/suicide in the multivariate models conducted in the surgery group. Interaction tests further indicated that the excess risk for self-harm/suicide related to bariatric surgery was stronger in men (sub-HR = 3.31, 95% CI = 1.73-6.31) than in women (sub-HR = 1.54, 95% CI = 1.02-2.32) (P = 0.007 for adjusted interaction). A simple-to-use score was developed to identify those at highest risk of these events in the surgery group. CONCLUSIONS: Our findings suggest that male sex, psychiatric disorder history, and sleep difficulties are important predictors for nonfatal self-harm and suicide in postbariatric patients. High-risk patients who undergo surgery might require regular postoperative psychosocial monitoring to reduce the risk for future self-harm behaviors.

Bariatric Surgery Versus Standard Obesity Treatment and the Risk of Severe Liver Disease: Data From the Swedish Obese Subjects Study.

Obesity is closely associated with nonalcoholic fatty liver disease. A minority of patients with nonalcoholic fatty liver disease progress to liver cirrhosis and end-stage liver disease.1 Weight loss results in improvement of liver histology in persons with nonalcoholic fatty liver disease.2 Because weight loss can be challenging to achieve and sustain in persons with obesity, bariatric surgery is considered a feasible therapeutic option for persons with severe obesity.3 Bariatric surgery leads to improved glucose tolerance, weight loss, and improved overall mortality.4 It is less well known if bariatric surgery also reduces the incidence of liver-related outcomes. Here, we analyzed liver-related outcomes in the Swedish Obese Subjects (SOS) cohort.5.

Long-term incidence of hypoglycaemia-related events after bariatric surgery or usual care in the Swedish Obese Subjects study: A register-based analysis.

AIMS: To examine the incidence of hypoglycaemia-related events over a period of up to 31 years in patients treated with bariatric surgery in the prospective, controlled Swedish Obese Subjects (SOS) study. MATERIALS AND METHODS: The SOS study (n = 4047) is a prospective controlled intervention study. The present analysis included 1989 patients treated with bariatric surgery and 2027 control patients with obesity who received usual care. Diagnosed hypoglycaemia and events commonly attributed to hypoglycaemia (confusion, syncope, epilepsy and seizures), requiring hospital or specialist outpatient treatment, were identified by searching the National Patient Register. Analyses were stratified by baseline glycaemic status. Hazard ratios were adjusted for inclusion year, age, sex, smoking, glycated haemoglobin (HbA1c) level and body mass index at baseline. At the time of analysis (December 31, 2018), the median follow-up was 22 years. RESULTS: Compared with usual care, bariatric surgery was associated with increased incidence of hypoglycaemia-related events in patients without baseline diabetes (168 and 219 events, respectively; log-rank P = .011), with a more pronounced risk during the first years of follow-up (test of time-treatment interaction P = .010). Multivariate analyses in patients without baseline diabetes indicated that male sex (P < .001), older age (P = .001) and higher HbA1c levels (P = .006) were associated with hypoglycaemia-related events. No association was found between risk of hypoglycaemia-related events and bariatric surgery in patients with baseline diabetes. CONCLUSIONS: Bariatric surgery is associated with an increased incidence of hypoglycaemia-related events in patients without baseline diabetes, especially during the first years after treatment.

Bariatric surgery and the incidence of rheumatoid arthritis - a Swedish Obese Subjects study.

OBJECTIVE: The aim of this study was to determine the effect of bariatric surgery on the incidence of RA in participants of the Swedish Obese Subjects (SOS) study. METHODS: The SOS is a longitudinal study aiming to assess the effect of bariatric surgery on mortality and obesity-related diseases. This report includes 2002 subjects with obesity who underwent bariatric surgery and 2034 matched controls; none of them had RA at baseline. Cases of incident RA were identified through the Swedish National Patient Register by searching for International Classification of Diseases codes. Both intention-to-treat analyses and per-protocol analyses are reported. In the per-protocol analysis, participants from the control group who underwent bariatric surgery later on during follow-up were censored at the time of surgery. RESULTS: During follow-up, 92 study participants developed RA. The median follow-up was 21 years (range 0-29). Bariatric surgery was neither associated with the incidence of RA in the intention-to-treat analysis [hazard ratio (HR) 0.92 (95% CI 0.59, 1.46), P = 0.74], nor in the per-protocol analysis [HR 0.86 (95% CI 0.54, 1.38), P = 0.53]. Weight change at the 2 year follow-up, expressed as the change in BMI compared with baseline, did not associate with the development of RA. Higher serum CRP levels and smoking associated with the future development of RA independent of other factors. CONCLUSIONS: We did not detect any association between bariatric surgery and the incidence of RA in subjects affected by obesity followed up for up to 29 years. CLINICALTRIALS.GOV: (http://clinicaltrials.gov): NCT01479452.

Surgical obesity treatment and the risk of heart failure.

AIMS: Obesity is associated with increased risk for heart failure. We analysed data from the Swedish Obese Subjects (SOS) study, a prospective matched cohort study, to investigate whether bariatric surgery reduces this risk. METHODS AND RESULTS: From the total SOS population (n = 4047), we identified 4033 obese individuals with no history of heart failure at baseline, of whom 2003 underwent bariatric surgery (surgery group) and 2030 received usual care (control group). First-time principal diagnoses of heart failure were identified by crosschecking the SOS database with the Swedish National Patient Register and the Swedish Cause of Death Register using diagnosis codes. During a median follow-up of 22 years, first-time heart failure occurred in 188 of the participants treated with surgery and in 266 of those receiving usual care. The risk of developing heart failure was lower in the surgery group than in the control group [sub-hazard ratio 0.65, 95% confidence interval (CI) 0.54-0.79; P < 0.001]. After pooling data from the two study groups, the quartile of subjects with the largest weight loss after 1 year (mean -41 kg) displayed the greatest risk reduction (sub-hazard ratio 0.51, 95% CI 0.30-0.70; P < 0.001). This association remained statistically significant after adjustment for surgical intervention and potential baseline confounders (sub-hazard ratio 0.60, 95% CI 0.36-0.97; P = 0.038). CONCLUSION: Compared with usual care, bariatric surgery was associated with reduced risk of heart failure among persons being treated for obesity. The risk of heart failure appeared to decline in parallel with a greater degree of weight loss. CLINICALTRIALS.GOV IDENTIFIER: NCT01479452.

Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.

Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was ≥ 34 kg/m2 in men and ≥38 kg/m2 in women. The surgery per-protocol group (n = 2007) underwent gastric bypass (n = 266), banding (n = 376), or vertical banded gastroplasty (n = 1365), and controls (n = 2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P = 0.002). The incidence differed between treatment groups (P < 0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P < 0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.

Use of subcutaneous and intravenous trastuzumab: real-world experience from three hospitals in Sweden.

Aim: We aimed to describe the use of subcutaneous (sc.) trastuzumab use in a real-world setting. Patients & methods: This retrospective cohort study evaluated electronic medical records of patients with early breast cancer and trastuzumab use from January 2010 to February 2018 in three hospitals in Sweden. Results: In total, 363 patients received trastuzumab during study period. Of these, 217 (59.8%) patients started treatment with sc. trastuzumab and 146 (40.2%) with intravenous trastuzumab. After sc. trastuzumab approval, use of sc. trastuzumab increased from 70.2% in 2014 to 100% in 2017. Since 2013, 34 of 35 (97.4%) patients who started with intravenous trastuzumab switched to sc. formulation. Conclusion: Trastuzumab sc. quickly became the prevailing formulation for treatment in HER2-positive early breast cancer.

Rapid testing of red blood cell parameters in primary care patients using HemoScreen™ point of care instrument.

BACKGROUND: Patients with anemia are frequently encountered in primary care. Once anemia is detected, it is essential to define the type and identify the underlying cause prior to initiation of treatment. In most cases, the cause can be determined using information from the patient history, physical exam, and complete blood counts (CBC). Point of care testing of blood cell counts would speed up the work up of anemia patients. The aim of the present study was to evaluate if the HemoScreen™ instrument (PixCell Medical, Yokneam Ilit, Israel) could be used for primary care samples. It is a POCT instrument that utilizes single sample cuvettes and image analysis of full blood count including RBC, Hemoglobin, MCV, MCH, platelets, WBC, and WBC 5-part differential. METHODS: We compared the HemoScreen™ and the Sysmex XN instrument results of 100 primary care patient samples focusing on the total white blood cells, red blood cell parameters RBC, Hemoglobin, MCH, MCV and platelets. RESULTS: Deming correlations between the HemoScreen™ and the Sysmex XN instruments for the CBC were WBCHemoScreen™ = 1.016* WBCSysmex + 0.34; r = 0.981, RBCHemoScreen™ = 0.988* RBCSysmex + 0.015; r = 0.974, HemoglobinHemoScreen™ = 1.081* HemoglobinSysmex - 11.25; r = 0.964, MCHHemoScreen™ = 0.978* MCHSysmex + 0.78; r = 0.939, MCVHemoScreen™ = 0.963* MCVSysmex + 8.68; r = 0.946, PlateletsHemoScreen™ = 0.964* PlateletsSysmex + 25.7; r = 0.953. CONCLUSION: The HemoScreen™ instrument could provide rapid and accurate test results for evaluation of the red blood cell parameters in primary care. This new technology is interesting as it allows the analysis red blood cell parameters also at small primary care centers.

Immune gene expression and response to chemotherapy in advanced breast cancer.

BACKGROUND: Transcriptomic profiles have shown promise as predictors of response to neoadjuvant chemotherapy in breast cancer (BC). This study aimed to explore their predictive value in the advanced BC (ABC) setting. METHODS: In a Phase 3 trial of first-line chemotherapy in ABC, a fine needle aspiration biopsy (FNAB) was obtained at baseline. Intrinsic molecular subtypes and gene modules related to immune response, proliferation, oestrogen receptor (ER) signalling and recurring genetic alterations were analysed for association with objective response to chemotherapy. Gene-set enrichment analysis (GSEA) of responders vs non-responders was performed independently. Lymphocytes were enumerated in FNAB smears and the absolute abundance of immune cell types was calculated using the Microenvironment Cell Populations counter method. RESULTS: Gene expression data were available for 109 patients. Objective response to chemotherapy was statistically significantly associated with an immune module score (odds ratio (OR)=1.62; 95% confidence interval (CI), 1.03-2.64; P=0.04). Subgroup analysis showed that this association was restricted to patients with ER-positive or luminal tumours (OR=3.54; 95%, 1.43-10.86; P=0.012 and P for interaction=0.04). Gene-set enrichment analysis confirmed that in these subgroups, immune-related gene sets were enriched in responders. CONCLUSIONS: Immune-related transcriptional signatures may predict response to chemotherapy in ER-positive and luminal ABC.

Effects of bariatric surgery on gout incidence in the Swedish Obese Subjects study: a non-randomised, prospective, controlled intervention trial.

OBJECTIVES: To assess the long-term effect of bariatric surgery on the incidence of gout and hyperuricaemia in participants of the Swedish Obese Subjects (SOS) study. METHODS: This report includes 1982 subjects who underwent bariatric surgery and 1999 obese controls from the SOS study, a prospective intervention trial designed to assess the effect of bariatric surgery compared with conventional treatment. None of the subjects had gout at baseline. An endpoint on gout incidence was created based on information on gout diagnosis and use of gout medications through national registers and questionnaires. Median follow-up for the incidence of gout was about 19 years for both groups. Moreover, the incidence of hyperuricaemia over up to 20 years was examined in a subgroup of participants having baseline uric acid levels <6.8 mg/dL. RESULTS: Bariatric surgery was associated with a reduced incidence of gout compared with usual care (adjusted HR 0.60, 95% CI 0.48 to 0.75, p<0.001). The difference in absolute risk between groups was 3 percentage points at 15 years, and the number of subjects needed to be treated by bariatric surgery to prevent one incident gout event was 32 (95% CI 22 to 59). The effect of bariatric surgery on gout incidence was not influenced by baseline risk factors, including body mass index. During follow-up, the surgery group had a lower incidence of hyperuricaemia (adjusted HR 0.47, 95% CI 0.39 to 0.58, p<0.001). The difference in absolute risk between groups was 12 percentage points at 15 years, and the number of participants needed to be treated by bariatric surgery to prevent hyperuricaemia was 8 (95% CI 6 to 13). CONCLUSIONS: Bariatric surgery prevents gout and hyperuricaemia in obese subjects. TRIAL REGISTRATION NUMBER: NCT01479452; Results.

Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study.

OBJECTIVE: To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. METHODS: The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 37-60years and BMI was ≥38kg/m2. Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1years (interquartile range 14.8-20.9years, maximum 26years). This study is registered with ClinicalTrials.gov, NCT01479452. RESULTS: Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio=0.71; 95% CI 0.59-0.85; p<0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio=0.68; 95% CI 0.52-0·88; p=0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value=0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio=0.56: 95% CI 0.35-0.89; p=0.014). CONCLUSIONS: In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline. FUNDING: This project was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK105948 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), the Swedish Research Council K2013-99X-22279-01, K2013-54X-11285-19, Sahlgrenska University Hospital ALF research grant and Swedish Diabetes Foundation.

Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease.

UNLABELLED: Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P < 0.05), had more-severe steatosis, necroinflammation, ballooning, and fibrosis (P < 0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23-2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25-0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P < 0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). CONCLUSIONS: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver.