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We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Background Population-based patient reported outcome data in oesophageal cancer are rare. The main purpose of this study was to describe health-related quality of life (HRQOL) 1 year after the diagnosis of oesophageal cancer, comparing subgroups of curatively and palliatively managed patients. Methods This is a nationwide population-based cohort study, based on the Swedish National Registry for Oesophageal and Gastric Cancer (NREV) with prospectively registered data, including HRQOL instruments from the European Organisation for Research and Treatment of Cancer including the core and disease specific questionnaires (EORTC QLQ-C30 and QLQ-OG25). Patients diagnosed with oesophageal cancer between 2009 and 2016 and with complete HRQOL data at 1 year follow-up were included. HRQOL of included patients was compared to a reference population matched by age and gender to to a previous cohort of unselected Swedish oesophageal cancer patients. Linear regression was performed to calculate mean scores with 95% confidence intervals (CI) and adjusted linear regression analysis was used to calculate mean score differences (MD) with 95% CI. Results A total of 1156 patients were included. Functions and global health/quality of life were lower in both the curative and palliative cohorts compared to the reference population. Both curatively and palliatively managed patients reported a severe symptom burden compared to the reference population. Patients who underwent surgery reported more problems with diarrhoea compared to those treated with definitive chemoradiotherapy (dCRT) (MD -14; 95% CI − 20 to − 8). Dysphagia was more common in patiens treated with dCRT compared to surgically treated patients (MD 11; 95% CI 4 to 18). Those with palliative intent due to advanced tumour stage reported more problems with dysphagia compared to those with palliative intent due to frailty (MD -18; 95% CI − 33 to − 3). Conclusions One year after diagnosis both curative and palliative intent patients reported low function scores and severe symptoms. Dysphagia, choking, and other eating related problems were more pronounced in palliatively managed patients and in the curative intent patients treated with dCRT.

Background The vasoconstricting peptide endothelin-1 (ET-1) is associated with endothelial dysfunction. The aim of this paper was to investigate whether circulating ET-1 levels predicts chronic kidney disease (CKD) in a prospective population study. Methods In 2002–2005, 2816 participants (30–74 years) were randomly selected from two municipalities in South-Western Sweden and followed up in a representative sample of 1327 individuals after 10 years. Endothelin-1 levels were assessed at baseline. Outcome was defined as CKD stage 3 or above based on eGFR 2. Those 1314 participants with successful analysis of ET-1 were further analyzed using binary logistic regression. Results At follow-up, 51 (8%) men and 47 (7,8%) women had CKD stage 3 and above. Based on levels of ET-1 the population was divided into quintiles showing that women in the highest quintile (n = 132) had a significantly increased risk of developing CKD during the follow up period (OR = 2.54, 95% CI:1.19–5.45, p = 0.02) compared with the other quintiles (1–4). The association was borderline significant after adjusted for age, current smoking, alcohol consumption, hypertension, diabetes, BMI, high- sensitive CRP and LDL-cholesterol (OR = 2.25, 95% CI:0.97–5.24, p = 0.06). No significant differences were observed between quintiles of ET-1 and development of CKD in men (NS). Conclusions High levels of ET-1 are associated with development of CKD in women.

For over 30 years, the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry has gathered data regarding transplant procedures, donor and recipient characteristics, and outcomes from a global community of transplant centers. Almost 70,000 adult lung transplant procedures have been reported to the Registry since its inception, each one providing an opportunity for a recipient with end-stage lung disease to regain quality of life and longevity. With each year’s report, we provide more detailed analyses on a particular focus theme important to recipient outcomes. Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; allograft ischemic time; multiorgan transplantation; and donor and recipient size matching.(1–7) In response to a changing regulatory environment, the ISHLT TTX Registry is undergoing an update in data acquisition, and the patient cohort examined in this report is therefore derived from the same data source or datasets as that examined in the 2019 annual reports.(2,8–10) We refer the reader to the 2019 and prior reports for a detailed description of the baseline characteristics of the cohort, and additional core analyses not directly related to the focus explored in this year’s report. To complement the 2020 report which focussed on donor characteristics, the goal of this year’s report was to focus entirely on changes in recipient factors over the past 3 decades and to identify important recipient characteristics and transplant processes that may influence post-transplant outcomes. Due to small numbers, heart-lung transplant recipient characteristics and transplant outcomes have not been included. This 38th annual adult lung transplant report is hence basedon data submitted to the ISHLT TTX Registry on 67,493 adult recipients of deceased recipient transplants between January 1, 1992 and June 30, 2018.

Background Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO). Methods Ninety-two proteins associated with CVD were analyzed in 517 (mean age 67 ± 6 years; 33.7% women) individuals with obesity (BMI ≥30 kg/m2) from the Malmö Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors. Results Of 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate Conclusions In middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.

Infectious keratitis is a potentially sight threatening ophthalmological emergency. Contact lens wear is a common risk factor. Diagnostic advances such as MALDI-TOF MS provides new insights into the spectrum of corneal pathogens and on microbes previously considered as commensals. Corynebacterium macginleyi was described in 1995, and in 2018, the genomic features of three isolates were reported after whole-genome sequencing. Here we describe the clinical characteristics of patients with infectious keratitis (n = 29) presumably caused by Corynebacterium macginleyi, and analyze the genomic features of C. macginleyi (n = 22) isolated from the corneal ulcers of these patients. The disease course was uneventful apart from minor interventions such as corneal cross-linking and amniotic membrane transplant. Genome sequencing and comparison revealed a highly conserved core genome of C. macginleyi. Based on the analyses of single nucleotide polymorphisms, the population could be divided into two main clades that also differed in a few clade-specific genomic islands. Patients infected with an isolate belonging to the minor clade (n = 7) presented a more severe disease. Comparisons with other corynebacterial species clearly separated C. macginleyi. C. macginleyi may be considered a corneal pathogen; genomic analysis provided insights into its population structure and disease-causing potential.

White coat patterning is a feature of many dog breeds and is known to be coded primarily by the gene micropthalmia-associated transcription factor (MITF). This patterning in the coat can be modified by other factors to produce the attractive phenotypes termed ‘ticked’ and ‘roan’ that describe the presence of flecks of color that vary in distribution and intensity within otherwise ‘clear’ white markings. The appearance of the pigment in the white patterning caused by ticking and roaning intensifies in the weeks after birth. We applied genome-wide association to compare English Cocker Spaniels of roan phenotype (N = 34) with parti-color (non-roan) English Cocker Spaniels (N = 9) and identified an associated locus on CFA 38, CFA38:11 057 040 (Praw = 8.9 × 10−10, Pgenome = 2.7 × 10−5). A local case–control association in English Springer Spaniels comparing 11 ticked and six clear dogs identified indicative association with a different haplotype, CFA38:11 122 467G>T (Praw = 1.7 × 10−5) and CFA38:11 124 294A>C (Praw = 1.7 × 10−5). We characterize three haplotypes in Spaniels according to their putative functional variant profiles at CFA38:11 111 286C>T (missense), CFA38:11 131 841–11 143 239DUP.insTTAA (using strongly linked marker CFA38:11 143 243C>T) and CFA38:11 156 425T>C (splice site). In Spaniels, the haplotypes work as an allelic series including alleles (t, recessive clear; T, dominant ticked/parti-color; and TR, incomplete dominant roan) to control the appearance of pigmented spots or flecks in otherwise white areas of the canine coat. In Spaniels the associated haplotypes are t (CCT), T (TCC) and TR (TTT) for SNP markers on CFA38 at 11 111 286C>T, 11 143 243C>T and 11 156 425T>C respectively. It is likely that other alleles exist in this series and together the haplotypes result in a complex range of patterning that is only visible when dogs have white patterning resulting from the epistatic gene Micropthalmia-associated transcription factor (the S-locus).

Background Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. Methods Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). Results CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1—48 mg/L and Mdn 1.1 mg/L range 0.1—33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values Conclusions Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.

Cardiac allografts from donors with a history of cocaine use (DHCU) are often discarded owing to concerns regarding organ quality. We investigated long-term outcomes of de novo adult heart transplantation (HTx) using DHCU.Using the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, we identified 24,430 adult recipients of primary, deceased donor, heart-alone transplants between January 1, 2000, and June 30, 2013. Transplants were categorized on the basis of DHCU. Survival rates were compared using Kaplan-Meier curves and log-rank tests.A total of 3,246 (13.3%) HTx were performed using DHCU during the study period. Of these, 1,477 (45.5%) were classified as current users. Organs from DHCU were transplanted at a later sequence number (data from a sub-group of patients transplanted in the United States) than those from the non-cocaine use group (mean sequence number 16.1 ± 55.6 vs 11.5 ± 38.2; p0.001), suggesting higher decline rates by centers. Kaplan-Meier estimates of survival were not different between groups (p = 0.16), with post-transplant survival rates at 1, 5, and 10 years of 88.1%, 75.8%, and 58.5%, respectively, in the non-cocaine use group and 90.0%, 76.7%, and 59.7%, respectively, in the DHCU group. On multivariate analysis, DHCU were not associated with mortality (hazard ratio [HR]: 0.94; 95% CI: 0.88-1.00; p = 0.050), cardiac allograft vasculopathy (HR: 1.02; 95% CI: 0.94-1.11; p = 0.56), or allograft rejection (HR: 0.98; 95% CI: 0.92-1.05; p = 0.61).Our findings demonstrate that adult HTx performed using DHCU is not associated with an adverse impact on long-term clinical outcomes. These findings should spur efforts to reduce discard rates of organs from DHCU.

Background Accumulating evidence suggests a survival benefit after curative oesophageal cancer surgery in women compared with men. The aim of this study was to explore sex disparities in survival after surgery with curative intent in patients with oesophageal cancer. Methods This was a population-based cohort study, including all patients with oesophageal or gastric cancer who underwent surgery with a curative intent between 2006 and 2017 in Sweden. Female versus male mortality rate ratio (MRR) and excess mortality rate ratio (EMRR) were used as measures of survival. Two different parametric models were designed to account for potential confounders. Patients with gastric cancer were used as a comparison group as no differences in survival between sexes were expected among these patients. Results A total of 1301 patients underwent resection for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. Women had a lower EMRR (0.76, 95 per cent c.i. 0.58 to 1.01, P = 0.056; 0.52, 95 per cent c.i. 0.32 to 0.84, P = 0.007 respectively) in both histological subtypes. The effect was more profound in early clinical stages, in patients receiving neoadjuvant treatment, and without postoperative complications. No sex-related difference was observed in survival of patients with gastric cancer. Conclusions Women undergoing resection for oesophageal carcinoma have better survival compared with men.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Objectives The aim of this study was to investigate the sentinel lymph node biopsy (SLNB) method in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) guided by preoperative hybrid single-photon emission tomography/computed tomography (SPECT/CT) lymphoscintigraphy. Methods Thirty-nine patients with stage T1-T3, any N-stage, M0 cancer of the oesophagus or GOJ planned for curatively intended esophagectomy underwent preoperative SPECT/CT lymphoscintigraphy following endoscopically guided submucosal injection of radiocolloid and intraoperative radio-guided SLNB using a hand-held gamma scintillation device. Results The detection rate in preoperative SPECT/CT imaging was 88%. The median number of detected SLN stations in preoperative imaging was 1 (range 0-4). At least one suspected SLN was identified in all intraoperative SLNP procedures. In six cases, no lymph nodes were identified in the SLNB. In six cases, the SLNB was false negative. The sensitivity for successful SLNB procedures was 20%, the specificity was 100% and the accuracy was 75%. Conclusions Preoperative SLN mapping using SPECT/CT yields a high number of detected SLN stations compared to previous studies using planar imaging. The accuracy of the SLNB method in patients with predominantly ≥T3-stage tumours and with a history of previous neoadjuvant treatment is poor, and the method is not recommended in these patient groups.

Contains fulltext : 225948.pdf (Publisher’s version ) (Open Access) Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

Background Gastrectomy including D2 lymphadenectomy is regarded as the standard curative treatment for advanced gastric cancer in Asia. This procedure has also been adopted gradually in the West, despite lack of support from RCTs. This study sought to investigate any advantage for long‐term survival following D2 lymphadenectomy in routine gastric cancer surgery in a Western nationwide population‐based cohort. Methods All patients who had a gastrectomy for cancer in Sweden in 2006–2017 were included in the study. Prospectively determined data items were retrieved from the National Register of Oesophageal and Gastric Cancer. Extent of lymphadenectomy was categorized as D1+/D2 or the less extensive D0/D1 according to the Japanese Gastric Cancer Association classification. Overall survival was analysed and, in addition, a variety of possible confounders were introduced into the Cox proportional hazards regression model. Results A total of 1677 patients underwent gastrectomy, of whom 471 (28·1 per cent) were classified as having a D1+/D2 and 1206 (71·9 per cent) a D0/D1 procedure. D1+/D2 lymphadenectomy was not associated with higher 30‐ or 90‐day postoperative mortality. Median overall survival for D1+/D2 lymphadenectomy was 41·5 months with a 5‐year survival rate of 43·7 per cent, compared with 38·5 months and 38·5 per cent respectively for D0/D1 (P = 0·116). After adjustment for confounders, in multivariable analysis survival was significantly higher after D1+/D2 than following D0/D1 lymphadenectomy (hazard ratio 0·81, 95 per cent c.i. 0·68 to 0·95; P = 0·012). Conclusion This national registry study showed that long‐term survival after gastric cancer surgery was improved after gastrectomy involving D1+/D2 lymphadenectomy compared with D0/D1 dissection., A nationwide prospective register‐based study examined the extent of lymphadenectomy in curative gastric cancer surgery and its effects on long‐term survival. More evidence in favour of thorough lymphadenectomy

Background Laparoscopic gastrectomy (LG) for cancer has been introduced in institutions worldwide in an effort to minimize surgical trauma, while aiming to provide comparable oncological outcomes to conventional open gastrectomy (OG). The aim of this study was to present our results during the period of implementation of the laparoscopic technique. Materials and methods In 2012, LG for the treatment of gastric cancer was introduced at our institution. The results presented are based on a retrospective analysis of data from a cohort of all patients treated with curative intent over the period 2010-2018. Results During the study period, 206 patients underwent surgery for gastric cancer: 129 patients (62.6%) had an OG and 77 patients (37.4%) an LG. The conversion rate due to technical reasons was 2.6%. LG was associated with significantly less intraoperative blood loss [mean (mL), OG 544 versus LG 176] and shorter hospital stay than OG [mean (d), OG 12 versus LG 8], fewer severe complications (Clavien-Dindo grade ≥ IIIb) [OG 29 (22.5%) versus LG 9 (11.7%), P = 0.081], significantly lower anastomotic leak rate [OG 18 (14.0%) versus LG 1 (1.3%)] and no 90-day mortality. The percentage of R0 resections was similar between the two groups (OG 82.2% versus LG 85.7%, P = 0.507), while the mean number of resected lymph nodes was significantly higher in the laparoscopic group [OG 34 versus LG 39, P = 0.030]. Conclusions Our data suggest that similar and, in some aspects, better short-term outcomes can be achieved with LG with maintained oncological quality.

Aim Previous studies have shown that individuals with impaired glucose tolerance (IGT) have lower self-rated health than normoglycaemic individuals. The aim of this study was to examine differences in self-rated health between individuals with IGT and those with impaired fasting glucose (IFG) and to consider the potentially mediating effect of physical activity. Methods In 2002–2005, a total of 2816 individuals were randomly selected for a population-based study in Sweden. All participants performed an oral glucose tolerance test (OGTT). Fasting venous blood samples were drawn, and questionnaires concerning lifestyles were completed. Self-rated health (SRH) and leisure time physical activity (LTPA) were reported on a five-graded and four-graded scale, respectively. A total of 213 individuals with IGT and 129 with IFG were detected. Results IGT, but not IFG, was associated with low self-rated health. The difference in self-rated health was seen particularly in men when adjusted for age and BMI (OR = 2.13, CI: 1.13–4.02, p = 0.020). The results became insignificant when including physical activity in the model (OR = 1.8, CI: 0.91–3.58, p = 0.094). Conclusion The low self-rated health adds further weight to the risk profile in men with IGT and stresses the importance of early detection and lifestyle interventions.

Aims Although the epidemiological association between Type 2 diabetes and congestive heart failure (CHF) as well as cardiovascular disease (CVD) is well established, associations between diabetes‐related single‐nucleotide polymorphisms (SNPs), CHF, and CVD have been surprisingly inconclusive. Our aim is to examine if 43 diabetes‐related SNPs were associated with prevalent diastolic dysfunction assessed by echocardiography and incident CVD and/or CHF. Methods and results We genotyped 43 SNPs that previously reported genome‐wide significant associations with Type 2 diabetes, in 1444 subjects from the population‐based Malmö Preventive Project‐Re‐examination Study (MPP‐RES) (mean age 68 years; 29% women, 36% prevalent diabetes) (discovery cohort) and in 996 subjects from the VARA cohort (mean age 51 years, 52% women, 7% prevalent diabetes) (replication cohort). Multivariable logistic regression was assessed. Genetic variants that reached significant association with diastolic dysfunction in both cohorts were then analysed for association with incident CVD/CHF in a larger sample of the MPP‐RES cohort (3,407 cases and 11,776 controls, median follow up >30 years) using Cox regression analysis. A common variant at the HNF1B [major allele (T) coded, also the risk allele for diabetes] was the only SNP associated with increased risk of prevalent diastolic dysfunction in both the discovery [MPP‐RES; odds ratio (OR) 1.21, P = 0.024), and the replication cohort (VARA; OR 1.38, P = 0.042]. Cox regression analysis showed that carriers of the T‐allele of rs757210 had an increased risk of future CVD (HR 1.05, P = 0.042). No significant association was seen for incident CHF. Conclusions The diabetes susceptibility locus HNF1B is associated with prevalent diastolic dysfunction in two independent Swedish cohorts as well as incident cardiovascular disease.

Background Computed tomography (CT) is used to monitor progression of structural lung disease (SLD) in children with cystic fibrosis (CF). Our goals were to identify the risk factors for the annual progression of SLD and the impacts of airway pathogens on SLD. Method Seventy-five school-aged children diagnosed with CF underwent 200 CT scans at Gothenburg CF Centre in the period 2003–2015. SLD was evaluated with a quantitative scoring system. Mixed models were used to calculate the yearly progression rates of SLD and FEV1 and to analyse the effects of common airway pathogens in CF. Results The yearly mean progression (95% CI) rates for total disease (%Dis), bronchiectasis (%Be), and FEV1 were 0.62 (0.38–0.86), 0.43 (0.28–0.58) and −0.16 (−0.18–0.13), respectively. Adjusting for airway pathogens, the yearly mean progression rates for %Dis, %Be and FEV1 were 0.23 (−0.04–0.51), 0.12 (0.00–0.25), and −0.12 (−0.16–0.08), respectively. A single infection with P aeruginosa was associated with significant increase in lung damage, assessed as %Dis (p = 0.044) and%Be (p = 0.0047), but not in FEV1 (p = 0.96). At age of 7 years, there was a good correlation between the extent of SLD and subsequent progression of %Dis (r = 0.63, p = 0.0042) and %Be (r = 0.74, p = 0.0057) while there was no significant correlation between the FEV1 and the rate of decline of FEV1 (r = −0.22, p = 0.12). Conclusion Intermittent respiratory infections with P aeruginosa were associated with significant SLD but no change in FEV1. More SLD at the age of 7 years signals a higher progression rate of SLD subsequently.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.METHODS: Targeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case-control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant- and gene-level enrichment analyses, was implemented to explore genotype-phenotype relations.RESULTS: Gene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle-specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.CONCLUSION: Our study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.

Purpose During the COVID-19 pandemic, teleconsultations have increasingly been used to reduce physical contact and thus risk of infection. This study investigated how patients with cancer experienced the COVID-19 pandemic and how they perceived the change from in-person consultations to telephone consultations in an oncology outpatient clinic. The aim was to provide insights that could optimize the future use of teleconsultations in cancer care. Methods This qualitative study included 15 patients with colorectal, breast, gynecological, lung, or prostate cancer treated at the outpatient clinic at the Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Denmark in June or July 2020. Data were collected through semi-structured individual interviews and analyzed by thematic analysis. Results Patients with cancer experienced social, psychological, and organizational consequences of the COVID-19 pandemic related to their cancer care. Not all patients were comfortable with telephone consultations. Six themes were identified: (1) double burden as a consequence of simultaneous cancer and the COVID-19 pandemic, (2) parameters for patient satisfaction with telephone consultations, (3) the importance of relatives attending consultations, (4) loss of information and nuances during telephone consultations, (5) the impact of physicians’ language and communicative skills during telephone consultations, and (6) patients’ suggestions for future telephone consultations. Conclusion Beyond the COVID-19 pandemic, it is important that hospitals offering teleconsultations involve patients’ preferences, consider for which patients and consultations the solution is suitable, which technology to use, how to prepare patients and relatives, and how to provide physicians with the necessary communicative skills.

Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with mantle cell lymphoma, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62-84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p=0.001) and role function (p=0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p=0.011) and role function (p=0.032) were independent factors associated with overall survival, and physical function (p=0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL. This article is protected by copyright. All rights reserved.

Significance Multiple representatives of eulipotyphlan mammals (shrews, hedgehogs, moles, and solenodons) are venomous, but little is known about the evolutionary history and composition of their oral venom systems. Herein we characterized venom from the endangered Hispaniolan solenodon (Solenodon paradoxus) and find that it consists of hypotensive proteins likely used to facilitate vertebrate prey capture. We demonstrate that venom has evolved independently on at least 4 occasions in eulipotyphlans, and that molecular components of these venoms have also evolved convergently, with kallikrein-1 proteins coopted as toxins in both solenodons and shrews following their divergence over 70 million years ago. Our findings present an elegant example of convergent molecular evolution and highlight that mammalian venom systems may be subjected to evolutionary constraints., Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.

Background To explore the determinants of incident hypertension, and especially the impact of baseline blood pressure categories, in a representative Swedish population. Methods A 10-year longitudinal study of residents aged 30–74. Blood pressures were measured and categorized according to ESH guidelines with optimal blood pressure Results Sixteen (2.6%) subjects with optimal baseline blood pressure had hypertension at follow up. Corresponding numbers for subjects with normal, high normal and unstable blood pressure were 55 (19.4%), 50 (39.1%) and 46 (74.2%), respectively. Compared with subjects in optimal group those in normal, high normal and unstable blood pressure categories had significantly higher risk to develop manifest hypertension with odds ratios OR and (95% CI) of 7.04 (3.89–12.7), 17.1 (8.88–33.0) and 84.2 (37.4–190), respectively, with adjustment for age, BMI and family history for hypertension. The progression to hypertension was also independently predicted by BMI (p Conclusions Subjects with high normal or unstable blood pressure should be identified in clinical practice, evaluated for global hypertension risk and offered personalized advice on lifestyle modification for early prevention of manifest hypertension and cardiovascular disease.

Funder: Swedish Brain Foundation, Funder: Karolinska Institutet; doi: http://dx.doi.org/10.13039/501100004047, Funder: Region Stockholm, Funder: National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme), Funder: National Institute for Health Research (NIHR), Funder: NIHR Cambridge Biomedical Research Centre, Funder: Royal College of Surgeons of England; doi: http://dx.doi.org/10.13039/501100000297, Funder: Royal College of Surgeons of England Pump Priming Grant, Funder: Swedish Society for Medical Research, Funder: StratNeuro, Funder: Stockholms Läns Landsting; doi: http://dx.doi.org/10.13039/501100004348, Funder: Karolinska Institute, Background: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. Methods: TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. Results: Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions: Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations. Graphical abstract

Background Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. Methods A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. Results Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. Conclusion These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Background: During the COVID-19 pandemic, teleconsultations (TC) have been increasingly used in cancer care as an alternative to outpatient visits. We aimed to examine patient-related and cancer-specific characteristics associated with experiences with TC among patients with cancer during the COVID-19 pandemic. Material and methods: This population-based survey included patients with breast, lung, gastrointestinal, urological, and gynaecological cancers with appointments in the outpatient clinics, Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Denmark in March and April 2020. Age- and sex-adjusted logistic regression analyses were used to study associations of sociodemographics, cancer and general health, anxiety, and health literacy with patients’ experiences of TC in regards to being comfortable with TC, confident that the doctor could provide information or assess symptoms/side effects and the perceived outcome of TC. Results: Of the 2119 patients with cancer receiving the electronic survey, 1160 (55%) participated. Two thirds of patients (68%) had consultations with a doctor changed to TC. Being male, aged 65–79 years, and having TC for test results were statistically significantly associated with more comfort, confidence, and perceived better outcome of TC. Having breast cancer, anxiety, low health literacy, or TC for a follow-up consultation were statistically significantly associated with less positive experiences with TC. Living alone, short education, disability pension, and comorbidity were statistically significantly associated with anxiety and low health literacy. Conclusions: Most patients reported positive experiences with TC, but in particular patients with anxiety and low health literacy, who were also the patients with fewest socioeconomic and health resources, felt less comfortable and confident with and were more likely to perceive the outcome negatively from this form of consultation. TC may be suitable for increasing integration into standard cancer care but it should be carefully planned to meet patients’ different information needs in order not to increase social inequality in cancer.

IntroductionEvidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D.Research design and methodsA 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today’s standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months.Results159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (−0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (−0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values ConclusionsNutrition education using an FBA, CC or RC is equivalent in terms of HbA1c and cardiovascular risk factors in persons with T1D with moderately impaired glycemic control. An FBA had benefits regarding food choices compared with CC and RC.

Purpose To describe predisposing risk factors, causative microorganisms and their antibiotic susceptibility patterns in infectious keratitis during an 11‐year period in Region Örebro County, Sweden. Methods This is a descriptive study conducted as a retrospective audit of clinical records. Patients who received treatment for infectious keratitis at any of the three ophthalmological departments within Region Örebro County, Sweden, between 2004 and 2014 were included if they fulfilled the predefined criteria for infectious keratitis. Data regarding culture results, antibiotic susceptibility pattern and risk factors for infectious keratitis were obtained from medical records and microbiological reports. Results In total, 398 episodes of infectious keratitis in 392 patients were included, and 285 were culture positive. The most common predisposing risk factor was contact lens wear (45%). Coagulase‐negative staphylococci (39.6%) was the most commonly isolated type of organism. Staphylococcus aureus (15.1%) followed by Moraxella spp. (7.4%) and Pseudomonas aeruginosa (6.7%) were among the most common isolated bacteria not considered to be commensal. Reduced susceptibility to fluoroquinolones was observed in five of 43 S. aureus isolates and in four of nine Streptococcus pneumoniae isolates. Conclusion The most common predisposing risk factor for keratitis was contact lens wear. Among the most common microbes, not considered to be exclusively commensals, isolated from the cornea in microbial keratitis were S. aureus, Moraxella spp. and P. aeruginosa. The antibiotic susceptibility patterns showed low proportion of resistance. Empiric treatment of suspected infectious keratitis with topical fluoroquinolones and chloramphenicol might be considered in a setting like ours pending culture results.

Objective Approximately 1 in 7 US adults have diabetes; and over 60% of deaths in patients with diabetes have cardiac disease as a principal or contributing cause. Both coronary and peripheral artery disease (PAD) identify high-risk cohorts among patients with diabetes. We have previously demonstrated improved cardiovascular outcomes with edetate disodium-based chelation in post-MI patients with diabetes, enrolled in the Trial to Assess Chelation Therapy (TACT). In these analyses we further studied the effect size of patients with diabetes and severe disease in 2 vascular beds; coronaries, and lower extremity arteries. We questioned whether greater atherosclerotic burden would attenuate the observed beneficial effect of edetate disodium infusions. Research design and methods The multicenter TACT used a double blind, placebo controlled, 2 × 2 factorial design with 1708 participants, randomly assigned to receive edetate disodium-based chelation, or placebo and high dose oral vitamins or placebo. There were 162 (9.5% of 1708) post-MI patients with a diagnosis of diabetes mellitus and PAD for this post hoc analysis. Patients received up to 40 double-blind intravenous infusions of edetate disodium-based chelation, or placebo. The composite primary endpoint of TACT consisted of death from any cause, myocardial infarction, stroke, coronary revascularization and hospitalization for angina. Results The median age was 66 years, 15% female, 5% non-Caucasian, and BMI was 31. Insulin was used by 32% of patients. Active infusions significantly reduced the primary endpoint compared with placebo infusions (HR, 0.52; 95% CI, 0.30–0.92; P = 0.0069), with a 30% absolute risk reduction in the primary endpoint. There was a marked reduction in total mortality from 24% to 11%, although of borderline significance (P = 0.052). Conclusion Atherosclerotic disease in multiple vascular beds did not attenuate the beneficial effect of edetate disodium infusions in post MI patients with diabetes. Studies now in progress will prospectively test this post hoc finding.

Background Middle-Eastern immigrants in Sweden are at increased risk for type 2 diabetes (T2D) and poor mental health. Physical activity not only prevents/delays onset of T2D but also shows favorable effects on mental health. However, the effects of a culturally adapted lifestyle intervention on mental health among Middle-Eastern immigrants have not been explored before. We aimed to study the effects of a randomized controlled, culturally adapted lifestyle intervention on anxiety and depression levels in diabetes-prone Iraqi immigrants. Methods Participants (n = 96) were randomized to intervention group, IG (n = 50) or control group, CG (n = 46). The IG received seven group sessions addressing lifestyle change and the CG received treatment as usual. Montgomery–Åsberg Depression Rating Scale (MADRS-S) and Hospital Anxiety and Depression Scale (HADS) assessed mental health at start, mid (2 months) and end of the study (4 months). Proportional odds ratio (OR) model was used to study the effect of the intervention. Results The odds of scoring lower on MADRS-S and HADS depression scale at visit 3 vs. baseline were higher in the IG compared to the CG (MADRS-S OR 5.9, 95% CI: 1.6–22.5; HADS OR 4.4, 95% CI: 0.9–20.3). The findings persisted after adjustment for age, sex, body mass index, time since migration, sedentary lifestyle and language spoken at home. Group differences were non-significant at visit 2 vs. baseline. Conclusion A culturally adapted lifestyle intervention addressing T2D prevention in Middle-Eastern immigrants has favorable effects on mental health. The effect was more pronounced at the 4 months than at 2 months follow-up, indicating beneficial effect of longer study duration. Trial registration www.clinicaltrials.gov NCT01420198.

Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.

Background: In the randomized Asian REGATTA trial, no survival benefit was shown for additional gastrectomy over chemotherapy alone in patients with advanced gastric cancer with a single incurable factor, thereby discouraging surgery for these patients. The purpose of this study was to evaluate treatment strategies for patients with metastatic gastric cancer in daily practice in five European countries, along with relative survival in each country. Methods: Nationwide population‐based data from Belgium, Denmark, the Netherlands, Norway and Sweden were combined. Patients with primary metastatic gastric cancer diagnosed between 2006 and 2014 were included. The proportion of gastric resections performed and the administration of chemotherapy (irrespective of surgery) within each country were determined. Relative survival according to country was calculated. Results: Overall, 15 057 patients with gastric cancer were included. The proportion of gastric resections varied from 8·1 per cent in the Netherlands and Denmark to 18·3 per cent in Belgium. Administration of chemotherapy was 39·2 per cent in the Netherlands, compared with 63·2 per cent in Belgium. The 6‐month relative survival rate was between 39·0 (95 per cent c.i. 37·8 to 40·2) per cent in the Netherlands and 54·1 (52·1 to 56·9) per cent in Belgium. Conclusion: There is variation in the use of gastrectomy and chemotherapy in patients with metastatic gastric cancer, and subsequent differences in survival.

The efficacy of fundoplication operations in the management of gastroesophageal reflux disease (GERD) has been documented. However, few prospective, controlled series report long-term (10 years) efficacy and postfundoplication concerns, particularly when comparing various types of fundoplication.To compare long-term (15 years) results regarding mechanical complications, reflux control, and quality of life between patients undergoing posterior partial fundoplication (PF) or total fundoplication (TF) (270° vs 360°) in surgical treatment for GERD.A double-blind randomized clinical trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from November 19, 2001, to January 24, 2006. A total of 456 patients were recruited and randomized. Data for this analysis were collected from August 1, 2019, to January 31, 2021.Laparoscopic 270° posterior PF vs 360° TF.The main outcome was dysphagia scores for solid and liquid food items after more than 15 years. Generic (36-Item Short-Form Health Survey) and disease-specific (Gastrointestinal Symptom Rating Scale) quality of life and proton pump inhibitor consumption were also assessed.Among 407 available patients, relevant data were obtained from 310 (response rate, 76%; mean [SD] age, 66 [11.2] years; 184 [59%] men). A total of 159 were allocated to a PF and 151 to a TF. The mean (SD) follow-up time was 16 (1.3) years. At 15 years after surgery, mean (SD) dysphagia scores were low for both liquids (PF, 1.2 [0.5]; TF, 1.2 [0.5]; P = .58) and solids (PF, 1.3 [0.6]; TF, 1.3 [0.5]; P = .97), without statistically significant differences between the groups. Reflux symptoms were equally well controlled by the 2 types of fundoplications as were the improvements of quality-of-life scores.The long-term findings of this randomized clinical trial indicate that PF and TF are equally effective for controlling GERD and quality of life in the long term. Although PF was superior in the first years after surgery in terms of less dysphagia recorded, this difference did not prevail when assessed a decade later.ClinicalTrials.gov Identifier: NCT04182178.