BACKGROUND & AIMS:Hypofibrinolysis is prevalent in obesity and type 2 diabetes mellitus (T2D) and may be involved in their pathophysiology. Metabolic bariatric surgery (MBS) markedly improves both obesity and T2D, but whether these improvements are related to fibrinolysis is not known. In this study, biomarkers of fibrinolysis were assessed before and after MBS in patients with and without T2D. METHODS:A single center prospective cohort study with 2-year follow-up. The participants were adults with obesity with (n = 28) or without T2D (n = 33) undergoing MBS preceded by 2 weeks of a low-calorie diet (LCD). The plasma concentrations of plasminogen activator inhibitor 1 activity (PAI-1act), tissue plasminogen activator activity (tPAact) and antigen (tPAag), plasmin-antiplasmin complexes (PAP) and fibrinogen were determined at baseline, after LCD and at 6 weeks, 1 and 2 years after MBS. RESULTS:After LCD and prior to MBS, PAI-1act decreased and PAP increased significantly. Two years after MBS, PAI-1act decreased from baseline 29.8 (63) to 3.8 (121) while tPAact increased (0.08 (390) to 0.23 (150) IU), and PAP increased (544 (54) to 814 (60) ng/mL). tPAag and fibrinogen decreased (16.4 (29) to 9.7 (51) ng/mL and 4.15 (23) to 3.82 (20) g/L, respectively); p < 0.001 for all; (geometric means, except tPAact which is arithmetic mean, coefficient of variation (%CV)). There were no differences in fibrinolysis between groups at baseline or after surgery. Multivariate analysis showed that reduction in body weight and fat mass had the most important influence on fibrinolysis. CONCLUSION:Fibrinolysis is significantly improved two years after MBS, as also indicated earlier after the two-week LCD. The lack of differences between patients with vs. without T2D suggests that fat mass reduction rather than improvement of glucose control is most important for improved fibrinolysis after MBS. In summary, our results support hypofibrinolysis as a mechanism in the pathophysiology in obesity.

OBJECTIVE:To assess incidence, indications, symptom relief, complications, and weight outcomes following Roux-en-Y gastric bypass (RYGB) reversal. BACKGROUND:RYGB is an effective treatment for obesity but may in rare cases be associated with severe long-term complications requiring RYGB reversal. Evidence on incidence and outcomes is limited. METHODS:This nationwide, multi-center, retrospective cohort study included all patients undergoing RYGB reversal in Sweden between 2007 and 2023. Data were obtained from the Scandinavian Obesity Surgery Registry (SOReg) and medical records. RESULTS:During the study period, 199 patients (84% female, mean age 42.5 y) underwent RYGB reversal at 13 centers, corresponding to an incidence of 0.3% of 63,797 RYGB-procedures performed. Patients usually had multiple indications, most often abdominal pain (70%), malnutrition (45%), gastrointestinal symptoms (34%), and postbariatric hypoglycemia (29%). Most procedures (84%) were performed laparoscopically, with a median hospital stay of 4 days. Mean body weight increased from 77 kg at reversal to 89 kg at one year. Overall, 86% of patients reported partial or complete symptom relief, highest rates among those with postbariatric hypoglycemia (94.6%). Early severe complications (Clavien-Dindo grade ≥IIIb) occurred in 24.6% and late severe complications in 21.6%, with seven not surgery-related deaths (3.5%) during follow-up. CONCLUSIONS:Reversal of RYGB is rare but can be considered in patients with a substantial burden of complications. Although postoperative morbidity was common, most patients achieved symptom relief. Careful patient selection, perioperative optimization, and realistic expectations are essential. Further studies are needed to determine optimal surgical techniques and long-term outcomes.

While it is well established that the cellular composition of white adipose tissue (WAT) varies between depots, the functional relevance of this heterogeneity remains unclear. By combining spatial and single-nucleus RNA sequencing, we provide a comprehensive map of subcutaneous and visceral (omental, mesenteric, mesocolic, and epiploic) WAT in both men and women. Our analyses reveal shared features, such as the spatial organization of adipogenesis, alongside depot-specific characteristics, including distinct cell-type enrichments and unique cell-cell communication routes. Epiploic WAT stands out by harboring high proportions of serum amyloid A expressing fat cells (encoded by SAA1/SAA2) and several leukocyte populations. Through mechanistic studies, we demonstrate that adipocyte SAA1/SAA2 expression is induced by inflammatory signals, including lipopolysaccharide, and that SAA1 activates immune responses in adipose-resident myeloid cells. Collectively, our findings suggest that visceral WAT exhibits distinct cytoarchitectural properties, with those located near the colon adapting by developing specialized adipocytes and immune cell populations.

Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) entail risks of vitamin and mineral deficiencies, and guidelines recommend lifelong supplementation. It remains unclear if postoperative intake of micronutrients differs between surgical methods. This exploratory cross-sectional substudy aimed to evaluate whether the reported intake of vitamins and minerals in diet and supplements differs between SG and RYGB one year after surgery. Between April 2017 and May 2023, 285 participants from the randomized controlled multicenter trial “Bypass Equipoise Sleeve Trial” (BEST) were consecutively included at seven metabolic bariatric surgery centers in Sweden. The intake of vitamins and minerals from diet and supplements was self-reported at one-year follow-up and calculated in Dietist Net®. The Goldberg cut-off method was used to exclude under-reporters. One year after surgery, the reported daily energy intake was 1673 kcal and 1651 kcal, after SG and RYGB, respectively. Compared with reference data on Swedish dietary habits from 2010 to 2011, participants reported daily intakes from diet below the daily recommended intake (RI) for a greater number of micronutrients. The reported intake of vitamin C from diet was 53 mg (SG) versus 72 mg (RYGB) (p = 0.001). Following both procedures most participants reported supplement intake consistent with the recommendations. The reported intake from supplements was 580 Retinol equivalents (RE) (SG) versus 656 RE (RYGB) for vitamin A (p = 0.017), and 374 µg (SG) versus 436 µg for folic acid (p = 0.014). Overall, the reported intake of energy and vitamins and minerals from diet and supplements did not differ between SG and RYGB one year after bariatric surgery. Minor differences were observed, with a higher intake of vitamin C from diet, and vitamin A and folic acid from supplements after RYGB. Reported intake of vitamins and minerals from diet and supplements was generally similar and satisfactory one year after SG and RYGB. Reported energy intake was comparable between SG and RYGB one year after bariatric surgery. Most participants reported consistent use of vitamin and mineral supplements one year after bariatric surgery.

Objective: To assess incidence, indications, symptom relief, complications, and weight outcomes following Roux-en-Y gastric bypass (RYGB) reversal. Background: RYGB is an effective treatment for obesity but may in rare cases be associated with severe long-term complications requiring RYGB reversal. Evidence on incidence and outcomes is limited. Methods: This nationwide, multi-center, retrospective cohort study included all patients undergoing RYGB reversal in Sweden between 2007 and 2023. Data were obtained from the Scandinavian Obesity Surgery Registry (SOReg) and medical records. Results: During the study period, 199 patients (84% female, mean age 42.5 y) underwent RYGB reversal at 13 centers, corresponding to an incidence of 0.3% of 63,797 RYGB-procedures performed. Patients usually had multiple indications, most often abdominal pain (70%), malnutrition (45%), gastrointestinal symptoms (34%), and postbariatric hypoglycemia (29%). Most procedures (84%) were performed laparoscopically, with a median hospital stay of 4 days. Mean body weight increased from 77 kg at reversal to 89 kg at one year. Overall, 86% of patients reported partial or complete symptom relief, highest rates among those with postbariatric hypoglycemia (94.6%). Early severe complications (Clavien–Dindo grade ≥IIIb) occurred in 24.6% and late severe complications in 21.6%, with seven not surgery-related deaths (3.5%) during follow-up. Conclusions: Reversal of RYGB is rare but can be considered in patients with a substantial burden of complications. Although postoperative morbidity was common, most patients achieved symptom relief. Careful patient selection, perioperative optimization, and realistic expectations are essential. Further studies are needed to determine optimal surgical techniques and long-term outcomes.

Abstract Topic Benign Disease: Esophageal Function and Motility Background Randomised clinical trials have demonstrated non-inferiority of peroral endoscopic myotomy (POEM) to laparoscopic Heller myotomy (LHM) in the treatment of achalasia. However, there is a lack of long-term follow-up data from population-based cohorts comparing POEM to LHM. We aimed to determine long-term rates of reintervention and reflux following POEM and LHM. Methods This was a population-based cohort study including all adults with achalasia who underwent either primary POEM or primary LHM between 1st January 1997 and 31st December 2024 in Sweden. POEM was the exposure, with LHM considered the comparison in all analyses. The primary outcome was reintervention for achalasia, defined as and subsequent myotomy (peroral or transabdominal), pneumatic dilatation, or oesophagectomy occurring during follow-up. The secondary outcome was gastroesophageal reflux, defined as the dispensation of a proton pump inhibitor equivalent to 36 months use after the primary procedure, or antireflux surgery. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) for both outcomes adjusted for age, sex, Charlson comorbidity index score, and calendar year. Results In total, 991 patients (median age 48 years [IQR 34-61], 58.1% male) with primary POEM or LHM for achalasia were included and followed for up to 14 (median 5.9) years. Of these, 381 (38.4%) patients underwent POEM and 610 (61.6%) underwent LHM. The cumulative incidence of reintervention was 18.6% (n=184) and gastroesophageal reflux occurred in 46.6% (n=462). POEM was associated with a similar risk of reintervention (HR 0.74, 95% CI 0.51-1.08), but the risk of gastroesophageal reflux disease was 40% increased after POEM (HR 1.40, 95% CI 1.11-1.77) as compared to LHM. Conclusion POEM and LHM have comparable long-term treatment durability for the management of achalasia. However, patients undergoing POEM have a higher risk of gastroesophageal reflux and so should be counselled regarding the potential need for long-term antireflux medications.

AIM:To determine the incidence of new persistent opioid use (NPOU) after elective colorectal surgery in Sweden and to identify associated patient-, procedure- and hospital-level factors. METHOD:This nationwide retrospective cohort study linked data from Swedish national health registries and included adults undergoing elective inpatient colorectal surgery between 2018 and 2022. Patients with an opioid dispensed 365 to 30 days before surgery, another surgical procedure within one year of the index operation, or death within 12 months postoperatively were excluded. NPOU was defined as at least one opioid dispensed within 90 days after surgery and at least one between 90 and 180 days. Associations were examined using multivariable logistic regression. RESULTS:Among 14,233 opioid-naïve patients, 374 (2.63%; 95% CI, 2.37-2.90%) developed NPOU. Longer operating time (aOR, 1.19 per hour; 95% CI, 1.13-1.26), preoperative non-opioid analgesics (aOR, 1.90; 95% CI, 1.52-2.37) or sedatives/anxiolytics (aOR, 1.66; 95% CI, 1.31-2.09), opioid dispensation within 7 days of surgery (aOR, 2.19; 95% CI, 1.76-2.72), and higher ASA classification (ASA 3: aOR, 1.89; 95% CI, 1.26-2.90; ASA 4: aOR, 3.29; 95% CI, 1.63-6.36) were independently associated with higher odds of NPOU, whereas male sex was associated with lower odds (aOR, 0.76; 95% CI, 0.61-0.95). CONCLUSION:In this low-prescribing setting, approximately one in 38 opioid-naïve patients developed NPOU 6 months after colorectal surgery. Operating time and opioid dispensation within 7 days of surgery were independently associated with NPOU; the latter, a modifiable prescribing decision, is a plausible target for opioid-sparing strategies.

BACKGROUND AND STUDY AIMS:Barrett's esophagus (BE) surveillance relies on endoscopy, which can limit accessibility and strain healthcare resources, a challenge in Nordic countries. Non-endoscopic alternatives could improve surveillance efficiency, but implementation data are limited. We assessed the feasibility of implementing EndoSign®, a novel capsule sponge, in Sweden. PATIENTS AND METHODS:This prospective, multicenter feasibility study across five Swedish hospitals (Dec 2023-Oct 2024), recruited 70 adults with histologically-confirmed BE undergoing routine surveillance. Trained nurses performed the capsule sponge procedure, with samples analyzed centrally for TFF3, atypia and p53. Feasibility objectives were technical success, patient acceptability and safety. We also assessed sample adequacy and risk stratification. RESULTS:Of 70 enrolled patients (median age 68 years [IQR 63-72]; 84.3% male), 68 (97.1%) completed the procedure successfully. Patient acceptability was high; median discomfort was 2/10 [IQR 1-3] during the procedure, decreasing to 0/10 [IQR 0-1] after 15 min. Most patients (71.4%) preferred the capsule sponge over gastroscopy. Minor adverse events (sore throat) were present in three patients (4.3%) at 7 days and one patient (1.4%) at 90 days; no serious adverse events were reported. Sample adequacy was 92.6% (63/68). Risk stratification (n = 60) categorized 20.0% as high-risk, leading to expedited endoscopy. CONCLUSIONS:This capsule sponge demonstrated successful implementation with high technical success, patient acceptability and safety. The nurse-led delivery model proved effective, supporting potential broader implementation. This technology could provide a viable, patient-centered component of BE surveillance, though larger validation studies are needed. ClinicalTrials.gov Identifier: NCT07036432.

Chronic kidney disease (CKD) is a strong risk factor for cardiovascular mortality and morbidity. We hypothesized that a senescent phenotype instigated by uremic toxins could account for early vascular aging (EVA) and vascular dysfunctions of microvasculature in end stage kidney disease (ESKD) patients which ultimately lead to increased cardiovascular complication. To test this hypothesis, we utilized both in vivo, and ex vivo approaches to study endothelial and smooth muscle function and structure, and characterized markers related to EVA in 82 ESKD patients (eGFR <15 ml/min) and 70 non-CKD controls. In vivo measurement revealed no major difference in endothelial function between ESKD and control group, aside from higher stiffness detected in the microcirculation of ESKD participants. In contrast, ex vivo measurements revealed a notable change in the contribution of endothelium-derived factors and increased stiffness in ESKD patients vs. controls. In support, we demonstrated that ex vivo exposure of arteries to uremic toxins such as Trimethylamine N-oxide, Phenylacetylglutamine, or extracellular vesicles from CKD patients impaired endothelial function via diminishing the contribution of endothelium-derived relaxing factors such as nitric oxide and endothelium derived hyperpolarizing factor. Uremic arteries displayed elevated expression of senescence markers (p21CIP1, p16INK4a, and SA-β-gal), calcification marker (RUNX2), and reduced expression of Ki67, sirtuin1, Nrf2, and MHY11 markers, indicating the accumulation of senescent cells and EVA phenotype. Correspondingly, treating uremic vessel rings ex vivo with senolytic agents (Dasatinib + Quercetin) effectively reduced the senescence-associated secretory phenotype and changed the origin of extracellular vesicles. Notably, sex differences exist for certain abnormalities suggesting the importance of biological sex in the pathogenesis of vascular complications. In conclusion, the uremic microvasculature is characterized by a "senescence signature", which may contribute to EVA and cardiovascular complications in ESKD patients and could be alleviated by treatment with senolytic agents.

After bariatric surgery, adherence to lifestyle recommendations is crucial. Health literacy and self-efficacy may impact recovery after surgery. In this multicentre study performed in three hospitals in Sweden, we evaluated any relation between preoperative health literacy and general self-efficacy on the one side and weight loss, health-related quality of life, length of stay, and complications up to 2 years after bariatric surgery on the other. Of 686 included patients, 56% (n = 382) had limited functional health literacy, 42% (n = 278) had limited communicative and critical health literacy, and 40% (n = 266) reported low general self-efficacy. Preoperative functional, communicative and critical health literacy, and general self-efficacy were not associated with the degree of weight loss at 1 or 2 years after surgery. However, limited health literacy and low general self-efficacy scores were associated with both reduced quality of life and obesity-related problems postoperatively. Further, a higher proportion of those with inadequate health literacy had a prolonged length of stay. Although patients with limited health literacy and self-efficacy may experience similar maximum weight loss after bariatric surgery as other patients, they still might have reduced health-related quality of life in terms of obesity-related problems. Increased awareness of this association as well as patient-centered support before and after bariatric surgery may be of benefit.

Early vascular aging plays a central role in chronic kidney disease (CKD), but its molecular causes remain unclear. Somatic mutations accumulate in various cells with age, yet their functional contribution to aging tissues is not well understood. Here we found progerin, the protein responsible for the premature aging disease Hutchinson-Gilford progeria syndrome, steadily recurring in vascular smooth muscle cells of patients with CKD. Notably, the most common progeria-causing mutation, LMNA c.1824C>T, was identified as a somatic mutation in CKD arteries. Clusters of proliferative progerin-expressing cells in CKD arteries and in vivo lineage-tracing in mice revealed clonal expansion capacity of mutant cells. Mosaic progerin expression contributed to genomic damage, endoplasmic reticulum stress and senescence in CKD arteries and resulted in vascular aging phenotypes in vivo. These findings suggest that certain somatic mutations may be clonally expanded in the arterial wall, contributing to the disease-related functional decline of the tissue.

Surgical repair of paraesophageal hernias (PEH) is associated with high recurrence rates. Various reinforcement techniques have failed to improve durability, warranting exploration of alternative strategies. The aim of this trial was to investigate whether adding a left-sided diaphragmatic relaxing incision to standard crural repair and fundoplication reduces recurrence rates. In this double-blind, dual-centre randomized clinical trial, patients undergoing PEH repair between August 2019 and August 2023 were randomized to receive either standard crural repair (control) or crural repair in combination with a left-sided diaphragmatic relaxing incision at the upper pole of the spleen. After crural repair, the incision was covered with synthetic mesh. All patients underwent total fundoplication. The primary endpoint was CT-verified PEH recurrence at 12 months. Secondary outcomes included perioperative course, reflux, dysphagia, abdominal symptoms, and Quality of Life (QoL) at 3, 6, and 12 months. Outcomes were analyzed by intention-to-treat. Seventy-six patients were randomized (38 per group). Groups were well balanced. Two patients (one per group) died within 90 days postoperatively. At 12 months, PEH recurrence was found in 23/35 (66%) in the control group and 20/37 (54%) in the intervention group (p = 0.313). Both groups reported postoperative improvements in swallowing, reflux, indigestion, and abdominal pain. RAND-36 QoL scores improved, primarily in physical functioning, without differences between neither allocated groups nor patients with or without recurrence. Radiological recurrence remains high following standard laparoscopic PEH repair with fundoplication. Addition of a left-sided diaphragmatic relaxing incision does not reduce recurrence risk at one year.

Introduction/Purpose Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) entail risks of vitamin and mineral deficiencies, and guidelines recommend lifelong supplementation. It remains unclear if postoperative intake of micronutrients differs between surgical methods. This exploratory substudy aimed to evaluate whether the reported intake of vitamins and minerals in diet and supplements differs between SG and RYGB one year after surgery. Methods Between April 2017 and May 2023, 285 participants from the randomized controlled multicenter trial “ Bypass Equipoise Sleeve Trial ” (BEST) were consecutively included at seven metabolic bariatric surgery centers in Sweden. The intake of vitamins and minerals from diet and supplements was self-reported at one-year follow-up and calculated in Dietist Net®. The Goldberg cut-off method was used to exclude under-reporters. Results One year after surgery, the reported daily energy intake was 1673 kcal and 1651 kcal, after SG and RYGB, respectively. Compared with reference data on Swedish dietary habits from 2010–2011, participants reported daily intakes from diet below the daily recommended intake (RI) for a greater number of micronutrients. The reported intake of Vitamin C from diet was 53 mg (SG) versus 72 mg (RYGB) (p = 0.001). Following both procedures most participants reported supplement intake consistent with the recommendations. The reported intake from supplements was 580 Retinol equivalents (RE) (SG) versus 656 RE (RYGB) for Vitamin A (p = 0.017), and 374 µg (SG) versus 436 µg for Folic Acid (p = 0.014). Conclusion In general, the reported intake of energy and vitamins and minerals from diet and supplements did not differ between SG and RYGB one year after bariatric surgery, except for a higher intake of vitamin C from diet, and vitamin A and folic acid from supplements after RYGB. These differences may reflect healthier food choices and better adherence to vitamin and mineral supplements following RYGB.

CONTEXT:Bariatric surgery is associated with reduced risk of cardiometabolic disease in obesity and type 2 diabetes (T2D). The mechanisms are not fully understood, but improvement in endothelial dysfunction has been implicated. OBJECTIVE:This work aimed to assess endothelial biomarkers before and after surgery. METHODS:A prospective cohort study with 2-year follow-up was conducted at a single center in Stockholm, Sweden. Participants included adults undergoing bariatric surgery, 28 with and 33 without T2D. Intervention included Roux-en-Y gastric bypass preceded by a 2-week low-calorie diet (LCD). Main outcome measures included plasma concentrations of glycocalyx biomarkers (hyaluronan [HA] and syndecan-1), E-Selectin, von Willebrand factor (VWF), and thrombomodulin (TM). RESULTS:At baseline, patients with diabetes had higher concentrations of E-Selectin (P = .041) whereas other biomarkers did not differ between groups. After LCD, E-Selectin, syndecan-1, and VWF were reduced. Two years after surgery, TM was unchanged whereas E-Selectin decreased, geometric mean (CV%) 41 (40) to 24 (61) ng/mL, syndecan-1 from 50 (73) to 38 (81) ng/mL, and VWF from 120 (52) to 103 (45)%, while HA increased from 25 (96) to 40 (78) ng/mL (P < .001 for all). E-Selectin initially declined faster in patients with diabetes (P < .003); otherwise the biomarker changes did not differ between groups. Variables with the highest predictive value for improvement in biomarkers were decrease in body weight and fat mass and increase in insulin sensitivity (HOMA-IR). CONCLUSION:Bariatric surgery is associated with sustained, beneficial alterations in biomarkers of glycocalyx and endothelial function in patients with obesity, both with and without T2D. It is suggested that reduced body weight/fat mass and improved insulin sensitivity are of particular importance for these alterations.

INTRODUCTION:New transoral and minimally invasive techniques for the treatment of gastroesophageal reflux disease (GERD) have emerged, warranting evaluation of their clinical efficacy and safety. METHODS:A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Based on the available amount of information about clinical efficacy, the review was restricted to Stretta, Esophyx/TIF, MUSE (Medigus ultrasonic surgical endostapler), LINX, and RefluxStop procedures. RESULTS:In total, 86 original studies evaluating the efficacy and safety of second-generation antireflux techniques were identified. The study populations are well described in which GERD is objectively verified. For Stretta, data were available from four double-blind, sham-controlled, randomized studies (RCT) albeit with a short follow-up time. Cohort-based data on 24-h pH monitoring, proton pump inhibitor (PPI) consumption, and QoL demonstrated a clinically significant long-term effect. For the Esophyx technique, two double-blind, sham-controlled randomized studies with 12 months of follow-up are available, which together with prospective cohort studies with longer follow-up demonstrate a sustained effect. The corresponding long-term effects of MUSE transoral technique need to be defined. The scientific documentation behind the LINX technique is incomplete, but data show the same level of efficacy in terms of objective assessments as for Esophyx. The scientific evidence for RefluxStop is still meager but promising. CONCLUSIONS:Both Esophyx and LINX seem to provide long-lasting symptom control with normalization of QoL in patients with chronic GERD. This seems to be true for patients with small hiatal hernia who responded well to treatment with PPI. MUSE and RefluxStop™ need better documentation to define their future role in clinical practice.

Chronic postoperative inguinal pain (CPIP) is a major adverse outcome of groin hernioplasty. Despite multiple CPIP studies, investigations involving unselected patients and sufficiently large cohorts to assess multiple predictors concurrently are still needed. This study evaluated the relative impact of preoperative predictors of CPIP after laparoendoscopic groin hernia repair. A secondary aim was to assess selection bias. This population-based cohort study included unilateral laparoendoscopic repairs from a prospective CPIP project within the Swedish Hernia Registry, where all groin hernia repairs recorded between September 2012 and December 2018 were surveyed at 1 year postoperatively. Responses were analyzed using multivariable logistic regression to assess whether any of 15 predetermined preoperative candidate variables, including demographics, comorbidities, and hernia-related factors, were associated with CPIP. Among 15 360 eligible patients, 10 525 (69

BACKGROUND & AIMS:Achalasia has been linked to increased mortality, but evidence from large population-based cohorts is scarce. We aimed to assess mortality in individuals with achalasia. METHODS:This nationwide cohort study included all adults in Sweden with incident achalasia (n = 704; 1969-2017; follow-up until December 31, 2021) without any other prior esophageal conditions. Achalasia was defined through International Classification of Disease codes in the Swedish National Patient Register in individuals who underwent endoscopic esophageal examination including biopsy as recorded in the histopathology cohort ESPRESSO. Individuals with achalasia were matched by age, sex, birth year, and county to up to 5 reference individuals (n = 3348) from the general population. In a secondary analysis, full siblings were used as secondary reference individuals. Mortality incidence rates (IRs) and multivariable-adjusted hazard ratios (aHRs) with 95% confidence intervals [Cis] for all-cause and cause-specific mortality were calculated using Cox proportional hazards modeling. RESULTS:During a median follow-up of 9.1 years, there were 270 deaths in individuals with achalasia, and 1023 in reference individuals (IR, 69.4 vs 51.9/1000 person-years). This corresponded to a 1.42-fold increased risk of death (95% CI, 1.21-1.65); or 1 extra death per every 6 individuals with achalasia followed for 10 years. Risk increases were seen for death from any cancer (IR, 17.4 vs 11.8; aHR, 1.65; 95% CI, 1.21-2.23), esophageal cancer (IR, 2.7 vs 0.2; aHR, 23.19; 95% CI, 3.27-164.55), and respiratory disease (IR, 7.4 vs 3.9; aHR, 2.22; 95% CI, 1.28-3.87), but not from cardiovascular disease (IR, 22.7 vs 19.6; aHR, 1.10; 95% CI, 0.84-1.45). Results remained robust across sensitivity analyses, including sibling comparisons. CONCLUSIONS:Individuals with achalasia had a 42% increased mortality rate compared with the general population. The elevated mortality risk indicates a need for long-term follow-up.

Background: Older adults undergoing surgeries face increased risks of postoperative neurocognitive disorders, which impair cognitive functions. Analog neurocognitive tests are commonly used, but digital tests offer faster, more accessible assessments. Objective: The primary aim of this study was to evaluate the feasibility of a digital cognitive test battery in older adults undergoing abdominal surgery. Feasibility included estimation of recruitment and retention rates, acceptability, perceived value, and usability of the test. The secondary aim was to explore outcome trajectories of cognition, depression, functional status, and quality of recovery. Methods: This nonrandomized feasibility study measured recruitment and retention rates using patient logs and expanded on these findings in semistructured interviews with nurses. Acceptability, perceived value, and usability were explored through interviews with patients and nurses, and the System Usability Scale (SUS). Cognitive functions were assessed with a digital cognitive test battery (Consortium to Establish a Registry for Alzheimer Disease [CERAD] word list learning test, Trail Making Test Parts A and B, Victoria Stroop Test, and Symbol Digit Pairing Test) and the Nursing Delirium Screening scale (NU-DESC), and depression with the Geriatric Depression Scale (GDS-15). Functional status was measured using the World Health Organization Disability Assessment Schedule (WHODAS), and postoperative recovery with the Swedish Quality of Recovery questionnaire (SwQoR-24). Quantitative data were analyzed using descriptive statistics and nonparametric tests and qualitative data with content analysis. Results: The test battery was feasible, acceptable, and demonstrated excellent usability. The mean SUS score was 87 (SD 17.9; 95% CI 78.9-95.2), and all predefined progression criteria were met. Recruitment spanned over 1.5 years, during which 24 patients were included (mean age of 77, SD 6.5 years; range: 63-90 years; n=13, 54% women). Most patients underwent laparoscopic colorectal cancer surgery. Three patients developed postoperative delirium for 1 day only. No patient developed delayed neurocognitive recovery or mild/major neurocognitive disorder at the postoperative follow-up. Qualitative data showed that both nurses and patients regarded the digital cognitive test battery as important for assessing cognitive function and found it easy to use and understand. Nurses reported that recruitment was challenging, partly because not all patients attended a preoperative in-person consultation before surgery. Conclusions: The digital, self-administered cognitive test battery was found to be feasible, acceptable, and usable in older adults undergoing abdominal surgery. However, recruitment challenges and a small, homogeneous sample limit generalizability and warrant careful consideration in a larger-scale study.