Henrik Toft Sørensen’s research while affiliated with Stanford University and other places

Objectives Given the potential role of vagus nerve stimulation in treating rheumatoid arthritis (RA), we examined the incidence of RA and osteoarthritis (OA) in patients who underwent different forms of vagotomy that disparately affect the inflammatory reflex. Methods Using nationwide health registries, we constructed cohorts of patients in Denmark who underwent truncal or superselective vagotomy between 1977 and 1995 and comparison members from the general population matched 10:1 on birth year, sex, and calendar year. We identified incident RA or OA and used Cox proportional hazards models to compute adjusted hazard ratios (aHRs) and corresponding 95% CI. Results Our cohorts consisted of 2,260 truncal vagotomy patients matched with 22,610 comparators, and 3,810 superselective vagotomy patients matched with 38,090 comparators. The incidence rate (IR) of RA per 1,000 person-years (95% CI) in the truncal vagotomy cohort was 10.2 (6.5–15.3) versus 7.2 (6.1–8.4) in the matched comparison cohort. The aHR (95% CI) for RA development was 2.62 (1.47–4.67) in the truncal vagotomy cohort and 1.05 (0.51–2.17) in the superselective vagotomy cohort, with respect to comparison cohorts. The risk of developing OA was not significantly different for either vagotomy cohort compared with comparison cohorts. Conclusion Truncal vagotomy was associated with an increased incidence of RA; this association was not observed with superselective vagotomy. No association with either form of vagotomy was seen with OA. These findings support the hypothesis that disruption of vagus nerve signaling impacts the inflammatory reflex and contributes to the development of RA.

Objective Obesity is associated with various gastrointestinal (GI) conditions. Because of the epidemic rise of obesity, we examined associations between overweight/obesity and incidence of individual GI diseases. Design Cohort study. Setting Denmark, 1997-2018. Participants Using nationwide healthcare registries, we identified All Danes ≥18 years with a hospital diagnosis of overweight/obesity. We created an age- and sex-matched general population comparison cohort. Exposure A diagnosis code of overweight/obesity. Main Outcomes and Measures We compared the incidence of hospital-diagnosed GI diseases from 1 year after overweight/obesity diagnosis. Results We included 129 466 patients with overweight/obesity (70.9% female, median age 49.3 years). Their incidence rate of GI disease was 30.1 per 1000 person years (95% CI: 29.8-30.5) vs 16.7 (95% CI: 16.5-16.8) for comparators, yielding an adjusted hazard ratio (aHR) of 1.7 (95% CI: 1.7-1.7). The aHRs indicated elevated risk of all GI disease sub-types in the overweight/obesity cohort, including cholelithiasis: 2.8 (95% CI: 2.7-2.9), cholecystitis: 2.6 (95% CI: 2.4-2.8), acute pancreatitis: 2.2 (95% CI: 2.0-2.4), stomach ulcer: 2.0 (95% CI: 1.9-2.1), cirrhosis: 1.5 (95% CI: 1.3-1.7), and obesity-associated GI cancer: 1.2 (95% CI: 1.2-1.3). The aHR for any GI disease was 1.4 (95% CI: 1.4-1.5) in men and 1.9 (95% CI: 1.8-1.9) in women. Among patients 18 to <30 years, the aHR was 2.6 (95% CI: 2.5-2.7) vs 1.3 (95% CI: 1.3-1.4) among individuals ≥70 years. Conclusions and Relevance Overweight/obesity is a risk factor for a wide range of GI diseases and is expected to become an even greater clinical challenge in the future.

OBJECTIVE Anticipated risks of urinary tract infections (UTI) and genital tract infections (GTI) associated with sodium–glucose cotransporter 2 inhibitors (SGLT2i) may prevent their use in clinical practice. We investigated whether initiation of SGLT2i, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs), was associated with an elevated risk of UTI and GTI in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In this cohort study emulating a target trial, we included all adult metformin users initiating SGLT2i or GLP-1RAs in Denmark in 2016–2021 and used inverse-probability of treatment (IPT) weighting to balance potential confounders. We estimated IPT-weighted risk and risk ratios of community- or hospital-treated UTI and GTI, performing both intention-to-treat and on-treatment analyses. RESULTS This study included 52,414 SGLT2i initiators and 27,023 GLP-1RA initiators with a median follow-up of 2.9 to 3.9 years. The estimated risks of UTI within the first year were nearly identical: 10.0% in SGLT2i and 10.2% in GLP-1RAs in intention-to-treat analyses corresponding to a risk ratio of 0.98 (95% CI 0.94, 1.03). For GTI, the 1-year risks were elevated under SGLT2i therapy at 2.0% vs. 0.7% (risk ratio 2.95 [95% CI 2.52, 3.44]). During the 5-year follow-up, the relative UTI risk remained almost constant (0.96 [95% CI 0.94, 0.99]) whereas the GTI risk ratio with SGLT2is decreased to 1.64 (95% CI 1.49, 1.80). CONCLUSIONS In routine clinical care, SGLT2i initiation is not associated with increased risk of UTI compared with GLP-1RA initiation. However, early GTI risk is up to threefold larger in SGLT2i users.

Aim To determine whether mortality for patients with diffuse large B‐cell lymphoma who survived 5 years (DLBCL5ys) returns thereafter to general population levels. Methods This population‐based cohort study included Danish residents between January 1, 2000, and December 31, 2023. Information on diagnoses, comorbidities, and vital status came from Danish health and administrative registries. Analyses included 4164 DLBCL5yr patients—55% of incident patients—and 41,640 individuals from the general population matched 10:1 by exact birth year, sex, and the calendar year of achieving DLBCL5yr status. We used Cox proportional hazards models to compute matched mortality hazard ratios (HRs) and 95% confidence intervals (CIs) and controlled for comorbidities by adding Charlson comorbidity index scores to our models. Results Mortality rates were elevated for DLBCL5yr patients soon after their 5‐year survival date. The absolute difference in mortality was 20 deaths per 1000 person‐years, and the HR adjusted for comorbidities was 1.5 (95% CI 1.4–1.6). Mortality was elevated similarly for men and women. The elevated mortality for DLBCL5yr patients varied in magnitude by age, calendar period, and comorbidity burden, and included excess mortality from DLBCL, cancers other than lymphoma, and respiratory diseases. Conclusions We found that mortality for DLBCL5yr patients did not return to general population levels.

Importance Although past research suggests an association between migraine and attempted suicide, there is limited research regarding risk of attempted and completed suicide across headache disorders. Objective To examine the risk of attempted and completed suicide associated with diagnosis of migraine, tension-type headache, posttraumatic headache, and trigeminal autonomic cephalalgia (TAC). Design, Setting, and Participants This was a population-based cohort study of Danish citizens from 1995 to 2020. The setting was in Denmark, with a population of 5.6 million people. Persons 15 years and older who were diagnosed with headache were matched by sex and birth year to persons without headache diagnosis with a ratio of 5:1. Data analysis was conducted from May 2023 to May 2024. Exposures First-time headache diagnoses identified from inpatient hospitalizations, emergency department visits, and outpatient specialty clinic visits using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) codes. Main Outcomes and Measures Diagnostic codes from the ICD-10 were used to identify attempted suicide from the Danish National Patient Registry and the Danish Psychiatric Central Research Register and completed suicides from the Danish Register of Causes of Death. Absolute risks (ARs) and risk differences (RDs) for attempted and completed suicide were calculated using the cumulative incidence function. Hazard ratios (HRs) for attempted and completed suicide associated with headache diagnosis were computed adjusting for age, sex, year, education, income, baseline comorbidities, and accounting for competing risk of death. Results In total, 119 486 persons (83 046 female [69.5%]) diagnosed with headache were identified and matched with 597 430 persons (415 230 female [69.5%]) drawn from the general population. Participants’ median (IQR) age was 40.1 (29.1-51.6) years. The 15-year AR of attempted suicide among persons diagnosed with headache was 0.78% (95% CI, 0.72%-0.85%) vs 0.33% (95% CI, 0.31%-0.35%) in the comparison cohort (RD, 0.45%; 95% CI, 0.39%-0.53%). The 15-year AR of completed suicide among persons diagnosed with headache was 0.21% (95% CI, 0.17%-0.24%) vs 0.15% (95% CI, 0.13%-0.16%) in the comparison cohort (RD, 0.06%; 95% CI, 0.02%-0.10%). The hazards of attempted suicide (HR, 2.04; 95% CI, 1.84-2.27) and completed suicide (HR, 1.40; 95% CI, 1.17-1.68) were elevated among persons with headache vs comparison cohort members. Findings were consistent across headache types, with stronger associations for TACs and posttraumatic headache. Conclusions and Relevance Results of this cohort study revealing the robust and persistent association of headache diagnoses with attempted and completed suicide suggest that behavioral health evaluation and treatment may be important for these patients.