Journal of Internal Medicine最新文献

Background: Methotrexate (MTX) is the mainstay initial treatment of rheumatoid arthritis (RA), but individual response varies and remains difficult to predict. The role of genetics remains unclear, but studies suggest its importance.

Methods: Incident RA patients starting MTX-monotherapy were identified through a large-scale Swedish register linkage. Demographic, clinical, medical, and drug history features were combined with fully imputed genotype data and used to train and evaluate multiple learning models to predict key MTX treatment outcomes.

Results: Among 2432 patients, we consistently observed an estimated area under the curve (AUC) of ∼0.62, outperforming models trained on sex and age. The best performance was observed for EULAR primary response (AUC = 0.67), whereas models struggled the most with predicting discontinuation. Genetics provided negligible improvements to prediction quality.

Conclusions: Despite an extensive study population with broad multi-modal data, predicting MTX treatment outcomes remains a challenge. Common genetic variants added minimal predictive power over clinical features.

Background: The risk of major osteoporotic fractures (MOFs) and osteoporosis in patients with autoimmune Addison's disease (AAD) is unclear.

Objective: To investigate the risk of MOF in patients with AAD and the possible correlation with adrenal hormone replacement doses.

Methods: Swedish national health registers were used to identify 1869 subjects with AAD and 16,844 matched controls. The primary outcome was MOF, and the secondary outcome was treatment with osteoporosis medications. Marginal Cox models were used to compare time-to-event outcomes. The study period spanned from 1 July 2005 until 31 December 2020. Individuals at risk were followed from inclusion until censored or the end of the study period.

Results: A total of 77 patients with AAD (7.1/1000 person-years [PY]), and 387 matched controls (3.9/1000 PY) were diagnosed with MOF. The risk of MOF was higher in patients with AAD compared to matched controls, with an adjusted hazard ratio (aHR) of 1.82 (95% confidence interval [CI], 1.41-2.35) and increased in both male and female patients, with aHR of 2.51 (95% CI, 1.56-4.02) and 1.65 (95% CI, 1.22-2.24), respectively. Patients with AAD had an increased risk of treatment with osteoporosis medications: aHR 3.25 (95% CI, 2.71-3.99), compared to controls. No significant differences in MOF rates were observed between patients treated with intermediate or high doses of glucocorticoids compared to low doses (p = 0.967 and p = 0.580, respectively). Similarly, stratification by mineralocorticoid dose (<0.10 vs. ≥0.10 mg/day) showed no significant association regarding MOF (p = 0.915).

Conclusions: The risk of MOF is increased in patients with AAD without any apparent correlation to adrenal hormone replacement doses.

Background: Chest radiograph can independently predict adverse outcomes in outpatients. We examined the associations of aortic knob width (AKW), ascending aortic length (AAL), and ascending aortic width (AAW) from chest x-ray with death and cardiovascular events in adults aged 50 and above.

Methods: Participants without cardiovascular disease were included from the Guangzhou Biobank Cohort Study (2003-2008). AKW, AAL, and AAW were indexed by body surface area. Aortic enlargement was defined using sex- and age-specific thresholds, calculated as the average value plus 1.96 multiplied by the standard deviation (SD). The associations of AKW, AAL, and AAW indices with all-cause and cause-specific mortality (cardiovascular and cancer), and incident nonfatal and fatal cardiovascular events, were examined through multivariate Cox regressions. Logistic regressions were performed to determine risk factors for aortic enlargement.

Results: Among 27,047 participants (mean age 62 years ± 7 years SD), there were 6977 deaths and 6478 cardiovascular events over an average follow-up period of 16.3 years. Each SD increase in AKW index was associated with a higher risk of all-cause mortality, cardiovascular mortality, and cardiovascular events, with hazard ratios (95% confidence interval [CI]) of 1.13 (1.11-1.16), 1.20 (1.15-1.25), and 1.11 (1.08-1.14), respectively. Similar findings were observed regarding the AAL and AAW indices. Hypertension was a strong risk factor for enlarged AKW (odds ratio 2.52, 95% CI 2.17-2.93), AAL (1.95, 1.63-2.32), and AAW (1.80, 1.56-2.09), respectively.

Conclusions: Thoracic aortic parameters measured through an accessible, cheap, and safe chest radiograph were associated with higher risks of death and cardiovascular events. Hypertension should be managed.

Background: Physical activity guidelines recommend accumulating moderate-to-vigorous physical activity but interpreting and monitoring these recommendations remains challenging. Although step-based metrics from wearable devices offer a simpler approach, their relationship with health outcomes requires validation against established accelerometer measurements.

Objectives: To evaluate how effectively step-based metrics capture health-related information from accelerometer data and determine optimal step cadence and intensity thresholds associated with cardiometabolic health in middle-aged adults.

Methods: Cross-sectional data from 4172 participants (aged 50-64 years) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) were analyzed. Physical activity was measured using ActiGraph accelerometers, collecting both step metrics (daily steps and cadence) and full accelerometer data. Both cardiorespiratory fitness, estimated using a submaximal cycle ergometer test, and cardiometabolic health, assessed using a composite score of waist circumference, blood pressure, lipids, and glycated hemoglobin (HbA1c), were considered outcomes. Associations between physical activity and outcomes were examined using linear regression and partial least squares analysis.

Results: Step counting metrics retained 88% of the health-related information from full accelerometer data. The optimal accelerometer intensity associated with cardiometabolic health was around four metabolic equivalents of tasks (METs). A step cadence of 80 steps/min, rather than the commonly used 100 steps/min, appeared more relevant for capturing moderate-intensity activity. Combining step and accelerometer data provided additional explanatory power for cardiometabolic health.

Conclusion: Step data capture most of the health-related information from accelerometer-measured physical activity in middle-aged adults. These findings support the use of step-based metrics for assessing and promoting physical activity while suggesting a need for recalibration of intensity thresholds in free-living conditions.

Russell G, Kalafatakis K, Durant C, Marchant N, Thakrar J, Thirard R, et al. Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial. J Intern Med. 295(1):2024;51–67. https://doi.org/10.1111/joim.13721. Epub 2023 Oct 19.

Acknowledgements should include Lina Alim and Elizabeth Hudson, two medical students who helped the authors with the processing and analysis of data. These two individuals were inadvertently missed in the original version.

The online version of the article has been updated.

We apologize for this error.

Background: Data on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and kidney cancer (KC) are conflicting. This study aimed to evaluate this association in the general population and in patients with extensive NSAID use: rheumatoid arthritis (RA) and spondyloarthritis (SpA).

Methods: We conducted a nationwide register-based cohort study of the Swedish general population and among patients with RA or SpA, among whom NSAID use was around five times higher. In each of these cohorts, we assessed the incidence of KC 2010 through 2021 by NSAID exposure as defined by repeated prescriptions. We also evaluated KC mortality in individuals treated (vs. not) with NSAIDs, taking the cancer stage into account. Adjusted hazard ratios (HRs) were calculated through Cox regression, taking age, sex, educational level, comorbidities and family history of KC into account.

Results: Based on 751 incident cases of KC among 393,709 individuals in the general population (33% NSAID-exposed), the HR for NSAID-exposure was 1.32 (95% confidence interval [CI] 1.13-1.54), with the highest HRs during the first year of follow-up (HR thereafter 1.20). The corresponding cancer stage-adjusted HR for mortality from KC with NSAID-exposure was 1.26 (95%CI 0.87-1.82). In RA and SpA, the HRs for KC incidence with NSAID exposure were 0.83 (95%CI 0.58-1.18) and 1.60 (95%CI 0.78-3.29), respectively.

Conclusions: We found up to a 30% increase in the overall incidence and mortality from KC with NSAID in the general population. This association was attenuated beyond the first year of follow-up and inconsistent in populations with much higher NSAID use.

Background: Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related expansion of blood cells carrying preleukemic mutations, is associated with immune aging. This study aimed to investigate the association between CHIP and established autoimmune diseases.

Methods: We analyzed baseline data from 456,692 UK Biobank participants with available whole-exome sequences. The primary outcome was 19 autoimmune disorders. Associations among any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and gene-specific CHIP subtypes with the incidence of autoimmune diseases were assessed using Cox regression. Mediation analysis was performed to explore the role of inflammation in the link between CHIP and autoimmune diseases.

Results: We identified 17,433 any CHIP and 11,970 large CHIP at baseline. Participants with any and large CHIP were associated with 44% and 43% higher risk for Crohn's disease, 25% and 33% higher risk for psoriasis, 13% and 14% higher risk for rheumatoid arthritis, and 35% and 55% higher risk for vasculitis, respectively. Participants with CHIP status were associated with increased levels of inflammatory markers, including white blood cell, platelets, neutrophils, and neutrophil-to-lymphocyte ratio, with overall mediation ratios of 16.3% for Crohn's disease, 7.1% for psoriasis, 23.2% for rheumatoid arthritis, and 7.2% for vasculitis.

Conclusions: CHIP was associated with an increased risk for incident multiple autoimmune diseases, including Crohn's disease, psoriasis, vasculitis, and rheumatoid arthritis, potentially mediated by elevated inflammatory levels. Future research is needed to clarify the mechanisms underlying these associations and to explore potential interventions to reduce the associated risk.

Lung transplantation remains the definitive treatment for end-stage lung disease, but several critical challenges persist. Key issues include the limited availability of donor organs, ongoing debates over optimal preservation methods, and the controversy surrounding the best intraoperative support systems. Additionally, the efficacy of bridging strategies to transplantation continues to be questioned. This review delves into these pressing topics. This includes a focus on donation after cardiac death as a potential solution to expand the donor pool and recent advancements in hypothermic preservation, including innovative portable devices, and the role of bridging strategies. By addressing these multifaceted challenges, this review highlights the importance of continued advancements in donor management, organ preservation, and perioperative care to ultimately improve outcomes for lung transplant recipients.

Background: The optimal systolic blood pressure (SBP) target in patients with increased cardiovascular risk remains uncertain. This study evaluated the efficacy and safety of intensive SBP control (<120 mm Hg) compared to standard SBP control (<140 mm Hg) in patients with increased cardiovascular risk.

Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and Cochrane Library for RCTs published from database inception through November 2024 that compared intensive SBP control (<120 mm Hg) with standard SBP control (<140 mm Hg) in adults with high cardiovascular risk. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (MACE), cardiovascular death, stroke, myocardial infarction (MI), and heart failure. Safety outcomes included hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities.

Results: Five RCTs comprising 39,434 patients were included. The all-cause mortality was significantly lower in the intensive SBP control group (672 of 19,712 [3.4%]) compared to the standard SBP control group (778 of 19,722 [3.9%]) (risk ratio 0.87 [95% confidence interval, 0.76-0.99, p = 0.03]). The incidence of MACE, cardiovascular death, MI, stroke, and heart failure was significantly lower in the intensive SBP control group as compared to standard SBP control group. The treatment effect (MACE) was consistent across all subgroups. Conversely, intensive SBP control was associated with an increased risk of hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities.

Conclusions: Targeting intensive SBP control to less than 120 mm Hg was associated with a lower incidence of all-cause mortality and MACE but a higher incidence of adverse events.

Background: Chronic kidney disease and heart allograft vasculopathy are the primary causes of morbidity and mortality after cardiac transplant. This study aimed to evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on transplant survival, cardiovascular events, dialysis, and all-cause mortality in diabetes patients who have undergone heart transplantation.

Methods: In this research, we adopted data from the TriNetX collaborative network to observe outcomes in patients who underwent heart transplants between January 01, 2015 and December 31, 2022. A total of 6494 transplant recipients were identified, from which 1063 matched pairs of SGLT2i users and non-users were selected using propensity score matching. The Kaplan-Meier analysis and Cox proportional hazards models were applied to compare the risks of various outcomes between the study and control groups.

Results: In propensity-matched cohorts, patients using SGLT2i exhibited a lower risk of dialysis [hazard ratio (HR) (95% confidence interval [CI]): 0.566 (0.385-0.833)], graft rejection and failure [0.873 (0.774-0.985)], hospitalizations [0.822 (0.739-0.916)], and all-cause death [0.767 (0.627-0.938)] compared to non-users. Yet, no significant differences were observed between the two groups in the risks of post-transplant infection or sepsis [0.891 (0.739-1.075)], ischemic heart disease (HR: 1.044, 95% CI: 0.939-1.161), and heart failure worsening [0.915 (0.733-1.144)].

Conclusion: This multicenter cohort study demonstrated that cardiac transplant recipients with diabetes who received SGLT2i had a significantly lower risk of dialysis, graft rejection, hospitalization, and all-cause mortality compared to those who did not receive SGLT2i.