Journal of Internal Medicine最新文献

Background: Cardiovascular risk factor control reduces the risk of recurrent events after acute coronary syndrome (ACS). Long-term post-ACS management is poorly studied.

Objectives: To assess frequency of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) monitoring and target achievement during 3 years post-ACS.

Methods: Data from all patients hospitalized for ACS in Uppsala between 2012 and 2020 were obtained from electronic health records (EHRs). The probability of measurement and target achievement was estimated with adjusted regression models. Associations were assessed for sex, participation in cardiac rehabilitation (CR), presence of diabetes with nurse-led follow-up and documentation of an ICD-10 code for chronic ischaemic heart disease in the EHR.

Results: Among 6083 patients (median age 73 years, 34% female), follow-up data were available for 72% in year 1, 56% in year 2 and 44% in year 3. Year 3 LDL-C was not measured in 48% of patients, and 19% were at target (<1.8 mmol/L). For SBP, 16% lacked a measurement, and 50% were at target (<140 mmHg). Female sex was associated with lower probability of having LDL-C measured or having LDL-C or SBP at target. CR participation, structured diabetes follow-up or having a chronic ischaemic heart disease code in the EHR was associated with a higher probability of LDL-C and SBP measurements at 2 and 3 years.

Conclusions: Lack of measurement and low risk factor achievement highlight missed opportunities in secondary prevention. Female sex, lack of structured follow-up and the absence of diagnostic labelling were associated with less frequent monitoring and poorer risk factor control.

Background: North Korean defectors in South Korea offer a rare natural model to trace cancer risk evolution after rapid environmental transition, given shared genetics but markedly contrasting early life exposures with South Korean residents.

Methods: Using the Korean National Health Insurance database, we constructed a nationwide matched cohort of 25,798 North Korean defectors and 1,276,601 South Korean residents (1:50 frequency matching by sex, age, and index year). We compared overall and site-specific cancer risks and examined time-varying hazard ratios (HRs) since resettlement.

Results: Overall cancer risk was higher among defectors (HR 1.13; 95% confidence interval, 1.07-1.18), particularly in men (HR 1.31). Liver (HR 2.53), uterine cervical (HR 2.10), and lung cancer (HR 1.69) were markedly elevated, reflecting infection- and deprivation-related legacies. In contrast, cancers more prevalent in developed countries, notably breast (HR 0.48) and colorectal (HR 0.71), were initially lower. However, HRs began to rise over time, especially for breast cancer, indicating a trend toward convergence with host-population patterns.

Conclusion: The cancer profile of North Korean defectors demonstrates a dual burden: persistent risks from infection-related cancers rooted in pre-defection exposures and growing vulnerability to lifestyle-related cancers after resettlement. These findings highlight the importance of dual-track prevention strategies that address both legacy and emerging cancer risks in rapidly transitioning populations.

Background: Current guidelines recommend at least 10 years of follow-up for all pheochromocytoma and paraganglioma (PPGL) patients and lifelong monitoring for high-risk individuals. Nonetheless, data identifying patients who may not require routine lifelong follow-up are scarce.

Methods: Among 999 patients with PPGL, 703 who were non-metastatic, non-hereditary, and had undergone complete resection were included. Variables that significantly differed between the recurrence (n = 50) and non-recurrence groups over 10 years (n = 83) were identified, and cutoff values were determined using receiver-operating characteristic curve analysis. These very low-risk criteria were validated in an internal cohort and an external dataset from the National Institutes of Health.

Results: The non-recurrence group was older and had smaller pheochromocytomas (PCCs) than the recurrence group, with cutoffs of 37 years and 5.7 cm, respectively. The non-recurrence group had a higher percentage of patients with pheochromocytoma of the adrenal gland scaled score (PASS) <4 or grading system for adrenal pheochromocytoma and paraganglioma (GAPP) score <3 (p = 0.027). Age >40 years (hazard ratio [HR] [95% confidence intervals] of 0.36 [0.17-0.76]), PCC size <6 cm (HR = 0.43 [0.19-0.98]), and PASS <4 or GAPP score <3 (HR = 0.37 [0.16-0.89]) were associated with lower recurrence risk. None of the patients meeting all these criteria in the internal (n = 114) and external (n = 13) validation sets experienced recurrence.

Conclusion: This study suggests that routine lifelong follow-up may be unnecessary for patients with sporadic PCC aged >40 years, size <6 cm, and PASS <4 or GAPP score <3.

Objective: To compare the efficacy and safety of extended interval (Q3-4W) enzyme replacement therapy (ERT) versus standard biweekly (Q2W) ERT in clinically stable type 1 Gaucher disease (GD) patients.

Methods: We emulated a target trial with a sequential trial design, using data from the French Gaucher Disease Registry. Eligible patients were treated for ≥2 years biweekly without clinical events. Every 3 months, switchers to Q3-4W were matched to Q2W patients by age, sex, referral center follow-up, disease history (bone events, anemia, thrombocytopenia, splenectomy, and hepatosplenomegaly), and dose of ERT. The primary outcome was a composite of GD-related events (bone events, anemia, and thrombocytopenia). A 10% non-inferiority margin was prespecified. Secondary outcomes were biomarker changes and economic analyses.

Results: Among 280 eligible GD patients, 63 switched to Q3-4W and were matched to a total of 215 Q2W patients, followed for an average of 6.3 years. No significant difference in the risk of clinical events was observed between groups (hazard ratio: 0.98 [95% confidence intervals (CI): 0.54-1.51]). During follow-up, absolute risk difference remained below the 10% non-inferiority threshold at all timepoints. Biomarkers remained stable or slightly decreased in the Q3-4W group. The dosing interval extension led to an average reduction of 55 infusions per patient, corresponding to approximately €450,000 saved per patient over 6 years.

Conclusion: In stable GD1 patients, extending ERT administration to every 3-4 weeks was non-inferior to the standard biweekly regimen, supporting personalized spacing strategies that may improve quality of life and reduce healthcare costs.

Background: Chronic intestinal pseudo-obstruction (CIPO) is a severe gastrointestinal motility disorder that may be idiopathic or associated with systemic disease. In idiopathic cases, the pathophysiological mechanisms remain poorly defined. Although mutations in angiogenic factors have been reported in mitochondrial forms of CIPO, their role in non-mitochondrial cases is still unclear.

Objective: To investigate genetic and molecular contributors to CIPO, with a specific focus on intestinal microvasculature.

Methods: Jejunal samples from patients with CIPO were analysed by whole exome sequencing (WES) and mitochondrial DNA (mtDNA) profiling. Morphometric and immunohistochemical studies assessed collagen remodelling, vascular architecture, neuromuscular integrity and hypoxia. Expression of angiogenic factors, including thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF), was evaluated.

Results: WES did not identify known CIPO-causing variants, but rare mutations in collagen-related genes were detected in a subset of patients. Tissue analysis revealed higher fibrosis, vascular remodelling with a predominance of very small vessels, thinning of the longitudinal muscle and neuronal loss. TP and VEGF expression were significantly reduced, whereas hypoxia-inducible factor-1α (HIF-1α) was markedly upregulated. mtDNA integrity and copy number were preserved, whereas haplogroup J was overrepresented. Multivariate analysis linked these alterations to a higher frequency of sub-occlusive episodes.

Conclusions: Vascular dysfunction and collagen abnormalities emerge as key contributors to neuromuscular degeneration in CIPO. These findings provide novel mechanistic insights into disease pathophysiology and support further exploration of vascular-targeted therapeutic strategies.

Background and objective: The development of Type 1 diabetes (T1D) is shaped by genetic predisposition and epigenetic regulation. Human leukocyte antigen (HLA) risk alleles are major genetic determinants, but the epigenetic landscape in relation to disease onset remains unclear. Early-life epigenetic modifications may reveal how environmental and epigenetic factors interact in T1D pathogenesis.

Methods: We investigated epigenetic differences in cord blood DNA from individuals with different HLA risk alleles who later developed T1D using epigenome-wide association studies.

Result: High-risk HLA carriers showed differentially methylated genes (DMGs) mainly involved in immune and autoimmune processes, resembling patterns in other autoimmune diseases. In contrast, low-to-neutral risk carriers exhibited DMGs linked to signaling cascades, metabolic pathways, and Type 2 diabetes-related mechanisms such as beta cell function and insulin signaling.

Conclusion: These findings indicate that heterogeneity in T1D pathogenetic mechanisms based on HLA background may influence disease development.

The integration of immune checkpoint inhibitors into perioperative management marks a major evolution in curative-intent oncology. This review examines the current evidence for perioperative immunotherapy encompassing neoadjuvant, adjuvant, and combined strategies in melanoma and non-melanoma skin cancers, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), esophageal and gastroesophageal junction cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, gynecological malignancies, and hepatocellular carcinoma. Neoadjuvant immunotherapy demonstrates biological advantages by exposing the immune system to intact tumor antigens, consistently improving event-free survival and pathological response rates across tumor types. Notable successes include CheckMate 816 in NSCLC, KEYNOTE-522 in TNBC, and emerging trials in melanoma that show superior outcomes compared to adjuvant-only approaches. Pathological complete response and major pathological response have emerged as robust surrogate endpoints correlating with long-term survival. In contrast, adjuvant immunotherapy shows more variable results, with demonstrated recurrence-free survival benefits but inconsistent overall survival (OS) advantages-particularly concerning given the risk of overtreatment in patients potentially cured by surgery alone. Critical challenges include the absence of predictive biomarkers in most cancer types, immune-related adverse events occurring in up to 30% of patients, substantial healthcare costs, and insufficient OS follow-up duration in many approved indications. Future priorities include biomarker development, adaptive trial designs incorporating response-guided therapy, and long-term toxicity assessment. Although perioperative immunotherapy is reshaping curative-intent cancer treatment, optimal patient selection, treatment sequencing, and safety optimization remain essential for widespread implementation.