Journal of Internal Medicine最新文献

Prader-Willi syndrome (PWS) is a rare, neurodevelopmental, multisystemic syndrome caused by lack of expression of paternal genes on chromosome 15q11.2-13. PWS is characterized by muscular hypotonia, abnormal body composition, hormone deficiencies, cognitive dysfunction and behavioural issues, including hyperphagia, increasing the risk of severe obesity. A single causative gene for hyperphagia has not been identified, and regulation of hunger and satiety is complex and multifactorial, making it difficult to identify a specific neuropeptide or hormone as the most important. Cornerstone treatments are a strict, controlled diet and regular physical activity. Several clinical trials with different pharmacological agents have been performed attempting to reduce or treat hyperphagia and obesity. However, many drug programmes have been discontinued due to adverse events or not reaching endpoints. In this review, we have focused on phenomenology and management of hyperphagia, treatment with oxytocin (OT), glucagon-like-peptide-1 receptor agonists (GLP-1RA) and diazoxide choline. We conclude that controlled food access is crucial; managing expectations about food mitigates food-related behaviour; OT treatment of infants with PWS results in less severe hyperphagia at ages 3 and 4 years old; and that the effects of GLP-1RA on body weight seem modest. Studies of diazoxide choline extended-release (DCCR), the first approved treatment of hyperphagia in PWS, have shown promising results, particularly in managing severe hyperphagia, reducing fat mass and improving behavioural issues. Thus, although progress is being made in targeted pharmacological therapies to control hyperphagia, controlled food access remains crucial to prevent obesity but is not sufficient for management of food and behaviour.

Glucagon-like peptide-1 (GLP-1) receptor agonists provide benefits in weight reduction, glycaemic control in Type 2 diabetes, and cardiovascular and renal outcomes. Their widespread use has given rise to concerns regarding rare but potentially serious adverse events. This narrative review appraises evidence regarding seven serious adverse events linked to GLP-1 receptor agonists: thyroid cancer, non-arteritic anterior ischaemic optic neuropathy (NAION), suicidal behaviours and self-harm, diabetic retinopathy complications, acute pancreatitis, gallbladder and biliary disease and intestinal obstruction. Evidence from mechanistic studies, spontaneous reports, randomized trials and cohort studies is considered. Gallbladder and biliary disease has the most consistent evidence supporting a causal association. Worsening of diabetic retinopathy appears most consistent with early worsening after rapid glycaemic improvement in patients with pre-existing retinopathy. For thyroid cancer, NAION, suicidal behaviour and self-harm, acute pancreatitis and intestinal obstruction, evidence regarding causality remains uncertain. Rare events, incomplete ascertainment in trials and residual confounding in observational studies limit inference. Because these events are rare, even substantial relative risk increases generally correspond to small absolute risk increases in broad populations but may become relevant in patients with high baseline risk. Treatment decisions should consider the strength and uncertainty of safety evidence, individual baseline risk, expected benefits relative to available alternatives and patient preferences.

Introduction: Fluid restriction is the current first-line therapy for hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD), yet up to 50% of patients do not achieve an adequate plasma sodium correction. Reported predictors of nonresponse include urine osmolality >500 mOsm/kg, the Furst ratio >1 [(UNa + UK)/(PNa)], urine sodium >130 mmol/L, and plasma urea >5 mmol/L. This study aimed to validate these cutoffs in an independent cohort.

Methods: This is a predefined secondary analysis of a randomized, controlled, prospective, and multicenter hyponatremia trial (plasma sodium <130 mmol/L). Response to fluid restriction was defined as an increase in plasma sodium of >3 mmol/L within the first 24 h.

Results: Of 839 patients with SIAD, 229 were treated with fluid restriction within the first 24 h and had complete laboratory data. Among these patients, 86 (38%) were classified as responders and 143 (62%) as nonresponders. Higher urine osmolality (p = 0.015) and higher plasma sodium levels (p < 0.001) were independently associated with nonresponse in multivariable logistic regression analysis. Urine osmolality >500 mOsm/kg had a specificity of 78% (positive likelihood ratio (LR+) 1.68), whereas urine sodium >130 mmol/L had a specificity of 97% (LR+ 3.81). The combination of both cutoffs markedly improved discriminatory performance (LR+ 9.62, positive predictive value 0.94).

Conclusion: The present study validated urine osmolality >500 mOsm/kg and urine sodium >130 mmol/L as cutoffs for predicting nonresponse to fluid restriction in patients with SIAD. Combining both cutoffs identifies patients at high risk of nonresponse, in whom early initiation of second-line therapy should be strongly considered.

Background: Liver cirrhosis is often diagnosed in working-age adults and carries a poor prognosis. A better understanding of variation by employment status and occupation may support earlier and more targeted diagnostic evaluation.

Objectives: To assess the odds of liver cirrhosis across labor-market status and occupations in working-age adults and whether these patterns differed by etiology.

Methods: In this nationwide case-control study, individuals aged 35-65 years with cirrhosis during 2002-2021 were identified from Swedish national registries and matched to up to four controls on age, sex, and municipality. Labor-market status in the year before diagnosis was classified as employed, unemployed, disability/activity benefit, long-term sick leave, or other. Employed individuals were classified into occupations. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, with physical and engineering professionals as the reference group.

Results: We included 23,033 cases and 92,106 controls. Cases were less often employed than controls (25.7% vs. 66.2%) and more often belonged to labor-market strata associated with a lower socioeconomic status. In analyses, including employed and unemployed individuals (7485 cases; 63,747 controls), unemployment was associated with the highest odds of cirrhosis. Among employed individuals, food preparation workers and refuse and recycling workers had the highest odds. Stratified by etiologies, associations were strongest for alcohol-related cirrhosis. Patterns across sex strata were similar, with generally larger effect sizes in men.

Conclusion: Among working-age adults, unemployment and selected occupations were strongly associated with incident cirrhosis. Routinely collected employment information may help identify groups who could benefit from earlier liver evaluation.

Conventional Swedish snus is used by millions in Scandinavia and increasingly worldwide, yet its cardiovascular effects remain poorly characterized. The emergence of nicotine pouches—commonly referred to as ‘white snus’ in Sweden—that deliver comparable nicotine without tobacco constituents adds complexity to a heterogeneous landscape and raises questions about whether cardiovascular risk follows nicotine exposure regardless of product type. We explore epidemiological and mechanistic evidence on snus and cardiovascular disease, the contributions of nicotine versus tobacco-specific nitrosamines (TSNAs) to risks, and identify knowledge gaps, with focus on novel nicotine products and the research opportunity offered by the Swedish Tobacco Cohort (SWETOC). Epidemiological evidence suggests elevated cardiovascular disease (CVD) mortality among snus users, with the most consistent signals for fatal myocardial infarction and heart failure. Associations with incident atherosclerotic events are more heterogeneous. Mechanistic evidence points to nicotine-mediated pathways, including sympathetic activation, endothelial dysfunction and increased arterial stiffness, whereas evidence for TSNA-driven CVD risk remains sparse, and declining TSNA levels in modern Swedish snus make that path less likely and harder to study. Nicotine pouches deliver comparable or higher systemic nicotine than conventional snus but lack long-term cardiovascular outcome data. Real-world cessation data from Denmark suggest structured programmes can achieve 6-month abstinence rates of approximately 53% among non-smoking nicotine users. The evidence supports nicotine as the primary driver of snus-associated CVD risk, with important implications for the cardiovascular safety of novel nicotine products. Evidence is needed to inform public health guidance, clinical advice and regulatory decisions. SWETOC represents a unique infrastructure to generate this evidence.

Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome, affects 10%–13% of women of reproductive age and remains underdiagnosed despite its substantial health burden. The introduction of the new PMOS nomenclature in 2026 reflects a fundamental shift in understanding the condition as a lifelong endocrine and metabolic disorder with prominent reproductive, psychological, dermatological, and cardiometabolic consequences. Once considered primarily a reproductive disorder, PMOS is now recognized as a multisystem condition. Insulin resistance and compensatory hyperinsulinemia are central pathophysiological mechanisms linking endocrine and metabolic features to reproductive dysfunction. In PMOS, insulin resistance affects 75% of lean and 95% of overweight women. Here we focus on the metabolic features. Recent advances in epidemiology include the first systematic review and meta-analysis examining regional variations in PMOS prevalence. In parallel, contemporary population-based studies of unselected women have confirmed that increased risks of metabolic complications observed in selected clinical cohorts also apply at the population level and have demonstrated increased risk of major adverse cardiovascular events (MACE). These studies report an almost 3-fold increased risk of Type 2 diabetes (OR 2.9) and MACE (HR 1.2–2.5), with cardiovascular risk diverging from approximately 35 years of age. In this review, we summarize recent advances in epidemiology, pathophysiology, metabolic dysfunction, and cardiovascular risk of PMOS, together with their implications for diagnosis and clinical management. Recognizing PMOS as an early-life marker of cardiometabolic disease highlights opportunities for earlier diagnosis, prevention, and individualized risk stratification, supporting integrated, patient-centered care across the life course.