Journal of Internal Medicine最新文献

{"title":"International multidisciplinary consensus statement on sepsis code guidelines: A Delphi approach","authors":"M Borges-Sa,&nbsp;A Giglio,&nbsp;I Martin-Loeches,&nbsp;J Nates,&nbsp;JM González del Castillo,&nbsp;Y Cárdenas,&nbsp;P Mergulhao,&nbsp;FJ Candel,&nbsp;R Zaragoza,&nbsp;MN Larrosa-Escartin,&nbsp;P Vidal-Cortés,&nbsp;E Maseda,&nbsp;R Reina,&nbsp;JA Paiva,&nbsp;JL del Pozo,&nbsp;MV Villegas,&nbsp;M Salavert,&nbsp;C Soriano,&nbsp;J Hidalgo,&nbsp;I Machuca,&nbsp;J Gonçalves-Pereira,&nbsp;A Manuel-Vázquez,&nbsp;T Lisboa,&nbsp;M Pichardo-Viñas,&nbsp;J Barberán,&nbsp;G Esparza,&nbsp;G Castillo-Abrego,&nbsp;A Estella,&nbsp;K Ortega,&nbsp;A. Matos,&nbsp;N Raimondi,&nbsp;R Ferrer,&nbsp;JR Sanchez,&nbsp;I Huelmo,&nbsp;LA Gorordo-Delsol,&nbsp;V Campozano,&nbsp;A Soriano,&nbsp;J Perez,&nbsp;A Rodriguez","doi":"10.1111/joim.70145","DOIUrl":"10.1111/joim.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis remains a major global health challenge. International guidelines exist, but their implementation is inconsistent, and supporting evidence largely comes from high-income settings. The objective of this study was to generate international, multidisciplinary expert consensus on controversial aspects of sepsis management within the framework of sepsis code programs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multinational modified Delphi study was conducted with 164 experts from 22 countries, 12 specialties, and 105 scientific societies. Seven domains were evaluated: early diagnosis, biomarkers, diagnostic microbiology, hemodynamic monitoring, source control, antimicrobial therapy, and hemodynamic management. Consensus was defined as ≥70% agreement across three iterative rounds using Likert scales (Rounds 1–2) and binary format (Round 3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Consensus was achieved for 40 statements. Strong endorsement (82%–95%) was reached for structured hospital sepsis programs, NEWS-2 as the preferred early recognition tool, biomarker use (notably procalcitonin) to complement clinical assessment, urgent source control within 6 h independent of hemodynamic status, rapid molecular diagnostics integrated with antimicrobial stewardship, and norepinephrine as first-line vasopressor therapy. Experts also supported pharmacokinetic- and pharmacodynamic-guided antibiotic dosing, prolonged infusion of time-dependent agents, and dynamic rather than fixed fluid strategies. No consensus was reached on routine reliance on Sepsis-2, Sepsis-3, or qSOFA; high mean arterial pressure targets; or universal combination antimicrobial therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results provide multidisciplinary guidance for sepsis management, with emphasis on rapid recognition, targeted antimicrobial therapy, timely source control, and hemodynamic management guided by patient physiology. The recommendations are applicable to high- and middle-income healthcare systems.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"779-801"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Ehlers–Danlos syndrome: A multidisciplinary clinical framework for early suspicion, emergency-safe management and lifelong care","authors":"Salvatore Corrao,&nbsp;Maria Irene Ruggeri,&nbsp;Antonino Di Benedetto,&nbsp;Giacomo Corrao,&nbsp;Luigi Calvo,&nbsp;Salvatore Scibetta","doi":"10.1111/joim.70165","DOIUrl":"10.1111/joim.70165","url":null,"abstract":"<p>Vascular Ehlers–Danlos syndrome (vEDS), caused by likely pathogenic COL3A1 variants, carries a high risk of arterial dissection or rupture, intestinal perforation and uterine rupture, and a median survival near 51 years. It is often recognized only at a catastrophe, and its acute management is deliberately counter-intuitive. The therapeutic landscape changed in 2025 with the first randomized evidence for an angiotensin-receptor blocker. We provide a clinical, practice-oriented review for internists and the multidisciplinary team. As is appropriate for a rare disease, case-level evidence was considered alongside cohorts and trials. Suspicion is the rate-limiting step, and we set out speciality-specific red flags. Diagnosis requires molecular confirmation, with differentiation from other heritable arteriopathies. Genotype is a probabilistic predisposition, not a deterministic predictor: there is ascertainment bias, reduced penetrance and intrafamilial variability temper inference. Emergency care is harm-avoidant—catheter angiography, elective endoscopy and unnecessary surgery should be avoided, and endovascular and tissue-sparing techniques preferred. Pharmacological prevention rests on celiprolol, with randomized evidence now supporting irbesartan added to background celiprolol, and expert-centred consideration of angiotensin-receptor blockade when celiprolol is not tolerated. Surveillance should be individualized along the European Reference Network on Rare Multisystemic Vascular Diseases logic. Pregnancy, psychosocial care and cascade testing complete lifelong management. In vEDS, earlier recognition and the avoidance of iatrogenic harm—not new molecules—offer the largest near-term gains in survival and quality of life.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"743-757"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer co-medication quality in older patients with polypharmacy: A large randomized trial testing a medication review versus usual care","authors":"Miriam Degen,&nbsp;Annette Kopp-Schneider,&nbsp;Tomislav Vlaski,&nbsp;Sigrid Carlsson,&nbsp;Peter Hallermann,&nbsp;Ludmilla Jewlanowa,&nbsp;Jana Barinoff,&nbsp;Valentin Goede,&nbsp;Christian Lüders,&nbsp;Thomas Kiefer-Trendelenburg,&nbsp;Diana Lüftner,&nbsp;Jasmin Doll,&nbsp;Jürgen Wagner,&nbsp;Birgit Leibbrand,&nbsp;Hermann Brenner,&nbsp;Ben Schöttker","doi":"10.1111/joim.70161","DOIUrl":"10.1111/joim.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evidence from randomized controlled trials (RCTs) testing medication reviews in geriatric oncology is sparse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a single-blinded RCT in ten rehabilitation clinics across Germany. Patients with common cancers, aged ≥ 65 years, and polypharmacy (regularly ≥ five drugs) were randomly allocated in equal proportions to usual care or a comprehensive pharmacist-led medication review conducted with the validated Fit fOR The Aged (FORTA) list. The FORTA score is the sum of drugs classified as potentially inappropriate medication (PIM) (each two points), drug underuse (each one point), and drug overuse (each one point). Changes in the FORTA score and its subcomponents from rehabilitation admission to discharge were tested using the chi-square test or the Wilcoxon's rank-sum test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>At admission, 66.1%, 94.6%, and 58.9% of 443 trial participants included in the intention-to-treat analysis were exposed to PIM, medication underuse, or overuse, respectively, and the median FORTA score was six. At discharge, participants of the intervention group (<i>n</i> = 234) had a statistically significant greater reduction in the mean FORTA score than the control group (<i>n</i> = 209): mean difference [95% confidence interval]: −3.7 [−4.2; −3.3] score points. Furthermore, the proportions of subjects with PIM, underuse, and overuse were statistically significantly reduced by the intervention by 41.3, 35.5, and 30.7 percentage points (all <i>p </i>&lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The pharmacist-led intervention with the FORTA list substantially improved the medication quality of older cancer patients with polypharmacy in clinical practice. A reduction of four FORTA score points (rounded) translates, for example, to the withdrawal of two PIMs or four drugs labeled overuse.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"802-820"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routine versus standardized blood pressure measurements: Agreement and association with cardiovascular disease","authors":"Olivia Gästgivars,&nbsp;Joachim Ögren,&nbsp;Bo Carlberg,&nbsp;Mattias Brunström","doi":"10.1111/joim.70164","DOIUrl":"10.1111/joim.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recommendations for blood pressure (BP) measurement are poorly followed in clinical practice, possibly leading to inaccurate BP estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To assess the agreement between routine and standardized BPs, and the association between BP level and cardiovascular disease (CVD) for each measurement type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Standardized BPs were recorded in a screening program for middle-aged people during 1992–2012 in Sweden. Intraindividual differences between standardized BP and routine BP from primary care were calculated. Association between BP level and composite CVD, and population-attributable fraction (PAF) explained by BP, were determined through adjusted Cox regression for each measurement type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 9567 participants, routine BPs were on average 4.0/1.7 mmHg higher than standardized BPs. Routine measurements frequently misclassified people into higher BP categories; 16% more had hypertension (≥130/80 mmHg), and 50% less had normal BP (&lt;120/80 mmHg), compared with standardized measurements. Analysis of 19,720 participants found a stronger association between BP level and CVD for standardized than for routine measurements, with increased risk from ≥120/80 and ≥140/90 mmHg, respectively. Adjusted hazard ratio for ≥140/90 mmHg compared to &lt;120/80 mmHg was 2.11 (95% confidence interval 1.77–2.51) for standardized BPs and 1.43 (1.15–1.77) for routine BPs. BP ≥120/80 mmHg explained 41.8% (32.0–50.1) of CVD events with standardized measurements and 19.3% (1.5–33.8) with routine measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Routine BPs deviate from standardized BPs, resulting in significant misclassification and attenuated association with CVD, reducing the PAF for BP to less than half. Our findings emphasize the need for accurate BP measurement in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"821-831"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists and serious adverse events: Evidence, uncertainty and clinical implications","authors":"Peter Ueda","doi":"10.1111/joim.70170","DOIUrl":"10.1111/joim.70170","url":null,"abstract":"<p>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.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"758-778"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European genomic: An untapped opportunity to strengthen the fight against antimicrobial resistance","authors":"Antonio Vitiello,&nbsp;Andrea Zovi","doi":"10.1111/joim.70163","DOIUrl":"10.1111/joim.70163","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Antimicrobial resistance (AMR) represents one of the most pressing threats to global and European public health, undermining the effectiveness of modern medicine and increasing morbidity, mortality, and healthcare costs. In 2019 alone, bacterial AMR was associated with a substantial burden of disease across the WHO European Region, highlighting the urgent need for stronger and more coordinated surveillance and response strategies [&lt;span&gt;1, 2&lt;/span&gt;]. Because multidrug-resistant organisms do not respect national borders, fragmented surveillance systems are increasingly inadequate to address their rapid emergence and cross-border dissemination.&lt;/p&gt;&lt;p&gt;Genomic sequencing has transformed our ability to characterize resistant pathogens, identify transmission chains, detect emerging resistance determinants, and investigate outbreaks [&lt;span&gt;3, 4&lt;/span&gt;]. However, its full public health potential depends on the capacity to integrate pathogen genomic information with clinical, epidemiological, microbiological, and antimicrobial-use data. Across Europe, these data remain distributed among heterogeneous national and regional systems, with differences in standards, interoperability, governance, sequencing capacity, and analytical pipelines [&lt;span&gt;3, 5&lt;/span&gt;]. The urgency of strengthening European AMR surveillance is illustrated by recent trends in key AMR reported in Table 1.&lt;/p&gt;&lt;p&gt;These divergent trajectories highlight the need for surveillance systems capable not only of measuring resistance trends, but also of identifying the resistant clones, transmission pathways, and emerging resistance mechanisms driving them. Although the European Centre for Disease Prevention and Control (ECDC), through the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the emerging European genomic surveillance framework, provides the core European architecture for AMR surveillance, systematic integration of pathogen genomic data with clinical, epidemiological, microbiological, and antimicrobial-use data remains limited.&lt;/p&gt;&lt;p&gt;In particular, the ECDC-coordinated EURGen-Net provides an important foundation for genomic surveillance of antimicrobial-resistant bacteria across Europe. Building on this existing framework, ECDC is well positioned to coordinate the development of a European approach that links routine AMR surveillance with pathogen genomic surveillance and relevant health-data infrastructures [&lt;span&gt;5&lt;/span&gt;]. Europe is simultaneously developing an unprecedented ecosystem for secure and interoperable access to genomic and health data. The 1 + Million Genomes (1 + MG) initiative aims to enable secure cross-border access to genomic and corresponding clinical data, supporting research, personalized healthcare, disease prevention, and health policy [&lt;span&gt;6&lt;/span&gt;]. Building on this vision, the Genomic Data Infrastructure (GDI) is establishing a federated and secure infrastructure through which genomic and associated phenotypic and ","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"844-846"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Employment status and occupation are associated with liver cirrhosis: A nationwide Swedish case–control study","authors":"Marie Zalesiak,&nbsp;Juan Vaz,&nbsp;Eralda Asllanaj,&nbsp;Martin Henriksson,&nbsp;Hannes Hagström,&nbsp;Ying Shang","doi":"10.1111/joim.70166","DOIUrl":"10.1111/joim.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To assess the odds of liver cirrhosis across labor-market status and occupations in working-age adults and whether these patterns differed by etiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"832-843"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European Consortium for Lipodystrophies consensus definition and classification framework for monogenic lipodystrophy","authors":"Robert K. Semple,&nbsp;Martin Wabitsch,&nbsp;Baris Akinci,&nbsp;Saif Alyaarubi,&nbsp;Marjoleine F. Broekema,&nbsp;Rebecca J. Brown,&nbsp;Giovanni Ceccarini,&nbsp;Carolina Cecchetti,&nbsp;Solaf M. Elsayed,&nbsp;Antía Fernández-Pombo,&nbsp;Alessandra Gambineri,&nbsp;Ingrid M. Jazet,&nbsp;Lotte Kleinendorst,&nbsp;Konstanze Miehle,&nbsp;Elif A. Oral,&nbsp;Flavia Prodam,&nbsp;Ferruccio Santini,&nbsp;David B. Savage,&nbsp;Nadia Shaukat Ali,&nbsp;Ekaterina Sorkina,&nbsp;Magdalena Szopa,&nbsp;Marie-Christine Vantyghem,&nbsp;Camille Vatier,&nbsp;Corinne Vigouroux,&nbsp;Julia von Schnurbein,&nbsp;David Araújo-Vilar","doi":"10.1111/joim.70157","DOIUrl":"10.1111/joim.70157","url":null,"abstract":"<p>Lipodystrophy comprises a heterogeneous group of disorders characterized by reduced adipose tissue often associated with severe metabolic complications. Lipodystrophy may be genetic, acquired, or secondary to medical therapies initiated for other conditions. Despite major advances in understanding adipose tissue biology and in human genetic technologies, diagnosis of lipodystrophy is still commonly delayed or missed. Conversely, increasing use of next-generation sequencing has led to proliferation of proposed new genetic causes of lipodystrophy with variable supporting evidence. To address these challenges, an international expert working group from the European Consortium for Lipodystrophies first developed a consensus definition of lipodystrophy as deficient development and/or inadequate maintenance of adipose tissue not attributable to nutritional deprivation or a systemic catabolic state. Anatomical adipose deficiency alone is generally insufficient for diagnosis, with evidence of adipose tissue dysfunction or pathology also usually required. Building on this definition, a framework for evaluating candidate monogenic lipodystrophy syndromes is suggested, based on the strength of human phenotypic, genetic, and biological evidence. Primacy was assigned to direct evidence from affected individuals, with genetic and biological evidence considered supportive but not determinative. This approach accommodates both the variable penetrance and expressivity characteristic of many lipodystrophy syndromes and potential discrepancies between human observations and experimental models. Although the proposed definition is applicable across all forms of lipodystrophy, the classification system described here is restricted to monogenic disorders. Together, these tools aim to improve clinical recognition, promote diagnostic consistency, and provide a robust and adaptable framework for evaluating emerging gene–disease associations in lipodystrophy.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"725-742"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sepsis care and management: Where do we stand?","authors":"Evangelos J. Giamarellos-Bourboulis","doi":"10.1111/joim.70154","DOIUrl":"10.1111/joim.70154","url":null,"abstract":"&lt;p&gt;Sepsis remains the top medical unmet need with almost 50 million new cases and 11 million deaths every year. Mortality may even reach 40% among patients with septic shock [&lt;span&gt;1&lt;/span&gt;]. The global epidemiology and lethality generate obvious concerns about our ability to manage. It is obvious that progress in an era of medical technology is lacking.&lt;/p&gt;&lt;p&gt;An article by Borges-Sa et al., published in this issue of the &lt;i&gt;Journal of Internal Medicine&lt;/i&gt;, provides some challenging answers to the emerging questions [&lt;span&gt;2&lt;/span&gt;]. The authors managed to bring together 164 experts from 22 countries around the globe, and they conducted a Delphi round where they asked for feedback on major topics of sepsis care, including early recognition, use of biomarkers and rapid microbiology testing (RMT), source control, antibiotic treatment, and hemodynamic monitoring and management. One major contribution value of this endeavor was that experts represented 12 different specialties, including not only clinicians but also clinical pharmacists and workers on public health. The Delphi process managed to provide consensus on most topics of sepsis care. However, the distribution of answers and the level of disagreement between experts raised major concerns. More precisely, considerable disagreement was raised regarding the value of the qSOFA (quick sequential organ failure assessment) score and the Sepsis-3 definitions for early recognition. Experts agreed that NEWS2 (new early warning score), sepsis teams, and tools of artificial intelligence are needed for early recognition. Regarding the use of biomarkers, consensus was reached for the role of procalcitonin and MDW (monocyte distribution width) and RMT. Surprisingly, the experts did not consider that RMT can replace standard microbiology. In the remaining topics, the level of disagreement was far more limited. Consensus was easily reached on intense hemodynamic monitoring, early source control, early administration of antibiotics, the need to cover multidrug-resistant organisms using new agents, including carbapenemase inhibitors, and supportive management.&lt;/p&gt;&lt;p&gt;No real differences exist between the consensus reached by the Delphi and the current Surviving Sepsis Campaign guidelines (SSC 2026) [&lt;span&gt;3&lt;/span&gt;]. The SSC 2026 guidelines underpin the importance of early sepsis recognition; they agree on the use of the NEWS2 score instead of the qSOFA score, and they suggest using “sepsis code” or “sepsis bundle” for early management [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Both the results of the Delphi by Borges-Sa et al. [&lt;span&gt;2&lt;/span&gt;] and the recommendations by the SSC 2026 [&lt;span&gt;3&lt;/span&gt;] indicate the need for early sepsis recognition and how behind we are in reaching this goal. This unmet need was further proven by the results of the European Sepsis Care Survey (ESCS), which was conducted between August 2021 and June 2022. In the ESCS, health care professionals (HCPs) from 1023 hospitals and 69 countries were asked t","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 6","pages":"722-724"},"PeriodicalIF":7.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharyngotonsillitis, aphthous stomatitis, and adenitis precede familial Mediterranean fever by two decades.","authors":"Eli Magen, Suhail Aamar, Israel Magen, Eugene Merzon, Ilan Green, Avivit Golan-Cohen, Shlomo Vinker, Ariel Israel","doi":"10.1111/joim.70177","DOIUrl":"https://doi.org/10.1111/joim.70177","url":null,"abstract":"<p><strong>Background: </strong>Familial Mediterranean fever (FMF) and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome share innate-immune features, but population-level data on oropharyngeal morbidity before FMF recognition are lacking.</p><p><strong>Objectives: </strong>To examine the magnitude, timing, specificity, and treatment burden of a PFAPA-like oropharyngeal phenotype in patients later diagnosed with FMF.</p><p><strong>Methods: </strong>Population-based matched case-control study in Leumit Health Services, Israel. FMF patients with colchicine dispensing (n = 3324) were matched 1:4 by birth year and sex to 13,296 controls. Oropharyngeal diagnoses, tonsil/adenoid surgery, antibiotic dispensing, and ear, nose, and throat (ENT) visits were compared across windows up to 20 and 10 years before diagnosis (30-day blackout), using streptococcal, hypertrophy, and non-ENT negative controls with false discovery rate (FDR) adjustment.</p><p><strong>Results: </strong>A PFAPA diagnostic code was recorded in 2.6% of FMF patients versus 0.1% of controls (odds ratio [OR] 25.4, 95% confidence interval 14.3-48.5). Up to 20 years before diagnosis, future FMF patients had more acute tonsillitis (35.6% vs. 27.2%; OR 1.48, 1.37-1.61), viral-labeled tonsillitis (OR 2.65), oral aphthae (OR 1.72), and cervical lymphadenitis (OR 1.62; all q < 0.05); associations persisted after diagnosis. Streptococcal sore-throat coding was not increased (lifelong OR 1.03, 0.94-1.14). Antibiotic dispensing and ENT visits were increased; tonsillectomy alone was more frequent (OR 2.51), although surgical comparisons did not survive FDR correction.</p><p><strong>Conclusions: </strong>FMF is associated with a non-streptococcal, PFAPA-like oropharyngeal phenotype detectable years before diagnosis. Recurrent pharyngotonsillitis with aphthae or cervical adenitis, without demonstrated streptococcal disease, may be a clinical cue to consider FMF in at-risk populations.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}